INFARCT SIZE-LIMITING PROPERTIES OF RO-40-5967, A NOVEL NONDIHYDROPYRIDINE CALCIUM-CHANNEL, IN ANESTHETIZED RATS - COMPARISON WITH VERAPAMIL

We assessed the hemodynamic and infarct size (IS)-limiting effects of the new calcium antagonist Ro 40-5967 in a rat model of ischemia/reper fusion and compared the effects of Ro 40-5967 with those of verapamil. Open-chest rats underwent 20-min coronary occlusion followed by 2-h r eperfusion. We determined area at risk (AAR) and IS at the end of repe rfusion by India ink injection and triphenyltetrazolium chloride (TTC) staining, using computerized analysis of enlarged sections after colo r video acquisition. Ro 40-5967 [0.3 mg/kg intravenous (i.v.) bolus 15 min before ischemia + 0.3 mg/kg/h i.v. infusion] and verapamil (0.3 m g/kg followed by 0.3 mg/kg/h) induced significant and similar limitati ons of IS (percentage of AAR: controls, 61.2 +/- 3.5%; Ro 40-5967, 41. 0 +/- 4.0%; verapamil, 43 +/- 4.8%; both p < 0.01 versus controls). Th e IS-limiting effect of Ro 40-5967 was not accompanied by any changes in heart rate (HR) or rate pressure product (RPP), whereas verapamil d ecreased both HR and RPP throughout ischemia/reperfusion. In contrast, verapamil administered at a lower dose (0.03 mg/kg followed by 0.03 m g/kg/h), which induced hemodynamic effects similar to those of Ro 40-5 967, had no effect on IS (57.1 +/- 5.2, p = NS). Furthermore, addition al hemodynamic studies performed in noninfarcted rats showed that Ro 4 0-5967 exerted negative inotropic effects that were less marked than t hose induced by verapamil. Therefore, Ro 40-5967 exerts myocardial pro tective effects that appear to be independent of changes in systemic h emodynamics or myocardial contractility.