Isoflurane produces only minor preconditioning in coronary artery bypass grafting.

OBJECTIVE: To investigate whether administration of isoflurane prior to cardiopulmonary bypass (CPB) could partly account for the observed protection of the myocardial function and to decrease myocardial injury in patients undergoing coronary artery bypass grafting (CABG). METHODS: Thirty-four patients with stable angina who were scheduled for isolated elective CABG operations were randomized into the control group or isoflurane (ISO) group. In the ISO group, isoflurane was inhaled for 5 min followed by another 5-min washout period before commencing CPB. The control group did not receive isoflurane. Hemodynamic data and biochemical markers of myocardial injury were measured perioperatively. RESULTS: There were no adverse effects related to isoflurane. Cardiac index (CI) increased postoperatively as compared with the baseline. In the ISO group, there was a tendency for a greater increase of CI than that in the control group (p = 0.054, ANOVA for repeated measurements). At 1 h after CPB, the change of CI was much higher in the ISO group than that in the controls (p = 0.001). Both the creatine kinase cardiac isoenzyme (CK-MB) and troponin I (TnI) reached peak value at 6 h after CPB. Isoflurane patients released slightly less CK-MB than the controls postoperatively, but the difference was not significant (p = 0.16, ANOVA for repeated measurements). The release of TnI was similar in both groups (p = 0.65, ANOVA for repeated measurements). CONCLUSIONS: Administration of isoflurane prior to commencing CPB may bring an improvement in early hemodynamic performance after CABG operations.

Bradykinin preconditioning in coronary artery bypass grafting.

BACKGROUND: Experimental studies have shown that activation of bradykinin B2 receptor is one of the most important triggers of ischemic preconditioning. However, the effect of exogenous administration of bradykinin in cardiac surgery is not yet known. The present prospective randomized study was designed to investigate the effect of bradykinin pretreatment in patients undergoing elective coronary artery bypass surgery. METHODS: Forty-one patients with multiple-vessel coronary artery disease and stable angina, admitted for the first time for elective coronary artery bypass surgery, were randomized into control or bradykinin (BK) groups. Patients in the BK group received bradykinin infusion for 7 minutes (total dose 25 microg) before the initiation of cardiopulmonary bypass. Perioperative cardiac specific troponin I (cTnI) and creatine kinase cardiac isoenzyme (CKMB) release and hemodynamics were recorded. RESULTS: Bradykinin infusion caused acute decrease of blood pressure in most of the cases and the mean minimum mean blood pressure during bradykinin infusion was 72.7% of the original mean blood pressure (MBP) level (74.7 +/- 7.9 vs 54.4 +/- 12.1 mm Hg, p < 0.01). There were no differences in baseline levels of cTnI and CKMB between the groups. The postoperative cTnI levels were lower than 10 ng/mL in most patients in both groups (18 in the BK group and 15 in the control group). There was no difference in cTnI between the groups. However, patients who received bradykinin released significantly less CKMB than did the controls postoperatively (6 hours, BK, 22.1 +/- 9.5 vs control, 23.6 +/- 12.7 U/L; 12 hours, BK, 19.4 +/- 12.4 vs control, 28.7 +/- 23.8 U/L; 24 hours, BK, 21.5 +/- 14.7 vs control, 35.5 +/- 28.9 U/L; 48 hours, BK, 14.4 +/- 7.5 vs control, 23.5 +/- 13.6 U/L; analysis of variance [ANOVA] for repeated measurement, p = 0.036). Maximum CKMB was also lower in the BK group (22.4 +/- 14.4 vs 37.7 +/- 27.5 U/L, p = 0.044). There was no significant difference between the groups in any of the hemodynamic variables. CONCLUSIONS: Exogenous bradykinin infusion showed weak cardioprotective effect in the low-risk patients undergoing coronary artery bypass surgery but the dose used in the study caused acute decrease of systemic blood pressure.

The anti-inflammatory effect of diazoxide in coronary artery bypass grafting.

Many therapeutic strategies have been designed to suppress the inflammatory response in patients undergoing coronary artery bypass grafting (CABG). Pharmacological preconditioning with diazoxide is an alternative in effective cardioprotective strategies, but more evidence is required to show its effect on the inflammatory response. Forty patients with stable angina who were scheduled for isolated elective CABG operations were randomized into control and diazoxide (DZX) groups. In the DZX group, 1.5 mg/kg diazoxide was infused intravenously in 5 min followed by a 5-min washout before commencing the cardiopulmonary bypass. In the control group, placebo infusion was given similarly. Blood samples for cytokine measurement were collected from the radial artery and coronary sinus perioperatively, and hemodynamic data were recorded. Thirty-six patients fulfilled the data collection. Cardiac index (CI) increased in both groups over time as compared with baseline. In the DZX group, the increase of CI was greater than that in the control group (P = 0.002). Systemic and coronary sinus plasma levels of IL-6, IL-8, and IL-10 increased significantly after reperfusion in both groups as compared with baseline (P < 0.05). IL-6 and IL-8 both reached the peak value at 6 h after cardiopulmonary bypass. IL-10 reached peak level at 20 min after reperfusion in both groups. There was significantly higher IL-10 in DZX groups (P = 0.015). The ratios of IL-6 to IL-10 and IL-8 to IL-10 were significantly lower in DZX groups than in controls (P = 0.025 and P = 0.041 for each, respectively). Pharmacological preconditioning with DZX in CABG patients shifts the circulating inflammatory cytokine balance toward the anti-inflammatory direction.

