ROLE OF BRADYKININ IN MYOCARDIAL PRECONDITIONING

The role of bradykinin in the cardioprotective action of ischemic prec onditioning was investigated in an anesthetized, open-chest rabbit mod el of acute coronary occlusion. A branch of the left main coronary art ery was reversibly ligated to produce ischemia followed by reperfusion , after which the degree of myocardial necrosis (infarct size as a per cent of area at risk) was assessed by tetrazolium staining. Before 30 min of coronary occlusion, rabbits received either ischemic preconditi oning (5 min occlusion followed by 10 min reperfusion), no preconditio ning, H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH (HOE 140) i.v. (bradykinin receptor antagonist, 1 mu g/kg) plus preconditioning, HOE 740 alone, a 5-min intra-atrial bradykinin infusion (250 mu g/kg/min) followed by a 10-min recovery period or HOE 140 plus bradykinin infusi on with 10 min recovery. Systemic hemodynamic responses were similar b etween treatment groups except that both bradykinin infusion groups ha d a significantly depressed rate of left ventricular pressure developm ent (LV+dP/dt(max)) after the 10-min recovery period. Preconditioning reduced infarct size significantly (12 +/- 2%, compared to non-precond itioned controls at 41 +/- 6%), whereas pretreatment with HOE 140 abol ished the cardioprotective effect (41 +/- 4%). In addition, bradykinin infusion reduced infarct size significantly (16 +/- 1%), an effect wh ich was also prevented by HOE 140 (41 +/- 5%). HOE 140 alone did not e xacerbate the degree of myocardial necrosis (43 +/- 4%). Myocardial ar ea at risk as a percentage of total left ventricular mass was not diff erent between the six treatment groups. The results indicate that endo genously generated bradykinin may mediate the cardioprotective events associated with ischemic preconditioning.