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Effects of open-heart surgery on carbohydrate and lipid metabolism
Effects of open-heart surgery on carbohydrate and lipid metabolism The concentrations of blood glucose, serum insulin, free fatty acids, and triglycerides were examined preoperatively, during anesthesia, during extracorporeal circulation, and during the following 3 postoperative days in 29 patients. The patients were divided into three groups according to the duration of extracorporeal circulation and the use of hypothermia: short perfusion group (SPG, bypass time shorter than 60 minutes, 15 patients), long perfusion group in normothermia (LPGN, bypass time longer than 60 minutes, 8 patients), and long perfusion group in hypothermia (LPGa, temperature during bypass below 33° C, 6 patients). In all three groups, the concentrations of free fatty acids and blood glucose rose significantly because of anesthesia (p < 0.001). After cardiopulmonary bypass, the concentrations of free fatty acids diminished significantly. The blood glucose remained at high level until the second postoperative day and was significantly higher in the LPG than in the SPG (p < 0.05). The serum insulin level remained low during anesthesia and extracorporeal circulation in the SPG and LPGH but rose during the postoperative period; the maximal values were recorded on the first postoperative day. There were no significant differences between the groups with regard to serum insulin during the study. These changes and their metabolic background are discussed.
L. S. Nuutinen, P. Mononen, M. Kairaluoma, and S. Tuononen, Oulu,
V^-hanges in body metabolism after accidental injury and after extensive surgery correlate with the magnitude of the trauma. 15, 16 The metabolic changes during and after open-heart surgery follow the usual injury pattern, with the metabolic state being converted to one of catabolism. 16 During cardiopulmonary bypass, lipid metabolism is dominant, 18 because free fatty acids are the principal substrate for energy production until glucose utilization and carbohydrate metabolism return to normal. 1 5 The concentrations of plasma lipids, 8 ' 24 blood glucose, 1 1 ' 1S and serum insulin 11 ' 25 have been studied before, but the duration of these studies was limited to the day of operation, with the length of the perfusion and the use of hypothermia being ignored. The purpose of this study was to determine the changes in plasma concentrations of free fatty acids, triglycerides, glucose, and insulin until the third postoperative day in patients having open-heart surgery, with special reference to the duration of cardiopulmonary bypass and the use of hypothermia. From the Departments of Anesthesiology and Surgery, University Central Hospital, Oulu, Finland. Received for publication July 19, 1976. Accepted for publication Nov. 5, 1976 680
Finland
Patients and methods The present work deals with 29 patients, who were divided into three groups according to the duration of cardiopulmonary bypass and the use of hypothermia: the short perfusion group (SPG), in which the perfusion time was less than 60 minutes; the long perfusion group with normothermia (LPG N ), in which the perfusion time was more than 60 minutes and the temperature in the esophagus during cardiopulmonary bypass was more than 33° C ) ; and the long perfusion group with hypothermia (LPG H ), in which the temperature during bypass was less than or equal to 33° C ) . The SPG consisted of 15 patients, the LPG N 8 patients, and the LPG H 6 patients. In the SPG, the operations were atrial septal defect corrections, in the LPG N mitral valve replacements, and in the LPG H aortic valve replacements. Table I shows the distribution of the patients by sex, weight, age, and duration of cardiopulmonary bypass. The patients in the SPG received 10 mg. of diazepam and 1 mg. per kilogram of pethidine (meperidine) intramuscularly, and the patients in both LPG's received 10 mg. of diazepam and 10 to 15 mg. of morphine intramuscularly as a premedication. Anesthesia was induced in the SPG by thiopentone, 5 mg. per kilogram,
Volume 73 Number 5 May, 1977
Carbohydrate and lipid metabolism
68 1
Table I. Data on the patients Sex (F/M)
Weight (Kg.)
(yr.)
Perf. time (min.)
SPG
9/6
43.3 ± 4.9 (19-80)
21.7 ± 3.9 (6-52)
37.4 ± 2.; (23-57)
LPGN > 33° C.
3/5
62 ± 2.9 (50-71)
46.1 ± 3.6 (31-57)
93.4 ± 5.7 (104-250)
LPGH £ 33° C.
2/4
70.5 ± 3 . 5 (54-78)
45.5 ± 2 (37-50)
Group
196.7 ± 26.3 (65-116)
Legend: SPG, Short perfusion group. LPGN, Long perfusion group in normothermia. LPGH, Long perfusion group in hypothermia. Mean values ± S.E.M., range in parentheses.
