Restriction of isoproterenol-induced myocardial Ca uptake and necrotization in rats by a new Ca-antagonistic compound (ethyl-4-(3,4,5-trimethoxycinnamoyl) piperazinyl acetate (Vascordil))

As shown in previous investigations overdoses of isoproterenol produce an abundant myocardial Ca uptake, followed by high energy phosphate breakdown, mitochondrial damage and, eventually, cardiac fibre necrotization. Conversely Ca antagonistic compounds such as verapamil, D 600 or prenylamine which reduce the transmembrane Ca influx into the heart muscle cells, can prevent high energy phosphate deficiency and cardiac lesions. Ethyl-4-(3,4,5-trimethoxycinnamoyl) poperazinyl acetate (Vascoril) is another compound which, according to our tracer studies, interferes with transmembrane Ca uptake into the myocardium. As expected the rat hearts were also protected by Vascoril against isoproterenol-induced metabolic disorders and structural alterations. Equiprotective subcutaneous doses, as studied on the right ventricular myocardium of rats, were 600 mg/kg Vascoril, 250 mg/kg prenylamine, 17 mg/kg verapamil or 10 mg/kg D 600.