Minxin Wei

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.

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.

Cytokine responses in patients undergoing coronary artery bypass surgery after ischemic preconditioning.

OBJECTIVE The release of proinflammatory cytokines has been shown to be associated with the development of complications after coronary artery bypass grafting with cardiopulmonary bypass. The purpose of the present study was to establish whether ischemic preconditioning (IP) could limit inflammatory cytokines release in patients undergoing elective coronary artery bypass surgery. METHODS Twenty-two patients with multiple-vessel coronary artery disease and stable angina admitted for first-time elective coronary artery bypass surgery were randomized into control or ischemic preconditioning groups. Patients in the IP group were exposed to two cycles of two-minute myocardial ischemia, followed by three minutes of reperfusion, at the beginning of the revascularization operation, before the cross-clamping and ischemic period used for coronary artery bypass graft anastomosis. Peripheral plasma levels of TNF-alpha, IL-6, IL-8 and IL-10 were measured perioperatively. RESULTS Significant elevation of IL-6, IL-8 and IL-10 were observed in both groups after reperfusion. Ischemic preconditioning has no effect on cytokine release in the early stage after reperfusion. Arterial blood IL-6 levels in the preconditioning group were significantly lower than in controls at 20 h after declamping (52.93 +/- 9.79 vs 96.04 +/- 17.56 pg/ml, p < 0.05). CONCLUSIONS The results indicate that ischemic preconditioning results in no effect on systemic inflammatory cytokine release in the early stage but a delayed reduction in IL-6 levels at 20 h after reperfusion.Objective - The release of proinflammatory cytokines has been shown to be associated with the development of complications after coronary artery bypass grafting with cardiopulmonary bypass. The purpose of the present study was to establish whether ischemic preconditioning (IP) could limit inflammatory cytokines release in patients undergoing elective coronary artery bypass surgery. Methods

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.

Tranexamic acid reduces postoperative bleeding in off-pump coronary artery bypass grafting

Objective. Tranexamic acid (TA) reduces blood loss in coronary artery surgery with cardiopulmonary bypass. The present prospective study was designed to investigate its hemostatic effect in off-pump coronary artery bypass (OPCAB). Method. Seventy-six patients undergoing elective OPCAB were randomized into two groups, received TA (0.75 g loading dose before surgery and 250 mg/h during surgery, gross dose: 1.5 g, n = 36) and saline solution (control, n = 40), respectively. Perioperative blood samples were collected. Hematochemical parameters including platelet adhesion rate, D-dimer and fibrinopeptide-A (FPA) were analysis. Volume of blood loss, blood transfusion and other clinical data were recorded throughout the perioperative period. Results. Cumulative blood loss was significantly reduced in the TA group as compared to the controls postoperatively (6 hrs (median [25th–75th]): TA: 200.0 [140.0–230.0] ml, Control: 225.0 [200.0–347.5.0] ml, p = 0.009; 24 hrs: TA: 440.0 [270.0–605.0] ml, Control: 655.0 [500.0–920.0] ml, p < 0.001). Number of patients received blood transfusion in each group was similar. Levels of D-dimer rose significantly after surgery, and were significantly lower in the TA group than that in controls. Platelet adhesion rate and FPA levels remained at baseline levels after the operation in two groups. Early clinical outcomes were similar between groups. Conclusion. The results indicated that tranexamic acid limits fibrinolysis and reduces blood loss after off-pump coronary artery bypass surgery.

The anti-inflammatory effect of bradykinin preconditioning in coronary artery bypass grafting (bradykinin and preconditioning)

Objective. The present study was designed to investigate the cardioprotective effect of exogenous administration of bradykinin (BK) in cardiac surgery. Methods. Forty-one patients who were scheduled for isolated coronary artery bypass grafting (CABG) were randomized into Control group and BK group. BK patients received 25 µg bradykinin infusion for 7 minutes before the cardiopulmonary bypass (CPB). Release of cardiac specific troponin I (TnI) and creatine kinase cardiac isoenzyme (CK-MB) was recorded. Perioperative circulating cytokine interleukin (IL)-6, 8 and 10 were measured. Results. There was no significant difference in TnI between groups. However, BK patients released significantly less CK-MB than the controls (p =0.043). Systemic plasma levels of IL-6, IL-8 and IL-10 increased significantly after reperfusion in both groups as compared with baseline (p <0.05). The ratio of IL-8 to IL-10 was significantly lower in BK groups than in controls (p =0.03). Conclusions. We conclude that exogenous administration of BK prior to CPB in CABG patients attenuates ischemic myocardial injury. It also shifts the circulating inflammatory cytokine balance towards the anti-inflammatory direction.

