Ann Thorac Surg 1997;63:1625-1633
© 1997 The Society of Thoracic Surgeons
Original Article: Cardiovascular
Addition of 
-Ketoglutarate to Blood Cardioplegia Improves Cardioprotection
Ulf W. Kjellman, MD,
Kerstin Björk, Eccp,
Rolf Ekroth, MD, PhD,
Hans Karlsson, Eccp,
Rudolf Jagenburg, MD, PhD,
Folke N. Nilsson, MD, PhD,
Gunnar Svensson, MD, PhD,
Jan Wernerman, MD, PhD
Department of Thoracic and Cardiovascular Surgery, Sahlgrenska University Hospital, Göteborg, and Department of Anesthesiology, Huddinge Hospital, Stockholm, Sweden
Accepted for publication November 12, 1996.
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Abstract
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Background. We hypothesized that myocardial content of 
-ketoglutarate (-KG), an intermediate of the Krebs cycle, can be critically low during heart operations, and that provision of -KG could reduce metabolic abnormalities and lead to improved myocardial protection.
Methods. Twenty-four men aged 46 to 78 years who were undergoing heart operations participated in a prospective, controlled, randomized study. In 13 patients, an average of 28 g of -KG was added to blood cardioplegia. Plasma creatine kinase isoenzyme MB and troponin T, and myocardial extraction of oxygen, substrates, and amino acids were measured.
Results. -Ketoglutarate treatment was associated with lower creatine kinase isoenzyme MB (F = 39.6, df = 1.172, p < 0.001) and lower troponin (F = 12.9, df = 1.172, p < 0.001). The values at 4 hours were 31 ± 2.4 µg/L versus 49 ± 4.9 µg/L (creatine kinase isoenzyme MB) and 1.1 ± 0.05 µg/L versus 2.0 ± 0.34 µg/L (troponin T). Myocardial oxygen extraction was higher during -KG cardioplegia (p < 0.01), but there were no significant differences in myocardial uptake or release of substrates or amino acids. Lactate release was observed in both groups during cardioplegia. Myocardial lactate release had ceased after 30 minutes of reperfusion in nearly half the -KG–treated patients (6 of 13) but remained in all the control patients (11 of 11, p = 0.016). There were no other differences after 30 minutes of reperfusion.
Conclusion. Provision of -KG during blood cardioplegia improves myocardial protection in patients undergoing coronary operations. This may be linked to enhanced oxidation.
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Introduction
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See also page 1633.
In spite of remarkable improvements in cardioprotective techniques, heart failure is the major cause of operative morbidity and mortality in patients undergoing heart operations. One important reason for myocardial dysfunction in the early postoperative period is the deranged metabolism of the heart. Prominent abnormal features are the low uptake of substrates [1–3] and reduced oxidative capacity [4]. To explain these findings, it has been suggested that the activity of the Krebs cycle is reduced, secondary to restricted availability of intermediates.
-Ketoglutarate (-KG) is an intermediate of the Krebs cycle. Previous work has indicated that the availability of -KG determines the recovery of muscle protein synthesis after surgical trauma [5], and other data suggest that myocardial content of -KG may be critically low during the conditions of heart operations [6]. The work of Lazar and colleagues [4], as well as others, gives substantial, but indirect, support for the critical role of -KG availability, because the provision of glutamate with blood cardioplegia improves myocardial metabolism and function. It has been suggested that glutamate is efficient because it provides -KG after transamination. However, direct evidence is lacking, and the present study was instigated to test the hypothesis that ample provision of -KG could improve myocardial oxidative capacity and myocardial protection in patients undergoing coronary revascularization. We also wanted to know whether the treatment improved substrate utilization, and whether this was reflected in amino acid metabolism.
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Material and Methods
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Patients
Twenty-four men aged 46 to 78 years, with symptomatic three-vessel coronary artery disease severe enough to motivate coronary revascularization (ejection fraction greater than 0.40) were included in the study after granting informed consent. Patients with diabetes mellitus, liver disease, or renal disease were excluded. Clinical data are shown in Table 1
. There were no significant differences between the two study groups.
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Clinical Routines
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Morphine (1 mg/kg) and scopolamine (0.4 mg) were used for premedication. Anesthesia was induced with thiopentone (3 to 5 mg/kg), and fentanyl (5 to 10 µg/kg). Neuromuscular blockade was achieved with pancuronium (0.1 mg/kg). Anesthesia was maintained with fentanyl and ventilation with oxygen in nitrous oxide, supplemented with a volatile anesthetic before cardiopulmonary bypass.
