Scand J Thor Cardiovasc Surg 9: 229-239, 1975
RIGHT DUCT LYMPH DURING AND AFTER OPEN-HEART SURGERY Hans Erik Hansson From the Departments of Thoracic Surgery and Clinical Chemistry, University Hospital, UppsaIa, Sweden
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
(Submitted for publication February 21, 1974)
Abstract. The right lymphatic duct (RLD) was cannulated in 26 patients operated upon with open-heart surgery. The thoracic duct was cannulated in 4 additional patients and both the thoracic and the right lymphatic ducts were cannulated in 2 further patients. The R LD was also cannulated in a control group consisting of 5 thoracotomy-operated patients. Lymph was collected continuously and its flow and content of albumin, electrolytes and the enzymes, GOT, GPT, CPK and L D H were analysed. A significant amount of cardiac lymph was present in about 60% of the cannulations. After cardiopulmonary bypass, lymph enzyme concentrations often rose rapidly to very high levels. The significance of the enzyme concentration-patterns and some characteristics of the flow pattern are discussed.
Rudbeck (1653) was the first to study the lymphatics of the heart. The first detailed anatomical study, however, was published as late as 1939 (Patek, 1939). In 1940, Drinker et al. published the now classic physiological study for flow and composition of canine cardiac lymph. After the technique of cannulating the efferent cardiac trunks was developed, several investigations on canine cardiac lymph were performed (Miller et al., 1964; Areskog et al., 1965; Ullal et al., 1972; Malmberg, 1972). Similar investigations have not been carried out on human cardiac lymph. It is difficult in practice to get an opportunity to cannulate the two efferent main trunks which presumably exist (Allisson & Sabiston, 1957; Kampmeier, 1928; Jdanov, 1959). There are also experimental results indicating cardiac damage after total obstruction of the lymph flow adjacent to the heart (Symbas et al., 1963; Kline et al., 1964). Cardiac lymph is mainly drained via the right lymphatic duct (Shore, 1928; RouvBre, 1932; Warren & Drinker, 1942; Leeds et al., 1959; Miller, 1963). We have cannulated the right lymphatic duct or the bronchomediastinal duct and presented some aspects concerning the surgical anatomy and the flow and
composition of the lymph (Hallkn & Hansson, 1974). Cardiac lymph in the right lymphatic duct (RLD) is diluted with lymph from the lungs, the right arm and the neck. It is conceivable to reduce the admixture to include only pulmonary lymph if the bronchomediastinal trunk is selectively cannulated. The aim of this investigation was to study the influence of open-heart surgery on the flow and composition of the lymph in the RLD or in the bronchomediastinal trunk.
PATIENTS Thirty-seven patients (25 men, 12 women) were examined, whose mean age was 53 years (range 23-67 years). Patients and diagnoses are presented in Table I. The R LD was cannulated in 26 open-heart surgery cases (cardiopulmonary bypass group RLD). Ten of these patients were diagnosed with aortic valve disease (designated A 1-10), 12 patients with mitral valve disease (M 1-12), and 4 cases with left ventricular aneurysm (LVA1-4). The R LD was also cannulated in a control group consisting of 5 patients thoracotomy-operated for other reasons. The thoracic duct was cannulated in 4 cases operated upon with open-heart surgery. Both the R L D and the thoracic duct were simultaneously cannulated in 2 cases.
METHODS Cannulation was performed as previously described (HallBn & Hansson, 1974), both following and simultaneous with the normal pre-operative preparations. The patients were under general anaesthesia. Selective cannulation of the bronchomediastinal duct was attempted. Using anatomical criteria, the procedure was considered successful in 18 cases ( 5 5 %). When the trunk was thin and poorly developed, o r when technical difficulties impeded a complete dissection, a central ligation was made and a catheter was placed in the main trunk. However, in the results all lymph is named right duct lymph (see Discussion). Anaesthesia was maintained with i.v. phenoperidine in doses of Scand J Thor Cardiovasc Surg 9
230 H. E. Hansson Table I Patients Cardiopulmonary bypass group RLD cannulations Aortic valve disease (Al-10) Mitral valve disease (M 1-12) Left ventricular aneurysm (LVA 1 4 )
No. of patients
10
12 4
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
26
Control group RLD cannulations Lung cancer Mitral stenosis Aortic aneurysm Cardiopulmonary bypass group Thoracic duct cannulations Aortic valve disease Aortic and mitral valve disease
3 1 4
Bilateral cannulations Aortic valve disease Left ventricular aneurysm
1 1 2
5-10 mg and d-tubocurarine in doses of 20-30 mg. In a few cases pancuroniumbromide was substituted for d-tubocurarine. The patients were ventilated with an Engstrom-respirator, equal parts of nitrous oxide and oxygen being given. During bypass, the patients were ventilated with 2 l/min of air using an endexpiratory pressure of 5 mmHg to prevent atelectasis. During the first post-operative night, the patients were respirator-treated and received in most cases repeated small doses of phenoperidine as an analgetic and sedative. A median sternotomy was performed in the aortic valve disease group, a right thoracotomyin the mitral valve disease group, and in the left ventricular aneurysm group, a bilateral thoracotomy was made in 2 cases and a sternotomy in 2 cases. Moderate hypothermia was induced (3Cb32"C) and coronary perfusion with oxygenated blood was used. Cross-clamping of the aorta was only employed in one case of mitral valve disease in two periods, 40 minutes and 30 minutes, respectively. The lymph was collected continuously, usually at one-hour intervals during the first 7-10 hours after cardiopulmonary bypass and thereafter at 3-hour intervals. In the middle of each lymph-collecting period a blood sample was taken as a reference. The samples were kept at +4"C and, after centrifugation, frozen to - 194°C. The samples were analysed in series as previously described (Halltn & Hansson, 1974). Only patients in whom drainage functioned satisfactorily for more than 9 hours were selected for inclusion.
COMPLICATIONS No serious complications occurred. In 4 cases a slight supraclavicular oedema developed which, howScand J Thor Cardiovasc Surg 9
ever, completely disappeared after a couple of days. In one case a haematoma developed which required surgical evacuation. At a routine follow-up 2 months postoperatively no complications were found. RESULTS Technical aspects It is a technically difficult procedure to cannulate a tiny lymphatic vessel in a limited time period prior to operation. It is also difficult to maintain drainage function. Now, after more than 120 cannulation attempts, it can be stated that with experience it is almost always possible to identify lymph ducts in the right venous angle. Lymph ducts were found in all but 4 cases. It also seems possible to cannulate the vessel and make the drainage function initially, i.e., during the first hour, in about 75% of the attempts. Continuous lymph drainage for more than 10 hours diminishes this high rate to 50%. The most common reasons for failure are dislocation of the catheter or clotting of the catheter in connection with a low flow and/or blood staining. Due to the valves in the lymph ducts, it is usually impossible to introduce the catheter more than a few millimetres, and therefore difficult to ensure safe fixation. Dislocation will occur when the patient is moved into position for operation and on transfer to the Intensive Care Unit. A slow flow rate inevitably seems to lead to clotting of the catheter and cessation of flow. This was most clearly observed immediately before the first heparin dose was given prior to bypass. In a few cases it was possible to restore the flow by cautious flushing of the catheter with a heparin solution. Observations on lymph fIow The rate of lymph flow showed wide variations, partially due to experimental artifacts, depending on technical difficulties in maintaining an optimal drainage through the catheter, and partially to anatomical variations of the lymphatics (see Discussion). The results shown below are therefore presented more as clinical observations than statistically corroborated facts. When the RLD or the bronchomediastinal trunk was cannulated, four phases were observed (cardiopulmonary bypass group, 26 patients):
Right duct lymph during and after open-heart surgery
".ci""
Lymph flow
AS 'A1
Albumin
In,m/x
10
B
1
2
3
4
5
6
7
8
9
W
h
u
Ti""'
40
in
5
10
1
A
A b
1
1
------__-
MS+MI
Lymph flow mi/hour
231
2 .I
s A
a
B
1 2 3 4 5 6 7 8 9 l O h o v s
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
b LymM flow
gr"'
L VA
"TWr
Albumin
Lymph flow
ml/hour
CONTROL GROUP
Albumin
g/100 ml
d
C
Lynph flow
THORACIC DUCT CANNULATED
Albumin
s/lm m l
I
I
A
Fig. l a . Aortic valve disease group. 10 patients. RLD cannulated. Fig. 16. Mitral valve disease group. 12 patients. RLD cannulated. Fig. I c . Left ventricular aneurysm group. 4 patients. RLD cannulated. Fig. I d . Control group. 5 patients. RLD cannulated. Fig. l e . Thoracic duct cannulated. 4 patients.
Ih
B
1
2
Fig. la-e. Lymph flow and concentration of albumin for the different groups. Bars denote lymph flow, unbroken lines concentration of albumin in lymph and dashed lines concentration of albumin in serum.
