Atrial Pressure and Hormonal and Renal Responses to Acute Cardiac Tamponade Markku Hynynen, MD, Markku Salmenpera, MD, Ari L. J. Harjula, MD, Ilkka Tikkanen, MD, Frej Fyhrquist, MD, and Jussi Heinonen, MD Department of Anaesthesia, Department of Thoracic and Cardiovascular Surgery, and Fourth Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
The effect of acute cardiac tamponade on atrial pressures, plasma atrial natriuretic factor concentration and renin activity, and renal water and electrolyte excretion was studied in pigs loaded intravenously with hydroxyethyl starch and maintained on a continuous intravenous infusion of isotonic saline solution. Saline solution was infused into the pericardial space in 6 anesthetized pigs until a predetermined decrease of 20% in mean arterial pressure was achieved. Another 6 sham-treated pigs served as controls. Tamponade increased atrial intracavitary pressures but decreased atrial transmural (distending) pressures. These changes in atrial pressures were
reversed after release of tamponade. Changes in plasma atrial natriuretic factor concentration correlated positively with changes in atrial transmural pressures. Tamponade increased plasma renin activity and decreased urine flow and renal sodium and potassium excretion, and release of tamponade reversed these changes. Thus, the tamponade-induced reduction in atrial distention is associated with hormonal changes, which may contribute to the reductions in diuresis and natriuresis observed in this connection.
I
only limited and preliminary data exist regarding concomitant changes in plasma concentration of ANF and renal function in compressive pericardial diseases [12-14]. Therefore, we also evaluated the renal water and electrolyte excretion in our animals.
t has been known for decades that alteration in atrial distention is associated with changes in urine flow and renal sodium excretion [l, 21. Atrial natriuretic factor (ANF) is a recently discovered polypeptide of cardiac origin with diuretic and natriuretic properties [3]. Numerous studies have demonstrated the relationship between atrial intracavitary pressures and plasma ANF concentration [4-71. Normally, a change in intraatrial pressure is accompanied by a parallel change in atrial wall distention. Therefore, it is difficult to separate the contributions of pressure and wall stretch in the release of ANF. Cardiac tamponade is a condition in which atrial intracavitary pressure is elevated, but transmural pressure, the true distending cavitary pressure, does not increase because of a concomitant increase in intrapericardial pressure. Therefore, cardiac tamponade offers a unique opportunity to evaluate the relative contributions of atrial intracavitary pressure and atrial transmural pressure in the regulation of ANF release. Atrial distention is also involved in renin [8] release, which may in part account for the renal responses to acute cardiac tamponade. Recent studies in dogs [9-111 have shown no change in plasma ANF concentration during acute cardiac tamponade. Atrial transmural pressures remained unchanged [lo] or decreased [ l l ] during tamponade. The present study reassessed the relative contributions of atrial pressure and atrial distention in ANF secretion and investigated changes in plasma levels of ANF and renin during and after acute cardiac tamponade. To our knowledge, Accepted for publication Dec 1, 1989 Address reprint requests to Dr Hynynen, Department of Anaesthesia, Helsinki University Central Hospital, Haartmaninkatu 4, SF-00290 Helsinki, Finland. 0 1990 by
The Society of Thoracic Surgeons
(Ann Thorac Surg 1990;49:632-7)
Material and Methods The study protocol was approved by the Laboratory Animal Committee of Helsinki University Central Hospital. All animals received humane care in compliance with the guidelines of the "Guide for the Care and Use of Laboratory Animals" published by the National Institutes of Health (NIH publication No. 85-23, revised 1985).
Anesthesia and Preparations Anesthesia for 12 pigs (mean weight, 14 kg; range, 10 to 20 kg) was induced with 25 mg/kg of ketamine, 10 mg of diazepam, and 40 mgkg of azaperone intramuscularly. After induction, 6 mg/kg of sodium pentobarbital was administered intravenously, and the trachea was intubated. Anesthesia was maintained with nitrous oxide in oxygen (inspired oxygen fraction, 0.30) and enflurane (inspired concentration, 0.6% to 0.8%).After intubation, a continuous infusion of d-tubocurarine (0.1 mg/kg per hour) was started for muscle relaxation and prevention of shivering. The animals were mechanically ventilated with a ventilator (Servo 900B) to normocarbia (arterial carbon dioxide tension, 35 to 45 mm Hg) as assessed with end-tidal CO, concentration and periodic arterial blood gas analyses. Surface insulation and warming blanket were used to prevent heat loss as adjusted by recording of the rectal temperature. To induce a continuous urine flow, an intravenous infusion of isotonic saline solution (15 mL/kg per hour) 0003-4975/90/$3.50
Ann Thorac Surg 1990;49632-7
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
was started after intubation and continued throughout the study. During cannulations, the animals were loaded with 30 mL/kg of hydroxyethyl starch administered intravenously within 15 to 30 minutes. The iliac artery and the iliac or jugular vein were cannulated for arterial blood pressure monitoring and blood sampling and for a vascular sheath, respectively. A 5F flow-directed thermodilution catheter with right atrial port (Edwards Laboratories, Santa Ana, CA) was advanced into the pulmonary artery. An indwelling catheter was surgically placed in the urinary bladder.
Tamponade The pericardium was approached through a subxiphoidal skin incision. A small incision was made in the parietal pericardium, and a fluid-filled 8F catheter was advanced into the pericardial cavity directed behind the heart. The pericardial incision was closed around the catheter with a pursestring suture. After a stabilizing period of at least 30 minutes, a 30-minute control period was started. After this control period, tamponade was induced in 6 pigs by injecting saline solution (37°C) slowly into the pericardial space through the previously placed catheter until a reduction of 20% in mean arterial pressure was observed. This was most often achieved with about 6 mL/kg of saline solution. Sixty minutes after induction of tamponade was started, the pericardial space was released by rapid gravity drainage and recovery of the fluid was confirmed. In another 6 sham-operated pigs, no tamponade was induced.
