Differentiation of various cardiovascular drugs by means of specific myocardial and vascular load tests. Experiments at the isolated perfused heart.

A new method is described for examining the contractile function of myocardium and coronary vasculature in the isolated perfused, electrically stimulated guinea-pig and rat heart which is suitable for investigation of cardiovascular drugs. The criterion used for functional efficiency of myocardium and coronary vasculature is--in addition to the usual evaluation of cardiac force and coronary flow in steady-state--the reaction of the heart to perfusion pressure changes: abrupt increase of the perfusion pressure (PP) leads to an increase in cardiac force (= heterometric autoregulation, HA) and simultaneously to triggering of the myogenic autoregulation (MA). Using this PP loading two different functional tests can be performed: 1. By successive PP increases in 10-20 mmHg steps it is possible to determine a) an equivalent of Frank-Starling cardiac function curves, and b) pressure-flow (p-F) curves of the coronary vasculature, e.g. before and after drug application. 2. By a single PP step of e.g. 40 mmHg HA and MA are triggered before and after drug application, calculated as percentages of the initial value and plotted as concentration-response curves. Both methods produce a physiologically based description of cardiac and coronary mechanics. In particular, the behaviour of the coronary vasculature in this procedure represents a more sensitive criterion than total coronary flow in steady-state. Since HA and MA depend partly (HA) or completely (MA) on the slow transmembrane Ca++ inward current the method is particularly suitable for a basic differentiation of Ca++ and Na+ antagonistic drugs.