Normothermic retrograde blood cardioplegia with or without preceding ischemic preconditioning.

BACKGROUND: Preconditioning has been suggested as the most powerful mechanism of myocardial protection against prolonged ischemia. However, whether preconditioning offers additional benefits over cardioplegia during coronary artery bypass grafting is not known. METHODS: Thirty patients undergoing coronary artery bypass grafting were randomized into two groups. After aortic cross-clamping, group 1 received antegrade blood and blood cardioplegia followed by normothermic retrograde blood cardioplegia (controls), whereas group 2 patients were subjected to 5 minutes of global ischemia followed by reperfusion with antegrade and retrograde blood cardioplegia (preconditioned). The transcardiac differences in oxygen saturation, pH, and lactate were measured during cardiopulmonary bypass. Myocardial biopsy specimens were taken from half of the patients for adenosine triphosphate determination. The extent of myocardial injury was estimated by monitoring the postoperative leakage of creatine kinase-MB and troponin T. Immediate hemodynamic recovery and postoperative complications were also observed. RESULTS: The 5-minute preconditioning induced marked lactate and acid production, and myocardial adenosine triphosphate levels tended to decrease. The heart continued to produce lactate and acid during retrograde cardioplegia, but the transcardiac pH and lactate differences were similar in both groups. Adenosine triphosphate level measured at the end of the cross-clamp period was decreased to a half and one third of the preclamp values in the control and preconditioned groups, respectively. The postoperative creatine kinase-MB and troponin T effluxes tended to be more elevated in the preconditioned group, yet hemodynamic recovery and the number of postoperative complications were similar in both groups. CONCLUSIONS: The results show that a 5-minute preconditioning ischemia does not offer any additional benefits over normothermic retrograde blood cardioplegia during coronary artery bypass grafting.

Myocardial protection during antegrade versus retrograde cardioplegia.

BACKGROUND: It has been suggested that the right ventricular myocardium is suboptimally protected during retrograde blood cardioplegia. METHODS: Twenty patients undergoing an elective coronary bypass procedure were randomized to receive antegrade or retrograde mild hypothermic blood cardioplegia. Transventricular differences in oxygen extraction, lactate production, and pH were monitored during aortic cross-clamping, and myocardial biopsy specimens were taken from both ventricles before cannulation and 15 minutes after aortic declamping for analysis of adenine nucleotides and their breakdown products. The extent of myocardial injury was estimated by monitoring postoperative leakage of troponin T and the MB isoenzyme of creatine kinase. Hemodynamic recovery and postoperative complications were noted. RESULTS: The preoperative characteristics of the two groups were similar. Oxygen extraction and lactate production in the right ventricular myocardium were higher in the retrograde group. In this group, the right ventricle also extracted more oxygen and produced more lactate and acid than did the left ventricle. Tissue levels of adenine nucleotides tended to decrease in both ventricles during operation, with no differences between them. The level of adenosine catabolites did increase somewhat in the right ventricular myocardium of the retrograde cardioplegia group after aortic declamping. There was a tendency for more prominent efflux of troponin T and the MB isoenzyme of creatine kinase in the retrograde group. Nevertheless, the postoperative course was uneventful in both groups. CONCLUSIONS: Retrograde mild hypothermic blood cardioplegia leads to metabolic changes compatible with right ventricular ischemia. Nevertheless, tissue levels of high-energy phosphates are well preserved, and the postoperative course seems to be unproblematic. Care should be taken when retrograde normothermic blood cardioplegia is provided for patients with right ventricular hypertrophy, poor right ventricular function, or severe preoperative myocardial ischemia.

Myocardial preservation during coronary surgery with and without cardiopulmonary bypass.

BACKGROUND: There is increased interest in coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB), although the preservation of the myocardium under such circumstances has not been properly investigated. The aim of this randomized study was to compare the changes in myocardial metabolism during CABG with and without CPB. METHODS: Myocardial energy metabolism and tissue injury during CABG was monitored in a series of 22 patients (11 with and 11 without CPB). RESULTS: The maximum myocardial lactate production was significantly higher (p = 0.02) in the group operated with CPB (0.56 mmol/L) than without it (0.17 mmol/L). A similar phenomenon was seen in the transcardiac pH differences (0.085 and 0.034 with and without CPB, p = 0.007). The postoperative peak values of creatine kinase-MB mass (15.1 vs 6.3 microg/L) and troponin I (13.8 vs 5.2 microg/L) were significantly higher (p < 0.001 and p = 0.008) with than without CPB. CONCLUSIONS: CABG on a beating heart is associated with better myocardial energy preservation and less myocardial damage compared with conventional CABG with CPB and intermittent antegrade mild hypothermic blood cardioplegia.