Measurements Hemodynamic measurements included mean arterial pressure (MAP), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), pericardial space pressure (PP), and cardiac output (CO). The pressures were measured with fluid-filled catheters connected to AE 840 pressure transducers (Aksjeselskapet Mikroelektronik, Horten, Norway) zeroed to the midthoracic level. The pressures were recorded by polygraph tracings and read at end-expiration. Cardiac output was measured in triplicate by thermodilution (model 9510 Cardiac Output Computer, Edwards Laboratories) by injecting 5 mL of saline solution (room temperature) into the right atrial port of the pulmonary artery catheter. Systemic vascular resistance (SVR) and transmural right (CVP,,) and left (PCWP,) atrial pressure were calculated according to the following formulas:
633
and urinary sodium and potassium concentrations were measured from stored (at -70°C) samples. Arterial blood samples for the determination of plasma ANF [15] and renin activity (PRA) [16] were drawn at the same stages of the study as the hemodynamic measurements were performed. Blood was taken into prechilled tubes containing ethylenediaminetetraacetic acid and 1,000 IU of aprotinin per milliliter of blood. An equal volume of saline solution was infused to replace the volume of blood sampled. The samples were centrifuged at +4"C and 3,000 rpm for ten minutes, and the plasma was stored at -70°C until assayed.
Statistical Analyses To hold the assumptions of the analysis of variance and regression analysis, square roots of the original ANF, PRA, and renal data were taken before the analyses. Two-way analysis of variance was used to assess whether thecourses of the variables differed significantly between the groups during the entire study period. When a significant difference between the groups was noted, analysis of variance for repeated measures was applied to identify a significant change in each variable within the groups during and after tamponade. If parallel significant change occurred within both groups, the difference between the groups was tested with two-way analysis of variance. Control values before tamponade and the changes from these control values to the ending values at termination of the experiment were compared between the groups with the t test for independent data. Owing to repeated measures during the study, the Bonferroni method was adjusted for p values in the latter case. Linear regression analysis was used to assess the interrelationship between the changes from control values in cardiac filling pressures, mean arterial pressure, plasma ANF, and PRA. The null hypothesis was rejected if the probability of type I error was less than 5%. The data are given as the arithmetic or geometric (in cases of converted data) mean -t standard error of the mean.
Results Hernodynamic and Hormonal Data
= PCWP - PP.
Mean arterial pressure was higher in the control group before the experiment (Table 1).All other control values of the hemodynamic and hormonal variables were similar in both groups. With the exception of systemic vascular resistance, the time courses of all hemodynamic and hormonal variables differed significantly between the groups when compared during the entire experimental period. All changes described throughout this section, ie, increases and decreases in the hemodynamic and hormonal variables induced by tamponade and release of tamponade, were statistically significant unless otherwise indicated.
Hemodynamic measurements were performed before tamponade, 30 and 60 minutes after start of tamponade, and 15, 30, and 60 minutes after release of tamponade. Urine was collected and recorded in 30-minute periods,
EFFECTS OF TAMPONADE. Cardiac tamponade decreased transmural right and left atrial pressures, while an increase occurred in central venous pressure and pulmonary capillary wedge pressure (Fig 1).During tamponade,
SVR = CVPt, PCWPt,
MAP - CVP
co
= CVP - PP,
x 80,
and
634
Ann Thorac Surg
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
1990;49632-7
Table 1. Hemodynamic Variables Before, During, and After Cardiac Tamponade in 6 Treated and 6 Control Pigs" Stage of Study Release of Tamponade (min)
Tamponade (min) Variable
Group
Control
30
60
15
30
60
T C T C T C T C
61 f 2 71 f 2 3.1 f 0.4 3.5 f 0.3 115 f 8 118 f 8 1,465 f 173 1,512 2 127
49 f 3 74 1 2.3 f 0.3 3.6 f 0.4 116 f 7 121 f 10 1,516 f 145 1,567 ? 187
47 f 3 78 f 2 1.7 f 0.2 3.6 f 0.4 139 +. 11 124 f 11 1,906 f 200 1,617 f 166
65 f 2 76 f 3 3.1 f 0.4 3.5 f 0.3 112 f 8 120 f 9 1,679 185 1,630 f 169
63 f 3 76 4 3.3 f 0.4 3.6 2 0.4 116 f 6 122 ? 10 1,458 f 112 1,657 ? 218
65 3 83 f 6 3.0 +. 0.3 3.7 f 0.4 115 f 6 126 12 1,629 ? 131 1,711 226
MAP (mm Hg) CO (L/min)
HR (beatdmin) SVR (dyne . s/cm5) a
Values are shown as mean
C = control group; tamponade group.
CO
f the
=
*
*
*
*
* *
standard error.
cardiac output;
HR = heart rate;
MAP = mean arterial pressure;
plasma ANF concentration decreased and PRA increased (Fig 2). Mean arterial pressure and cardiac output decreased (Table 1). In the control group, no change occurred in any of these variables. Heart rate increased in both groups, but the increase was significantly greater in the tamponade group than in the control group (Table 1).
SVR
=
systemic vascular resistance;
T=
Tamponade
As measured onward from the values at 60 minutes of tamponade, transmural right and left atrial pressures increased, while a decrease was observed in central venous pressure and pulmonary capillary wedge pressure (see Fig 1).Plasma ANF concentration increased and PRA decreased (see Fig 2). Mean arterial pressure and cardiac output increased, and heart rate decreased (Table 1).No significant changes in any of these variables were observed in the control pigs. At the end of the experiment, no difference in the changes from the control values measured before tamponade was observed between the groups in any hemodynamic or hormonal variable. EFFECTS OF RELEASE OF TAMPONADE.
T
RELATIONSHIPS BETWEEN PLASMA HORMONE LEVELS, ATRIAL PRESSURES, AND BLOOD PRESSURE. When the data from both groups were pooled, the change from the control value in plasma ANF concentration was positively correlated with the corresponding changes in transmural right (r = 0.71, p < 0.001) and left ( r = 0.54, p < 0.001) atrial pressures. The relationships between the change in plasma ANF and the changes in intracavitary atrial pressures were not significant. The change in PRA was not significantly related to the changes in atrial intracavitary or transmural pressures, mean arterial pressure, or plasma ANF concentration.
