Resuscitation, 5,175-181
Changes in blood viscosity and plasma proteins in myocardial infarction ’ A. BONDOLI, E. MARANA, S. I. MAGALINI, A. SABATO, R. RANIERI and E. SCRASCIA Instituto di Anestesiologia e Rianimazione, Universita Gzttolica de1 Sacro Cuore. Facolta di Medicina e Chin&a, Via della Pineta Sacchetti 526, 00168 Romh, Italy
A clinical study of some biological and biochemical factors was carried out on patients with acute myocardial infarction. It was shown that: (i) the plasma viscosity was highly correlated to the clinical evolution of myocardial infarction; (ii) the variations of plasma viscosity were related to changes in the connection of fibrinogen and globulin; (iii) the highest correlation was between the plasma viscosity and ol&obulin concentration, The monitoring of these may be useful in the clinical evaluation of myocardial infarction, Introduction Studies on acute myocardial infarction have indicated that changes of some biochemical and rheological factors could play an important role in the clinical course (Pedersen & Persson, 1%7; Ditzel, Bang & Thorsen, 1968; Dintenfass, 1969, 1974; Gordon, Snyder, Trite1 & Taylor, 1974). In particular the viscosities of the plasma and whole blood appear to be significant variables to monitor the fibrinogen, plasma protein composition and other blood constituents (Rand, Barker & Lacombe, 1970; Leonhardt & Bungert, 1972). The latter authors found that the ‘whole-blood’viscosity was strongly dependent upon the plasma viscosity and suggested that the rheological modifications represent a specific effect of changes in fibrinogen and globulin concentrations. In an attempt to evaluate the prognostic value of this variable and the quantitative relationship existing between the fibrinogen and serum protein profde, serial measurements have been made of the plasma viscosity in patients with acute myocardial infarction. Materials and methods
Samples of blood and urine of the 10 patients (Table 1) with acute myocardial infarction developed within the first 24 h after the onset of the chest pain, were analysed for 7 days. The diagnosis of myocardial infarction was established by clinical data, electrocardiography and changes in serum glutamic-oxaloacetic and glutamic-pyruvic transaminases. Only patients with uncomplicated myocardial infarction were included in the study. All blood 175
176 A. BONDOLI AND OTHERS Table 1. Details of age, sex and sites of infarction for the 10 patients studied. Patient 1
Age (years) 55 77 54 70 57 80 49 36
M M M M M F M M
Type of myocardial infarction Anterior Anterior Anterior Anterior Inferior Anterior Anterior Anterior
9
72 58
M M
Inferior Lateral-anterior
10
Sex
400,
x .‘: ?i
300.
E :
7i
290 280 -1
: a P
270.
(+I (+I
(+I
(+I
6
7
'E a
(+I (+)
1
2
3
(+I
Fig. 1. Course of plasma and urine osmolality (mosmol/kg of water) and acid-base myocardial infarction.
balance in acute
samples were analysed for relative viscosity (Coulter Harkness Viscometer; C. Erba-Milano); fibrinogen (by the method of Parfentiev, Johnson & Clifton, 1953); total serum proteins (Golberg Refractometer); albumin, cq, cu2,f3, y-globulins (by electrophoresis); acid-base balance (Corning 165 potentiometer); osmolality (Knauer R micro-osmometer; C. ErbaMilano). The urine osmolality was also measured. Samples of blood were withdrawn every morning at 08.00 hours. Respiratory and non-
BLOOD CHANGES IN MYOCARDIAL
INFARCTION
177
1.90. x c ._ H
0 Y
1.80.
; :
1.70.
H ._ >
z > ._
1.60.
‘0 ;
L 0
1.50.
I
i
i
i3
i
i
s
7
t (days) Fig. 2. Plasma viscosity in uncomplicated
myocardial infarction.
Viscosity relative to water (=I).