Cardiopulmonary bypass was conducted with a membrane oxygenator (Sarns Turbo Membrane Oxygenator, Sarns; 3M Health Care, Ann Arbor, MI) with a roller pump generating nonpulsatile flow of 2.4 L/m2. The extracorporeal circuit was primed with 2,000 mL of Ringer's acetate and 200 mL of mannitol (150 mg/mL). Hemodilution (hematocrit 20% to 25%) and moderate hypothermia (30°C) were used. Rewarming was commenced after release of the aortic clamp. Cardiopulmonary bypass was terminated when the rectal temperature had returned to 36°C.
Antegrade blood cardioplegia was delivered in the aortic root with a separate pump and heat exchanger. A crystalloid solution (Plegisol; Abbott Laboratories, Chicago, IL) plus extra potassium chloride yielding 40 mmol/L and sodium bicarbonate (10 mL of 8.4%) was added to cardiopulmonary bypass blood at a 1:4 ratio and infused with 1,000 mL after aortic cross-clamping. Repeated doses were delivered after the completion of each peripheral anastomosis at a rate of 160 mL/min. The temperature of blood cardioplegia was 6° to 8°C, until the terminal infusion, which was started after completion of the last anastomosis (a left internal mammary artery graft was anastomosed to the left anterior descending coronary artery), when blood cardioplegia was delivered at 30°C (equal to nasopharyngeal temperature).
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Study Protocol and Measurements
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The patients were randomly allocated to either of two groups. The surgeon was not aware of the study group. Blood cardioplegia was delivered in the same way in both groups, with the exception that -KG was added to the crystalloid solution in the -KG group. The total dose of -KG, which was determined by the duration of aortic cross-clamping time, was 28 ± 2 g. The cardioplegia volume was 3,727 ± 109 mL in the control group and 3,766 ± 199 mL in the -KG group (not statistically significant). A balloon catheter was inserted into the coronary sinus through a stab incision in the right atrium for sampling of coronary sinus blood. The corresponding "arterial" blood was collected from the line delivering blood cardioplegia. Arterial and coronary sinus samples were obtained simultaneously at the end of the third cold infusion, at the end of warm cardioplegia (samples were collected when 400 mL of cardioplegia had been infused and the infusion was continued during sampling), and 30 minutes after release of the aortic clamp. These samples were analyzed for oxygen content, lactate, glucose, free fatty acids, and amino acids.
Blood gases were analyzed immediately. All other samples were spun in a cooling centrifuge, either for immediate analysis (glucose, lactate, troponin T [TNT], and creatine kinase isoenzyme MB [CK-MB] or for storage at -80°C until later analysis (free fatty acids and amino acids).
Creatine kinase isoenzyme MB and TNT were analyzed from arterial samples obtained during cold and warm cardioplegia, 5 and 30 minutes after the aortic cross-clamp was removed, and then after 1, 2, 3, and 4 hours. Blood gases were measured with the ABL510 (Radiometer, Copenhagen). Oxygen content (mmol/L) was calculated according to the following formula: hemoglobin (g/L) x HbSO2 (%) x 0.00062) + PO2 (kPa) x 0.01. Myocardial oxygen extraction was calculated as arterial blood oxygen content minus coronary sinus blood oxygen content (Table 2), and also in percentage of arterial oxygen content (Fig 1).
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Fig 1. . Myocardial oxygen extraction (Ox.extr.) calculated as percent of arterial oxygen content (means ± SEM) during cold and warm blood cardioplegia (BCP), and 30 minutes after declamping of the aorta (REP +30 min). Filled circles represent -ketoglutarate–treated patients and open circles represent control patients. Significance level of the group factor (two-way analysis of variance) during cardioplegia is given, and significance level according to the Mann-Whitney U test (30 minutes after declamping of the aorta).
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Plasma lactate and glucose levels were analyzed in duplicate with an automatic analyzer (YSI2300 Stat plus; Yellow Springs Instruments, Yellow Springs, OH). Levels of free fatty acids in serum were analyzed with the NEFA C test kit (Wako Chemicals GmbH, Neuss, Germany) using an enzymatic colorimetric method, and were measured with a Beckman DU 640 Spectrophotometer (Beckman Instruments Inc, Fullerton, CA).