T
I 12 d[
T
Renal Responses The renal variables (Fig 3) were similar in both groups at the start of the experiment. The time courses of the renal responses to the experiment differed significantly between the groups. In the tamponade group, decreases in urine flow and urinary sodium and potassium excretion were observed during tamponade and a recovery occurred after release of tamponade. In this group, the patterns of diuresis and kaliuresis, but not that of natri-
1
I
I
I
0
30
60
90
J 120
TIME ( m i d
Fig 1 . Atrial pressure responses to acute cardiac tamponade in 6 treated (solid circles) and 6 control (open circles) pigs. (CVP = central venous pressure; CVP,, = transmural right atrial pressure; PCWP = pulmona y capillay wedge pressure; PCWP,, = transmural left atrial pressure.)
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
Ann Thorac Surg 1990;49632-7
.
635
volume-replete [lo] dogs, or in dogs under conditions of fluid balance not clearly defined [ l l ] . No change in plasma ANF level during acute cardiac tamponade was demonstrated in those studies. When the nonvolumeloaded dogs received approximately 35 mL/kg of Ringer’s solution within five minutes, however, plasma ANF level was increased and then decreased for the next 15 to 30 minutes by tamponade [9]. Because the study lacked a control group, the possibility of a time-related effect must be taken into account in this decrease. Nevertheless, the normal ANF response to rapid volume loading was abolished by tamponade in these dogs, which supports our finding of decreased plasma ANF level during tamponade. We paid particular attention to the fluid balance by loading our animals with hydroxyethyl starch and maintaining them on a continuous infusion of saline solution. Therefore, our animals were probably better volumerepleted than those of other investigators. In support of this view, we measured higher plasma ANF levels before tamponade than those reported by other investigators. The volume repletion and hence higher initial plasma ANF level might have enabled us to detect the decrease in the hormone level.
Tamponade
m
T c5
\ c
0.7L
-1
E
Y
I
I
I
I
I
0
30
60
90
120
50
.>
TIME ( m i d
0
Fig 2. Plasma hormonal responses to acute cardiac tamponade in 6 treated (solid circles) and 6 control (open circles) pigs. (ANF = atrial natriuretic factor; PRA = plasma renin activity.)
uresis, were significant over time. In the control group, a time-related marked increase in diuresis, natriuresis, and kaliuresis occurred. At the end of the experiment, the changes from the control values in diuresis, natriuresis, and kaliuresis differed significantly between the groups.
.-C
2oo
A
[
E
‘p 150 w 1
.>m Y
z
3
50
Comment By using acute cardiac tamponade as the study model, we could differentiate the individual changes occurring in distending atrial pressure and intraatrial pressure during our experiment. We found significant interrelationships between the changes in plasma ANF concentration and transmural (ie, distending) atrial pressures, but not between those in ANF concentration and intraatrial pressures during and after tamponade. Thus, our results appear to support the view that atrial stretch, not pressure, is a principal determinant controlling acute release of ANF [9, 101. We observed a decrease in plasma ANF concentration during tamponade. In this respect, our result clearly differs from those reported previously during tamponade induced by insufflation of air [9] or instillation of fluid [lo, 111 into the pericardial space in nonvolume-loaded [9] or
.-
loo
c5 C
r
T
E
\
P
w
a
50
.>Y Y
3
0
Pre
Per
Post
Fig 3. Rennl water and electrolyte excretory responses to acute cardiac tamponade in 6 treated (hatched bars) and 6 control (open bars) pigs. (Per = during tamponade; Post = after tamponade; Pre = before tamponade; UKV = urine potassium excretion; UN,V = urine sodium excretion; V = urine flow.)
636
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
After release of tamponade, plasma ANF level increased from that measured at the end of the tamponade period in our animals. Again, the recent studies with dogs [9-111 have not been able to demonstrate any change in plasma ANF as measured five to 120 minutes after release of acute tamponade. The different management of fluid balance may explain the discrepancy in the results. In patients undergoing pericardiocentesis or pericardiotomy for cardiac tamponade [12, 13, 171 or pericardiectomy for chronic constrictive pericarditis [14], however, an increase in plasma ANF occurred after the procedures. Simultaneously, increases in atrial transmural pressures [12, 13, 17, 181 and in echocardiographic atrial volumes and atrial wall tension [13] were observed. Thus, our results and those obtained in the patient studies suggest that relief of acute or chronic constriction of the atria permits enlargement of the chambers with increased stretch and hence increased ANF release. Increased atrial distention suppresses renin secretion [8]. In keeping with this, we found an increase in PRA during tamponade with decreased atrial distention. A similar renin response to tamponade has also been demonstrated by other investigators [9]. Activation of the renin-angiotensin-aldosterone system during tamponade has also been demonstrated by increased plasma aldosterone concentration [111. No significant negative relationship existed between the changes in PRA and atrial transmural pressures in our animals. Therefore, further studies are needed to clarify the role of atrial stretch in the regulation of renin release during tamponade. The systemic hypotension and the decreased renal perfusion pressure induced by the tamponade and the reduced inhibition of renin release by decreased plasma ANF level [19] may also have contributed to the increase in PRA. The hormonal changes observed during and after tamponade may have accounted for the changes in renal function in our animals. Thus, the reduction in renal water and sodium excretion during tamponade may have resulted from the decrease in ANF release and the increased secretion of renin. After release of tamponade, an inverse course in plasma levels of the hormones occurred simultaneously with a recovery in renal water and electrolyte excretion. According to two preliminary reports [12, 131 and 1 clinical case [14], relief of cardiac tamponade or constrictive pericarditis in patients can cause increased diuresis and natriuresis but only a slight increase in kaliuresis, together with an increased plasma ANF level. Similar renal changes also occur during infusion of a pharmacological dose of ANF [20]. The changes in hemodynamics should not be excluded in speculations regarding the etiological factors of renal derangement during tamponade. Recently an acute reduction in chronically elevated intracavitary left atrial pressure was shown to result in significant reductions in urine output and sodium excretion postoperatively in patients undergoing cardiac operations for valvular or coronary artery disease [21]. The changes were accompanied by a decrease in plasma ANF level and an increase in PRA. Although the type of experimental cardiac tamponade produced in the present
Ann Thorac Surg 1990;49:632-7
study may not accurately mimic that seen postoperatively, our results suggest that the major atrial determinant of hormone release in the patients [21] was the degree of distention. In any event, these findings stress the importance of atrial aspects in the renal function of cardiac surgical patients. In conclusion, the present study of cardiac tamponade confirms previous observations that acute changes in atrial distention are accompanied by changes in renal water and electrolyte excretion. Although the hemodynamic depression produced by cardiac tamponade undoubtedly contributes to the renal derangement, the changes in plasma ANF and PRA may also have a role. The experimental model of cardiac tamponade enables us to conclude that the major determinant in the release of ANF is atrial distention rather than atrial pressure. Further studies are needed to explain the role of atrial transmural pressure in the regulation of renin release. ~~
This study was supported by grants from the Nordisk Insulinfond, Copenhagen, Denmark, and the Paulo Foundation, Helsinki, Finland.