PREOR PRE POST 6p.m. 1st BYPASS BYPASS day
2nd day
3rd day
Fig. 1. Mean values of serum insulin, free fatty acids, triglycerides, and cholesterol during the study. LPG includes the patients of both long perfusion groups, and the figure shows the effect of cardiopulmonary bypass time on the parameters investigated. The changes of serum cholesterol are presented here, and a decreasing trend was seen in both groups. SPG, short perfusion group (perfusion time less than 60 minutes). and in the LPG by 50 to 80 mg. of morphine and 100 to 150 mg. of thiopentone. Pancuronium bromide was used as a relaxant in each group for intubation and subsequent muscular relaxation. All patients received 0.25 to 1.0 per cent halothane with nitrous oxide and oxygen as an inhalation mixture. Thalamonal (Innovar), or fentanyl was used for analgesia. The Rygg-Kyvsgaard heart-lung machine23 with a
bubble oxygenator was used. The priming solution consisted of 1,000 ml. of whole fresh heparinized blood and 1,000 ml. of gelatin solution (Haemaccel). Flow rates were maintained at 2.4 to 2.6 L. per square meter of body surface area during perfusion; hypothermia (31 to 32° C.) was used during aortic valve replacements. Five per cent glucose in water, 500 to 700 ml. per square meter of body surface area, was given intravenously on the day of operation, and 40 mmol. of potassium and 40 mmol. of sodium were added routinely per day in intravenous fluids. The fluid intake was 700 to 800 ml. per square meter on the first and second postoperative days. Whole blood and albumin were given at the end of the operation as well as postoperatively to maintain an adequate blood volume and colloid osmotic pressure. Blood samples were taken as follows: preoperatively in the ward (venous blood specimen), just before perfusion via the central venous pressure catheter, at the end of the operation, postoperatively at 6 P.M., and in the first, second, and third postoperative mornings via the central venous pressure catheter. Free fatty acids were measured according to the method of Duncombe,7 serum triglycerides according to the method of Bucolo and David,4 and serum insulin by the radioimmunoassay method.6 Data were analyzed with Student's t test, p < 0.05 being considered significant. Results Free fatty acids. The changes during the study are presented in Table II and Fig. 1. The concentration of free fatty acids rose significantly in all groups (p < 0.001) because of anesthesia. After cardiopulmonary bypass, the concentration of free fatty acids diminished significantly (p < 0.001) in all three groups. During the prebypass period, the free fatty acid
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Table II. Free fatty acids, triglycerides, blood glucose, and serum insulin at different stages of the study Group
Preop.
Prebypass
Postbypass
6.
e.M.
First day
Second day
Third day
FFA (mmol./L.)
SPG LPGN LPG„
0.48 ± 0.1 0.38 ± 0.1 0.39 ± 0.1
1.31 ± 0.1 1.4 ± 0.2 1.65 ± 0.1
0.75 ± 0.1 0.83 ± 0.1 0.88 ± 0.1
0.84 ± 0.1 0.96 ± 0.1 0.85 ± 0.1
0.66 ± 0 . 1 0.65 ± 0.1 0.63 ± 0.1
0.42 ± 0.1 0.64 ± 0.1 0.55 ± 0.2
0.38 ± 0.1 0.59 ± 0.04 0.53 ± 0.1
Trigly. (mmol./L.)
SPG LPGN LPGH
1.63 ± 0.2 2.33 ± 0.3 1.77 ± 0 . 2
1.54 ± 0.3 1.4 ± 0.3 1.2 ± 0 . 3
0.98 ± 0.1 1.0 ± 0.1 1.0 ± 0.1
0.98 ± 0.1 1.3 ± 0.1 1.1 ± 0.2
0.8 1.0 1.1
1.31 ± 0.1 1.3 ± 0.2 1.4 ± 0.2
1.1 1.2 1.5
± 0.1 ± 0.2 ± 0.2
Glucose (mmol./L.)
SPG LPGN LPGH
3.6 ± 0.1 3.9 ± 0.3 4.0 ± 0.3
8.1 ± 0.4 7.9 ± 0.6 8.2 ± 0.7
7.4 ± 0.2 8.6 ± 0.3 9.7 ± 1.0
8.0 ± 0.5 8.5 ± 0.6 10.0 ± 0.6
6.8 ± 0.3 7.4 ± 0 . 3 8.9 ± 0.7
7.2 8.8 8.5
5.7 8.1 6.4
± 0.4 ± 1.3 ± 0.6
S-Insulin ;u.U/ml.)
