Abstract

Isolated, spontaneously beating atria, isolated Langendorff-perfused hearts, isometrically contracting strips of atrial and papillary muscle, newly transplanted cardiac homografts and intact dogs have been used to study the chronotropic and inotropic effects of ST 155. Over a wide dose range ST 155 did not alter the frequency of contraction in isolated atria, in isolated perfused intact hearts or in recently transplanted homografts. In intact dogs the slowing of the heart caused by ST 155 was dose-dependent and was greatly reduced after stellate ganglionectomy and bilateral sympathovagotomy. Since previous results indicate that the effect of ST 155 on heart rate did not result from an increase in vagal activity, the present results have been interpreted to mean that the slowing of the heart caused by ST 155 reflects a reduction in sympathetic activity and not a direct effect on the myocardium. In intact animals small doses of ST 155 cause a fall in cardiac output. These same doses of ST 155 failed to have any significant negative inotropic effect either on isolated Langendorff-perfused hearts or on strips of atrial and papillary muscle which were stimulated to contract at a regular rate. The fall in cardiac output caused by ST 155 therefore cannot be explained simply in terms of a negative inotropic response. Depending upon the dose used, ST 155 either reduced, abolished or reversed the fall in arterial blood preniure caused by inflating the lungs.