References 1. Henry JP, Gauer OH, Reeves JL. Evidence of the atrial location of receptors influencing urine flow. Circ Res 1956; 4%-90. 2. Goetz KL, Hermreck AS, Slick GL, Starke HS. Atrial recep-
3. 4. 5. 6. 7.
8.
9.
10.
11.
tors and renal function in conscious dogs. Am J Physiol 1970;219:1417-23. Needleman P, Greenwald JE. Atriopeptin: a cardiac hormone intimately involved in fluid, electrolyte and blood-pressure homeostasis. N Engl J Med 1986;314:828-34. Lang RE, Tholken H, Ganten D, Luft FC, Ruskoaho H, Unger Th. Atrial natriuretic factor-a circulating hormone stimulated by volume loading. Nature 1985;314:264-6. Raine AEG, Erne P, Burgisser E, et al. Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med 1986;315:533-7. Burnett JC Jr, Kao PC, Hu DC, et al. Atrial natriuretic peptide elevation in congestive heart failure in the human. Science 1986;231:1145-7. Hynynen M, Tikkanen I, Salmenpera M, Heinonen J, Fyhrquist F. Plasma atrial natriuretic peptide concentrations during induction of anesthesia and acute volume loading in patients undergoing cardiac surgery. J Cardiothorac Anesth 1987;1:401-7. Zehr JE, Hasbargen JA, Kurz KD. Reflex suppression of renin secretion during distension of cardiopulmonary receptors in dogs. Circ Res 1976;38:232-9. Mancini GBJ, McGillem MJ, Bates ER, Weder AB, DeBoe SF, Grekin RJ. Hormonal responses to cardiac tamponade: inhibition of release of atrial natriuretic factor despite elevation of atrial pressures. Circulation 1987;76:884-90. Edwards BS, Zimmerman RS, Schwab TR, Heublein DM, Burnett JC Jr. Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor. Circ Res 1988;62:191-5. Zions H, Karayannacos P, Zerva C, Alevizou-Terzaki V, Pavlatos F, Skalkeas G. Atrial natriuretic peptide levels during and after acute cardiac tamponade in dogs. J Am Coll Cardiol 1989;13:936-40.
Ann Thorac Surg 1990;49:632-7
12. VanBenthuysen KM, Whitman G, Yee B, et al. Release of atrial natriuretic peptide following relief of cardiac tamponade [Abstract]. Circulation 1987;76(Suppl 4):319. 13. Panayiotou H, Haitas 8, Hollister AS. Atrial wall tension, not pressure, determines plasma atrial natriuretic factor levels in tamponade [Abstract]. Clin Res 1989;37284A. 14. Wolozin MW, Ortola FV, Spodick DH, Seifter JL. Release of atrial natriuretic factor after pericardiectomy for chronic constrictive pericarditis. Am J Cardiol 1988;62:1323-5. 15. Tikkanen I, Fyhrquist F, Metsarinne K, Leidenius R. Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers. Lancet 1985;2:6&9. 16. Fyhrquist F, Soveri P, Puutula L, Stenman U-H. Radioimmunoassay of plasma renin activity. Clin Chem 1976;22:250-6. 17. Koller PT, Grekin RJ, Nicklas JM. Paradoxical response of
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
18. 19.
20. 21.
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plasma atrial natriuretic hormone to pericardiocentesis in cardiac tamponade. Am J Cardiol 1987;59:491-2. Koller P, Grekin RJ, Nicklas JM. Reply to: Spodick DH. Atrial natriuretic hormone, cardiac tamponade and true filling (transmural) pressures [Letter]. Am J Cardiol 1987;60200. Maack T, Marion DN, Camargo MJF, et al. Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs. Am J Med 1984; 771069-75. Hynynen M, Kupari M, Salmenpera M, et al. Hemodynamic effects of a-human atrial natriuretic peptide in healthy volunteers. J Cardiovasc Pharmacol 1988;11:711-5. Shannon RP, Libby E, Elahi D, et al. Impact of acute reduction in chronically elevated left atrial pressure on sodium and water excretion. Ann Thorac Surg 1988;46:430-7.
Notice From the American Board of Thoracic Surgery The American Board of Thoracic Surgery began its recertification process in 1984. Diplomates interested in participating in this examination should maintain a documented list of the operations they performed during the year prior to application for recertification. They should also keep a record of their attendance at thoracic surgical meetings, and other continuing medical education activities, for the 2 years prior to application. A minimum of 100 hours of approved CME activity is required. In place of a cognitive examination, candidates for recertification will be required to complete both the general thoracic and cardiac portions of the SESATS I11 syllabus (Self-EducatiodSelf-Assessment in Thoracic Surgery). It is not necessary for candidates to purchase SESATS I11 booklets prior to applying for recertification.
SESATS I11 booklets will be forwarded to candidates after their applications have been accepted. Diplomates whose 10-year certificates will expire in 1992 may begin the recertification process in 1990. This new certificate will be dated 10 years from the time of expiration of the original certificate. Recertification is also open to any diplomate with an unlimited certificate and will in no way affect the validity of the original certificate. The deadline for submission of applications is July 1, 1990. A recertification brochure outlining the rules and requirements for recertification in thoracic surgery is available upon request from the American Board of Thoracic Surgery, One Rotary Center, Suite 803, Evanston, IL 60201.