respiratory indices of acid-base balance were calculated according to a method previously described (Bondoli, Villani, Magalini & Scrascia, 1975). Acid-base status was maintained in the normal range by the method previous proposed (Magalini, Bondoli & Scrascia, 1973) and fluids were given to the patients according to the osmotic balance. Results The values of plasma and urine osmolality and acid-base balance of the 10 patients with acute myocardial infarction are shown (Fig. 1). Plasma osmolality was elevated immediately after the onset of the attack and returned to normal during the following days. In the same period the urine osmolality did not change significantly, and only slight nonrespiratory acidosis was observed. The changes in plasma viscosity in the patients with an uneventful course of the disease as seen by an absence of major cardiac arrhythmia or pulmonary dysfunction are shown in Fig. 2. In this group the plasma viscosity remained within the normal range until the third day, when it increased significantly. A particular pattern of plasma viscosity was observed in two patients (Fig. 3). In Fig. 3 the broken line represents the values for the relative viscosity in the plasma of one patient, who died with low cardiac output on the fourth day; his renal and pulmonary functions were changed considerably on the first day of admission. The broken line represents the relative viscosity of a second patient who, on the third day, developed complete atrio ventricular block requiring implantation of a pacemaker. In this case the plasma viscosity increased sharply during the acute phase, and returned to within the normal range on the following day.
178 A. BONDOLI AND OTHERS 2.1a
:i t : t t : t
2.00. x c ._ : 1.90, 5: ._ > ; G X
1.80.
1.70,
f ._ 5 a L
1.60.
1
2
3
4
5
6
7
t(d6ys)
Fig. 3. Plasma viscosity in two patients with acute myocudial infarction (see the text). Viscosity relative to water (=l).
The average concentrations of total plasma proteins and individual fractions are given (Table 2). The QZ- and y-globulins were increasing progressively, and serum albumin concentration showed a significant decrease since the fust day of infarction.
Discussion The severity of damage in acute myocardial infarction is probably because the tissue oxygen supply is insufficient owing to changes in oxygen transport (Gordon et al., 1974). These may also be related to changes in haematocrit and plasma viscosity (Crowell, Ford & Lewis, 1959; Guyton, 1963; Burch & De Pasquale, 1965; Crowellk Smith, 1%7; Finch & Lenfant, 1972). In particular a high plasma viscosity may reflect changes in concentration of fibrinogen and of large asymmetric plasma proteins, thus causing reduction in coronary perfusion. The elevation in plasma viscosity is primarily due to the increase in fibrinogen concentration, however, only if this protein is raised; the subendocardial oxygen transport is reduced greatly. In such cases, changes in the fibrinogen concentration could assume prognostic value. Furthermore, high concentrations of fibrinogen and globulins play a significant role in the development of thromboembolic complications. The magnitude of these phenomena frequently is not clinically expressed, although they are very important
Fibrinogen (mg/l 00 ml)
a1 a2 P r 380*50
0.30+0.05 0.67kO.05 1.17+-0.03 O.SlkO.33
3.48+0.12
Albumin (mg/lOOml)
Globulins (mg/ 1 OOml)
7kO.39
Total protein (mg/l OOml)
Day 1
470*27
0.41+0.04 0.92*0.11 1.26kO.08 1.24io.29
2.78iO.20
6.8*0.29
Day 2
559*22
0.43kO.05 1.10*0.07 1.17i0.12 1.15kO.20
2.84kO.19
7.4*0.39
Day 3
501+51
0.52+0.10 1.15iO.16 1.15kO.08 1.0720.25
2.57kO.10
6.8kO.36
Day 4
501*63
0.44kO.10 1.03*0.10 1.17+0.03 0.97iO.10
2.70+0.10
6.4iO.19
Day 5
575233
0.46*0.04 1.00*0.11 1.10~0.06 0.89iO.05
2.43kO.05
6.2kO.20
Day 6
Table 2. Total protein, albumin, globulins and fibrinogen in blood of 10 patients during the 7 days after myocardial infarction.
439*24
0.43io.04 0.93t0.02 0.92io.12 0.88+0.12
2.47k0.18
6.350.45
Day 7
2
g
E
E u
2
2
8
%
S
8
rm
180
A. BONDOLI AND OTHERS
. . . . ..d.GLOBULIN
/ /
r
......
. . . . . . ..TOTAL PROTEIN LOBULIN ......
7P
FIBRINOGEN
.... ..d;GLOBULI
......
N
P -GLOBULIN
....