3
4
5
6
7
6
9
1
0
I. Initially, after the cannulation, there was often
a high lymph flow, in 10 cases more than 10 ml/h (max 96 ml/h). During the period prior to bypass (1-2 hours), some patients showed an increase and others a decrease in the flow rate, i.e. no uniform tendency was observed in the flow rate when thoracotomy was started. 11. During cardiopulmonary bypass the flow usually diminished or ceased completely. In 6 cases the flow ceased, in 12 cases there was a considerable,
decrease and in 8 cases (of which 6 patients with mitral valve disease) the flow was unchanged. 111. After bypass, when the heart started to beat and the lungs were fully ventilated, the lymph flow usually increased; in the mitral valve disease group, however, only in 7 cases out of 12. This increase was observed in a few cases almost immediately when the heart was converted from ventricular fibrillation, but usually after a delay of up to 1/21 hour. During the following 3-5 hours, both the flow and urine production were often high. The lymph and urine flows showed the same dependency on the systolic blood pressure, especially in cornbination with hypovolaemia. If the blood pressure Scand J Thor Cardiovasc Surg 9
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
232 H . E. Hansson decreased, reflecting a moderate hypovolaemia, both the lymph and urine flows diminished. Blood-staining of the lymph was regularly observed after bypass. The blood-staining usually increased during the first few hours until the lymph was sanguineous. Then a stabilization occurred and the colour remained unchanged. In a few cases the lymph became clearer 4-6 hours after cardiopulmonary bypass. There were also a few cases with increasing blood admixture. Exceptionally, the sanguinolent colour remained after centrifugation as a sign of haemolysis. In these cases there was also haemolysis in the blood samples. IV. During the late postoperative period, after the first 5 hours, the lymph flow diminished gradually and ceased completely within 16 hours in 11/26 cases. In 10 cases the flow was essentially unchanged and in 5 cases it increased. In the latter cases all patients were in left ventricular failure. The three different diagnostic groups are compared in Fig. 1 a-c. Patients with aortic valve disease have a comparatively lower lymph flow, while the mitral group often have a high lymph flow, also during bypass. In the control group (Fig. 1d) there was generally a low lymph flow. Especially the two cases with lung cancer had a low flow, which was in agreement with the findings in earlier cannulations. Bloodstaining was observed in 3 cases. In 2 cases operated upon with transventricular dilatation of the mitral ostium, a higher flow was observed together with a small postoperative increase. Both the right lymphatic duct and the thoracic duct were cannulated in 2 cases. In the case of aortic valve stenosis, the flow in the thoracic duct diminished considerably 8 hours after the operation and at about the same time the flow in the RLD increased considerably, giving the impression of a collateral communication between the left and right side. As anticipated, a rather high flow was found when the thoracic duct was cannulated (Fig. le). During the bypass, the flow diminished. Blood-staining was observed in all 4 cases, with a tendency towards clearing after about 5-6 hours. In one case the lymph was opalescent, which is remarkable considering that the patient had not received food during the preceding 15 pre-operative hours. The albumin concentration was relatively constant both in lymph and in serum (Fig. 1). The concentration was always lower in lymph as compared with serum. During and after bypass the albumin Scand J Thor Cardiovasc Surg 9
was lowest and thereafter rose somewhat. In general, there was a tendency towards a low albumin concentration in connection with a high lymph flow. Electrolytes The following electrolytes were analysed: Na+, K+, Ca++ and C1-, in most cases in both lymph and serum. However, not unexpectedly, the results showed a very confusing picture. Electrolyte infusion, which often had to be given peroperatively, also complicated the analysis of the figures. It may be of interest that the potassium concentrations often showed rapid variations. Enzymes The following enzymes were analysed, GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), LDH (lactate dehydrogenase) and CPK (creatine phosphokinase). Haemolysis, which interferes with LDH activity and to some extent GOT activity, was observed in the following cases in lymph (figures within parentheses denote hours after bypass): A 2 (4), A6 (114), A7 (0-16), A9 (2-14), A10 (2-4), M1 (0), M 2 (2), M7 (1-5), M9 (2-9), M10 (2-14), M11 (1-3; 9-16), M12 (4; 11-13), LVAl (0-6). In serum, haemolysis occurred in the following samples: A7 (3), M3 (l), M5 (l), M7 (3), M 8 (l), MI2 (0-3), LVA 4 (0-1). Thoracic duct cannulations: The thoracic duct was cannulated in 4 cases, in all of which the enzyme concentrations were lower in lymph than in serum throughout the observation period, usually about 20 hours. However, the concentrations gradually increased, reflecting on a lower-displaced level the enzyme concentration curves of the serum. Bilateral cannulations: The RLD and the thoracic duct were both cannulated simultaneously, in two cases of which there was a more rapid rise in enzyme activity after the bypass in the RLD compared with the thoracic duct or the serum. The first case (Fig. 2a) had a left ventricular aneurysm which was resected. The postoperative course was uncomplicated and with good cardiac function. The rise in enzyme content in lymph and serum was comparatively moderate during the first few hours after bypass. The second case (Fig. 2b) had a severe aortic stenosis with a gradient of 110 mmHg. A low cardiac
Right duct lymph during and after open-heart surgery RIGHT DUCT LYMPH CPK unit / 1
L 00
LDH unit / ml
WT,GPT RIGHT DUCT LYMPH unit / ml OPERATION ECC
CPK unit / I
h
10000 .-1000
233
- 5000
200 GPT
0
2
4
6
8
10
2000
1000
hours
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
0 LDH unit ,'rnl
1oov"o
LEFT DUCT LYMPH
I CPK
LDH IGOT,GPT unit / rnl unit /
I4
unit / 1
400 40
LDH GOT CPK GPT
200 20 I
0
2
4
6
8
10
-200
5000
I
2
GOT, GPT unit / rnl
I-
8
6
10
12
:I' t
I hours
2 000
I
2
4
8
6
10
12
600 400
200
a
0
2
L
6
8
10
16 hours
SERUM
/
CPK unit / 1
300
14
unit / m /
t
GPT
CPK
-100
unit / ml
2 00 20
16 hours
LEFT DUCT LYMPH
500
0
LDH unit/ml
14
OPERATION ECC
1000
]
4
t
OPERATION ,GP'/5000
100 hours
b
0
2
4
6
8
10
12
I4
16 hours
Fig. 2. Bilateral cannulations. (a) Patient with left ventricular aneurysm operated upon with resection of the aneurysm. (b) Patient with aortic stenosis operated upon with valve re-
placement. N.B. the rapid rise in enzyme concentrations in RLD as compared with those in serum and the thoracic duct.
output syndrome developed postoperatively with progressive left ventricular failure and the patient died 25 hours after operation. The enzyme concentrations reached extremely high values, with a first maximum peak in RLD lymph 1 hour after bypass. Control group: Only small changes were observed. Fig. 3 shows the mean values. The LDH activity rose somewhat in both lymph and serum. The CPK activity also rose slightly in the lymph. The changes were insignificant in respect of GOT and GPT.
RLD cannulations, cardiopulmonary bypass group: In 26 cases operated upon with the aid of extracorporeal circulation, the RLD or the bronchomediastinal trunk was cannulated. In 16 cases (61 %), much higher concentrations of enzymes were found in lymph after the bypass as compared with serum, while in 10 cases (39%) the concentrations were lower (Table 11). Among these 16 cases, the enzyme values before and in the beginning of bypass were approximately
16- 752916
Scand J Thor Cardiovasc Surg 9
234 H . E. Hansson unrt/ml 1 Gun,t/ml LDH OT.GPI
A
LYMPH
2
L
6
8
LYMPH
12
10
11
16 hours CPK un,t/l
500 250 A
2
4
6
8
10
12
14
16 hours
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
SERUM
Fig. 3. Control group mean enzyme values. Only small changes are observed.
the same. Fig. 4 shows a typical pattern. At the end of bypass or during the first hour afterwards, a sharp rise in GOT, LDH and CPK activity commenced. This rapid phase usually lasted 3-5 hours. The variation between enzyme curves then became considerable, but essentially two types of patterns can be distinguished. In about 60% of the cases, enzyme values followed a plateau-shaped course, with a distinct maximum in a few cases. In the other #%, the enzyme activity showed a continuous rise. Only moderate changes were observed in GPT activity. In 10 cases the enzyme concentrations were lower in the lymph (Table 11). This was always valid for GOT, LDH and GPT, but CPK very often showed a somewhat higher concentration in the lymph (as compared with serum). This is of certain importance and indicates that
0
2
4
8
6
10
I2
K
16
18
bows
Fig. 4. Patient with aortic stenosis operated upon with valve replacement showing typically comparative enzyme patterns for lymph and serum after cardiopulmonary bypass.