SPG LPGN LPGH
12.1 ± 2.1 11.1 ± 4.6 8.5 ± 2.5
17.6 ± 3.3 22.3 ± 6.7 14.5 ± 1.3
14.4 ± 2.3 15.9 ± 5.4 14.8 ± 2.5
16.2 ± 2.2 25.1 ± 8.6 17.9 ± 3.4
22.7 ± 4.0 24.8 ± 5.3 33.6 ± 7.8
± 0.1 ± 0.1 ± 0.3
± 0.3 ± 1.2 ± 0.7
21.0 ± 5.5 23.7 ± 3.7 28.7 ± 5.8
22.8 ± 6.3 18.8 ± 4.1 21.1 ± 7.6
Legend: SPG, Short perfusion group. LPGN, Long perfusion group in normothermia. LPGH, Long perfusion group in hypothermia (<33° C ) . Mean values ± S.E.M.
value was significantly higher in the LPGH than in the SPG (p < 0.05). The intergroup difference was also significant on the second and third postoperative days between the SPG and LPGN (p < 0.05). Triglycerides. The results are presented in Table II and Fig. 1. The only intergroup difference was seen in the preoperative values, the triglyceride level being significantly higher in the LPGN than in the other two groups (p < 0.05). The triglyceride levels diminished from the preoperative values in all groups during the study. In the LPGH, however, an increase was seen during the second and third days. Blood glucose. The blood glucose levels rose significantly, because of the influence of anesthesia, in all groups (p < 0.001) and remained significantly higher during the whole study than those recorded preoperatively. Postoperatively, the blood glucose value was higher in the LPGN and LPGH than in the SPG. Significant differences were seen on the first day between the SPG and the LPGH and during the third day between the SPG and LPGN. Serum insulin. There were no significant differences between the groups during the study. The secretion of insulin was deprimed during the postbypass period in relation to the high blood glucose concentration, but it increased later, the highest values being recorded on the first postoperative day (Table II and Fig. 1). Discussion In the present study, the observed changes in lipid and carbohydrate metabolism were similar in the short perfusion and in both long perfusion groups. The mild hypothermia (32° C.) used in this work appears to leave all parameters almost unaffected during the post-
bypass period. The changes are similar to those observed in the other patients who have had operative trauma.12- 13, 1 6 , 2 0 In our study, the infusate was a basic fluid of 5 per cent glucose, and the priming solution was gelatin and fresh heparinized whole blood in a ratio 1:1. The observed rise in blood glucose was as great as those reported by Hill,11 MacDonald,15 and their colleagues, who used 5 per cent dextrose as the priming solution. However, in their studies, unlike ours, the glucose values decreased rapidly postoperatively. In our study, the blood glucose level in the LPG was higher than in the SPG postoperatively. Hyperglycemia after trauma has been found to correlate with the intensity of the trauma.5, 12 Many hormonal factors do change during open-heart operations: The concentrations of catecholamines1, 22 and growth hormone15 rise. Both these hormones tend to increase the concentrations of glucose and free fatty acids but decrease the level of insulin. In the present series, the serum insulin level was relatively low, despite hyperglycemia, during anesthesia and bypass; this is in accordance with the results of Allison2 and Hill and associates.11 Some investigators have found that the plasma insulin level rises after the start of extracorporeal circulation.10, 1 9 , 2 4 , 25 The differences in anesthetic technique, priming solution, and use of hypothermia explain many of the differences between the studies. The mobilization of triglycerides as free fatty acids from the adipose tissue is, primarily, a physiological mechanism for mobilization and distribution of energy to organs or tissues where fuel is continuously needed.17 The myocardium obtains energy mainly from fatty acids.26 Hyperglycemia and insulin decrease
Volume 73 Number 5 May, 1977
plasma free fatty acids, 21 a fact which our data support (Table II, Fig. 1). The increase in activity of the lipoprotein lipase induced by heparin may be an important stimulating factor for the rising concentration of free fatty acids and decreasing concentration of triglycerides. 9, 24 Very high concentrations of free fatty acids may have an adverse effect on the myocardium by causing arrhythmias. 14 A reduction of plasma insulin levels during hypothermia has been reported. 10, 24 Hypothermia causes the catecholamine level to increase, 3 and catecholamines tend to increase the concentration of glucose and free fatty acids. During the postbypass period, our data show greater concentrations of glucose and free fatty acids in the LPG H than in the LPG N . The serum insulin level was lower in the LPG H than in the LPG N , but the scatter resulted in failure to reach statistical significance. In conclusion, our results show the trend toward hyperglycemia with an initial rise in free fatty acids and a later rise in serum insulin concentration. The net elimination of glucose is considerably impaired during and after extracorporeal circulation, and insulin antagonism is suggested postoperatively. REFERENCES 1 Alexander, R. W., Kuzela, L., Keith, W. J., Harrison, J., and Gerbode, F.: Adrenal Catecholamine and Cortisol Secretion During Extracorporeal Circulation in Dogs, J. THORAC. CARDIOVASC. SURG. 58: 250, 1969.