ALBUMIN
Fig. 4. Bravais-Pearson protein profile.
correlation coefficients (r) for plasma viscosity, fibrinogen and plasma
because they affect the microcirculation directly. The monitoring of plasma viscosity could help to interpret their pathological significance. Our results show also that plasma viscosity is highly related to the clinical evolution of myocardial infarction. An uneventful clinical course is characterized by lack of significant variation of plasma viscosity (Fig. 2), but high values of this factor have been observed in two severe cases (Fig. 3). It has been reported that in myocardial infarction plasma cortisol reaches its peak on the third day after the onset of chest pain (Sabato, Petrozzi, Marana, Magalini, Scrascia & Bondoli, 1976). This indirectly indicates that the ‘stress’ may have its maximal effect at this time; the observed increase of plasma viscosity and serum glutamic-oxaloacetic and glutamic-pyruvic transaminases occurring at the same time is of particular interest. Moreover, our results demonstrate that the electrophoretic pattern of serum proteins in myocardial infarction is characterized by a significant rise of the q-globulin fraction, which suggest potential changes of haptoglobulin and q-macroglobulin concentrations. Increase of cr2-macroglobulin has been recorded in states of altered vascular permeability (nephrotic syndrome, protein-losing enteropathies, burns) and haptoglobulin eleva-
BLOOD CHANGES IN MYOCARDIAL INFARCTION
181
tion is observed in physiopathological conditions characterized by tissue destruction or necrosis (myocardial infarction). Angiotensinogen is also a component of the q-globulin fraction, and a specific globulin that is secreted in hypoxic conditions and stimulates erythropoiesis, together with renal erythropoietic factor (Ganong, 1973). The high correlation existing between plasma viscosity and cq-globulin concentration (Fig. 4) indicates that plasma viscosity could represent a rapid and simple method to monitor early biochemical changes that may precede the development of complications in the microcirculation in acute myocardial infarction. This work was in part supported by grant no.76.01433.04 Professor Corrado Manni.
from C.N.R. Director of the Institute is
References Bondoli, A., Villani, A., Magalini, S. I. & Scrascia, E. (1975) The acid-base status: a mathematical approach to its definition. Resuscitation, 4,243-247. Burch, G. E. & De Pasquale, N. P. (1965) Hematocrit, viscosity and coronary blood flow. Dis. Chest. 48,225-232. Crowell, J. W., Ford, R. G. & Lewis, W. M. (1959) Oxygen transport in hemorrhagic shock as function of the hematocrit ratio. Am. J. Physiol. l%, 1033-1038. Crowell, J. W. & Smith, E. E. (1967) Determination of the optimal hematocrit. J. A&. Physiol. 22, 501-504. Dintenfass, L. (1969) Blood rheology in pathogenesis of coronary heart diseases. Am. Heart J. 77, 139-146. Dintenfass, L. (1974) Blood rheology as diagnostic and predictive tool in cardiovascular diseases. Angiology, 25, 365-371. Dintenfass, L. & Forbes, C. D. (1973) Viscosity of blood in patients with myocardial infarction, haemophilia and thyroid diseases. Effect of fibrinogen, albumin and globulin. Biorheol. 10, 457-462. Ditzel, J., Bang, H. 0. & Tborsen, N. (1968) Myocardial infarction and whole-blood viscosity. Acta Med. Stand. 183,577-579. Finch, C. A. & Lenfant, C. (1972) Oxygen transport in man. N. Engl. J. Med. 226,407-415. Ganong, W. F. (1973) Review ofMedical Physiology, 6th edn, pp. 342-345. Lange Medical Publications, Los Altos, California. Gordon, R. J., Snyder, G. K., Tritel, H. & Taylor, W. J. (1974) Potential significance of plasma viscosity and hematocrit variations in myocardial ischemia. Am. Heart J. 87, 175-182. Guyton, A. C. (1963) Circulatory Physiology: Cardiac Output and its Regulation, p. 358. W. B. Saunders Co., Philadelphia and London. Leonhardt, H. & Bungert, H. J. (1972) Untersuchunger uber die wechselwirkung von fibrinogen, globulinen und albumin auf die plasmaviscositat. CZin Chim. Acta, 42,181- 187. Magalini, S. I.,‘Bondoli, A. & Scrascia, E. (1973) A nomogram for the emergency treatment of metabolic acidosis. Resuscitation, 2, 151-156. Parfentiev, 1. A., Johnson, M. L. & Clifton, E.E. (1953) The determination of plasma fibrinogen by turbidity with ammonium sulfate. Arch. Biochem. Biophys. 46,470-475. Pedersen, T. & Persson, I. (1967) The viscosity of blood in coronary occlusion. Cardiologia, 51, 283-292. Rand, P. W., Barker, N. & Lacombe, E. (1970) Effects of plasma viscosity and aggregation on wholeblood viscosity. Am. J. Physiol. 218,681-687. Sabato, A., Petrozzi, U., Marana, E., Magalini, S. I., Scrascia, E. & Bondoli, A. (1976) Plasma cortisol monitoring in acute myocardial infarction. Resuscitation, 5, 169-173.