no or only small amounts of cardiac lymph were present in the collected lymph (see Discussion). No anatomical criteria distinguished these 10 patients from the others. In serum there was in all 26 cases a continuous, slow rise in the enzyme concentrations. No maximum occurred during the first 24 hours, but usually during the second or third day after the operation. In Figs. 5-8, the individual enzyme curves for each of the 26 cases are presented according to diagnosis group. The 10 patients with lower enzyme-
Table I1 End of bypass
Pre-op
2 h after bypass
4 h after bypass
6 h after bypass
10 h after bypass
16 h after bypass
Lymph Serum Lymph Serum Lymph Serum Lymph Serum Lymph Serum Lymph Serum Lymph Serum A. 16 patients GOT, unit/ml GPT, unit/ml CPK, unit/l LDH, unit/ml
20 21 58 433
33 30 47 5 74
15
25 23 64 374
51 20 260 513
46 26 118 587
137 25 798 1059
102 32 319 812
201 33 1235 1416
19
32 16 85 45 1
35 12 281 509
51
20 160 541
48 15 415 605
289 148 42 36 420 1588 988 1757
173 355 41 62 548 1512 1165 1936
195 403 48 57 525 1512 1048 2025
206 55 555 1087
B. 10 paiients GOT, unit/ml GPT, unit/ml CPK, unit/l LDH, unit/ml
11
56 217
Scand J Thor Cardiouasc Surg 9
11
I05 309
60 21 238 586
52 17 430 609
66 25 285 677
70 22 564 666
94 31 415 720
98 27 919 768
102 31 608 660
Right duct lymph during and after open-heart surgery GOT umt/ ml
LYMPH
. LV43 P., ,
'.d
umt/
500
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
235
- m'
LYMPH
PM3
100-
300 -
ua 200.
M7
M 12
3 100MS
M6
A
a
D 0
2
L
6
8
10
12
1I
b hours
A
~~
6'0
2
4
6
8
10
12
Y
16hwm
b
Figs. 5-8. Individual curves for 26 patients presented according to diagnostic group. On the abscissa, A denotes half a n hour before bypass, B in the middle of bypass and number 1-16 denote hours after bypass. All enzyme concentrations values are interpolated to these times. A rapid rise in enzyme concentration after bypass and a fairly constant relationship between enzyme curves within individual cases
concentrations compared with serum included 3 cases from the aortic group, indicated A2, A 6 and A8, 5 cases from the mitral group indicated M2, M5, M6, M8 and M 12 and 2 cases from the left ventricular aneurysm group indicated LVA2 and LVA4. A general finding was a fairly constant relationship between enzyme curves within individual cases. The rise occurred almost simultaneously for GOT, CPK and LDH, and later on the curves showed in general the same pattern of variations. To a certain extent this was also valid for GPT. This indicates a simultaneous escape of enzymes from the damaged heart cells.
can be seen. In the following cases serum enzyme levels exceeded those in lymph: A2, A6, A8, M2, M 5 , M6, M8, M 12, LVA2 and LVA4. Fig. 5 a . Aortic valve disease group+LVA group. GOT activity. Fig. 5b. Mitral valve disease group. GOT activity.
The aortic valve group and the LVA group (Figs. 5a-8a) showed in general a higher enzyme rise com-
pared with the mitral valve group (Figs. 5b-8b). In the aortic group case no. A l , AS and A10 showed very high values. Case A 1 was a high risk patient with a severe aortic stenosis and calcified valves. After valve replacement procedure, a serious left ventricular failure made it difficult to discontinue the cardiopulmonary bypass. Bypass time, including left heart bypass, lasted 343 minutes. Postoperatively a LOW cardiac output syndrome developed and the patient died 36 hours after operation. Autopsy revealed a fresh myocardial infarction in the left ventricle.
Scand J Thor Cardiooasc Surg 9
236 H. E. Hansson LYMPH
LYMPH
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
A
A
8
0
2
4
6
8
10
I2
I(
5 h m
b Fig. 6a. Aortic valve disease group activity.
+ LVA
group. CPK
Fig. 6b. Mitral valve disease group. CPK activity.
C LVA3
i
LYMPH
MI1
MV M7 M9 M8 M5 M6
A
Scand J Thor Cardiouasc Surg 9
0
2
4
6
___ 10
I4
b
a Fig. 7a. Aortic valve disease group activity.
8
+ LVA
group. LDH
Fig. 7b. Mitral valve disease group. LDH activity.
16
hcurs
Right duct lymph during and after open-heart surgery
$c5m, LYMPH
LYMPH
%>ml
P LVA3
"1
IT-
"1
*-.- ..XA1 105
A
B
0
2
4
6
8
10
12
14
Fig. 8 a . Aortic valve disease group activity.
I
16 hours
a
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
237
A
B 0
2
4
6
8
W
12
14
16 h o v r
b
+ LVA
group. G P T
Case A 5 was a patient with a calcified aortic stenosis, gradient 92 mmHg, and a rapid progressive cardiac decompensation. The immediate postoperative course was uncomplicated. However, 20 hours after the operation the patient suddenly developed a n asystole and resuscitation was unsuccessful. At autopsy there was a massive left ventricular myocardial infarction. The right coronary artery was very thin. The left coronary artery had two wide branches, but the bifurcation was only 3 mm from the ostium. Probably only one of the branches was cannulated and perfused during bypass. Case A10 had a congenital aortic stenosis and was operated upon in 1970 with implantation of a clothed Starr-Edwards prosthesis. Due to haemolysis, he now had to be re-operated and a Bjork-Shiley prosthesis was implanted. The operation was uneventful except for a period of various arrythmias after bypass. Postoperative ECG showed depression of the ST-T-segment. The patient recovered normally after the operation.
In the LVA group, case LVAl and LVA3 showed very high values. In both cases resection of large aneurysms was performed. In the mitral valve group, case M 3 developed the highest enzyme activity. Case M 3 had a stenosis and insufficiency of the calcified mitral valves, previously operated upon with transventricular dilation. Implantation of a Bjork-Shiley prosthesis was now performed. The operation was technically complicated and due to regurgitation of blood through the incompetent aortic valves, cross-clamping of the aorta had to be performed in two periods, 40 minutes and 30 minutes, respectively. The first attempt to discontinue cardiopulmonary bypass failed because of a massive left ventricular failure and left heart bypass had to be started. It was possible to discontinue the bypass after one hour. The patient survived and recovered.
The material can be further investigated concerning factors which are correlated to a high or a low efflux of enzymes after operation. The examples referred to obviously indicate some factors of importance. These problems will, however, be further studied in a current investigation.
Fig. 86. Mitral valve disease group. GPT activity.
DISCUSSION Cannulation of the RLD or the bronchomediastinal trunk can be regarded as a method for investigating, metabolic changes which are better reflected in lymph fluid than in serum. As such an investigation has not previously been performed on human lymph, this is to a great extent a study of the application of the method. A great problem is the variability in the lymphatic anatomy, which imparts a certain inaccuracy regarding the drainage areas of the collected lymph. In 18 cases the bronchomediastinal trunk was probably cannulated. However, the inaccurate anatomical criteria used are not considered sufficient to warrant separate reports on these cases. Therefore all collected lymph was designated as right duct lymph in the results. One possibility of gaining some insight into the amount of cardiac lymph present in the samples would be the use of a tracer substance. This was not possible in this clinical investigation. Another possibility is to compare quantitatively cardiac-specific enzymes in the collected lymph with serum taken at the same time. Samples with a higher enzyme concentration in the lymph must have contained a significant amount of cardiac lymph. In the remaining cases it cannot be excluded that the existence of the cardiac-specific enzymes may be explained by leakage of enzymes from the serum. Among the group of 26 cases operated upon with the aid of extracorporeal circulation, 16 cases (61 %) showed higher enzyme concentrations in the lymph. This indicates that by using the method of right duct cannulation, lymph containing a significant amount of cardiac lymph can be collected in about 60% of the cases.
