Modulation of myocardial function and [Ca2+] sensitivity by moderate hypothermia in guinea pig isolated hearts

Cardiac hypothermia alters contractility and intracellular Ca2+ concentrati on ([Ca2+](i)) homeostasis. We examined how left ventricular pressure (LVP) is altered as a function of cytosolic [Ca2+](i) over a range of extracellu lar CaCl2 concentration ([CaCl2](e)) during perfusion of isolated, paced gu inea pig hearts at 37 degrees C, 27 degrees C, and 17 degrees C. Transmural LV phasic [Ca2+] was measured using the Ca2+ indicator indo 1 and calibrat ed (in nM) after correction was made for autofluorescence, temperature, and noncytosolic Ca2+. Noncytosolic [Ca2+](i), cytosolic diastolic and systoli c [Ca2+](i), phasic [Ca2+](i), and systolic Ca2+ released per beat (area Ca 2+) were plotted as a function of 0.3-4.5 mM [CaCl2](e), and indexes of con tractility [LVP, maximal rates of LVP development(+dLVP/dt) and relaxation (-dLVP/dt), and the integral of the LVP curve per beat (LVParea)] were plot ted as a function of [Ca2+](i). Hypothermia increased systolic [Ca2+](i) an d slightly changed systolic LVP but increased diastolic LVP and [Ca2+](i). The relationship of diastolic and noncytosolic [Ca2+] to [CaCl2](e) was shi fted upward at 17 degrees C and 27 degrees C, whereas that of phasic [Ca2+] (i) to [CaCl2](e) was shifted upward at 17 degrees C but not at 27 degrees C. The relationships of phasic [Ca2+](i) to developed LVP, +dLVP/dt, and LV Parea were progressively reduced by hypothermia so that maximal Ca2+-activa ted LVP decreased and hearts were desensitized to Ca2+. Thus mild hypotherm ia modestly increases diastolic and noncytosolic Ca2+ with little effect on systolic Ca2+ or released (area) Ca2+, whereas moderate hypothermia marked ly increases diastolic, noncytosolic, peak systolic, and released Ca2+ and results in reduced maximal Ca2+-activated LVP and myocardial sensitivity to systolic Ca2+.