Protective effect of the serotonin receptor antagonist cinanserin in two canine models of pacing-induced myocardial ischemia.
Previous studies have indicated that structurally dissimilar serotonin2 (5HT2) antagonists can protect globally ischemic/reperfused reperfused rat hearts. We therefore determined if the 5HT2 antagonist cinanserin can protect the ischemic myocardium in two models of pacing-induced ischemia in anesthetized dogs. In one model, dogs were subjected to repeated 5-min episodes of pacing superimposed upon left anterior descending coronary artery stenosis such that an ST segment elevation of 10-11 mV was obtained and upon cessation of pacing, a return of ST segment elevation to baseline. In vehicle-treated animals, this ST segment elevation to baseline. In vehicle-treated animals, this ST segment elevation was constant for all pacing-induced ischemic episodes. After infusion of 20 micrograms/kg/min cinanserin (intracoronary, i.c.), ST segment elevation was significantly reduced during pacing-induced ischemia at all 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, recovery of shortening was assessed. In vehicle-treated dogs, function recovered to only 40% of baseline at 3 h into recovery. Pretreatment with 5 micrograms/kg/min cinanserin i.c. significantly improved recovery of postischemic function. In both protocols, cinanserin had no effect on ischemic regional blood flow or peripheral hemodynamics. Thus, cinanserin appears to exert profound protective effects in two models of effort-induced ischemia.
Grover
G J
GJ
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Parham
C S
CS
Youssef
S
S
Ogletree
M L
ML
D000704:Analysis of Variance; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D002928:Cinanserin / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000517:prevention & control*
D002928:Cinanserin