Changes in blood viscosity and plasma proteins in myocardial infarction ’ A. BONDOLI, E. MARANA, S. I. MAGALINI, A. SABATO, R. RANIERI and E. SCRASCIA Instituto di Anestesiologia e Rianimazione, Universita Gzttolica de1 Sacro Cuore. Facolta di Medicina e Chin&a, Via della Pineta Sacchetti 526, 00168 Romh, Italy
A clinical study of some biological and biochemical factors was carried out on patients with acute myocardial infarction. It was shown that: (i) the plasma viscosity was highly correlated to the clinical evolution of myocardial infarction; (ii) the variations of plasma viscosity were related to changes in the connection of fibrinogen and globulin; (iii) the highest correlation was between the plasma viscosity and ol&obulin concentration, The monitoring of these may be useful in the clinical evaluation of myocardial infarction, Introduction Studies on acute myocardial infarction have indicated that changes of some biochemical and rheological factors could play an important role in the clinical course (Pedersen & Persson, 1%7; Ditzel, Bang & Thorsen, 1968; Dintenfass, 1969, 1974; Gordon, Snyder, Trite1 & Taylor, 1974). In particular the viscosities of the plasma and whole blood appear to be significant variables to monitor the fibrinogen, plasma protein composition and other blood constituents (Rand, Barker & Lacombe, 1970; Leonhardt & Bungert, 1972). The latter authors found that the ‘whole-blood’viscosity was strongly dependent upon the plasma viscosity and suggested that the rheological modifications represent a specific effect of changes in fibrinogen and globulin concentrations. In an attempt to evaluate the prognostic value of this variable and the quantitative relationship existing between the fibrinogen and serum protein profde, serial measurements have been made of the plasma viscosity in patients with acute myocardial infarction. Materials and methods
Samples of blood and urine of the 10 patients (Table 1) with acute myocardial infarction developed within the first 24 h after the onset of the chest pain, were analysed for 7 days. The diagnosis of myocardial infarction was established by clinical data, electrocardiography and changes in serum glutamic-oxaloacetic and glutamic-pyruvic transaminases. Only patients with uncomplicated myocardial infarction were included in the study. All blood 175
176 A. BONDOLI AND OTHERS Table 1. Details of age, sex and sites of infarction for the 10 patients studied. Patient 1
Age (years) 55 77 54 70 57 80 49 36
M M M M M F M M
Type of myocardial infarction Anterior Anterior Anterior Anterior Inferior Anterior Anterior Anterior
9
72 58
M M
Inferior Lateral-anterior
10
Sex
400,
x .‘: ?i
300.
E :
7i
290 280 -1
: a P
270.
(+I (+I
(+I
(+I
6
7
'E a
(+I (+)
1
2
3
(+I
Fig. 1. Course of plasma and urine osmolality (mosmol/kg of water) and acid-base myocardial infarction.
balance in acute
samples were analysed for relative viscosity (Coulter Harkness Viscometer; C. Erba-Milano); fibrinogen (by the method of Parfentiev, Johnson & Clifton, 1953); total serum proteins (Golberg Refractometer); albumin, cq, cu2,f3, y-globulins (by electrophoresis); acid-base balance (Corning 165 potentiometer); osmolality (Knauer R micro-osmometer; C. ErbaMilano). The urine osmolality was also measured. Samples of blood were withdrawn every morning at 08.00 hours. Respiratory and non-
BLOOD CHANGES IN MYOCARDIAL
INFARCTION
177
1.90. x c ._ H
0 Y
1.80.
; :
1.70.
H ._ >
z > ._
1.60.
‘0 ;
L 0
1.50.
I
i
i
i3
i
i
s
7
t (days) Fig. 2. Plasma viscosity in uncomplicated
myocardial infarction.
Viscosity relative to water (=I).
respiratory indices of acid-base balance were calculated according to a method previously described (Bondoli, Villani, Magalini & Scrascia, 1975). Acid-base status was maintained in the normal range by the method previous proposed (Magalini, Bondoli & Scrascia, 1973) and fluids were given to the patients according to the osmotic balance. Results The values of plasma and urine osmolality and acid-base balance of the 10 patients with acute myocardial infarction are shown (Fig. 1). Plasma osmolality was elevated immediately after the onset of the attack and returned to normal during the following days. In the same period the urine osmolality did not change significantly, and only slight nonrespiratory acidosis was observed. The changes in plasma viscosity in the patients with an uneventful course of the disease as seen by an absence of major cardiac arrhythmia or pulmonary dysfunction are shown in Fig. 2. In this group the plasma viscosity remained within the normal range until the third day, when it increased significantly. A particular pattern of plasma viscosity was observed in two patients (Fig. 3). In Fig. 3 the broken line represents the values for the relative viscosity in the plasma of one patient, who died with low cardiac output on the fourth day; his renal and pulmonary functions were changed considerably on the first day of admission. The broken line represents the relative viscosity of a second patient who, on the third day, developed complete atrio ventricular block requiring implantation of a pacemaker. In this case the plasma viscosity increased sharply during the acute phase, and returned to within the normal range on the following day.