Flow The flow rate would probably be somewhat higher if the main stem of the right lymphatic duct were Scand J Thor Cardiouasc Surg 9
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
238 H . E. Hansson cannulated. However, as the broncho-mediastinal trunk contributes most of the flow, especially in connection with cardiac disease, the difference should be insignificant. In every case the flow pattern was the same. Anaesthesia may have influenced the flow rate to some extent. It is known that ether anaesthesia increases lymph flow (Drinker & Yoffey, 1941). A not unusual observation was dilated lymph vessels and a high lymph flow in cases with pulmonary stasis, as in mitral valve disease and left ventricular aneurysm. During cardiopulmonary bypass, the flow usually diminished, probably due to a decreased propulsive force when the heart was in ventricular fibrillation or asystole and the lungs ventilated minimally. The hypothermia and compatible low blood pressure probably also influenced the flow. It is known that cardiopulmonary bypass decreases the flow of canine cardiac lymph (Kluge, 1971). An increase in flow rate is therefore natural when the heart is beating again, and the patient is warm, with normal blood pressure. Haemodilution due to the priming volume of the heart-lung machine may also be of some importance. The observed decrease of the flow during the first postoperative night may possibly be explained by a more effective central circulation with decreasing pulmonary stasis, since the cardiac valve disease or the ventricular aneurysm had been operated upon, and/or a progressive clotting of the inserted catheter. The blood-staining which regularly occurred certainly seems to be an expression of the well known ability of the lymphatic system to drain erythrocytes occurring outside the vessels (Clark & Clark, 1937). The large exposed tissues in combination with heparin treatment offer ideal conditions for extracapillary-occurring erythrocytes. Errors in estimated enzyme activity
Haemolysis occurred in many lymph samples. Simultaneous with haemolysis, the LDH activity, and to some extent the GOT activity, increased and therefore these enzyme values must be interpreted with caution. LDH is present not only in erythrocytes but also in pulmonary tissue. Thus right-sided thoractomy, which interferes with the lung, may therefore influence the LDH concentration. Patients operated upon with mitral valve replacement using a right thoracotomy had, 5 hours after bypass, a mean Scand J Thor Cardiovasc Surg 9
LDH/GOT ratio in lymph of 10; in serum, 10. Patients operatzd upon with aortic valve replacement (sternotomy) had a mean ratio of 6 in the lymph and 6 in the serum. Accordingly, there was a constant relationship in lymph and serum, respectively, but with a higher ratio in the mitral cases, indicating efflux of enzymes from the lung. CPK is present in skeletal muscle and is easily liberated. There is also GOT in skeletal muscle, but the activity in serum is only moderately influenced by the thoracotomy procedure per se. In the aortic group, 5 hours after bypass, the mean CPK/GOT ratio was in the lymph 4, in the serum 3; in the mitral group 12 and 5, respectively. As the highest CPK/GOT ratio was found in the mitral group, this suggests that a certain amount of the measured CPK activity originated from skeletal muscle.
Efflux of enzymes Different time courses for enzyme escape after myocardial infarction have been reported. In serum, CPK activity is usually reported to rise first. followed by GOT and GPT and about 6 hours later by LDH (Hamolsky, 1967; Wilkinson, 1970). Measurement of enzyme activity in cardiac lymph during the first period after myocardial infarction gives a more accurate picture of the time course of enzyme efflux. In canine cardiac lymph, evidence of simultaneous escape of enzymes after experimental myocardial infarction has been reported (Malmberg, 1972). This investigation has likewise found a simultaneously and subsequently parallel efflux of GOT, CPK and LDH in lymph. The GPT activity was low and more difficult to evaluate. The initial phase of rapid enzyme increase after bypass can to a certain extent be explained by a “wash-out effect” of enzymes accumulated in the heart during the bypass when the drainage of lymph was ineffective. The enzyme content in lymph showed basically two distinct patterns, i.e., plateau-shaped or continuall y-rising. When the enzyme curve takes the form of a plateau, in certain cases with a maximum, a rapid depletion of myocardial enzymes is indicated. Accordingly the efflux of enzymes from the cells to the interstitial space, drained by the lymphatics, is reduced. Subsequently the enzyme content of the lymph is restored by the turnover of enzymes from the blood stream to the interstitial space, i.e., the lymph. The turnover
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
Right duct lymph during and after open-heart surgery
of serum enzymes is a complex problem, but the early rapid exit of serum enzymes into the interstitial space is well-known (Dawson, 1969; Posen, 1970; Shell, 1971). The plateau-skaped curve with a moderate enzyme increase seems to indicate minor damage to the myocardial cells, the result of either a diffuse ischaemia, with a change of the cellular permeability and escape of enzymes, or a minor myocardial infarction which is well perfused. When the enzyme curve in lymph follows a continually-rising course and attains comparatively high values, a large myocardial infarction is indicated with continuous efflux of enzymes adding to the enzymes leaked from the blood stream. In all cases the concentration of enzymes in lymph and serum converged with time. This phenomenon is explained by the depletion of enzymes in the myocardium and the turnover of enzymes from the blood stream into the interstitial space. Thus the method of cannulating the RLD with the subsequent interpretation of lymph enzyme content is only valid during the first few hours after cardiac trauma. Using this procedure, several cases with very high enzyme activity have been found, presumably reflecting significant heart damage. Apart from the pre-operative condition of the heart, the mode of cardiac protection during bypass would also appear to influence strongly the efflux of enzymes. The cardiac tolerance for ischaemia is a basic problem in cardiac protection and will be further studied in a current investigation. ACKNOWLEDGEMENTS This investigation was supported by grants from the Gronberg Foundation. The excellent technical assistance of Mrs Britta Morlin, Mrs Christina Nylander and Mrs Lisbeth Wester is gratefully acknowledged.
REFERENCES Allisson, P. R. & Sabiston, Jr, D. C. 1957. Experimental studies on the cardiac lymphatics. Surg Forum 98, 21 1 . Areskog, N. H., Arturson, G. & Grotte, G. 1965. Heartlymph: Electrolyte composition and changes induced by cardiac glycosides. Biochem Pharmacol 14, 783. Clark, E. R. & Clark, E. L. 1937. Observations on living mammalian lymphatic capillaries. Their relation to the blood vessels. Am J Anat 60, 253. Dawson, D. M., Alper, C. A., Seidman, J. & Mendelsohn, J. 1969. Measurement of serum enzyme turnover rates. Ann Intern Med 70. 799.
239
Drinker, C. K., Warren, M.F., Maurer, F. W. & McCarell, J. D. 1940. The flow, pressure and composition of cardiac lymph. Am J Physiol 130, 43. Drinker, C. K. & Yoffey, J. M. 1941. Lymphatics, lymph and lymphoid tissue. Harvard Univ Press, Cambridge, Mass. Hallbn, A. & Hansson, H. E. 1974. Cannulation of the right lymphatic duct in man. Scand J Thor Cardiouasc Surg, in press. Hamolsky, M. W. 1967. Editorial. Enzymes in acute myocardial infarction. Circulation 35, 427. Jdanov, D. A. 1959. Anatomie du canal thoracique et des principaux collecteurs lymphatiques du tronc chez I’homme. Acta Anat 37, 20. Kampmeier, D. F. 1928. On the lymph flow of the human heart, with reference to the first development of the channels and the first appearance, distribution, and physiology of their valves. Am Heart J 4, 210. Kline, I. K., Miller, A. J., Pick, R. & Katz, L. N. 1964. The effects of chronic impairment of cardiac lymph flow on myocardial reactions after coronary artery ligation in dogs. Am Heart J 68, 515. Kluge, T. 1971. Hjertets lymfesirkulasjon. Nord Med 86, 1325. Leeds, S . E., Uhley, H. N., Sampson, J. J. & Friedman, M. 1959. A new method for measurement of lymph flow from the right duct in the dog. Am J Surg 98, 211. Malmberg, P. 1972. Heart-lymph enzyme activity in myocardial cell injury. Diss. Uppsala. Miller, A. J. 1963. The lymphatics of the heart. Arch Intern Med 112, 501. Miller, A. J., Ellis, A. & Katz, L. N. 1964. Cardiac lymph: flow rates and composition in dogs. Am J Physiol 206, 63. Patek, P. R. 1939. Morphology of the lymphatics of the mammalian heart. Am J Anat 64, 203. Posen, S . 1970. Turnover of circulating enzymes. Clin Chem 16, 71. Rouvibre, H. 1932. Anatomie des lymphatiques de l’homme. Libraires de I’acadbmie de mbdecine, Paris. Rudbeck, 0. 1653. Nova exercitutio anatomica, exhibens ductus hepaticos aquosos, et vasa glandulorum serosa. Upsala. Shell, W. E., Kjekshus, J. K. & Sobel, B. E. 171. Quantitative assessment of the extent of myocardial infarction in the conscious dog by means of analysis of serial changes in serum creatine phosphokinase activity. J Clin Znuesr 50, 2614. Shore, L. R. 1928. The lymphatic drainage of the human heart. J Anat 63, 291. Symbas, P. N., Cooper, T., Gantner, G. A. & Willman, V. L. 1963. Lymphatic drainage of the heart: Effects of experimental Interruption of lymphatics. Surg Forum 14, 254. Ullal, S . R., Kluge, T. H., Kerth, W. J. & Gerbode, F. 1972. Changes in cardiac lymph of dogs during and after anoxia. Ann Surg 175, 472. Warren, M. F. & Drinker, C. K. 1942. The flow of lymph from the lungs of the dog. Am J PhysioIl36, 207. Wilkinson, J. H. 1970. Clinical significance of enzyme activity measurements. Clin Chem 16, 882.
