P-31 NUCLEAR-MAGNETIC-RESONANCE STUDY OF THE EFFECTS OF THE CALCIUM-ION CHANNEL ANTAGONIST FANTOFARONE ON THE RAT-HEART

The biochemical and mechanical effects of a new calcium ion channel an tagonist, fantofarone hy1)-amino)proploxy)benzenesulfonyl))-indolizine ), on isovolumic perfused rat heart have been assessed by using P-31 n uclear magnetic resonance (NMR) spectroscopy together with simultaneou s monitoring of myocardial mechanical function. Cytosolic pH and phosp hocreatine, adenosine triphosphate and inorganic phosphate contents we re monitored by using P-31 NMR. Heart rate, coronary flow and left ven tricular developed pressure were measured routinely to assess mechanic al function. Perfusion with 10 nM, 100 nM or 1 mu M fantofarone for a period of 48 min did not cause any measurable metabolic changes. Howev er, coronary vasodilatation and !a partial positive inotropic effect w ere noted. A 15-min pretreatment with 100 nM did not protect against t he deleterious effects of an Is-min period of normothermic, zero-now i schemia. In contrast, a 20-min pretreatment period with 1 mu M fantofa rone significantly improved the recovery of mechanical performance, me tabolic activity and pH after the same 18 min of ischemia. While only a slight protection of the ATP pool was noted during the ischemic peri od, major beneficial effects were observed during the reperfusion peri od, such that reflow was characterized by high recoveries of left vent ricular pressure and rate pressure product (70-80%), low end diastolic pressure (< 10 mm Hg), significant recovery of ATP content (to 55%), a complete repletion of the phosphocreatine pool and a fast return of cytosolic pH to normal value.