The effect of acute cardiac tamponade on atrial pressures, plasma atrial natriuretic factor concentration and renin activity, and renal water and electrolyte excretion was studied in pigs loaded intravenously with hydroxyethyl starch and maintained on a continuous intravenous infusion of isotonic saline solution. Saline solution was infused into the pericardial space in 6 anesthetized pigs until a predetermined decrease of 20% in mean arterial pressure was achieved. Another 6 sham-treated pigs served as controls. Tamponade increased atrial intracavitary pressures but decreased atrial transmural (distending) pressures. These changes in atrial pressures were
reversed after release of tamponade. Changes in plasma atrial natriuretic factor concentration correlated positively with changes in atrial transmural pressures. Tamponade increased plasma renin activity and decreased urine flow and renal sodium and potassium excretion, and release of tamponade reversed these changes. Thus, the tamponade-induced reduction in atrial distention is associated with hormonal changes, which may contribute to the reductions in diuresis and natriuresis observed in this connection.
I
only limited and preliminary data exist regarding concomitant changes in plasma concentration of ANF and renal function in compressive pericardial diseases [12-14]. Therefore, we also evaluated the renal water and electrolyte excretion in our animals.
t has been known for decades that alteration in atrial distention is associated with changes in urine flow and renal sodium excretion [l, 21. Atrial natriuretic factor (ANF) is a recently discovered polypeptide of cardiac origin with diuretic and natriuretic properties [3]. Numerous studies have demonstrated the relationship between atrial intracavitary pressures and plasma ANF concentration [4-71. Normally, a change in intraatrial pressure is accompanied by a parallel change in atrial wall distention. Therefore, it is difficult to separate the contributions of pressure and wall stretch in the release of ANF. Cardiac tamponade is a condition in which atrial intracavitary pressure is elevated, but transmural pressure, the true distending cavitary pressure, does not increase because of a concomitant increase in intrapericardial pressure. Therefore, cardiac tamponade offers a unique opportunity to evaluate the relative contributions of atrial intracavitary pressure and atrial transmural pressure in the regulation of ANF release. Atrial distention is also involved in renin [8] release, which may in part account for the renal responses to acute cardiac tamponade. Recent studies in dogs [9-111 have shown no change in plasma ANF concentration during acute cardiac tamponade. Atrial transmural pressures remained unchanged [lo] or decreased [ l l ] during tamponade. The present study reassessed the relative contributions of atrial pressure and atrial distention in ANF secretion and investigated changes in plasma levels of ANF and renin during and after acute cardiac tamponade. To our knowledge, Accepted for publication Dec 1, 1989 Address reprint requests to Dr Hynynen, Department of Anaesthesia, Helsinki University Central Hospital, Haartmaninkatu 4, SF-00290 Helsinki, Finland. 0 1990 by
The Society of Thoracic Surgeons
(Ann Thorac Surg 1990;49:632-7)
Material and Methods The study protocol was approved by the Laboratory Animal Committee of Helsinki University Central Hospital. All animals received humane care in compliance with the guidelines of the "Guide for the Care and Use of Laboratory Animals" published by the National Institutes of Health (NIH publication No. 85-23, revised 1985).
Anesthesia and Preparations Anesthesia for 12 pigs (mean weight, 14 kg; range, 10 to 20 kg) was induced with 25 mg/kg of ketamine, 10 mg of diazepam, and 40 mgkg of azaperone intramuscularly. After induction, 6 mg/kg of sodium pentobarbital was administered intravenously, and the trachea was intubated. Anesthesia was maintained with nitrous oxide in oxygen (inspired oxygen fraction, 0.30) and enflurane (inspired concentration, 0.6% to 0.8%).After intubation, a continuous infusion of d-tubocurarine (0.1 mg/kg per hour) was started for muscle relaxation and prevention of shivering. The animals were mechanically ventilated with a ventilator (Servo 900B) to normocarbia (arterial carbon dioxide tension, 35 to 45 mm Hg) as assessed with end-tidal CO, concentration and periodic arterial blood gas analyses. Surface insulation and warming blanket were used to prevent heat loss as adjusted by recording of the rectal temperature. To induce a continuous urine flow, an intravenous infusion of isotonic saline solution (15 mL/kg per hour) 0003-4975/90/$3.50
Ann Thorac Surg 1990;49632-7
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
was started after intubation and continued throughout the study. During cannulations, the animals were loaded with 30 mL/kg of hydroxyethyl starch administered intravenously within 15 to 30 minutes. The iliac artery and the iliac or jugular vein were cannulated for arterial blood pressure monitoring and blood sampling and for a vascular sheath, respectively. A 5F flow-directed thermodilution catheter with right atrial port (Edwards Laboratories, Santa Ana, CA) was advanced into the pulmonary artery. An indwelling catheter was surgically placed in the urinary bladder.
Tamponade The pericardium was approached through a subxiphoidal skin incision. A small incision was made in the parietal pericardium, and a fluid-filled 8F catheter was advanced into the pericardial cavity directed behind the heart. The pericardial incision was closed around the catheter with a pursestring suture. After a stabilizing period of at least 30 minutes, a 30-minute control period was started. After this control period, tamponade was induced in 6 pigs by injecting saline solution (37°C) slowly into the pericardial space through the previously placed catheter until a reduction of 20% in mean arterial pressure was observed. This was most often achieved with about 6 mL/kg of saline solution. Sixty minutes after induction of tamponade was started, the pericardial space was released by rapid gravity drainage and recovery of the fluid was confirmed. In another 6 sham-operated pigs, no tamponade was induced.