Scand J Thor Cardiouasc Surg 9
RIGHT DUCT LYMPH DURING AND AFTER OPEN-HEART SURGERY Hans Erik Hansson From the Departments of Thoracic Surgery and Clinical Chemistry, University Hospital, UppsaIa, Sweden
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
(Submitted for publication February 21, 1974)
Abstract. The right lymphatic duct (RLD) was cannulated in 26 patients operated upon with open-heart surgery. The thoracic duct was cannulated in 4 additional patients and both the thoracic and the right lymphatic ducts were cannulated in 2 further patients. The R LD was also cannulated in a control group consisting of 5 thoracotomy-operated patients. Lymph was collected continuously and its flow and content of albumin, electrolytes and the enzymes, GOT, GPT, CPK and L D H were analysed. A significant amount of cardiac lymph was present in about 60% of the cannulations. After cardiopulmonary bypass, lymph enzyme concentrations often rose rapidly to very high levels. The significance of the enzyme concentration-patterns and some characteristics of the flow pattern are discussed.
Rudbeck (1653) was the first to study the lymphatics of the heart. The first detailed anatomical study, however, was published as late as 1939 (Patek, 1939). In 1940, Drinker et al. published the now classic physiological study for flow and composition of canine cardiac lymph. After the technique of cannulating the efferent cardiac trunks was developed, several investigations on canine cardiac lymph were performed (Miller et al., 1964; Areskog et al., 1965; Ullal et al., 1972; Malmberg, 1972). Similar investigations have not been carried out on human cardiac lymph. It is difficult in practice to get an opportunity to cannulate the two efferent main trunks which presumably exist (Allisson & Sabiston, 1957; Kampmeier, 1928; Jdanov, 1959). There are also experimental results indicating cardiac damage after total obstruction of the lymph flow adjacent to the heart (Symbas et al., 1963; Kline et al., 1964). Cardiac lymph is mainly drained via the right lymphatic duct (Shore, 1928; RouvBre, 1932; Warren & Drinker, 1942; Leeds et al., 1959; Miller, 1963). We have cannulated the right lymphatic duct or the bronchomediastinal duct and presented some aspects concerning the surgical anatomy and the flow and
composition of the lymph (Hallkn & Hansson, 1974). Cardiac lymph in the right lymphatic duct (RLD) is diluted with lymph from the lungs, the right arm and the neck. It is conceivable to reduce the admixture to include only pulmonary lymph if the bronchomediastinal trunk is selectively cannulated. The aim of this investigation was to study the influence of open-heart surgery on the flow and composition of the lymph in the RLD or in the bronchomediastinal trunk.
PATIENTS Thirty-seven patients (25 men, 12 women) were examined, whose mean age was 53 years (range 23-67 years). Patients and diagnoses are presented in Table I. The R LD was cannulated in 26 open-heart surgery cases (cardiopulmonary bypass group RLD). Ten of these patients were diagnosed with aortic valve disease (designated A 1-10), 12 patients with mitral valve disease (M 1-12), and 4 cases with left ventricular aneurysm (LVA1-4). The R LD was also cannulated in a control group consisting of 5 patients thoracotomy-operated for other reasons. The thoracic duct was cannulated in 4 cases operated upon with open-heart surgery. Both the R L D and the thoracic duct were simultaneously cannulated in 2 cases.
METHODS Cannulation was performed as previously described (HallBn & Hansson, 1974), both following and simultaneous with the normal pre-operative preparations. The patients were under general anaesthesia. Selective cannulation of the bronchomediastinal duct was attempted. Using anatomical criteria, the procedure was considered successful in 18 cases ( 5 5 %). When the trunk was thin and poorly developed, o r when technical difficulties impeded a complete dissection, a central ligation was made and a catheter was placed in the main trunk. However, in the results all lymph is named right duct lymph (see Discussion). Anaesthesia was maintained with i.v. phenoperidine in doses of Scand J Thor Cardiovasc Surg 9
230 H. E. Hansson Table I Patients Cardiopulmonary bypass group RLD cannulations Aortic valve disease (Al-10) Mitral valve disease (M 1-12) Left ventricular aneurysm (LVA 1 4 )
No. of patients
10
12 4
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
26
Control group RLD cannulations Lung cancer Mitral stenosis Aortic aneurysm Cardiopulmonary bypass group Thoracic duct cannulations Aortic valve disease Aortic and mitral valve disease
3 1 4
Bilateral cannulations Aortic valve disease Left ventricular aneurysm
1 1 2
5-10 mg and d-tubocurarine in doses of 20-30 mg. In a few cases pancuroniumbromide was substituted for d-tubocurarine. The patients were ventilated with an Engstrom-respirator, equal parts of nitrous oxide and oxygen being given. During bypass, the patients were ventilated with 2 l/min of air using an endexpiratory pressure of 5 mmHg to prevent atelectasis. During the first post-operative night, the patients were respirator-treated and received in most cases repeated small doses of phenoperidine as an analgetic and sedative. A median sternotomy was performed in the aortic valve disease group, a right thoracotomyin the mitral valve disease group, and in the left ventricular aneurysm group, a bilateral thoracotomy was made in 2 cases and a sternotomy in 2 cases. Moderate hypothermia was induced (3Cb32"C) and coronary perfusion with oxygenated blood was used. Cross-clamping of the aorta was only employed in one case of mitral valve disease in two periods, 40 minutes and 30 minutes, respectively. The lymph was collected continuously, usually at one-hour intervals during the first 7-10 hours after cardiopulmonary bypass and thereafter at 3-hour intervals. In the middle of each lymph-collecting period a blood sample was taken as a reference. The samples were kept at +4"C and, after centrifugation, frozen to - 194°C. The samples were analysed in series as previously described (Halltn & Hansson, 1974). Only patients in whom drainage functioned satisfactorily for more than 9 hours were selected for inclusion.
COMPLICATIONS No serious complications occurred. In 4 cases a slight supraclavicular oedema developed which, howScand J Thor Cardiovasc Surg 9
ever, completely disappeared after a couple of days. In one case a haematoma developed which required surgical evacuation. At a routine follow-up 2 months postoperatively no complications were found. RESULTS Technical aspects It is a technically difficult procedure to cannulate a tiny lymphatic vessel in a limited time period prior to operation. It is also difficult to maintain drainage function. Now, after more than 120 cannulation attempts, it can be stated that with experience it is almost always possible to identify lymph ducts in the right venous angle. Lymph ducts were found in all but 4 cases. It also seems possible to cannulate the vessel and make the drainage function initially, i.e., during the first hour, in about 75% of the attempts. Continuous lymph drainage for more than 10 hours diminishes this high rate to 50%. The most common reasons for failure are dislocation of the catheter or clotting of the catheter in connection with a low flow and/or blood staining. Due to the valves in the lymph ducts, it is usually impossible to introduce the catheter more than a few millimetres, and therefore difficult to ensure safe fixation. Dislocation will occur when the patient is moved into position for operation and on transfer to the Intensive Care Unit. A slow flow rate inevitably seems to lead to clotting of the catheter and cessation of flow. This was most clearly observed immediately before the first heparin dose was given prior to bypass. In a few cases it was possible to restore the flow by cautious flushing of the catheter with a heparin solution. Observations on lymph fIow The rate of lymph flow showed wide variations, partially due to experimental artifacts, depending on technical difficulties in maintaining an optimal drainage through the catheter, and partially to anatomical variations of the lymphatics (see Discussion). The results shown below are therefore presented more as clinical observations than statistically corroborated facts. When the RLD or the bronchomediastinal trunk was cannulated, four phases were observed (cardiopulmonary bypass group, 26 patients):
Right duct lymph during and after open-heart surgery
".ci""
Lymph flow
AS 'A1
Albumin
In,m/x
10
B
1
2
3
4
5
6
7
8
9
W
h
u
Ti""'
40
in
5
10
1
A
A b
1
1
------__-
MS+MI
Lymph flow mi/hour
231
2 .I
s A
a
B
1 2 3 4 5 6 7 8 9 l O h o v s
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
b LymM flow
gr"'
L VA
"TWr
Albumin
Lymph flow
ml/hour
CONTROL GROUP
Albumin
g/100 ml
d
C
Lynph flow
THORACIC DUCT CANNULATED
Albumin
s/lm m l
I
I
A
Fig. l a . Aortic valve disease group. 10 patients. RLD cannulated. Fig. 16. Mitral valve disease group. 12 patients. RLD cannulated. Fig. I c . Left ventricular aneurysm group. 4 patients. RLD cannulated. Fig. I d . Control group. 5 patients. RLD cannulated. Fig. l e . Thoracic duct cannulated. 4 patients.
Ih
B
1
2
Fig. la-e. Lymph flow and concentration of albumin for the different groups. Bars denote lymph flow, unbroken lines concentration of albumin in lymph and dashed lines concentration of albumin in serum.