Levels of amino acids in plasma were determined by ion exchange chromatography using an automated amino acid analyzer (Alpha Plus; LKG Products, Bromma, Sweden) using DC-6 ion exchange resin (Durrum, CA) and lithium citrate buffers. Orthophthaldialdehyde was used for postcolumn derivatization and fluorescent detection (Shimatsu RF-535) at an excitation wavelength of 350 nm and an emission wavelength of 420 nm.
The mass concentration of CK-MB was determined by the Abbott Laboratories IMx system. Troponin T level was measured by the Boehringer (Mannheim, Germany) Enzymun-test system.
Myocardial temperature was measured in the ventricular septum of the heart near the left anterior descending coronary artery with a myocardial probe (Sorin Biomedical Inc, Irvine, CA). The arteriovenous difference was defined as the arterial concentration content minus the coronary sinus concentration content. Uptake was defined as a significantly positive myocardial arteriovenous concentration difference, and release was defined as a significantly negative myocardial arteriovenous concentration difference.
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Statistical Methods
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Creatine kinase isoenzyme MB and TNT values were analyzed by two-way variance analysis with group assignment and time of sampling used as predictors. For other metabolic variables, it was reasoned that values during cardioplegia (both cold and warm) and values after cardioplegia should be analyzed separately. Hence, the values during cardioplegia were analyzed with two-way variance analysis using group and time as independent predictors. The measurements after cardioplegia (30 minutes after declamping the aorta) were analyzed with the Mann-Whitney U test. In addition, the frequency of myocardial lactate release at this measurement was analyzed with Fisher's exact test. This test also was used for the frequency data in Table 1
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Hemodynamic variables (systemic arterial pressure, diastolic arterial pressure, and heart rate) were analyzed separately before and after bypass with two-way analysis of variance using groups assignment and time as predictors. Extraction values (myocardial arteriovenous concentration differences) of substrates were tested versus 0 at each measurement in each group with one sample sign rank test. Means plus or minus standard errors of the mean are given in the tables and figures.
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Ethics
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The study protocol was in accordance with the Helsinki declaration of human rights, and was approved by the ethics committee of the University of Göteborg.
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Results
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Clinical Course
The clinical course was uneventful. There were no differences in cross-clamp time, extracorporeal circulation time (see Table 1), or myocardial temperature (see Table 2) between the two groups. The extracorporeal circulation could be terminated without inotropic support and without delay. There was no need to defibrillate the heart after declamping the aorta. Prebypass and postbypass heart rates and arterial diastolic pressures are given in Tables 3 and 4. There were no differences between groups in systolic arterial pressure or heart rate. A small difference was seen in diastolic arterial pressure. All patients were discharged from the hospital within 10 days, having recovered normally. There were no electrocardiographic signs of perioperative myocardial infarction and no other symptoms or signs of complications.
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Arterial Creatine Kinase Isoenzyme MB and Troponin T
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Creatine kinase isoenzyme MB levels were lower after -KG treatment (Figs 2, 3). Thus, for the group assignment factor, the F value was 39.6, df = 1,172, p < 0.001; for the time factor, it was 86.5, df = 7,187, p < 0.001; and for the interaction, it was 4.55, df = 7,187, p < 0.001. Troponin T levels also were lower. For the group assignment factor, the F value was 12.9, df = 1,172, p < 0.001; for the time factor, it was 26.1, df = 7,195, p < 0.001; and for the interaction, it was 2.28, df = 7,195, p = 0.03.
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Fig 2. . Arterial creatine kinase isoenzyme MB (CK MB; means ± SEM) up to 4 hours after declamping of the ascending aorta (REP). Filled circles represent -ketoglutarate–treated patients and open circles represent control patients. Significance level of the group factor is given (two-way analysis of variance).
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Fig 3. . Arterial troponin T (TNT; means ± SEM) up to 4 hours after declamping of the ascending aorta (REP). Filled circles represent -ketoglutarate–treated patients and open circles represent control patients. Significance level of the group factor is given (two-way analysis of variance).
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Myocardial Extraction of Oxygen
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During cardioplegia, the oxygen content of coronary sinus blood was lower in the -KG group (see Table 2). Correspondingly, the oxygen extraction was higher in the -KG group (group factor: F = 7.9, df = 151, p = 0.007; sampling time factor: F = 21.7, df = 151, p < 0.001; and interaction: F = 0.16, df = 151, p = 0.69). Oxygen extraction also was calculated as the percent of arterial oxygen content (see Fig 1). The difference between groups was amplified when extraction was related to arterial content of oxygen, because the arterial content was somewhat lower in the -KG group.
