Cardioprotective effect of newly synthesized acyl amino substituted propanolamine derivatives, DPJ 955 and DPJ 890 against isoprenaline induced myocardial necrosis

Two newly synthesized blockers, DPJ 955 and DPJ 890 were studied for cardioprotective action against isoprenaline induced myocardial necrosis and anti lipid peroxidation potential against ferric chloride induced lipid peroxidation. Administration of isoprenaline (300 mg/kg, s.c.) for 3 days at an interval of 24 hours significantly increased LDH, CK, AST and ALT levels as compared to normal animals. Treatment with DPJ 955 (10 mg/kg) and DPJ 890 (3 mg/kg) for 4 days followed by administration of isoprenaline (300mg/kg, s.c.) for a period of 3 days significantly reduced the concentration of marker enzymes in serum. Histological examination of hearts revealed that DPJ 890 (3 mg/kg, i.p.) reduced the severity of infarction produced by isoprenaline. The mortality was found to be very high (50%) with isoprenaline alone treated group. Pretreatment with DPJ 955 (10 mg/kg), DPJ 890 (3 mg/kg) reduced the mortality rate as compared to isoprenaline treated group. The cardioprotective effect produced by DPJ 890 was superior to propranolol. DPJ 955, DPJ 890, propranolol and carvedilol produced concentration dependent reduction in lipid peroxidation induced by ferric chloride. The rank order potency of anti lipid peroxidation activity was found to be carvedilol > DPJ 955 > propranolol = DPJ 890. These results suggest that prevention of myocardial damage produced by isoprenaline in rats pretreated with DPJ 955, DPJ 890 and propranolol may be mainly due to the blocking activity as these compounds lacked lipid peroxidation activity.