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

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