Ketamine, but not S(+) -ketamine, blocks ischemic preconditioning in rabbit hearts in vivo

Background. Ketamine blocks K-ATP channels in isolated cells and abolishes the cardioprotective effect of ischemic preconditioning in vitro. The autho rs investigated the effects of ketamine and S(+)-ketamine on ischemic preco nditioning in the rabbit heart in vivo. Methods: In 46 alpha -chloralose-anesthetized rabbits, left ventricular pre ssure (tip manometer), cardiac output (ultrasonic flow probe), and myocardi al infarct size (triphenyltetrazolium staining) at the end of the experimen t were measured. All rabbits were subjected to 30 min of occlusion of a maj or coronary artery and 2 h of subsequent reperfusion. The control group und erwent the ischemia-reperfusion program without preconditioning. Ischemic p reconditioning was elicited by 5-min coronary artery occlusion followed by 10 min of reperfusion before the 30 min period of myocardial ischemia (prec onditioning group). To test whether ketamine or S(+)-ketamine blocks the pr econditioning-induced cardioprotection, each (10 mg kg(-1)) was ad minister ed 5 min before the preconditioning ischemia. To test any effect of ketamin e itself, ketamine was also administered without preconditioning at the cor responding time point. Results: Hemodynamic baseline values were not significantly different betwe en groups [left ventricular pressure, 107 +/- 13 mmHg (mean +/- SD); cardia c output, 183 +/- 28 ml/min]. During coronary artery occlusion, left ventri cular pressure was reduced to 83 +/- 14% of baseline and cardiac output to 84 +/- 19%. After 2 h of reperfusion, functional recovery was not significa ntly different among groups (left ventricular pressure, 77 +/- 19%; cardiac output, 86 +/- 18%). Infarct size was reduced from 45 +/- 16% of the area at risk in controls to 24 +/- 17% in the preconditioning group (P = 0.03). The administration of ketamine had no effect on infarct size in animals wit hout preconditioning (48 +/- 18%), but abolished the cardioprotective effec ts of ischemic preconditioning (45 +/- 19%, P = 0.03). S(+)-ketamine did no t affect ischemic preconditioning (25 +/- 11%, P = 1.0). Conclusions: Ketamine, but not S(+)-ketamine blocks the cardioprotective ef fect of ischemic preconditioning in vivo.