Soluble Adhesion Molecules and Myocardial Injury during Coronary Artery Bypass Grafting

Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery. Leukocyte-endothelial binding followed by neutrophil migration appears to play a central role. These interactions are mediated by adhesion molecules on the surface of activated cells. The present study compared the perioperative levels of soluble adhesion molecules after coronary artery bypass grafting (CABG) in patients with or without cardiopulmonary bypass (CPB). Altogether, 9 patients underwent off-pump revascularization and 11 did so with CPB. Plasma levels of soluble adhesion molecules sE-selectin and sP-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) were measured before anesthesia induction and 1, 4, and 20 hours after reperfusion to the myocardium. The baseline plasma levels of the adhesion molecules were similar in the two groups. Perioperative levels of sE-selectin remained the same and did not differ between groups. Plasma sP-selectin increased in both groups, the change being significantly greater in the CPB group than that in the off-pump group (p = 0.001). Plasma sICAM-1 decreased during an early stage after CABG with CPB, recovering at 4 hours after reperfusion; and a significant increase in ICAM-1 was observed 20 hours later. In the off-pump group, sICAM-1 levels did not change at 1 and 4 hours after reperfusion but increased 20 hours later. Postoperative creatine kinase–muscle bound (CK-MB) levels were significantly higher in the CPB group than in the off-pump group (p = 0.001). The change in sP-selectin levels also showed a correlation with CK-MB values (r = 0.676, p = 0.001). The results indicated that off-pump revascularization is associated with reduced endothelial activation and myocardial injury.

Cardioprotective Effect of Pump Prime Aprotinin in Coronary Artery Bypass Grafting

AbstractBackground: 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 44.5 ± 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.

Cytokine Responses in Low-Risk Coronary Artery Bypass Surgery.

Inflammatory cytokines have been implicated in myocardial function, severe congestive heart failure and sepsis. The present study tested the hypothesis that cytokine levels are elevated after low-risk coronary artery bypass surgery (CABG), and that they may be associated with postoperative cardiac dysfunction. Twenty male patients undergoing elective CABG in cardiopulmonary bypass (CPB) were studied. Plasma levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-10 were measured before anesthesia induction, 5 minutes after, and 1, 4, and 20 hours after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were measured postoperatively. Hemodynamic data were also recorded. Myocardial ischemia was followed by an increase in the plasma levels of IL-6, IL-8, and IL-10. The duration of IL-6 response lasted throughout the postoperative period studied. Plasma cytokine levels at 1 hour after reperfusion correlated with the maximum CK-MB value (IL-6, r=0.587, p<0.01; IL-8, r=0.460, p<0.05; IL-10, r=0.570, p<0.05). Higher plasma IL-6 and IL-8 levels after reperfusion tended to be linked with lower cardiac index. The present results confirm that the levels of inflammatory cytokines IL-6, IL-8, and IL-10 are elevated after CABG. Increased systemic pro-inflammatory cytokine levels were partially associated with postoperative myocardial dysfunction.

Imbalance of pro- and anti-inflammatory cytokine responses in elderly patients after coronary artery bypass grafting

Background and aims: Increased inflammatory activity has been observed in elderly people. The aim of this study was to determine whether cytokine responses after coronary artery bypass grafting (CABG) in elderly patients are different from those in younger patients. Methods: Fifty-five male patients admitted for first-time elective coronary artery bypass surgery were divided into two age groups: group I, patients younger than 70 years (N=40); and group II, patients aged 70 years or older (N=15). Perioperative levels of cytokines and CK-MB were measured. Hemodynamic data were recorded. Results: Marginally higher IL-6 (p=0.048) and IL-8 (p=0.041) levels were observed during the intensive care unit (ICU) stay in the elderly as compared with younger patients. Lower IL-10 levels were detected in the elderly 5 minutes after reperfusion to the myocardium (p<0.05). Although the postoperative hemodynamic change was similar in both groups, the elderly needed vasopressor treatment more often during the ICU stay. This was associated with lower IL-10 levels 5 minutes after reperfusion. Conclusions: The present results show the age-related imbalance of pro- and anti-inflammatory responses after CABG, associated with hemodynamic instability in the elderly.