There were no differences in oxygen variables 30 minutes after cardioplegia. During cold cardioplegia, the hematocrit was 22.4% ± 1.2% in cardioplegic blood and 22.2% ± 1.2% in coronary sinus blood (p = 0.81). During warm cardioplegia, the corresponding figures were 22.3%± 1.2% in cardioplegic blood and 22% ± 1.2% in coronary sinus blood (p = 0.86).
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Substrates and Amino Acids
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There was a release of lactate in both groups during cardioplegia (see Table 2). This did not differ significantly between groups, although it tended to be more pronounced in -KG–treated patients (p = 0.09). Thirty minutes after declamping of the aorta, the release of lactate had ceased in 6 of 13 patients in the -KG group, whereas it continued in all patients in the control group (11 of 11 patients; Fisher's exact test, p = 0.016). There were no differences between the groups regarding the uptake of glucose or free fatty acids during or after cardioplegia (see Table 2). Arterial concentrations and the uptake and release of amino acids are given in Table 5. The arterial concentrations of amino acids were low during hypothermia and increased to normal values during reperfusion (normothermia). The arterial concentrations of glutamate and glutamine were higher in the -KG group. There were no other differences between the groups.
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Comment
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Our findings support the hypothesis that provision of -KG enhances myocardial oxidation during cardioplegia and improves myocardial protection in patients undergoing heart operations. Contrary to our hypothesis, -KG did not improve substrate uptake, and myocardial uptake and release of amino acids was not modified during cardioplegia. The observation that myocardial release of lactate was attenuated 30 minutes after declamping of the aorta suggests that a more complete oxidation was resumed earlier in this group.
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Oxygen and Substrate Utilization
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Myocardial metabolism is changed during heart operations. Lazar and colleagues [4], as well as others, have reported that the consumption of oxygen is reduced even if its availability is unrestricted. It was suggested that this is explained by reduced activity of the Krebs cycle, secondary to depleted pools of the Krebs cycle intermediates. This suggestion has been supported by the beneficial effects produced by providing glutamate and aspartate, which generate -KG and oxaloacetate, respectively [7].
Our group made a similar observation regarding brain metabolism after deep hypothermic total circulatory arrest. Cerebral oxygen extraction was low during the first hours after reperfusion was started. At the same time, a release of lactate was observed, suggesting a deficient aerobic capacity. These changes did not happen after deep hypothermic procedures when systemic and cerebral flow were maintained (albeit reduced to 25% during profound hypothermia), which suggests a causal relation to ischemia [8, 9].
Myocardial utilization of substrates also is abnormal in patients undergoing cardiac operations. Previous work indicates that the uptake of free fatty acids and glucose is low or undetectable, and the normally high uptake of lactate is markedly reduced or even turned into a release [1–3]. Our data verify the previous findings, with undetectable uptake of free fatty acids during cardioplegia and continued release of lactate 30 minutes after declamping of the aorta. According to previous work, and in keeping with our data, amino acids were extracted in the early postoperative period, and we previously suggested that this was an adaptive measure to compensate for the low uptake of normal substrates, and possibly to replenish the Krebs cycle intermediates [10]. The uptake of amino acids, however, could not cover the whole deficit of exogenous substrates, suggesting that endogenous substrates, such as glycogen and amino acids, were important for energy metabolism. These findings are compatible with restricted activity of the Krebs cycle, with a reduced capacity for aerobic degradation. As reviewed previously, these changes probably are the combined effect of myocardial ischemia and systemic neurohumoral changes resulting from the operative trauma [11].
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Myocardial -Ketoglutarate
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There is evidence suggesting that the size of the -KG pool of the Krebs cycle may be reduced during heart operations, and possibly for more than one reason. The first reason relates to myocardial ischemia. Rat experiments indicate that -KG is consumed rapidly in myocardial ischemia, possibly for anaerobic adenosine triphosphate production through phosphorylation at the substrate level [6]. The heart is exposed to ischemia in cardiac operations. In spite of cardioplegia, as our data verify, most patients exhibit a postoperative release of biochemical markers of myocardial ischemia. Further, other workers have found that not even continuous blood cardioplegia, with a blood flow well in excess of demand of oxygen delivery, prevents a decline of myocardial adenosine triphosphate levels, or the release of lactate and creatine kinase [12].