3
4
5
6
7
6
9
1
0
I. Initially, after the cannulation, there was often
a high lymph flow, in 10 cases more than 10 ml/h (max 96 ml/h). During the period prior to bypass (1-2 hours), some patients showed an increase and others a decrease in the flow rate, i.e. no uniform tendency was observed in the flow rate when thoracotomy was started. 11. During cardiopulmonary bypass the flow usually diminished or ceased completely. In 6 cases the flow ceased, in 12 cases there was a considerable,
decrease and in 8 cases (of which 6 patients with mitral valve disease) the flow was unchanged. 111. After bypass, when the heart started to beat and the lungs were fully ventilated, the lymph flow usually increased; in the mitral valve disease group, however, only in 7 cases out of 12. This increase was observed in a few cases almost immediately when the heart was converted from ventricular fibrillation, but usually after a delay of up to 1/21 hour. During the following 3-5 hours, both the flow and urine production were often high. The lymph and urine flows showed the same dependency on the systolic blood pressure, especially in cornbination with hypovolaemia. If the blood pressure Scand J Thor Cardiovasc Surg 9
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
232 H . E. Hansson decreased, reflecting a moderate hypovolaemia, both the lymph and urine flows diminished. Blood-staining of the lymph was regularly observed after bypass. The blood-staining usually increased during the first few hours until the lymph was sanguineous. Then a stabilization occurred and the colour remained unchanged. In a few cases the lymph became clearer 4-6 hours after cardiopulmonary bypass. There were also a few cases with increasing blood admixture. Exceptionally, the sanguinolent colour remained after centrifugation as a sign of haemolysis. In these cases there was also haemolysis in the blood samples. IV. During the late postoperative period, after the first 5 hours, the lymph flow diminished gradually and ceased completely within 16 hours in 11/26 cases. In 10 cases the flow was essentially unchanged and in 5 cases it increased. In the latter cases all patients were in left ventricular failure. The three different diagnostic groups are compared in Fig. 1 a-c. Patients with aortic valve disease have a comparatively lower lymph flow, while the mitral group often have a high lymph flow, also during bypass. In the control group (Fig. 1d) there was generally a low lymph flow. Especially the two cases with lung cancer had a low flow, which was in agreement with the findings in earlier cannulations. Bloodstaining was observed in 3 cases. In 2 cases operated upon with transventricular dilatation of the mitral ostium, a higher flow was observed together with a small postoperative increase. Both the right lymphatic duct and the thoracic duct were cannulated in 2 cases. In the case of aortic valve stenosis, the flow in the thoracic duct diminished considerably 8 hours after the operation and at about the same time the flow in the RLD increased considerably, giving the impression of a collateral communication between the left and right side. As anticipated, a rather high flow was found when the thoracic duct was cannulated (Fig. le). During the bypass, the flow diminished. Blood-staining was observed in all 4 cases, with a tendency towards clearing after about 5-6 hours. In one case the lymph was opalescent, which is remarkable considering that the patient had not received food during the preceding 15 pre-operative hours. The albumin concentration was relatively constant both in lymph and in serum (Fig. 1). The concentration was always lower in lymph as compared with serum. During and after bypass the albumin Scand J Thor Cardiovasc Surg 9
was lowest and thereafter rose somewhat. In general, there was a tendency towards a low albumin concentration in connection with a high lymph flow. Electrolytes The following electrolytes were analysed: Na+, K+, Ca++ and C1-, in most cases in both lymph and serum. However, not unexpectedly, the results showed a very confusing picture. Electrolyte infusion, which often had to be given peroperatively, also complicated the analysis of the figures. It may be of interest that the potassium concentrations often showed rapid variations. Enzymes The following enzymes were analysed, GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), LDH (lactate dehydrogenase) and CPK (creatine phosphokinase). Haemolysis, which interferes with LDH activity and to some extent GOT activity, was observed in the following cases in lymph (figures within parentheses denote hours after bypass): A 2 (4), A6 (114), A7 (0-16), A9 (2-14), A10 (2-4), M1 (0), M 2 (2), M7 (1-5), M9 (2-9), M10 (2-14), M11 (1-3; 9-16), M12 (4; 11-13), LVAl (0-6). In serum, haemolysis occurred in the following samples: A7 (3), M3 (l), M5 (l), M7 (3), M 8 (l), MI2 (0-3), LVA 4 (0-1). Thoracic duct cannulations: The thoracic duct was cannulated in 4 cases, in all of which the enzyme concentrations were lower in lymph than in serum throughout the observation period, usually about 20 hours. However, the concentrations gradually increased, reflecting on a lower-displaced level the enzyme concentration curves of the serum. Bilateral cannulations: The RLD and the thoracic duct were both cannulated simultaneously, in two cases of which there was a more rapid rise in enzyme activity after the bypass in the RLD compared with the thoracic duct or the serum. The first case (Fig. 2a) had a left ventricular aneurysm which was resected. The postoperative course was uncomplicated and with good cardiac function. The rise in enzyme content in lymph and serum was comparatively moderate during the first few hours after bypass. The second case (Fig. 2b) had a severe aortic stenosis with a gradient of 110 mmHg. A low cardiac
Right duct lymph during and after open-heart surgery RIGHT DUCT LYMPH CPK unit / 1
L 00
LDH unit / ml
WT,GPT RIGHT DUCT LYMPH unit / ml OPERATION ECC
CPK unit / I
h
10000 .-1000
233
- 5000
200 GPT
0
2
4
6
8
10
2000
1000
hours
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
0 LDH unit ,'rnl
1oov"o
LEFT DUCT LYMPH
I CPK
LDH IGOT,GPT unit / rnl unit /
I4
unit / 1
400 40
LDH GOT CPK GPT
200 20 I
0
2
4
6
8
10
-200
5000
I
2
GOT, GPT unit / rnl
I-
8
6
10
12
:I' t
I hours
2 000
I
2
4
8
6
10
12
600 400
200
a
0
2
L
6
8
10
16 hours
SERUM
/
CPK unit / 1
300
14
unit / m /
t
GPT
CPK
-100
unit / ml
2 00 20
16 hours
LEFT DUCT LYMPH
500
0
LDH unit/ml
14
OPERATION ECC
1000
]
4
t
OPERATION ,GP'/5000
100 hours
b
0
2
4
6
8
10
12
I4
16 hours
Fig. 2. Bilateral cannulations. (a) Patient with left ventricular aneurysm operated upon with resection of the aneurysm. (b) Patient with aortic stenosis operated upon with valve re-
placement. N.B. the rapid rise in enzyme concentrations in RLD as compared with those in serum and the thoracic duct.
output syndrome developed postoperatively with progressive left ventricular failure and the patient died 25 hours after operation. The enzyme concentrations reached extremely high values, with a first maximum peak in RLD lymph 1 hour after bypass. Control group: Only small changes were observed. Fig. 3 shows the mean values. The LDH activity rose somewhat in both lymph and serum. The CPK activity also rose slightly in the lymph. The changes were insignificant in respect of GOT and GPT.
RLD cannulations, cardiopulmonary bypass group: In 26 cases operated upon with the aid of extracorporeal circulation, the RLD or the bronchomediastinal trunk was cannulated. In 16 cases (61 %), much higher concentrations of enzymes were found in lymph after the bypass as compared with serum, while in 10 cases (39%) the concentrations were lower (Table 11). Among these 16 cases, the enzyme values before and in the beginning of bypass were approximately
16- 752916
Scand J Thor Cardiovasc Surg 9
234 H . E. Hansson unrt/ml 1 Gun,t/ml LDH OT.GPI
A
LYMPH
2
L
6
8
LYMPH
12
10
11
16 hours CPK un,t/l
500 250 A
2
4
6
8
10
12
14
16 hours
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
SERUM
Fig. 3. Control group mean enzyme values. Only small changes are observed.
the same. Fig. 4 shows a typical pattern. At the end of bypass or during the first hour afterwards, a sharp rise in GOT, LDH and CPK activity commenced. This rapid phase usually lasted 3-5 hours. The variation between enzyme curves then became considerable, but essentially two types of patterns can be distinguished. In about 60% of the cases, enzyme values followed a plateau-shaped course, with a distinct maximum in a few cases. In the other #%, the enzyme activity showed a continuous rise. Only moderate changes were observed in GPT activity. In 10 cases the enzyme concentrations were lower in the lymph (Table 11). This was always valid for GOT, LDH and GPT, but CPK very often showed a somewhat higher concentration in the lymph (as compared with serum). This is of certain importance and indicates that
0
2
4
8
6
10
I2
K
16
18
bows
Fig. 4. Patient with aortic stenosis operated upon with valve replacement showing typically comparative enzyme patterns for lymph and serum after cardiopulmonary bypass.