Measurements Hemodynamic measurements included mean arterial pressure (MAP), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), pericardial space pressure (PP), and cardiac output (CO). The pressures were measured with fluid-filled catheters connected to AE 840 pressure transducers (Aksjeselskapet Mikroelektronik, Horten, Norway) zeroed to the midthoracic level. The pressures were recorded by polygraph tracings and read at end-expiration. Cardiac output was measured in triplicate by thermodilution (model 9510 Cardiac Output Computer, Edwards Laboratories) by injecting 5 mL of saline solution (room temperature) into the right atrial port of the pulmonary artery catheter. Systemic vascular resistance (SVR) and transmural right (CVP,,) and left (PCWP,) atrial pressure were calculated according to the following formulas:
633
and urinary sodium and potassium concentrations were measured from stored (at -70°C) samples. Arterial blood samples for the determination of plasma ANF [15] and renin activity (PRA) [16] were drawn at the same stages of the study as the hemodynamic measurements were performed. Blood was taken into prechilled tubes containing ethylenediaminetetraacetic acid and 1,000 IU of aprotinin per milliliter of blood. An equal volume of saline solution was infused to replace the volume of blood sampled. The samples were centrifuged at +4"C and 3,000 rpm for ten minutes, and the plasma was stored at -70°C until assayed.
Statistical Analyses To hold the assumptions of the analysis of variance and regression analysis, square roots of the original ANF, PRA, and renal data were taken before the analyses. Two-way analysis of variance was used to assess whether thecourses of the variables differed significantly between the groups during the entire study period. When a significant difference between the groups was noted, analysis of variance for repeated measures was applied to identify a significant change in each variable within the groups during and after tamponade. If parallel significant change occurred within both groups, the difference between the groups was tested with two-way analysis of variance. Control values before tamponade and the changes from these control values to the ending values at termination of the experiment were compared between the groups with the t test for independent data. Owing to repeated measures during the study, the Bonferroni method was adjusted for p values in the latter case. Linear regression analysis was used to assess the interrelationship between the changes from control values in cardiac filling pressures, mean arterial pressure, plasma ANF, and PRA. The null hypothesis was rejected if the probability of type I error was less than 5%. The data are given as the arithmetic or geometric (in cases of converted data) mean -t standard error of the mean.
Results Hernodynamic and Hormonal Data
= PCWP - PP.
Mean arterial pressure was higher in the control group before the experiment (Table 1).All other control values of the hemodynamic and hormonal variables were similar in both groups. With the exception of systemic vascular resistance, the time courses of all hemodynamic and hormonal variables differed significantly between the groups when compared during the entire experimental period. All changes described throughout this section, ie, increases and decreases in the hemodynamic and hormonal variables induced by tamponade and release of tamponade, were statistically significant unless otherwise indicated.
Hemodynamic measurements were performed before tamponade, 30 and 60 minutes after start of tamponade, and 15, 30, and 60 minutes after release of tamponade. Urine was collected and recorded in 30-minute periods,
EFFECTS OF TAMPONADE. Cardiac tamponade decreased transmural right and left atrial pressures, while an increase occurred in central venous pressure and pulmonary capillary wedge pressure (Fig 1).During tamponade,
SVR = CVPt, PCWPt,
MAP - CVP
co
= CVP - PP,
x 80,
and
634
Ann Thorac Surg
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
1990;49632-7
Table 1. Hemodynamic Variables Before, During, and After Cardiac Tamponade in 6 Treated and 6 Control Pigs" Stage of Study Release of Tamponade (min)
Tamponade (min) Variable
Group
Control
30
60
15
30
60
T C T C T C T C
61 f 2 71 f 2 3.1 f 0.4 3.5 f 0.3 115 f 8 118 f 8 1,465 f 173 1,512 2 127
49 f 3 74 1 2.3 f 0.3 3.6 f 0.4 116 f 7 121 f 10 1,516 f 145 1,567 ? 187
47 f 3 78 f 2 1.7 f 0.2 3.6 f 0.4 139 +. 11 124 f 11 1,906 f 200 1,617 f 166
65 f 2 76 f 3 3.1 f 0.4 3.5 f 0.3 112 f 8 120 f 9 1,679 185 1,630 f 169
63 f 3 76 4 3.3 f 0.4 3.6 2 0.4 116 f 6 122 ? 10 1,458 f 112 1,657 ? 218
65 3 83 f 6 3.0 +. 0.3 3.7 f 0.4 115 f 6 126 12 1,629 ? 131 1,711 226
MAP (mm Hg) CO (L/min)
HR (beatdmin) SVR (dyne . s/cm5) a
Values are shown as mean
C = control group; tamponade group.
CO
f the
=
*
*
*
*
* *
standard error.
cardiac output;
HR = heart rate;
MAP = mean arterial pressure;
plasma ANF concentration decreased and PRA increased (Fig 2). Mean arterial pressure and cardiac output decreased (Table 1). In the control group, no change occurred in any of these variables. Heart rate increased in both groups, but the increase was significantly greater in the tamponade group than in the control group (Table 1).
SVR
=
systemic vascular resistance;
T=
Tamponade
As measured onward from the values at 60 minutes of tamponade, transmural right and left atrial pressures increased, while a decrease was observed in central venous pressure and pulmonary capillary wedge pressure (see Fig 1).Plasma ANF concentration increased and PRA decreased (see Fig 2). Mean arterial pressure and cardiac output increased, and heart rate decreased (Table 1).No significant changes in any of these variables were observed in the control pigs. At the end of the experiment, no difference in the changes from the control values measured before tamponade was observed between the groups in any hemodynamic or hormonal variable. EFFECTS OF RELEASE OF TAMPONADE.
T
RELATIONSHIPS BETWEEN PLASMA HORMONE LEVELS, ATRIAL PRESSURES, AND BLOOD PRESSURE. When the data from both groups were pooled, the change from the control value in plasma ANF concentration was positively correlated with the corresponding changes in transmural right (r = 0.71, p < 0.001) and left ( r = 0.54, p < 0.001) atrial pressures. The relationships between the change in plasma ANF and the changes in intracavitary atrial pressures were not significant. The change in PRA was not significantly related to the changes in atrial intracavitary or transmural pressures, mean arterial pressure, or plasma ANF concentration.
