Screening of inotropic drugs on isolated rat and guinea pig hearts

A technique is described for screening the effects of inotropic drugs on isolated rat or guinea pig hearts perfused at constant coronary pressure and at a frequency of 6 Hz. Their performances, including function curves, were recorded using an intraventricular balloon. Both preparations became either sensitive from initially having been insensitive, or more sensitive from having been slightly sensitive at the outset, to inotropic interventions, provided the external calcium concentration was reduced to 0.25 mM for the rat and 0.50 mM for the guinea pig. The inotropic effect of drugs such as isoproterenol, forskolin, and theophylline was only slightly altered by lowering [Ca]o. Amrinone, sulmazole, and beta agonists such as xamoterol, cicloprolol, pindolol, or RU 42173 almost never caused an inotropic effect at the serum calcium concentration of 2.50 mM, whereas they did provoke a positive response at low [Ca]o. Other compounds such as ouabain, salbutamol, and pimobendan were toxic at high [Ca]o, although at reduced [Ca]o their positive effect on contractility was quite evident.