PRECONDITIONING IMPROVES MYOCARDIAL-FUNCTION AND REFLOW, BUT NOT VASODILATOR REACTIVITY, AFTER ISCHEMIA AND REPERFUSION IN ANESTHETIZED DOGS

1, The present study examines whether three cycles of brief coronary a rtery occlusion and reperfusion (i,e, ischaemic preconditioning; PC) c an prevent vasodilator dysfunction and the impairment of myocardial re flow caused by prolonged ischaemia, Coronary blood flow,left ventricul ar dP/dt, systemic arterial blood pressure and heart rate were measure d in open-chest anaesthetized dogs. 2, Sixty minute occlusion of the l eft circumflex coronary artery (LCx) and 60 min LCx reperfusion (ISC/R EP; group 1) significantly reduced resting coronary blood flow (CBF, i nitial 29+/-3 mL/min; ISC/REP 20+/-3 mL/min, P<0,05 vs initial) and in creased coronary vascular resistance (CVR, initial 4.1+/-0,6 mmHg/min per mt; ISC/REP 5.8 +/- 1.0 mmHg/min per mt, P<0.05 vs initial). By co ntrast CBF and CVR were not affected in dogs subjected to precondition ing before ischaemia (group 2: CBF, initial 24+/-4mL/min; PC+ISC/REP 2 3+/- 4mL/min; CVR, initial 4,7+/-0,6 mmHg/min per mt; PCS ISC/REP 5,3/-1,0 mmHg/min per mt). These data suggest that ischaemic precondition ing prevents the ischaemia-induced impairment of myocardial reflow. 3, Ischaemia and reperfusion impaired coronary dilator responses to the endothelium-dependent dilator acetylcholine (Delta CBF, after ISC/REP: 50+/-6% of initial) and the endothelium-independent dilator glyceryl trinitrate (Delta CBF, ISC/REP: 46+/-6% of initial). Despite the impro vement in reperfusion in the preconditioned group, there was no signif icant improvement in responses to acetylcholine (PC+ISC/REP 52+/-6% of initial) or glyceryl trinitrate (PC+ISC/REP 59+/-6% of initial) after ischaemia and reperfusion, 4, The reduction in left ventricular dP/dt after ischaemia and reperfusion was significantly smaller in the prec onditioned group indicating a lower level of impairment of cardiac con tractility. In addition, we confirmed that preconditioning caused a si gnificant reduction in infarct size and a reduction in the release of lactate dehydrogenase indicating less cardiac injury. 5, These results suggest that although ischaemic preconditioning was able to improve b oth myocardial reperfusion and contractility, it was not able to prese rve vasodilator function. Such a reduction in vasodilator reserve coul d prevent adequate myocardial perfusion under conditions of elevated o xygen demand.