Amrinone and energy output of rabbit papillary muscles

We studied the effects of amrinone (300 micrograms X ml-1) on the mechanical and energetic outputs of nonfailing rabbit papillary muscles at 27 degrees C using a myothermic technique. Amrinone was found to markedly stimulate the basal (i.e., nonbeating) metabolism. In mechanical experiments, at a 0.5-Hz stimulus rate, amrinone increased the rate of stress development and peak active stress but shortened the time to peak stress and the contractile duration. The linear relationship between total (active + passive) stress and heat production was altered by amrinone such that there was a 68% increase in the activation heat component (intercept) and an 11% increase in the energy cost per unit stress development (slope). In afterloaded isotonic experiments amrinone increased the capacity of papillary muscles to accomplish external work (W) by approximately 50% on average; however, this effect was associated with an increased total energy usage per beat (ET) such that the overall mechanical efficiency (W/ET X 100%) was not significantly altered at any load level. We conclude that amrinone greatly increases calcium delivery to the myofilaments and slightly increases the cost of stress development. These effects are examined in the light of amrinone's postulated mode of action, and possible reasons for the clinical observation of a decrease in myocardial oxygen consumption after amrinone administration are considered.