Myocardial metabolism and hemodynamics during coronary surgery without cardiopulmonary bypass.

BACKGROUND: Although renewed interest has recently been shown in coronary artery bypass grafting without cardiopulmonary bypass, no reports are available on myocardial metabolism and hemodynamics during temporary coronary occlusion and rotation of the contracting heart. METHODS: Changes in myocardial energy metabolism and hemodynamics were monitored in 12 patients undergoing elective coronary artery bypass grafting without cardiopulmonary bypass, and the postoperative efflux of creatine kinase-MB mass and troponin T were also determined. RESULTS: There was a significant increase in myocardial production of ATP degradation products (p = 0.026) and lactate (p = 0.004) during the operation. Myocardial oxygen extraction decreased (p = 0.012) in correlation with use of the short-acting beta-blocker, esmolol (r = -0.71). Apart from a decrease in mean arterial blood pressure (p = 0.002), there were no significant hemodynamic changes during the operation. The overall postoperative troponin T and creatine kinase-MB mass changes remained nonsignificant during the first two postoperative days. One patient had a myocardial infarction, diagnosed by electrocardiography, on the second postoperative day, but otherwise there were no major complications. CONCLUSIONS: Coronary artery bypass grafting without cardiopulmonary bypass seems to be well tolerated as only minor changes in myocardial energy metabolism and hemodynamics are observed during the operation.

Anti-inflammatory effect of high-dose insulin treatment after urgent coronary revascularization surgery.

BACKGROUND: The administration of insulin has been shown to exert cardioprotective and immunomodulatory properties. Ischemia and inflammation are typical features of acute coronary syndrome, thus it was hypothesized that high-dose glucose-insulin-potassium (GIK) treatment could suppress the systemic inflammatory reaction and attenuate myocardial ischemia-reperfusion injury in patients with unstable angina pectoris after urgent coronary artery bypass surgery. METHODS: Forty patients with unstable angina pectoris scheduled for urgent coronary artery bypass surgery and cardiopulmonary bypass were randomly assigned to receive either high-dose insulin treatment (short-acting insulin 1 IU/kg/h with 30% glucose 1.5 ml/kg/h administered separately) or control treatment (saline). Blood glucose levels were targeted to 6.0-8.0 mmol/l in both groups by adjusting the rate of glucose infusion in the GIK group and by additional insulin in the control group as needed. RESULTS: High-dose insulin treatment was associated with significantly lower average C-reactive protein (23.8 vs. 40.1 mg/l, P= 0.008) and free fatty acid levels (0.22 vs. 0.41 mmol/l, P= < 0.001) post-operatively. Average blood glucose levels were comparable during the intensive care unit (ICU) stay (7.1 vs. 6.9 mmol/l, P= 0.5) and 95% of the control patients received supplemental insulin. The pro-inflammatory cytokine response [interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha)] did not differ between the groups and beneficial effects on myocardial injury were not detected. CONCLUSIONS: High-dose insulin treatment has potential anti-inflammatory properties independent of its ability to lower blood glucose levels. Even profound suppression of free fatty acid levels, the attenuation of myocardial ischemia-reperfusion injury was not detected.

Prebypass glucose-insulin-potassium infusion in elective nondiabetic coronary artery surgery patients.

Perioperative GIK therapy has been advocated to ensure adequate energy substrate levels during cardiac surgery. However, hyperglycemia should be avoided because it may worsen neurologic outcome after cerebral ischemia. A prospective, randomized, clinical comparison was performed between two prebypass infusion regimens in 32 elective nondiabetic CABG patients. Sixteen patients (GIK group) received glucose, 0.6 g/kg/h, insulin, 0.12 U/kg/h, and KCl, 0.12 mmol/kg/h, from the induction of anesthesia to the start of CPB; while the remaining 16 patients (R group) received only Ringer's acetate. The pump prime was glucose free and a blood cardioplegia technique was used in both groups. No differences were found between the groups with regard to myocardial injury; the CK-MB enzyme fractions were elevated to a similar degree and the frequency of postoperative ECG changes were similar in both groups. Likewise, there were no differences in hemodynamic changes, need for inotropic support, arrhythmia frequency, or duration of ICU stay. The GIK patients had higher blood glucose (P < 0.05) and insulin levels (P < 0.01); blood glucose increased to 12.4 +/- 5.4 mmol/L (mean +/- SD) at cannulation, with a drop after starting bypass. Interindividual variation in GIK patients was great, with glucose values ranging between 20.1 mmol/L at cannulation to 2.0 mmol/L after starting CPB. A hyperglycemic response was seen in both groups during rewarming: 15.0 +/- 4.2 and 15.0 +/- 3.1 mmol/L in GIK and R patients, respectively. It is concluded that prebypass GIK infusion had no clinical benefits for elective CABG patients as compared to Ringer's acetate.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural changes in myocardium during mild hypothermic retrograde blood cardioplegia.