178 A. BONDOLI AND OTHERS 2.1a
:i t : t t : t
2.00. x c ._ : 1.90, 5: ._ > ; G X
1.80.
1.70,
f ._ 5 a L
1.60.
1
2
3
4
5
6
7
t(d6ys)
Fig. 3. Plasma viscosity in two patients with acute myocudial infarction (see the text). Viscosity relative to water (=l).
The average concentrations of total plasma proteins and individual fractions are given (Table 2). The QZ- and y-globulins were increasing progressively, and serum albumin concentration showed a significant decrease since the fust day of infarction.
Discussion The severity of damage in acute myocardial infarction is probably because the tissue oxygen supply is insufficient owing to changes in oxygen transport (Gordon et al., 1974). These may also be related to changes in haematocrit and plasma viscosity (Crowell, Ford & Lewis, 1959; Guyton, 1963; Burch & De Pasquale, 1965; Crowellk Smith, 1%7; Finch & Lenfant, 1972). In particular a high plasma viscosity may reflect changes in concentration of fibrinogen and of large asymmetric plasma proteins, thus causing reduction in coronary perfusion. The elevation in plasma viscosity is primarily due to the increase in fibrinogen concentration, however, only if this protein is raised; the subendocardial oxygen transport is reduced greatly. In such cases, changes in the fibrinogen concentration could assume prognostic value. Furthermore, high concentrations of fibrinogen and globulins play a significant role in the development of thromboembolic complications. The magnitude of these phenomena frequently is not clinically expressed, although they are very important
Fibrinogen (mg/l 00 ml)
a1 a2 P r 380*50
0.30+0.05 0.67kO.05 1.17+-0.03 O.SlkO.33
3.48+0.12
Albumin (mg/lOOml)
Globulins (mg/ 1 OOml)
7kO.39
Total protein (mg/l OOml)
Day 1
470*27
0.41+0.04 0.92*0.11 1.26kO.08 1.24io.29
2.78iO.20
6.8*0.29
Day 2
559*22
0.43kO.05 1.10*0.07 1.17i0.12 1.15kO.20
2.84kO.19
7.4*0.39
Day 3
501+51
0.52+0.10 1.15iO.16 1.15kO.08 1.0720.25
2.57kO.10
6.8kO.36
Day 4
501*63
0.44kO.10 1.03*0.10 1.17+0.03 0.97iO.10
2.70+0.10
6.4iO.19
Day 5
575233
0.46*0.04 1.00*0.11 1.10~0.06 0.89iO.05
2.43kO.05
6.2kO.20
Day 6
Table 2. Total protein, albumin, globulins and fibrinogen in blood of 10 patients during the 7 days after myocardial infarction.
439*24
0.43io.04 0.93t0.02 0.92io.12 0.88+0.12
2.47k0.18
6.350.45
Day 7
2
g
E
E u
2
2
8
%
S
8
rm
180
A. BONDOLI AND OTHERS
. . . . ..d.GLOBULIN
/ /
r
......
. . . . . . ..TOTAL PROTEIN LOBULIN ......
7P
FIBRINOGEN
.... ..d;GLOBULI
......
N
P -GLOBULIN
....