2 Allison, S. P.: Changes in Insulin Secretion During Open Heart Surgery, Br. J. Anaesth. 43: 138, 1971. 3 Blair, E.: A Physiologic Classification of Clinical Hypothermia, Surgery 58: 607, 1965. 4 Bucolo, G., and David, H.: Quantitative Determination of Serum Triglycerides by the Use of Enzymes, Clin. Chem. 19: 476, 1973. 5 Carey, L. C , Lowery, B. D., and Cloutier, C. T.: Blood Sugar and Insulin Response of Humans in Shock, Ann. Surg. 172: 342, 1970. 6 Ceska, M., Grossmuller, F., and Lundkvist, C : SolidPhase Radioimmunoassay of Insulin, Acta Endocrinol. 64: 111, 1970. 7 Duncombe, W. G.: The Colorimetric Micro-determination of Nonesterifled Fatty Acids in Plasma, Clin. Chim. Acta 9: 122, 1964. 8 Ghirardi, P., Marzo, A., Rossi, C , Respighi E., and Brusoni, B.: Plasma Lipids During Extracorporeal Circu-
Carbohydrate
683
11 Hill, D. G., Sonksen, P. H., and Braimbridge, M. V.: Levels of Plasma Insulin and Glucose After Open-Heart Surgery, J. THORAC. CARDIOVASC SURG. 67: 712, 1974.
12 Johnston, I. D. A.: The Metabolic and Endocrine Response to Injury: A Review, Br. J. Anaesth. 45: 252, 1973. 13 Kaniaris, P., Lekakis, D., Kykoniatis, M., and Kastanas, E.: Serum Free Fatty Acid and Blood Sugar Levels in Children Under Halothane, Thiopentone and Ketamine Anaesthesia (Comparative Study), Can. Anaesth. Soc. J. 22: 509, 1975. 14 Kurien, V. A., and Oliver, M. F.: A Metabolic Cause for Arrhythmias During Acute Myocardial Hypoxia, Lancet 1: 813, 1970. 15 MacDonald, R. G., Buckler, J. M. H., Deverall, P. B., Watson, D. A., and Ballint, M.: Growth Hormone and Blood-Glucose Concentrations During Cardiopulmonary Bypass, Br. J. Anaesth. 47: 713, 1973. 16 Manners, J.: Nutrition After Cardiac Surgery, Anaesthesia 29: 675, 1974. 17 Meng, H. C : Changes in Lipid Metabolism Under Stress, in Lang, K., Frey, R., and Halmagyi, H.: Stoffwechsel, Anaesth. Resusc. Intensive Ther. 58: 66, 1972. 18 Moffitt, E. A., Rosevear, J. W., and McGoon, D. C : Myocardial Metabolism in Open Heart Surgery, Anesth. Analg. (Cleve.) 48: 4, 1969. 19 Moffitt, E. A., Rosevear, J. W., Molnar, G. D., and McGoon, D. C : The Effects of Glucose-InsulinPotassium Solution on Ketosis Following Cardiac Surgery, Anesth. Analg. (Cleve.) 50: 291, 1971. 20 Nuutinen, L., and Hollmen, A.: Comparison of the Use of 5 and 10% Glucose solution in Operative and Postoperative Fluid Therapy, Ann. Chir. Gynaecol. Fenn. 62: 281, 1973. 21 Oyama, T., and Matsuki, A.: Effects of Spinal Anaesthesia and Surgery on Carbohydrate and Fat Metabolism in Man, Br. J. Anaesth. 42: 723, 1970. 22 Replogle, R., Levy, M., DeWall, R.A., and Lillehei, R. C : Catecholamine and Serotonin Response to Cardiopulmonary Bypass, J. THORAC CARDIOVASC SURG.
23
24
25
lation, J. CARDIOVASC. THORAC. SURG. 70: 661, 1975.
