Fantofarone (SR 33557): effect on post-ischaemic functional recovery in perfused rat hearts.
Fantofarone (SR 33557) is a novel, highly potent calcium channel antagonist representative of a new class of slow channel blockers. In this study, we have assessed its ability to influence cardiac function in two, isolated, perfused heart models and then assessed its ability to modify post-ischaemic functional recovery. In isolated, rat hearts perfused in the Langendorff mode, fantofarone increased coronary flow by 25% at 100 and 1000 nM with no effect on left ventricular pressure or heart rate below 100 nM. In working hearts, fantofarone again increased coronary flow within a similar concentration range. A significant reduction (approximately 40%) was observed in peak systolic pressure and dP/dtmax when hearts were perfused with 1000 nM fantofarone. Working rat hearts were also subjected to a 30 min period of global, low-flow (0.1 ml/min) ischaemia, followed by a 30 min period of reperfusion. Perfusion with 1 or 10 nM fantofarone, began 20 min prior to the onset of ischaemia and continued throughout the ischaemic and reperfusion periods. The addition of 1 nM fantofarone did not cause a significant increase in the recovery of cardiac function during the reperfusion phase. In contrast, perfusion with 10 nM fantofarone resulted in a substantial increase in the recovery of several indices of cardiac function such as aortic output, dP/dtmax and peak systolic pressure. Thus, in the working rat heart, at concentrations which cause minimal alterations to normal cardiac function, fantofarone can improve significantly functional recovery following an ischaemic insult.
Manning
A
A
S.A. Sanofi-Pharma N.V., Brussels, Belgium.
Mouton
J
J
Chatelain
P
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007212:Indolizines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D002121:Calcium Channel Blockers; D007212:Indolizines; D010627:Phenethylamines; C059901:fantofarone