no or only small amounts of cardiac lymph were present in the collected lymph (see Discussion). No anatomical criteria distinguished these 10 patients from the others. In serum there was in all 26 cases a continuous, slow rise in the enzyme concentrations. No maximum occurred during the first 24 hours, but usually during the second or third day after the operation. In Figs. 5-8, the individual enzyme curves for each of the 26 cases are presented according to diagnosis group. The 10 patients with lower enzyme-
Table I1 End of bypass
Pre-op
2 h after bypass
4 h after bypass
6 h after bypass
10 h after bypass
16 h after bypass
Lymph Serum Lymph Serum Lymph Serum Lymph Serum Lymph Serum Lymph Serum Lymph Serum A. 16 patients GOT, unit/ml GPT, unit/ml CPK, unit/l LDH, unit/ml
20 21 58 433
33 30 47 5 74
15
25 23 64 374
51 20 260 513
46 26 118 587
137 25 798 1059
102 32 319 812
201 33 1235 1416
19
32 16 85 45 1
35 12 281 509
51
20 160 541
48 15 415 605
289 148 42 36 420 1588 988 1757
173 355 41 62 548 1512 1165 1936
195 403 48 57 525 1512 1048 2025
206 55 555 1087
B. 10 paiients GOT, unit/ml GPT, unit/ml CPK, unit/l LDH, unit/ml
11
56 217
Scand J Thor Cardiouasc Surg 9
11
I05 309
60 21 238 586
52 17 430 609
66 25 285 677
70 22 564 666
94 31 415 720
98 27 919 768
102 31 608 660
Right duct lymph during and after open-heart surgery GOT umt/ ml
LYMPH
. LV43 P., ,
'.d
umt/
500
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
235
- m'
LYMPH
PM3
100-
300 -
ua 200.
M7
M 12
3 100MS
M6
A
a
D 0
2
L
6
8
10
12
1I
b hours
A
~~
6'0
2
4
6
8
10
12
Y
16hwm
b
Figs. 5-8. Individual curves for 26 patients presented according to diagnostic group. On the abscissa, A denotes half a n hour before bypass, B in the middle of bypass and number 1-16 denote hours after bypass. All enzyme concentrations values are interpolated to these times. A rapid rise in enzyme concentration after bypass and a fairly constant relationship between enzyme curves within individual cases
concentrations compared with serum included 3 cases from the aortic group, indicated A2, A 6 and A8, 5 cases from the mitral group indicated M2, M5, M6, M8 and M 12 and 2 cases from the left ventricular aneurysm group indicated LVA2 and LVA4. A general finding was a fairly constant relationship between enzyme curves within individual cases. The rise occurred almost simultaneously for GOT, CPK and LDH, and later on the curves showed in general the same pattern of variations. To a certain extent this was also valid for GPT. This indicates a simultaneous escape of enzymes from the damaged heart cells.
can be seen. In the following cases serum enzyme levels exceeded those in lymph: A2, A6, A8, M2, M 5 , M6, M8, M 12, LVA2 and LVA4. Fig. 5 a . Aortic valve disease group+LVA group. GOT activity. Fig. 5b. Mitral valve disease group. GOT activity.
The aortic valve group and the LVA group (Figs. 5a-8a) showed in general a higher enzyme rise com-
pared with the mitral valve group (Figs. 5b-8b). In the aortic group case no. A l , AS and A10 showed very high values. Case A 1 was a high risk patient with a severe aortic stenosis and calcified valves. After valve replacement procedure, a serious left ventricular failure made it difficult to discontinue the cardiopulmonary bypass. Bypass time, including left heart bypass, lasted 343 minutes. Postoperatively a LOW cardiac output syndrome developed and the patient died 36 hours after operation. Autopsy revealed a fresh myocardial infarction in the left ventricle.
Scand J Thor Cardiooasc Surg 9
236 H. E. Hansson LYMPH
LYMPH
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
A
A
8
0
2
4
6
8
10
I2
I(
5 h m
b Fig. 6a. Aortic valve disease group activity.
+ LVA
group. CPK
Fig. 6b. Mitral valve disease group. CPK activity.
C LVA3
i
LYMPH
MI1
MV M7 M9 M8 M5 M6
A
Scand J Thor Cardiouasc Surg 9
0
2
4
6
___ 10
I4
b
a Fig. 7a. Aortic valve disease group activity.
8
+ LVA
group. LDH
Fig. 7b. Mitral valve disease group. LDH activity.
16
hcurs
Right duct lymph during and after open-heart surgery
$c5m, LYMPH
LYMPH
%>ml
P LVA3
"1
IT-
"1
*-.- ..XA1 105
A
B
0
2
4
6
8
10
12
14
Fig. 8 a . Aortic valve disease group activity.
I
16 hours
a
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
237
A
B 0
2
4
6
8
W
12
14
16 h o v r
b
+ LVA
group. G P T
Case A 5 was a patient with a calcified aortic stenosis, gradient 92 mmHg, and a rapid progressive cardiac decompensation. The immediate postoperative course was uncomplicated. However, 20 hours after the operation the patient suddenly developed a n asystole and resuscitation was unsuccessful. At autopsy there was a massive left ventricular myocardial infarction. The right coronary artery was very thin. The left coronary artery had two wide branches, but the bifurcation was only 3 mm from the ostium. Probably only one of the branches was cannulated and perfused during bypass. Case A10 had a congenital aortic stenosis and was operated upon in 1970 with implantation of a clothed Starr-Edwards prosthesis. Due to haemolysis, he now had to be re-operated and a Bjork-Shiley prosthesis was implanted. The operation was uneventful except for a period of various arrythmias after bypass. Postoperative ECG showed depression of the ST-T-segment. The patient recovered normally after the operation.
In the LVA group, case LVAl and LVA3 showed very high values. In both cases resection of large aneurysms was performed. In the mitral valve group, case M 3 developed the highest enzyme activity. Case M 3 had a stenosis and insufficiency of the calcified mitral valves, previously operated upon with transventricular dilation. Implantation of a Bjork-Shiley prosthesis was now performed. The operation was technically complicated and due to regurgitation of blood through the incompetent aortic valves, cross-clamping of the aorta had to be performed in two periods, 40 minutes and 30 minutes, respectively. The first attempt to discontinue cardiopulmonary bypass failed because of a massive left ventricular failure and left heart bypass had to be started. It was possible to discontinue the bypass after one hour. The patient survived and recovered.
The material can be further investigated concerning factors which are correlated to a high or a low efflux of enzymes after operation. The examples referred to obviously indicate some factors of importance. These problems will, however, be further studied in a current investigation.
Fig. 86. Mitral valve disease group. GPT activity.
DISCUSSION Cannulation of the RLD or the bronchomediastinal trunk can be regarded as a method for investigating, metabolic changes which are better reflected in lymph fluid than in serum. As such an investigation has not previously been performed on human lymph, this is to a great extent a study of the application of the method. A great problem is the variability in the lymphatic anatomy, which imparts a certain inaccuracy regarding the drainage areas of the collected lymph. In 18 cases the bronchomediastinal trunk was probably cannulated. However, the inaccurate anatomical criteria used are not considered sufficient to warrant separate reports on these cases. Therefore all collected lymph was designated as right duct lymph in the results. One possibility of gaining some insight into the amount of cardiac lymph present in the samples would be the use of a tracer substance. This was not possible in this clinical investigation. Another possibility is to compare quantitatively cardiac-specific enzymes in the collected lymph with serum taken at the same time. Samples with a higher enzyme concentration in the lymph must have contained a significant amount of cardiac lymph. In the remaining cases it cannot be excluded that the existence of the cardiac-specific enzymes may be explained by leakage of enzymes from the serum. Among the group of 26 cases operated upon with the aid of extracorporeal circulation, 16 cases (61 %) showed higher enzyme concentrations in the lymph. This indicates that by using the method of right duct cannulation, lymph containing a significant amount of cardiac lymph can be collected in about 60% of the cases.
