Analysis of the cardiotoxic effect of isoproterenol in chick embryo.

Intraamnial administration of isoproterenol (IPRO) to chick embryo induces different types of pathological changes of the myocardial and liver tissue: their character depends upon the developmental period during which the drug was administered. Analysis of the embryotoxic effect of IPRO has revealed that the time-course of in vivo uptake of [3H]IPRO by the developing heart appears to present the same pattern as the embryonic liver tissue; both peak values (10 min and 6 h after injection) were, however, significantly higher in the liver as compared with the myocardium. IPRO is rapidly metabolized to 3-o-methyl-IPRO; the proportion of this fraction in both organs represents approximately 40% of total radioactivity as early as 5 min after administration. Intraamnial administration of IPRO significantly increases the cAMP content in the myocardium; dibutyryl cAMP-induced myocardial lesions occurred, however, only occasionally and in comparison with IPRO they were significantly less pronounced. The cardiotoxic effect of IPRO can be significantly reduced by beta-blockade; calcium antagonist, verapamil, was found to have no protective effect. Our results suggest that the following factors may participate in the IPRO-induced embryotoxicity: (1) IPRO, (2) its toxic metabolites, (3) cAMP.