Inotropic effect of ketamine on rat cardiac papillary muscle

Abstract

The direct effect of ketamine on cardiac muscle was studied using rat left ventricular papillary muscle. At an extracellular calcium concentration [( Ca++]0) of 2.5 mM, rat myocardial contractility is nearly maximum, and a positive inotropic effect was demonstrated by an increase in maximum shortening velocity (Vmax) with ketamine at 10(-5) M but not 10(-4) M. At a [Ca++]0 of 0.5 mM, ketamine 10(-5) and 10(-4) M had a positive inotropic effect as shown by an increase in Vmax (135% +/- 22% and 147% +/- 33%, respectively) and in isometric active force (AF/s) (120% +/- 10% and 152% +/- 44%, respectively). The positive inotropic effect of ketamine was not related to catecholamine uptake inhibition and/or alpha/beta receptor stimulation because it persisted after phentolamine and propranolol and because ketamine had no relaxing effect. Ketamine 10(-5) and 10(-4) M impaired isotonic relaxation, contraction-relaxation coupling under low loading conditions, and the load sensitivity of relaxation, which suggests impairment of the calcium sequestering systems, especially the sarcoplasmic reticulum (SR). Ketamine modified postrest recovery: the first beat (B1) after a 1-min rest period was decreased by ketamine 10(-4) M but not ketamine 10(-5) M. Moreover, the beat-to-beat postrest recovery has been demonstrated to be exponential, and tau, the time constant of the decay was increased by ketamine 10(-4) M (5.4 +/- 0.3 vs. 3.9 +/- 0.2 beats) but not by ketamine 10(-5) M (3.4 +/- 0.4 vs. 3.7 +/- 0.2 beats). These effects on postrest recovery suggest that ketamine impairs SR function. The authors suggest that ketamine had a dual action on rat myocardium: a positive inotropic effect without any relaxing effect, probably related to an increase in calcium influx, and an impairment of SR function. Nevertheless, impairment of SR is only significant at high concentration (10(-4) M) and might overcome the positive inotropic effect only at supratherapeutic concentration.