EFFECT OF HEMODYNAMIC PRESSURE OVERLOAD OF THE ADULT FERRET RIGHT VENTRICLE ON INOTROPIC RESPONSIVENESS TO EXTERNAL CALCIUM AND REST PERIODS

The inotropic effects of external calcium concentration ([Ca2+]o] and rest periods have been compared in papillary muscles isolated from control (n = 4) and pressure-overloaded right (n = 5) ventricles of adult ferrets. Hypertrophy was induced by pulmonary artery clipping for 30-45 days. Under control conditions (3 mM [Ca2+]o, 0.1 Hz), the isometric twitch force of hypertrophied muscles was decreased by 75%, time to peak was increased by 30% and time to half-relaxation was increased by 50% compared with non-hypertrophied preparations. The sensitivity of contraction to [Ca2+]o was decreased in hypertrophied muscles compared with control ([Ca2+] required for half-maximal contraction: 4.1 mM vs 1.7 mM) and the maximal contraction reached at high [Ca2+]o was smaller in pressure-overloaded muscles compared with control (8.3 +/- 2.0 mN mm-2 vs 19.0 +/- 2.1 mN mm-2 respectively). In both groups, rest periods longer than the steady-state interval were initially accompanied by a potentiation of the first post-rest contraction compared with steady-state. Peak potentiation occurred after a rest of 120 s in hypertrophied muscles and after a rest of 60 s in control. The maximal relative potentiation. i.e. compared with the steady-state twitch, was higher in hypertrophied muscles (+75%) than in control (+20%). After peak potentiation, the amplitude of the first post-rest contraction progressively decreased with increasing periods of rest, although at a slower rate in hypertrophy compared with control. The time constants of post-rest decay were 1203 +/- 99 s and 528 +/- 24 s respectively. These results suggest that intracellular Ca2+ availability is decreased in this model of pressure overload and cannot be compensated by an increase of [Ca2+]o. The slower time course of the twitch and the decreased inotropic responsiveness to [Ca2+]o in hypertrophy suggests that Ca2+ uptake by the sarcoplasmic reticulum (SR) is slower. A model that accounts for the time course of post-rest contractility indicates that, during rest, the rate of recovery of the Ca2+ release process. as well as the rate of Ca2+ loss from the SR, may be slower in hypertrophied preparations. The latter may possibly be due to a lower SR Ca2+ content and a depressed Ca2+ efflux through the sarcolemmal sodium/calcium exchanger.