Isoproterenol enhances myofilament Ca(2+) sensitivity during hypothermia in isolated guinea pig beating hearts.

Abstract

Isoproterenol is often required to treat acute left ventricular dysfunction during separation from cardiopulmonary bypass for cardiac surgery. We hypothesized that heart rate and intracellular Ca(2+) concentration ([Ca(2+)]i) homeostasis may be important factors when isoproterenol improves the cardiac function during hypothermia. Accordingly, we investigated the effect of isoproterenol on the cardiac functional variables, [Ca(2+)]i, and myofilament Ca(2+) sensitivity under spontaneous beating during hypothermia. Intact guinea pig hearts were perfused with a modified Krebs-Ringer solution (baseline) and Krebs-Ringer solution containing isoproterenol (1 nM) at 37 degrees C, 32 degrees C, and 27 degrees C while all cardiac variables and [Ca(2+)]i were recorded. Isoproterenol increased developed left ventricular pressure (LVP), maximum rate of increase in LVP, and coronary inflow at 27 degrees C, and it also increased heart rate and maximum rate of decrease in LVP at each temperature (P < 0.05). Isoproterenol produced a leftward shift of the curve of developed LVP as a function of available [Ca(2+)]i at 32 degrees C and 27 degrees C (P < 0.05), without changing available [Ca(2+)]i. Isoproterenol improves the cardiac function, especially systolic ventricular function, by enhancement of myofilament Ca(2+) sensitivity under spontaneous beating during hypothermia in intact guinea pig hearts. Enhancement of myofilament Ca(2+) sensitivity is involved in the improvement of cardiac function by isoproterenol under spontaneous beating during hypothermia.