9 Goodman, L., and Gilman, A.: The Pharmacological Basis of Therapeutics, New York, 1975, Macmillan Publishing Co., Inc. 10 Hewitt, R. L., Woo, R. D., Ryan, J. R., and Drapanas, T.: Plasma Insulin and Glucose Relationships During Cardiopulmonary Bypass, Surgery 71: 905, 1972.
and lipid metabolism
26
44: 638, 1962. Rygg, I. H., Frederiksen, T., and Jorgensen, M.: Gas Exchange in the Rygg-Kyvsgaard Bubble Oxygenator, Thorax 18: 220, 1964. Stremmel, W., Schlosser, V., Bartak, A., and Keul, J.: Das Verhalten der Blutlipide bei offenen Herzoperationen mit extracorporalerZirkulation, Thoraxchirurgie 21: 286, 1973. Valentin, N., and Rasmussen, S. M.: Plasma Potassium and Insulin During Extracorporeal Circulation Using a Glucose-Containing Pump Prime, Scand. J. Thorac. Cardiovasc. Surg. 9: 169, 1975. Williamson, J. R., and Krebs, H. A.: Acetoacetate as Fuel of Respiration in the Perfused Rat Heart, Biochem. J. 80: 540, 1961.
L. S. Nuutinen, P. Mononen, M. Kairaluoma, and S. Tuononen, Oulu,
V^-hanges in body metabolism after accidental injury and after extensive surgery correlate with the magnitude of the trauma. 15, 16 The metabolic changes during and after open-heart surgery follow the usual injury pattern, with the metabolic state being converted to one of catabolism. 16 During cardiopulmonary bypass, lipid metabolism is dominant, 18 because free fatty acids are the principal substrate for energy production until glucose utilization and carbohydrate metabolism return to normal. 1 5 The concentrations of plasma lipids, 8 ' 24 blood glucose, 1 1 ' 1S and serum insulin 11 ' 25 have been studied before, but the duration of these studies was limited to the day of operation, with the length of the perfusion and the use of hypothermia being ignored. The purpose of this study was to determine the changes in plasma concentrations of free fatty acids, triglycerides, glucose, and insulin until the third postoperative day in patients having open-heart surgery, with special reference to the duration of cardiopulmonary bypass and the use of hypothermia. From the Departments of Anesthesiology and Surgery, University Central Hospital, Oulu, Finland. Received for publication July 19, 1976. Accepted for publication Nov. 5, 1976 680
Finland
Patients and methods The present work deals with 29 patients, who were divided into three groups according to the duration of cardiopulmonary bypass and the use of hypothermia: the short perfusion group (SPG), in which the perfusion time was less than 60 minutes; the long perfusion group with normothermia (LPG N ), in which the perfusion time was more than 60 minutes and the temperature in the esophagus during cardiopulmonary bypass was more than 33° C ) ; and the long perfusion group with hypothermia (LPG H ), in which the temperature during bypass was less than or equal to 33° C ) . The SPG consisted of 15 patients, the LPG N 8 patients, and the LPG H 6 patients. In the SPG, the operations were atrial septal defect corrections, in the LPG N mitral valve replacements, and in the LPG H aortic valve replacements. Table I shows the distribution of the patients by sex, weight, age, and duration of cardiopulmonary bypass. The patients in the SPG received 10 mg. of diazepam and 1 mg. per kilogram of pethidine (meperidine) intramuscularly, and the patients in both LPG's received 10 mg. of diazepam and 10 to 15 mg. of morphine intramuscularly as a premedication. Anesthesia was induced in the SPG by thiopentone, 5 mg. per kilogram,
Volume 73 Number 5 May, 1977
Carbohydrate and lipid metabolism
68 1
Table I. Data on the patients Sex (F/M)
Weight (Kg.)
(yr.)
Perf. time (min.)
SPG
9/6
43.3 ± 4.9 (19-80)
21.7 ± 3.9 (6-52)
37.4 ± 2.; (23-57)
LPGN > 33° C.
3/5
62 ± 2.9 (50-71)
46.1 ± 3.6 (31-57)
93.4 ± 5.7 (104-250)
LPGH £ 33° C.
2/4
70.5 ± 3 . 5 (54-78)
45.5 ± 2 (37-50)
Group
196.7 ± 26.3 (65-116)
Legend: SPG, Short perfusion group. LPGN, Long perfusion group in normothermia. LPGH, Long perfusion group in hypothermia. Mean values ± S.E.M., range in parentheses.
