Pharmacological preconditioning (PPC) has begun to show its potent ability of myocardial protection. However, studies of PPC effects in cardiac surgery are rare and controversial. The present series of studies were designed to investigate if pharmacological agents, who were mostly tested in the animal experiments, could elicit cardioprotection. The myocardial protective effect and the anti-inflammatory response of the diazoxide, bradykinin and isoflurane were evaluated in on-pump CABG patients. The finding demonstrated that pharmacological preconditioning with intravenously infused diazoxide (1.5mg/kg), a highly selected mitoKATP channel opener, prior to commencing CPB in CABG patients with stable angina resulted in significant improvement in hemodynamic performance as well as in tendency of reducing postoperative CK-MB release as compared with the cardioplegia alone. The benefit of this additional protection effect was mostly from the attenuated myocardial stunning and infarction. PPC with diazoxide could also elicit anti-inflammatory response. It augments the postischemic anti-inflammatory cytokine IL-10 production and shifts the systemic circulating cytokines balance (ratio of pro- to anti-inflammatory cytokine, IL-8/IL-10 and IL-6/IL10) to anti-inflammatory direction. This was most likely not due to an effect attributable to the heart. Exogenous bradykinin (total dose 25 ìg) infusion immediately prior to the commencing of CPB appears to limit myocardial injury after CABG. BK patients released significantly less CK-MB than the controls, and the maximum CK-MB was also lower in the BK group. However, the protocol used here failed to show beneficial effect on postoperative hemodynamic parameters. In the BK group, it has been shown that the postoperative IL-10 level was higher than that in the controls, although the difference did not reach the statistical significance. As the results show, the ratios of systemic IL-8/IL-10 in the BK group were significantly lower than that in the control group. This strongly suggests that BK serves as a pharmacological preconditioning stimulus and shifts the cytokine balance towards the anti-inflammatory direction. The results indicate that administration of isoflurane (1 MAC) prior to commencing CPB in CABG patients with stable angina may bring a significant early improvement in hemodynamic performance 1 hour after CPB as well as tendency of reducing postoperative CK-MB release as compared with the cardioplegia alone. Isoflurane produces only minor preconditioning in coronary artery bypass grafting. This series of study suggested that beyond the traditional cardioplegia protection, there is still some room left for pharmacological additives, such as bradykinin, diazoxide and isoflurane, to confer extra cardioprotection in coronary artery bypass surgery. The exact underlying mechanism and optimal dose of pharmacological precondition in clinical setting warrants further study.