Flow The flow rate would probably be somewhat higher if the main stem of the right lymphatic duct were Scand J Thor Cardiouasc Surg 9
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
238 H . E. Hansson cannulated. However, as the broncho-mediastinal trunk contributes most of the flow, especially in connection with cardiac disease, the difference should be insignificant. In every case the flow pattern was the same. Anaesthesia may have influenced the flow rate to some extent. It is known that ether anaesthesia increases lymph flow (Drinker & Yoffey, 1941). A not unusual observation was dilated lymph vessels and a high lymph flow in cases with pulmonary stasis, as in mitral valve disease and left ventricular aneurysm. During cardiopulmonary bypass, the flow usually diminished, probably due to a decreased propulsive force when the heart was in ventricular fibrillation or asystole and the lungs ventilated minimally. The hypothermia and compatible low blood pressure probably also influenced the flow. It is known that cardiopulmonary bypass decreases the flow of canine cardiac lymph (Kluge, 1971). An increase in flow rate is therefore natural when the heart is beating again, and the patient is warm, with normal blood pressure. Haemodilution due to the priming volume of the heart-lung machine may also be of some importance. The observed decrease of the flow during the first postoperative night may possibly be explained by a more effective central circulation with decreasing pulmonary stasis, since the cardiac valve disease or the ventricular aneurysm had been operated upon, and/or a progressive clotting of the inserted catheter. The blood-staining which regularly occurred certainly seems to be an expression of the well known ability of the lymphatic system to drain erythrocytes occurring outside the vessels (Clark & Clark, 1937). The large exposed tissues in combination with heparin treatment offer ideal conditions for extracapillary-occurring erythrocytes. Errors in estimated enzyme activity
Haemolysis occurred in many lymph samples. Simultaneous with haemolysis, the LDH activity, and to some extent the GOT activity, increased and therefore these enzyme values must be interpreted with caution. LDH is present not only in erythrocytes but also in pulmonary tissue. Thus right-sided thoractomy, which interferes with the lung, may therefore influence the LDH concentration. Patients operated upon with mitral valve replacement using a right thoracotomy had, 5 hours after bypass, a mean Scand J Thor Cardiovasc Surg 9
LDH/GOT ratio in lymph of 10; in serum, 10. Patients operatzd upon with aortic valve replacement (sternotomy) had a mean ratio of 6 in the lymph and 6 in the serum. Accordingly, there was a constant relationship in lymph and serum, respectively, but with a higher ratio in the mitral cases, indicating efflux of enzymes from the lung. CPK is present in skeletal muscle and is easily liberated. There is also GOT in skeletal muscle, but the activity in serum is only moderately influenced by the thoracotomy procedure per se. In the aortic group, 5 hours after bypass, the mean CPK/GOT ratio was in the lymph 4, in the serum 3; in the mitral group 12 and 5, respectively. As the highest CPK/GOT ratio was found in the mitral group, this suggests that a certain amount of the measured CPK activity originated from skeletal muscle.
Efflux of enzymes Different time courses for enzyme escape after myocardial infarction have been reported. In serum, CPK activity is usually reported to rise first. followed by GOT and GPT and about 6 hours later by LDH (Hamolsky, 1967; Wilkinson, 1970). Measurement of enzyme activity in cardiac lymph during the first period after myocardial infarction gives a more accurate picture of the time course of enzyme efflux. In canine cardiac lymph, evidence of simultaneous escape of enzymes after experimental myocardial infarction has been reported (Malmberg, 1972). This investigation has likewise found a simultaneously and subsequently parallel efflux of GOT, CPK and LDH in lymph. The GPT activity was low and more difficult to evaluate. The initial phase of rapid enzyme increase after bypass can to a certain extent be explained by a “wash-out effect” of enzymes accumulated in the heart during the bypass when the drainage of lymph was ineffective. The enzyme content in lymph showed basically two distinct patterns, i.e., plateau-shaped or continuall y-rising. When the enzyme curve takes the form of a plateau, in certain cases with a maximum, a rapid depletion of myocardial enzymes is indicated. Accordingly the efflux of enzymes from the cells to the interstitial space, drained by the lymphatics, is reduced. Subsequently the enzyme content of the lymph is restored by the turnover of enzymes from the blood stream to the interstitial space, i.e., the lymph. The turnover
Scand Cardiovasc J Downloaded from informahealthcare.com by UB Heidelberg on 11/16/14 For personal use only.
Right duct lymph during and after open-heart surgery
of serum enzymes is a complex problem, but the early rapid exit of serum enzymes into the interstitial space is well-known (Dawson, 1969; Posen, 1970; Shell, 1971). The plateau-skaped curve with a moderate enzyme increase seems to indicate minor damage to the myocardial cells, the result of either a diffuse ischaemia, with a change of the cellular permeability and escape of enzymes, or a minor myocardial infarction which is well perfused. When the enzyme curve in lymph follows a continually-rising course and attains comparatively high values, a large myocardial infarction is indicated with continuous efflux of enzymes adding to the enzymes leaked from the blood stream. In all cases the concentration of enzymes in lymph and serum converged with time. This phenomenon is explained by the depletion of enzymes in the myocardium and the turnover of enzymes from the blood stream into the interstitial space. Thus the method of cannulating the RLD with the subsequent interpretation of lymph enzyme content is only valid during the first few hours after cardiac trauma. Using this procedure, several cases with very high enzyme activity have been found, presumably reflecting significant heart damage. Apart from the pre-operative condition of the heart, the mode of cardiac protection during bypass would also appear to influence strongly the efflux of enzymes. The cardiac tolerance for ischaemia is a basic problem in cardiac protection and will be further studied in a current investigation. ACKNOWLEDGEMENTS This investigation was supported by grants from the Gronberg Foundation. The excellent technical assistance of Mrs Britta Morlin, Mrs Christina Nylander and Mrs Lisbeth Wester is gratefully acknowledged.
REFERENCES Allisson, P. R. & Sabiston, Jr, D. C. 1957. Experimental studies on the cardiac lymphatics. Surg Forum 98, 21 1 . Areskog, N. H., Arturson, G. & Grotte, G. 1965. Heartlymph: Electrolyte composition and changes induced by cardiac glycosides. Biochem Pharmacol 14, 783. Clark, E. R. & Clark, E. L. 1937. Observations on living mammalian lymphatic capillaries. Their relation to the blood vessels. Am J Anat 60, 253. Dawson, D. M., Alper, C. A., Seidman, J. & Mendelsohn, J. 1969. Measurement of serum enzyme turnover rates. Ann Intern Med 70. 799.
239
Drinker, C. K., Warren, M.F., Maurer, F. W. & McCarell, J. D. 1940. The flow, pressure and composition of cardiac lymph. Am J Physiol 130, 43. Drinker, C. K. & Yoffey, J. M. 1941. Lymphatics, lymph and lymphoid tissue. Harvard Univ Press, Cambridge, Mass. Hallbn, A. & Hansson, H. E. 1974. Cannulation of the right lymphatic duct in man. Scand J Thor Cardiouasc Surg, in press. Hamolsky, M. W. 1967. Editorial. Enzymes in acute myocardial infarction. Circulation 35, 427. Jdanov, D. A. 1959. Anatomie du canal thoracique et des principaux collecteurs lymphatiques du tronc chez I’homme. Acta Anat 37, 20. Kampmeier, D. F. 1928. On the lymph flow of the human heart, with reference to the first development of the channels and the first appearance, distribution, and physiology of their valves. Am Heart J 4, 210. Kline, I. K., Miller, A. J., Pick, R. & Katz, L. N. 1964. The effects of chronic impairment of cardiac lymph flow on myocardial reactions after coronary artery ligation in dogs. Am Heart J 68, 515. Kluge, T. 1971. Hjertets lymfesirkulasjon. Nord Med 86, 1325. Leeds, S . E., Uhley, H. N., Sampson, J. J. & Friedman, M. 1959. A new method for measurement of lymph flow from the right duct in the dog. Am J Surg 98, 211. Malmberg, P. 1972. Heart-lymph enzyme activity in myocardial cell injury. Diss. Uppsala. Miller, A. J. 1963. The lymphatics of the heart. Arch Intern Med 112, 501. Miller, A. J., Ellis, A. & Katz, L. N. 1964. Cardiac lymph: flow rates and composition in dogs. Am J Physiol 206, 63. Patek, P. R. 1939. Morphology of the lymphatics of the mammalian heart. Am J Anat 64, 203. Posen, S . 1970. Turnover of circulating enzymes. Clin Chem 16, 71. Rouvibre, H. 1932. Anatomie des lymphatiques de l’homme. Libraires de I’acadbmie de mbdecine, Paris. Rudbeck, 0. 1653. Nova exercitutio anatomica, exhibens ductus hepaticos aquosos, et vasa glandulorum serosa. Upsala. Shell, W. E., Kjekshus, J. K. & Sobel, B. E. 171. Quantitative assessment of the extent of myocardial infarction in the conscious dog by means of analysis of serial changes in serum creatine phosphokinase activity. J Clin Znuesr 50, 2614. Shore, L. R. 1928. The lymphatic drainage of the human heart. J Anat 63, 291. Symbas, P. N., Cooper, T., Gantner, G. A. & Willman, V. L. 1963. Lymphatic drainage of the heart: Effects of experimental Interruption of lymphatics. Surg Forum 14, 254. Ullal, S . R., Kluge, T. H., Kerth, W. J. & Gerbode, F. 1972. Changes in cardiac lymph of dogs during and after anoxia. Ann Surg 175, 472. Warren, M. F. & Drinker, C. K. 1942. The flow of lymph from the lungs of the dog. Am J PhysioIl36, 207. Wilkinson, J. H. 1970. Clinical significance of enzyme activity measurements. Clin Chem 16, 882.
Scand J Thor Cardiouasc Surg 9