PREOR PRE POST 6p.m. 1st BYPASS BYPASS day
2nd day
3rd day
Fig. 1. Mean values of serum insulin, free fatty acids, triglycerides, and cholesterol during the study. LPG includes the patients of both long perfusion groups, and the figure shows the effect of cardiopulmonary bypass time on the parameters investigated. The changes of serum cholesterol are presented here, and a decreasing trend was seen in both groups. SPG, short perfusion group (perfusion time less than 60 minutes). and in the LPG by 50 to 80 mg. of morphine and 100 to 150 mg. of thiopentone. Pancuronium bromide was used as a relaxant in each group for intubation and subsequent muscular relaxation. All patients received 0.25 to 1.0 per cent halothane with nitrous oxide and oxygen as an inhalation mixture. Thalamonal (Innovar), or fentanyl was used for analgesia. The Rygg-Kyvsgaard heart-lung machine23 with a
bubble oxygenator was used. The priming solution consisted of 1,000 ml. of whole fresh heparinized blood and 1,000 ml. of gelatin solution (Haemaccel). Flow rates were maintained at 2.4 to 2.6 L. per square meter of body surface area during perfusion; hypothermia (31 to 32° C.) was used during aortic valve replacements. Five per cent glucose in water, 500 to 700 ml. per square meter of body surface area, was given intravenously on the day of operation, and 40 mmol. of potassium and 40 mmol. of sodium were added routinely per day in intravenous fluids. The fluid intake was 700 to 800 ml. per square meter on the first and second postoperative days. Whole blood and albumin were given at the end of the operation as well as postoperatively to maintain an adequate blood volume and colloid osmotic pressure. Blood samples were taken as follows: preoperatively in the ward (venous blood specimen), just before perfusion via the central venous pressure catheter, at the end of the operation, postoperatively at 6 P.M., and in the first, second, and third postoperative mornings via the central venous pressure catheter. Free fatty acids were measured according to the method of Duncombe,7 serum triglycerides according to the method of Bucolo and David,4 and serum insulin by the radioimmunoassay method.6 Data were analyzed with Student's t test, p < 0.05 being considered significant. Results Free fatty acids. The changes during the study are presented in Table II and Fig. 1. The concentration of free fatty acids rose significantly in all groups (p < 0.001) because of anesthesia. After cardiopulmonary bypass, the concentration of free fatty acids diminished significantly (p < 0.001) in all three groups. During the prebypass period, the free fatty acid
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6 8 2 Nuutinen et al.
Surgery
Table II. Free fatty acids, triglycerides, blood glucose, and serum insulin at different stages of the study Group
Preop.
Prebypass
Postbypass
6.
e.M.
First day
Second day
Third day
FFA (mmol./L.)
SPG LPGN LPG„
0.48 ± 0.1 0.38 ± 0.1 0.39 ± 0.1
1.31 ± 0.1 1.4 ± 0.2 1.65 ± 0.1
0.75 ± 0.1 0.83 ± 0.1 0.88 ± 0.1
0.84 ± 0.1 0.96 ± 0.1 0.85 ± 0.1
0.66 ± 0 . 1 0.65 ± 0.1 0.63 ± 0.1
0.42 ± 0.1 0.64 ± 0.1 0.55 ± 0.2
0.38 ± 0.1 0.59 ± 0.04 0.53 ± 0.1
Trigly. (mmol./L.)
SPG LPGN LPGH
1.63 ± 0.2 2.33 ± 0.3 1.77 ± 0 . 2
1.54 ± 0.3 1.4 ± 0.3 1.2 ± 0 . 3
0.98 ± 0.1 1.0 ± 0.1 1.0 ± 0.1
0.98 ± 0.1 1.3 ± 0.1 1.1 ± 0.2
0.8 1.0 1.1
1.31 ± 0.1 1.3 ± 0.2 1.4 ± 0.2
1.1 1.2 1.5
± 0.1 ± 0.2 ± 0.2
Glucose (mmol./L.)
SPG LPGN LPGH
3.6 ± 0.1 3.9 ± 0.3 4.0 ± 0.3
8.1 ± 0.4 7.9 ± 0.6 8.2 ± 0.7
7.4 ± 0.2 8.6 ± 0.3 9.7 ± 1.0
8.0 ± 0.5 8.5 ± 0.6 10.0 ± 0.6
6.8 ± 0.3 7.4 ± 0 . 3 8.9 ± 0.7
7.2 8.8 8.5
5.7 8.1 6.4
± 0.4 ± 1.3 ± 0.6
S-Insulin ;u.U/ml.)
SPG LPGN LPGH
12.1 ± 2.1 11.1 ± 4.6 8.5 ± 2.5
17.6 ± 3.3 22.3 ± 6.7 14.5 ± 1.3
14.4 ± 2.3 15.9 ± 5.4 14.8 ± 2.5
16.2 ± 2.2 25.1 ± 8.6 17.9 ± 3.4
22.7 ± 4.0 24.8 ± 5.3 33.6 ± 7.8
± 0.1 ± 0.1 ± 0.3
± 0.3 ± 1.2 ± 0.7
21.0 ± 5.5 23.7 ± 3.7 28.7 ± 5.8
22.8 ± 6.3 18.8 ± 4.1 21.1 ± 7.6
Legend: SPG, Short perfusion group. LPGN, Long perfusion group in normothermia. LPGH, Long perfusion group in hypothermia (<33° C ) . Mean values ± S.E.M.