ALBUMIN
Fig. 4. Bravais-Pearson protein profile.
correlation coefficients (r) for plasma viscosity, fibrinogen and plasma
because they affect the microcirculation directly. The monitoring of plasma viscosity could help to interpret their pathological significance. Our results show also that plasma viscosity is highly related to the clinical evolution of myocardial infarction. An uneventful clinical course is characterized by lack of significant variation of plasma viscosity (Fig. 2), but high values of this factor have been observed in two severe cases (Fig. 3). It has been reported that in myocardial infarction plasma cortisol reaches its peak on the third day after the onset of chest pain (Sabato, Petrozzi, Marana, Magalini, Scrascia & Bondoli, 1976). This indirectly indicates that the ‘stress’ may have its maximal effect at this time; the observed increase of plasma viscosity and serum glutamic-oxaloacetic and glutamic-pyruvic transaminases occurring at the same time is of particular interest. Moreover, our results demonstrate that the electrophoretic pattern of serum proteins in myocardial infarction is characterized by a significant rise of the q-globulin fraction, which suggest potential changes of haptoglobulin and q-macroglobulin concentrations. Increase of cr2-macroglobulin has been recorded in states of altered vascular permeability (nephrotic syndrome, protein-losing enteropathies, burns) and haptoglobulin eleva-
BLOOD CHANGES IN MYOCARDIAL INFARCTION
181
tion is observed in physiopathological conditions characterized by tissue destruction or necrosis (myocardial infarction). Angiotensinogen is also a component of the q-globulin fraction, and a specific globulin that is secreted in hypoxic conditions and stimulates erythropoiesis, together with renal erythropoietic factor (Ganong, 1973). The high correlation existing between plasma viscosity and cq-globulin concentration (Fig. 4) indicates that plasma viscosity could represent a rapid and simple method to monitor early biochemical changes that may precede the development of complications in the microcirculation in acute myocardial infarction. This work was in part supported by grant no.76.01433.04 Professor Corrado Manni.
from C.N.R. Director of the Institute is
References Bondoli, A., Villani, A., Magalini, S. I. & Scrascia, E. (1975) The acid-base status: a mathematical approach to its definition. Resuscitation, 4,243-247. Burch, G. E. & De Pasquale, N. P. (1965) Hematocrit, viscosity and coronary blood flow. Dis. Chest. 48,225-232. Crowell, J. W., Ford, R. G. & Lewis, W. M. (1959) Oxygen transport in hemorrhagic shock as function of the hematocrit ratio. Am. J. Physiol. l%, 1033-1038. Crowell, J. W. & Smith, E. E. (1967) Determination of the optimal hematocrit. J. A&. Physiol. 22, 501-504. Dintenfass, L. (1969) Blood rheology in pathogenesis of coronary heart diseases. Am. Heart J. 77, 139-146. Dintenfass, L. (1974) Blood rheology as diagnostic and predictive tool in cardiovascular diseases. Angiology, 25, 365-371. Dintenfass, L. & Forbes, C. D. (1973) Viscosity of blood in patients with myocardial infarction, haemophilia and thyroid diseases. Effect of fibrinogen, albumin and globulin. Biorheol. 10, 457-462. Ditzel, J., Bang, H. 0. & Tborsen, N. (1968) Myocardial infarction and whole-blood viscosity. Acta Med. Stand. 183,577-579. Finch, C. A. & Lenfant, C. (1972) Oxygen transport in man. N. Engl. J. Med. 226,407-415. Ganong, W. F. (1973) Review ofMedical Physiology, 6th edn, pp. 342-345. Lange Medical Publications, Los Altos, California. Gordon, R. J., Snyder, G. K., Tritel, H. & Taylor, W. J. (1974) Potential significance of plasma viscosity and hematocrit variations in myocardial ischemia. Am. Heart J. 87, 175-182. Guyton, A. C. (1963) Circulatory Physiology: Cardiac Output and its Regulation, p. 358. W. B. Saunders Co., Philadelphia and London. Leonhardt, H. & Bungert, H. J. (1972) Untersuchunger uber die wechselwirkung von fibrinogen, globulinen und albumin auf die plasmaviscositat. CZin Chim. Acta, 42,181- 187. Magalini, S. I.,‘Bondoli, A. & Scrascia, E. (1973) A nomogram for the emergency treatment of metabolic acidosis. Resuscitation, 2, 151-156. Parfentiev, 1. A., Johnson, M. L. & Clifton, E.E. (1953) The determination of plasma fibrinogen by turbidity with ammonium sulfate. Arch. Biochem. Biophys. 46,470-475. Pedersen, T. & Persson, I. (1967) The viscosity of blood in coronary occlusion. Cardiologia, 51, 283-292. Rand, P. W., Barker, N. & Lacombe, E. (1970) Effects of plasma viscosity and aggregation on wholeblood viscosity. Am. J. Physiol. 218,681-687. Sabato, A., Petrozzi, U., Marana, E., Magalini, S. I., Scrascia, E. & Bondoli, A. (1976) Plasma cortisol monitoring in acute myocardial infarction. Resuscitation, 5, 169-173.
