PROTECTIVE EFFECT OF THE SEROTONIN RECEPTOR ANTAGONIST CINANSERIN IN 2 CANINE MODELS OF PACING-INDUCED MYOCARDIAL-ISCHEMIA

Previous studies have indicated that structurally dissimilar serotonin (2) (5HT(2)) antagonists can protect globally ischemic/reperfused rat hearts. We therefore determined if the 5HT(2) antagonist cinanserin ca n protect the ischemic myocardium in two models of pacing-induced isch emia in anesthetized dogs. In one model, dogs were subjected to repeat ed 5-min episodes of pacing superimposed upon left anterior descending coronary artery stenosis such that an ST segment elevation of 10-11 m V was obtained and upon cessation of pacing, a return of ST segment el evation to baseline. In vehicle-treated animals, this ST segment eleva tion was constant for all pacing-induced ischemic episodes. After infu sion of 20 mu g/kg/min cinanserin (intracoronary, i.c.), ST segment el evation was significantly reduced during pacing-induced ischemia at al l times measured postdrug. In the second model, animals were subjected to pacing-induced ischemia for 15 min such that segmental shortening was reduced to zero. Upon cessation of pacing-induced ischemia, recove ry of shortening was assessed. In vehicle-treated dogs, function recov ered to only 40% of baseline at 3 h into recovery. Pretreatment with 5 mu g/kg/min cinanserin i.c. significantly improved recovery of postis chemic function. In both protocols, cinanserin had no effect on ischem ic regional blood flow or peripheral hemodynamics. Thus, cinanserin ap pears to exert profound protective effects in two models of effort-ind uced ischemia.