value was significantly higher in the LPGH than in the SPG (p < 0.05). The intergroup difference was also significant on the second and third postoperative days between the SPG and LPGN (p < 0.05). Triglycerides. The results are presented in Table II and Fig. 1. The only intergroup difference was seen in the preoperative values, the triglyceride level being significantly higher in the LPGN than in the other two groups (p < 0.05). The triglyceride levels diminished from the preoperative values in all groups during the study. In the LPGH, however, an increase was seen during the second and third days. Blood glucose. The blood glucose levels rose significantly, because of the influence of anesthesia, in all groups (p < 0.001) and remained significantly higher during the whole study than those recorded preoperatively. Postoperatively, the blood glucose value was higher in the LPGN and LPGH than in the SPG. Significant differences were seen on the first day between the SPG and the LPGH and during the third day between the SPG and LPGN. Serum insulin. There were no significant differences between the groups during the study. The secretion of insulin was deprimed during the postbypass period in relation to the high blood glucose concentration, but it increased later, the highest values being recorded on the first postoperative day (Table II and Fig. 1). Discussion In the present study, the observed changes in lipid and carbohydrate metabolism were similar in the short perfusion and in both long perfusion groups. The mild hypothermia (32° C.) used in this work appears to leave all parameters almost unaffected during the post-
bypass period. The changes are similar to those observed in the other patients who have had operative trauma.12- 13, 1 6 , 2 0 In our study, the infusate was a basic fluid of 5 per cent glucose, and the priming solution was gelatin and fresh heparinized whole blood in a ratio 1:1. The observed rise in blood glucose was as great as those reported by Hill,11 MacDonald,15 and their colleagues, who used 5 per cent dextrose as the priming solution. However, in their studies, unlike ours, the glucose values decreased rapidly postoperatively. In our study, the blood glucose level in the LPG was higher than in the SPG postoperatively. Hyperglycemia after trauma has been found to correlate with the intensity of the trauma.5, 12 Many hormonal factors do change during open-heart operations: The concentrations of catecholamines1, 22 and growth hormone15 rise. Both these hormones tend to increase the concentrations of glucose and free fatty acids but decrease the level of insulin. In the present series, the serum insulin level was relatively low, despite hyperglycemia, during anesthesia and bypass; this is in accordance with the results of Allison2 and Hill and associates.11 Some investigators have found that the plasma insulin level rises after the start of extracorporeal circulation.10, 1 9 , 2 4 , 25 The differences in anesthetic technique, priming solution, and use of hypothermia explain many of the differences between the studies. The mobilization of triglycerides as free fatty acids from the adipose tissue is, primarily, a physiological mechanism for mobilization and distribution of energy to organs or tissues where fuel is continuously needed.17 The myocardium obtains energy mainly from fatty acids.26 Hyperglycemia and insulin decrease
Volume 73 Number 5 May, 1977
plasma free fatty acids, 21 a fact which our data support (Table II, Fig. 1). The increase in activity of the lipoprotein lipase induced by heparin may be an important stimulating factor for the rising concentration of free fatty acids and decreasing concentration of triglycerides. 9, 24 Very high concentrations of free fatty acids may have an adverse effect on the myocardium by causing arrhythmias. 14 A reduction of plasma insulin levels during hypothermia has been reported. 10, 24 Hypothermia causes the catecholamine level to increase, 3 and catecholamines tend to increase the concentration of glucose and free fatty acids. During the postbypass period, our data show greater concentrations of glucose and free fatty acids in the LPG H than in the LPG N . The serum insulin level was lower in the LPG H than in the LPG N , but the scatter resulted in failure to reach statistical significance. In conclusion, our results show the trend toward hyperglycemia with an initial rise in free fatty acids and a later rise in serum insulin concentration. The net elimination of glucose is considerably impaired during and after extracorporeal circulation, and insulin antagonism is suggested postoperatively. REFERENCES 1 Alexander, R. W., Kuzela, L., Keith, W. J., Harrison, J., and Gerbode, F.: Adrenal Catecholamine and Cortisol Secretion During Extracorporeal Circulation in Dogs, J. THORAC. CARDIOVASC. SURG. 58: 250, 1969.