Second, Newsholme and colleagues [13] proposed that -KG is drained from the Krebs cycle in skeletal muscles during operative trauma and other immunologically active conditions, to be exported to the immune system in large quantities, after conversion to glutamine. The kidneys also consume glutamine at an amplified rate in the severely ill for acid–base regulation. As a consequence of these processes, impairment of the Krebs cycle develops in skeletal muscle. This proposition also may be valid for myocardial metabolism, because the heart is a major (in relation to size) exporter of glutamine during heart operations [10].
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Provision of -Ketoglutarate
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The addition of -KG to blood cardioplegia reduced the appearance of CK-MB and TNT in peripheral blood. Both CK-MB and TNT are sensitive markers of myocardial ischemic injury, and our finding infers that postischemic myocardial dysfunction had been attenuated. The peak values of CK-MB and TNT in our study were, according to our reference values, in the range that is associated with an uncomplicated, clinically straightforward postoperative course without need of inotropic support. The clinical significance of differences within a normal postoperative range may be debated. However, it seems probable that a 35% to 45% reduction of CK-MB and TNT levels can be clinically significant at more severe ischemia and in patients with preoperatively low functional reserves.
The mechanism behind the improved myocardial protection has not been established by our work, although our data are in line with our hypothesis that treatment would enhance oxidation. Provision of -KG did not improve myocardial uptake of lipids, carbohydrates, or amino acids. If anything, it amplified the release of lactate during cardioplegia. It could have been anticipated that a general enhancement of the activity of the Krebs cycle would be associated with increased uptake of substrates and reduced release of lactate. However, previous work has indicated the accumulation of acylcoenzyme A with incomplete free fatty acid oxidation after ischemia [14]. Improved activity of the Krebs cycle could lead to a more complete oxidation without necessarily increasing the uptake of free fatty acids. To evaluate this possibility, it could have been valuable to measure myocardial ketone production. The unchanged extraction of glucose may not be contradictory to the enhancement of oxidation, because glucose extraction is controlled primarily by insulin and not by the activity of the Krebs cycle [1]. -Ketoglutarate did not reduce the release of lactate from the heart during cardioplegia, but 30 minutes after declamping, the release of lactate was less pronounced in control patients. This suggests that aerobic lactate oxidation recovered more rapidly in treated patients.
In addition, or alternatively, to generally enhanced activity of the Krebs cycle, our findings could be explained by stimulated aspartate–malate shuttle activity. This is suggested by the experimental work of Wiesner and colleagues [15], as well as others. The shuttle transports NADH+ from cytosol to mitochondria for reoxidation and is essential for glycolysis. -Ketoglutarate is an important participant in the shuttle, and when the availability of -KG is critically low, glycolysis will suffer. The provision of -KG appeared to enhance glycolysis, provided our data represent a true amplified lactate release. This could imply that the availability of -KG was critically low and rate-limiting for glycolysis. The aspartate–malate shuttle also involves glutamate. The lack of effect on myocardial extraction of aspartate and glutamate could argue against this mechanism. This is particularly true because systemic levels of glutamate and glutamine were elevated by -KG treatment, without concomitant detectable effects on myocardial uptake and release of these amino acids. Although it could have been expected that -KG utilization by heart muscle would be accompanied by changes in amino acid balances, our data are in line with the findings of Roth and colleagues [16], as well as others. Roth and colleagues observed that provision of -KG was followed by a substantial uptake of -KG in muscle tissue, without alteration of glutamine or glutamate utilization in muscle. However, there was an increase in the release of these amino acids from renal tissue, which could explain their higher plasma levels [16].
In addition to general enhancement of the activity of the Krebs cycle and support of glycolysis, -KG can be oxidized anaerobically in the Krebs cycle with succinate production. According to the experimental work of Wiesner and colleagues [17], provision of -KG is beneficial predominantly because of enhancement of glycolysis [14].
An unexpected finding in our study was that there was no uptake of the normally extracted glutamate, aspartate, and branched-chain amino acids during cold cardioplegia. Instead, a release was observed. The reason for this abnormality is not known, but it may be suggested that transport is inactivated by cardioplegia, hypothermia, or both. The effects of -KG during cardioplegia could suggest that this substrate is utilized more efficiently than substances such as glutamate during hypothermia. This area needs further exploration to clarify the uptake kinetics of these amino acids during cardioplegia at different temperatures.