T
I 12 d[
T
Renal Responses The renal variables (Fig 3) were similar in both groups at the start of the experiment. The time courses of the renal responses to the experiment differed significantly between the groups. In the tamponade group, decreases in urine flow and urinary sodium and potassium excretion were observed during tamponade and a recovery occurred after release of tamponade. In this group, the patterns of diuresis and kaliuresis, but not that of natri-
1
I
I
I
0
30
60
90
J 120
TIME ( m i d
Fig 1 . Atrial pressure responses to acute cardiac tamponade in 6 treated (solid circles) and 6 control (open circles) pigs. (CVP = central venous pressure; CVP,, = transmural right atrial pressure; PCWP = pulmona y capillay wedge pressure; PCWP,, = transmural left atrial pressure.)
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
Ann Thorac Surg 1990;49632-7
.
635
volume-replete [lo] dogs, or in dogs under conditions of fluid balance not clearly defined [ l l ] . No change in plasma ANF level during acute cardiac tamponade was demonstrated in those studies. When the nonvolumeloaded dogs received approximately 35 mL/kg of Ringer’s solution within five minutes, however, plasma ANF level was increased and then decreased for the next 15 to 30 minutes by tamponade [9]. Because the study lacked a control group, the possibility of a time-related effect must be taken into account in this decrease. Nevertheless, the normal ANF response to rapid volume loading was abolished by tamponade in these dogs, which supports our finding of decreased plasma ANF level during tamponade. We paid particular attention to the fluid balance by loading our animals with hydroxyethyl starch and maintaining them on a continuous infusion of saline solution. Therefore, our animals were probably better volumerepleted than those of other investigators. In support of this view, we measured higher plasma ANF levels before tamponade than those reported by other investigators. The volume repletion and hence higher initial plasma ANF level might have enabled us to detect the decrease in the hormone level.
Tamponade
m
T c5
\ c
0.7L
-1
E
Y
I
I
I
I
I
0
30
60
90
120
50
.>
TIME ( m i d
0
Fig 2. Plasma hormonal responses to acute cardiac tamponade in 6 treated (solid circles) and 6 control (open circles) pigs. (ANF = atrial natriuretic factor; PRA = plasma renin activity.)
uresis, were significant over time. In the control group, a time-related marked increase in diuresis, natriuresis, and kaliuresis occurred. At the end of the experiment, the changes from the control values in diuresis, natriuresis, and kaliuresis differed significantly between the groups.
.-C
2oo
A
[
E
‘p 150 w 1
.>m Y
z
3
50
Comment By using acute cardiac tamponade as the study model, we could differentiate the individual changes occurring in distending atrial pressure and intraatrial pressure during our experiment. We found significant interrelationships between the changes in plasma ANF concentration and transmural (ie, distending) atrial pressures, but not between those in ANF concentration and intraatrial pressures during and after tamponade. Thus, our results appear to support the view that atrial stretch, not pressure, is a principal determinant controlling acute release of ANF [9, 101. We observed a decrease in plasma ANF concentration during tamponade. In this respect, our result clearly differs from those reported previously during tamponade induced by insufflation of air [9] or instillation of fluid [lo, 111 into the pericardial space in nonvolume-loaded [9] or
.-
loo
c5 C
r
T
E
\
P
w
a
50
.>Y Y
3
0
Pre
Per
Post
Fig 3. Rennl water and electrolyte excretory responses to acute cardiac tamponade in 6 treated (hatched bars) and 6 control (open bars) pigs. (Per = during tamponade; Post = after tamponade; Pre = before tamponade; UKV = urine potassium excretion; UN,V = urine sodium excretion; V = urine flow.)
636
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
After release of tamponade, plasma ANF level increased from that measured at the end of the tamponade period in our animals. Again, the recent studies with dogs [9-111 have not been able to demonstrate any change in plasma ANF as measured five to 120 minutes after release of acute tamponade. The different management of fluid balance may explain the discrepancy in the results. In patients undergoing pericardiocentesis or pericardiotomy for cardiac tamponade [12, 13, 171 or pericardiectomy for chronic constrictive pericarditis [14], however, an increase in plasma ANF occurred after the procedures. Simultaneously, increases in atrial transmural pressures [12, 13, 17, 181 and in echocardiographic atrial volumes and atrial wall tension [13] were observed. Thus, our results and those obtained in the patient studies suggest that relief of acute or chronic constriction of the atria permits enlargement of the chambers with increased stretch and hence increased ANF release. Increased atrial distention suppresses renin secretion [8]. In keeping with this, we found an increase in PRA during tamponade with decreased atrial distention. A similar renin response to tamponade has also been demonstrated by other investigators [9]. Activation of the renin-angiotensin-aldosterone system during tamponade has also been demonstrated by increased plasma aldosterone concentration [111. No significant negative relationship existed between the changes in PRA and atrial transmural pressures in our animals. Therefore, further studies are needed to clarify the role of atrial stretch in the regulation of renin release during tamponade. The systemic hypotension and the decreased renal perfusion pressure induced by the tamponade and the reduced inhibition of renin release by decreased plasma ANF level [19] may also have contributed to the increase in PRA. The hormonal changes observed during and after tamponade may have accounted for the changes in renal function in our animals. Thus, the reduction in renal water and sodium excretion during tamponade may have resulted from the decrease in ANF release and the increased secretion of renin. After release of tamponade, an inverse course in plasma levels of the hormones occurred simultaneously with a recovery in renal water and electrolyte excretion. According to two preliminary reports [12, 131 and 1 clinical case [14], relief of cardiac tamponade or constrictive pericarditis in patients can cause increased diuresis and natriuresis but only a slight increase in kaliuresis, together with an increased plasma ANF level. Similar renal changes also occur during infusion of a pharmacological dose of ANF [20]. The changes in hemodynamics should not be excluded in speculations regarding the etiological factors of renal derangement during tamponade. Recently an acute reduction in chronically elevated intracavitary left atrial pressure was shown to result in significant reductions in urine output and sodium excretion postoperatively in patients undergoing cardiac operations for valvular or coronary artery disease [21]. The changes were accompanied by a decrease in plasma ANF level and an increase in PRA. Although the type of experimental cardiac tamponade produced in the present
Ann Thorac Surg 1990;49:632-7
study may not accurately mimic that seen postoperatively, our results suggest that the major atrial determinant of hormone release in the patients [21] was the degree of distention. In any event, these findings stress the importance of atrial aspects in the renal function of cardiac surgical patients. In conclusion, the present study of cardiac tamponade confirms previous observations that acute changes in atrial distention are accompanied by changes in renal water and electrolyte excretion. Although the hemodynamic depression produced by cardiac tamponade undoubtedly contributes to the renal derangement, the changes in plasma ANF and PRA may also have a role. The experimental model of cardiac tamponade enables us to conclude that the major determinant in the release of ANF is atrial distention rather than atrial pressure. Further studies are needed to explain the role of atrial transmural pressure in the regulation of renin release. ~~
This study was supported by grants from the Nordisk Insulinfond, Copenhagen, Denmark, and the Paulo Foundation, Helsinki, Finland.