2 Allison, S. P.: Changes in Insulin Secretion During Open Heart Surgery, Br. J. Anaesth. 43: 138, 1971. 3 Blair, E.: A Physiologic Classification of Clinical Hypothermia, Surgery 58: 607, 1965. 4 Bucolo, G., and David, H.: Quantitative Determination of Serum Triglycerides by the Use of Enzymes, Clin. Chem. 19: 476, 1973. 5 Carey, L. C , Lowery, B. D., and Cloutier, C. T.: Blood Sugar and Insulin Response of Humans in Shock, Ann. Surg. 172: 342, 1970. 6 Ceska, M., Grossmuller, F., and Lundkvist, C : SolidPhase Radioimmunoassay of Insulin, Acta Endocrinol. 64: 111, 1970. 7 Duncombe, W. G.: The Colorimetric Micro-determination of Nonesterifled Fatty Acids in Plasma, Clin. Chim. Acta 9: 122, 1964. 8 Ghirardi, P., Marzo, A., Rossi, C , Respighi E., and Brusoni, B.: Plasma Lipids During Extracorporeal Circu-
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11 Hill, D. G., Sonksen, P. H., and Braimbridge, M. V.: Levels of Plasma Insulin and Glucose After Open-Heart Surgery, J. THORAC. CARDIOVASC SURG. 67: 712, 1974.
12 Johnston, I. D. A.: The Metabolic and Endocrine Response to Injury: A Review, Br. J. Anaesth. 45: 252, 1973. 13 Kaniaris, P., Lekakis, D., Kykoniatis, M., and Kastanas, E.: Serum Free Fatty Acid and Blood Sugar Levels in Children Under Halothane, Thiopentone and Ketamine Anaesthesia (Comparative Study), Can. Anaesth. Soc. J. 22: 509, 1975. 14 Kurien, V. A., and Oliver, M. F.: A Metabolic Cause for Arrhythmias During Acute Myocardial Hypoxia, Lancet 1: 813, 1970. 15 MacDonald, R. G., Buckler, J. M. H., Deverall, P. B., Watson, D. A., and Ballint, M.: Growth Hormone and Blood-Glucose Concentrations During Cardiopulmonary Bypass, Br. J. Anaesth. 47: 713, 1973. 16 Manners, J.: Nutrition After Cardiac Surgery, Anaesthesia 29: 675, 1974. 17 Meng, H. C : Changes in Lipid Metabolism Under Stress, in Lang, K., Frey, R., and Halmagyi, H.: Stoffwechsel, Anaesth. Resusc. Intensive Ther. 58: 66, 1972. 18 Moffitt, E. A., Rosevear, J. W., and McGoon, D. C : Myocardial Metabolism in Open Heart Surgery, Anesth. Analg. (Cleve.) 48: 4, 1969. 19 Moffitt, E. A., Rosevear, J. W., Molnar, G. D., and McGoon, D. C : The Effects of Glucose-InsulinPotassium Solution on Ketosis Following Cardiac Surgery, Anesth. Analg. (Cleve.) 50: 291, 1971. 20 Nuutinen, L., and Hollmen, A.: Comparison of the Use of 5 and 10% Glucose solution in Operative and Postoperative Fluid Therapy, Ann. Chir. Gynaecol. Fenn. 62: 281, 1973. 21 Oyama, T., and Matsuki, A.: Effects of Spinal Anaesthesia and Surgery on Carbohydrate and Fat Metabolism in Man, Br. J. Anaesth. 42: 723, 1970. 22 Replogle, R., Levy, M., DeWall, R.A., and Lillehei, R. C : Catecholamine and Serotonin Response to Cardiopulmonary Bypass, J. THORAC CARDIOVASC SURG.
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9 Goodman, L., and Gilman, A.: The Pharmacological Basis of Therapeutics, New York, 1975, Macmillan Publishing Co., Inc. 10 Hewitt, R. L., Woo, R. D., Ryan, J. R., and Drapanas, T.: Plasma Insulin and Glucose Relationships During Cardiopulmonary Bypass, Surgery 71: 905, 1972.
and lipid metabolism
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44: 638, 1962. Rygg, I. H., Frederiksen, T., and Jorgensen, M.: Gas Exchange in the Rygg-Kyvsgaard Bubble Oxygenator, Thorax 18: 220, 1964. Stremmel, W., Schlosser, V., Bartak, A., and Keul, J.: Das Verhalten der Blutlipide bei offenen Herzoperationen mit extracorporalerZirkulation, Thoraxchirurgie 21: 286, 1973. Valentin, N., and Rasmussen, S. M.: Plasma Potassium and Insulin During Extracorporeal Circulation Using a Glucose-Containing Pump Prime, Scand. J. Thorac. Cardiovasc. Surg. 9: 169, 1975. Williamson, J. R., and Krebs, H. A.: Acetoacetate as Fuel of Respiration in the Perfused Rat Heart, Biochem. J. 80: 540, 1961.