Cardioprotection associated with preconditioning in the anesthetized ferret

The cardioprotective effect of ischemic preconditioning (PC) was investigated in the anesthetized ferret model of myocardial ischemia followed by reperfusion. PC of 2, 5, or 10-min duration, followed by 10-min reflow, was studied in animals subjected to 60-min sustained LAD coronary artery ischemia followed by 5-h reperfusion. Infarct size was determined by tetrazolium staining. Sham PC ferrets had a mean infarct of 72% of risk zone. A 2-min or 5-min cycle of PC significantly reduced tissue damage to 54% (p < 0.05) and 44% (p < 0.01), respectively. Infarct reduction associated with 10-min ischemic PC was not significant (57% of AAR). The cardioprotective effects of 5-min PC were lost when sustained ischemia was prolonged to 75 or 90-min. Myocardial salvage afforded by 5-min PC was also abolished by both a) inhibition of ATP-sensitive potassium channels using either glyburide or 5-HD and b) blockade of adenosine receptors with the A1 selective agent DPCPX. In the absence of PC, activation of ATP-sensitive potassium channels with the cardiac-selective agonist BMS-180448 significantly (p < 0.01) reduced infarct size from 66% to 37% of the risk zone. Cardioprotection, or its loss, was not the result of hemodynamic alterations occurring during PC, drug administration, or the coronary occlusion and reperfusion phases. Based upon its body size and lack of extensive myocardial collateral circulation the ferret offers a usefull alternative small species for study of ischemia and reperfusion salvage. It is concluded in the ferret that: a) the threshold for PC is less than in either the rat, rabbit, or dog; unlike the dog and pig, the beneficial effects of PC are b) reduced when the ischemic PC interval is extended to 10-min or c) lost if sustained coronary occlusion is maintained for a period of 75-min or longer; and last, a role in PC for both d) ATP-sensitive potassium channels and e) adenosine A1 receptors can be demonstrated.