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Methodologic Issues
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The major end points in our study were postischemic plasma concentrations of CK-MB and TNT, which were determined serially during the first 4-hour period after declamping of the aorta. It can be argued that the sampling time should have been prolonged to ascertain that peak enzyme values actually were obtained. Previous work by us and others has shown that the peak CK-MB concentration occurs within 4 hours in operations that are not complicated by myocardial infarction [19]. This supports the validity of our CK-MB data. The peak TNT value appears to occur later (within 6 hours according to our unpublished data), which could reduce the validity of our TNT measurements. However, the resemblance between CK-MB and TNT kinetics in our patients is noteworthy.
Another methodologic issue relates to the evaluation of myocardial uptake and release of oxygen, substrates, and amino acids. We have based our conclusions on myocardial extraction (defined as concentration differences between blood entering and leaving the coronary vessels). Extraction is critically dependent on coronary blood flow, which was not measured in this study. Cardioplegia was delivered at the same rate and with the same pump in all patients. The actual coronary blood flow during cardioplegia should equal the sum of cardioplegia flow and collateral flow of noncoronary origin. An estimate of the contribution of collateral flow can be made by comparing the cardioplegic and coronary sinus hematocrits, because cardioplegic blood is diluted by the crystalloid component. A significant contribution of collateral flow to coronary sinus blood would increase the hematocrit of coronary blood in comparison with cardioplegic blood. In our series, there was no significant difference between the cardioplegic and coronary sinus hematocrits, which indicates that collateral flow was negligible. Because the cardioplegia flow rate was the same, it can be assumed that coronary flow during cardioplegia was the same in the two groups. This supports the validity of comparing extraction values during cardioplegia. In contrast, the measurements made 30 minutes after the start of reperfusion are more difficult to evaluate, because myocardial blood flow could have differed between groups. In this period, another method of assessing myocardial lactate production is to count the number of patients who had negative values and compare the number in each group by frequency analysis. This technique of assessment is independent of differences in coronary blood flow.
A third issue is the role of hemodynamic variables in our study. It is of utmost interest to know whether the biochemical signs of improvement in our study are associated with hemodynamic improvement in the postoperative period. This was beyond the scope of the study protocol, which was restricted to evaluating biochemical effect variables. To include hemodynamic assessment in the protocol, it would have been necessary to enlarge the sample size considerably, at least if standard clinical variables were to be used. Still, hemodynamic variables were included, because these could have influenced the studied parameters. Thus, a preoperative or early postoperative difference between groups in hemodynamic variables related to myocardial energy supply, demand, or both could act as a predictor of biochemical differences. According to the analysis of prebypass and early postbypass arterial pressures and heart rate, this was not the case.
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Clinical Implications
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Our data indicate that the addition of -KG to blood cardioplegia improves myocardial protection. Lazar and associates [4], as well as others [7], advocate the addition of glutamate (and aspartate) to blood cardioplegia for warm induction and warm conclusion, because these measures improve postischemic myocardial recovery. The beneficial effects of glutamate have been attributed to two factors: it may enhance glycolytic flux during ischemia by eliminating pyruvate (after transamination to alanine) without producing lactate and hydrogen ion, and it provides -KG. It appears that provision of glutamate and -KG may be beneficial for the same reason. The relative efficacy of glutamate and -KG is not known. However, glutamate is an excitatory amino acid (which arouses concern of adverse neurocerebral effects), and can cause hypotension and intracellular acidification in tissues with low clearing capacity.
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Acknowledgments
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This work was supported by grants from the Swedish Heart and Lung Foundation, The Göteborg Medical Society, The Swedish Medical Council Foundation, The Sahlgrenska University Foundation, and The Scandinavian Heart Center Foundation.
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Footnotes
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Address reprint requests to Dr Kjellman, Department of Thoracic and Cardiovascular Surgery, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden (e-mail: rolf.ekroth{at}hjl.gu.se).
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References
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- Svensson S, Svedjeholm R, Ekroth R, Milocco I, Nilsson F, Sabel KG. Trauma metabolism and the heart: uptake of substrates and effects of insulin early after cardiac operations. J Thorac Cardiovasc Surg 1990;99:1063–73.[Abstract]
- Svedjeholm R, Ekroth R, Joachimsson PO, Svensson S, Tydén H, Ronquist G. Myocardial uptake of amino acids and other substrates in relation to myocardial oxygen consumption four hours after cardiac operations. J Thorac Cardiovasc Surg 1991;101:688–94.[Abstract]
- Svedjeholm R, Ekroth R, Hallhagen S, Joachimsson PO, Ronquist G. Dopamine a
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Abstract
Introduction
