Isolated working rat heart adaptation after abrupt changes in extracellular Ca2+ concentration.

In isolated working rat hearts, a rapid up- or downward change in perfusate Ca2+ concentration by the factors 2, 4, or 8 in the range between 1.25 and 10 mM resulted within 1 min in the well-known change of left ventricular contractility as evaluated by maximum left ventricular pressure change velocity (LVdP/dt max) and left ventricular end-diastolic pressure (LVEDP). However, within about 10 min thereafter, contractility showed an adaptive behaviour opposite to the initial change, with t 1/2 values for LVdP/dt max between 1.45 and 2.8 min. The adaptive LVdP/dt max reactions amounted to 10-35% of the initial change. With an abrupt fall from 10 mM to 1.25 mM Ca2+ (not tolerated by all hearts), LVdP/dt max decreased initially by 4.260 mmHg/s (LVEDP +9.7 mmHg) and increased thereafter by 524 mmHg/s (LVEDP -6.8 mmHg). The adaptive inotropic behaviour cannot be related to changes in heart rate or coronary flow and is not affected by thapsigargin (1 microM) or the amiloride derivative benzamil (10 microM). This suggests that sarcoplasmatic Ca2+-ATPase and sarcolemmal Na+-Ca2+ exchange do not play a decisive role in this adaptive behaviour. In conclusion, an intrinsic regulatory mechanism of the myocardium attenuates the inotropic effect of acute changes in Ca2+ concentration. This phenomenon might protect the heart against Ca2+ overload after an acute rise in catecholamine concentration.