References 1. Henry JP, Gauer OH, Reeves JL. Evidence of the atrial location of receptors influencing urine flow. Circ Res 1956; 4%-90. 2. Goetz KL, Hermreck AS, Slick GL, Starke HS. Atrial recep-
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tors and renal function in conscious dogs. Am J Physiol 1970;219:1417-23. Needleman P, Greenwald JE. Atriopeptin: a cardiac hormone intimately involved in fluid, electrolyte and blood-pressure homeostasis. N Engl J Med 1986;314:828-34. Lang RE, Tholken H, Ganten D, Luft FC, Ruskoaho H, Unger Th. Atrial natriuretic factor-a circulating hormone stimulated by volume loading. Nature 1985;314:264-6. Raine AEG, Erne P, Burgisser E, et al. Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med 1986;315:533-7. Burnett JC Jr, Kao PC, Hu DC, et al. Atrial natriuretic peptide elevation in congestive heart failure in the human. Science 1986;231:1145-7. Hynynen M, Tikkanen I, Salmenpera M, Heinonen J, Fyhrquist F. Plasma atrial natriuretic peptide concentrations during induction of anesthesia and acute volume loading in patients undergoing cardiac surgery. J Cardiothorac Anesth 1987;1:401-7. Zehr JE, Hasbargen JA, Kurz KD. Reflex suppression of renin secretion during distension of cardiopulmonary receptors in dogs. Circ Res 1976;38:232-9. Mancini GBJ, McGillem MJ, Bates ER, Weder AB, DeBoe SF, Grekin RJ. Hormonal responses to cardiac tamponade: inhibition of release of atrial natriuretic factor despite elevation of atrial pressures. Circulation 1987;76:884-90. Edwards BS, Zimmerman RS, Schwab TR, Heublein DM, Burnett JC Jr. Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor. Circ Res 1988;62:191-5. Zions H, Karayannacos P, Zerva C, Alevizou-Terzaki V, Pavlatos F, Skalkeas G. Atrial natriuretic peptide levels during and after acute cardiac tamponade in dogs. J Am Coll Cardiol 1989;13:936-40.
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12. VanBenthuysen KM, Whitman G, Yee B, et al. Release of atrial natriuretic peptide following relief of cardiac tamponade [Abstract]. Circulation 1987;76(Suppl 4):319. 13. Panayiotou H, Haitas 8, Hollister AS. Atrial wall tension, not pressure, determines plasma atrial natriuretic factor levels in tamponade [Abstract]. Clin Res 1989;37284A. 14. Wolozin MW, Ortola FV, Spodick DH, Seifter JL. Release of atrial natriuretic factor after pericardiectomy for chronic constrictive pericarditis. Am J Cardiol 1988;62:1323-5. 15. Tikkanen I, Fyhrquist F, Metsarinne K, Leidenius R. Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers. Lancet 1985;2:6&9. 16. Fyhrquist F, Soveri P, Puutula L, Stenman U-H. Radioimmunoassay of plasma renin activity. Clin Chem 1976;22:250-6. 17. Koller PT, Grekin RJ, Nicklas JM. Paradoxical response of
HYNYNEN ET AL HORMONAL RESPONSES TO CARDIAC TAMPONADE
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plasma atrial natriuretic hormone to pericardiocentesis in cardiac tamponade. Am J Cardiol 1987;59:491-2. Koller P, Grekin RJ, Nicklas JM. Reply to: Spodick DH. Atrial natriuretic hormone, cardiac tamponade and true filling (transmural) pressures [Letter]. Am J Cardiol 1987;60200. Maack T, Marion DN, Camargo MJF, et al. Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs. Am J Med 1984; 771069-75. Hynynen M, Kupari M, Salmenpera M, et al. Hemodynamic effects of a-human atrial natriuretic peptide in healthy volunteers. J Cardiovasc Pharmacol 1988;11:711-5. Shannon RP, Libby E, Elahi D, et al. Impact of acute reduction in chronically elevated left atrial pressure on sodium and water excretion. Ann Thorac Surg 1988;46:430-7.
Notice From the American Board of Thoracic Surgery The American Board of Thoracic Surgery began its recertification process in 1984. Diplomates interested in participating in this examination should maintain a documented list of the operations they performed during the year prior to application for recertification. They should also keep a record of their attendance at thoracic surgical meetings, and other continuing medical education activities, for the 2 years prior to application. A minimum of 100 hours of approved CME activity is required. In place of a cognitive examination, candidates for recertification will be required to complete both the general thoracic and cardiac portions of the SESATS I11 syllabus (Self-EducatiodSelf-Assessment in Thoracic Surgery). It is not necessary for candidates to purchase SESATS I11 booklets prior to applying for recertification.
SESATS I11 booklets will be forwarded to candidates after their applications have been accepted. Diplomates whose 10-year certificates will expire in 1992 may begin the recertification process in 1990. This new certificate will be dated 10 years from the time of expiration of the original certificate. Recertification is also open to any diplomate with an unlimited certificate and will in no way affect the validity of the original certificate. The deadline for submission of applications is July 1, 1990. A recertification brochure outlining the rules and requirements for recertification in thoracic surgery is available upon request from the American Board of Thoracic Surgery, One Rotary Center, Suite 803, Evanston, IL 60201.