Novel pharmacological preconditioning with diazoxide attenuates myocardial stunning in coronary artery bypass grafting.

OBJECTIVE: To investigate whether novel pharmacological preconditioning with diazoxide could protect the myocardial function and decrease myocardial injury in patients undergoing coronary artery bypass grafting (CABG). METHODS: Forty patients with stable angina who were scheduled for isolated elective CABG operations were randomized into control group (n=20) and diazoxide (DZX) group (n=20). In the DZX group, 1.5 mg/kg diazoxide was infused intravenously within 5 min followed by a 5-min washout before commencing the cardiopulmonary bypass (CPB). In the control group, a time-matched period of placebo infusion was given. Hemodynamic data and biochemical markers of myocardial injury were measured perioperatively. RESULTS: There were no adverse effects related to diazoxide. Cardiac index (CI) increased postoperatively as compared with baseline. In the DZX group, the improvement of CI was better than that in the control group (p=0.001). Left and right ventricular stroke work indexes decreased postoperatively, and recovered much faster in the DZX group (p=0.027 and p=0.049, respectively). There were no statistically significant differences in the other hemodynamic parameters. The creatine kinase cardiac isoenzyme (CK-MB) was highest in both groups on the first postoperative day (control 28.8+/-23.8 and DZX 27.3+/-19.4, N.S.). The cumulative release of CK-MB postoperatively was lower in the DZX patients as compared with the controls, but the difference remained not significant (p=0.09). CONCLUSIONS: Pharmacological preconditioning of the human heart with diazoxide is feasible; it confers additional myocardial protection beyond that provided by the cardioplegia alone by attenuating myocardial stunning after CABG operations.

Relation of cytokines to vasodilation after coronary artery bypass grafting.

Hemodynamic instability is frequent after coronary surgery. The present study tested the hypothesis that inflammation, as determined by circulating cytokine levels, may contribute to the difficulty of controlling arterial blood pressure after coronary artery bypass grafting. A group of 44 male patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass were studied. Plasma levels of tumor necrosis factor-alpha, interleukin-6 (IL-6), IL-8, and IL-10 were measured before anesthesia induction, 5 minutes and 1 hour after reperfusion to the myocardium, and 2 and 18 hours after arriving in the intensive care unit (ICU). The 29 patients who did not need a vasopressor (norepinephrine) during their ICU stay were designated group I. They were compared to group II, which consisted of 15 patients who required a pressor agent in the ICU. Although no significant differences between groups were found regarding their hemodynamic variables, IL-6 and IL-8 levels were higher in the patients who used a pressor agent in the ICU. The norepinephrine dosage used in the ICU correlated with plasma IL-8 levels 2 hours after arriving in the ICU (r = 0.56, p = 0.031). Circulating IL-6 levels in group II were significantly higher than those in group I 2 hours after arriving in the ICU (126.5 +/- 90.5 vs. 66.5 +/- 48.2 pg/ml; p < 0.05). The mean IL-8 levels were higher in group II at 5 minutes (34.9 +/- 25.7 vs. 17.3 +/- 11.3 pg/ml) and 1 hour (38.6 +/- 30.5 vs. 22.4 +/- 16.7 pg/ml) after reperfusion, and 2 hours (33.0 +/- 21.6 vs. 22.8 +/- 16.7 pg/ml) after arriving in the ICU (p = 0.036). Postoperative vasodilation was associated with increased circulating IL-8 levels. Strategies that modulate cytokine responses may improve hemodynamic stability after coronary artery bypass grafting.

Cardioprotective effect of pump prime aprotinin in coronary artery bypass grafting.

BACKGROUND: Several studies have reported that high-dose aprotinin is cardioprotective in coronary surgery. The cardioprotective efficacy of low-dose aprotinin is less well defined. The present randomised study evaluated the cardioprotective and anti-inflammatory effects of pump prime aprotinin in patients undergoing coronary bypass surgery. METHODS: Sixty-four male patients admitted for first-time elective coronary artery bypass surgery were randomised into control or aprotinin groups. Patients in the aprotinin group received 280 mg of aprotinin in the pump prime. Postoperative CK-MB release, leukocyte counts and hemodynamics were recorded. Perioperative myeloperoxidase, IL-6, IL-8 and IL-10 levels were measured in a subgroup of patients (15 patients in each group). RESULTS: There were no significant differences between the groups in mechanical ventilation time and ICU and hospital stay. Postoperative bleeding was less serious in the aprotinin group than in the controls (742.0 +/- 361.1 versus 885.2 +/- 335.1 ml, p = 0.12) and CK-MB values were significantly lower (6 hrs, 35.5 +/- 11.8 versus 4.5 +/- 24.0 U/L; 24 hrs, 32.3 +/- 25.0 versus 40.2 +/- 26.8 U/L; 48 hrs, 15.9 +/- 7.0 versus 24.7 +/- 21.1 U/L; p=0.041). Perioperative hemodynamics was similar in both groups. There was a tendency towards less vasopressor and inotropes use in the pump prime aprotinin group. There was no significant difference between groups in terms of perioperative myeloperoxidase, IL-6, IL-8 and IL-10 levels. CONCLUSIONS: Pump prime aprotinin marginally limits myocardial enzyme release, but fails to limit inflammatory responses after elective coronary surgery.