Uniformity of myocardial protection during retrograde blood cardioplegia is still a controversial area. We conducted a study on electron microscopic changes in the myocardium during mild hypothermic retrograde cardioplegia (31-32 degrees C) in 12 patients undergoing coronary artery bypass grafting. Biopsies for electron microscopy were taken from the right and left ventricular myocardium before and at the end of aortic cross-clamping and after 15 min reperfusion. The intercellular junctions, intracellular and extracellular oedema, mitochondria, capillaries, nuclei and myofibrils were analysed separately in each specimen, using a semiquantative method with scoring from 0 (unchanged) to 3 (severe changes), and the total scores were correlated with the severity of right and left coronary artery disease and with ischaemia time during aortic cross-clamping. Mild to moderate ultrastructural changes occurred in the myocardium during the cardiopolegia, most typically myofibrillar injury and oedema. These changes increased during aortic cross-clamping and reperfusion, especially in the right ventricle. The total ultrastructural score for the right ventricle correlated negatively with the severity of right coronary artery disease at the end of cross-clamping. No such correlation was found in the left ventricle. Apart from one case of perioperative myocardial infarction, the clinical outcome was unproblematic. Myocardial structure thus was by and large well preserved during mild hypothermic retrograde blood cardioplegia, with the right ventricle seemingly somewhat less protected than the left.

Amino acid-enriched glucose-insulin-potassium infusion improves hemodynamic function after coronary bypass surgery. A double-blind study in patients with unstable angina and/or compromised left ventricular function.

OBJECTIVE: The goal of this study was to assess the effects of a combination of glucose-insulin-potassium (GIK) and the amino acids aspartate and glutamate upon perioperative hemodynamics in coronary surgery patients with unstable angina and/or compromised left ventricular function. DESIGN: Prospective, randomized, and double-blind clinical study. SETTING: Operating theatre and intensive care unit (ICU) of a university hospital. PATIENTS: 44 coronary artery bypass graft (CABG) patients with unstable angina and/or compromised left ventricular function. INTERVENTIONS: 22 patients (group A) were given 1l of an infusion with 250g glucose, 100 I.U. fast-acting human insulin, 72 mmol potassium, 32 mmol magnesium, 20 mmol phosphate, 65 mmol aspartate, and 65 mmol glutamate, while another 22 patients (group C) were given 1l of an infusion with 50 g glucose, 72 mmol potassium, 32 mmol magnesium, and 8 mmol phosphate. The infusion rate was 1.2 ml/kg/h from the anesthesia induction onward to the commencement of cardiopulmonary bypass, when it was reduced to 0.8 ml/kg/h. When 11 had been infused, but not later than 4 a.m., the infusion was continued by giving 10% glucose at the same rate to both groups. Additional insulin (median: 14.2 I.U., range: 0-41.5) or saline was given during bypass to the A and C patients, respectively. A blood cardioplegia technique containing aspartate and glutamate was used in both groups. RESULTS: At aortic cannulation, the cardiac index (CI) had increased from the pre-anesthetic level by 15.3% (mean) (SD: 31.7%) in group A and decreased by 7.7% (15.1%) in C patients, p = 0.0069. Also the changes in stroke index (SI; p = 0.022), left (LVSWI; p = 0.0037) and right ventricular stroke work index (RVSWI; p = 0.0097) were more favorable in group A. Despite longer aortic cross-clamp, p = 0.031, and perfusion times, p = 0.042, in A patients, the change in cardiac index was also better in this group after bypass: At decannulation, the difference between mean values was 31.8%, p = 0.0001, and at arrival in the ICU it was 16.1%, p = 0.028. The same was also seen 8 h postoperatively and on the 1st and 2nd postoperative mornings; p = 0.034, 0.040, and 0.037, respectively (Wilcoxon test). Favorable changes were seen for the A patients also regarding SI at decannulation (p = 0.0002) and after 8 h (p = 0.017); LVSWI at decannulation (p = 0.0002), at arrival in the ICU (p = 0.0023), and after 8 h (p = 0.0011); and RVSWI at decannulation (p = 0.0027), at the ICU (p = 0.021), after 8 h (p = 0.014), and on the 1st postoperative morning (p = 0.039). However, the response to a hemodynamic loading test (6% hydroxyethyl starch 5 ml/kg) was similar in the 2 groups, and there was no difference in the need for inotropic support. CONCLUSIONS: Amino acid-enriched GIK infusion improves hemodynamic function in CABG patients with unstable angina and/or compromised left ventricular function.