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

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Abstract
Cardiac hypothermia alters contractility and intracellular Ca2+concentration ([Ca2+]i) homeostasis. We examined how left ventricular pressure (LVP) is altered as a function of cytosolic [Ca2+]iover a range of extracellular CaCl2concentration ([CaCl2]e) during perfusion of isolated, paced guinea pig hearts at 37°C, 27°C, and 17°C. Transmural LV phasic [Ca2+] was measured using the Ca2+indicator indo 1 and calibrated (in nM) after correction was made for autofluorescence, temperature, and noncytosolic Ca2+. Noncytosolic [Ca2+]i, cytosolic diastolic and systolic [Ca2+]i, phasic [Ca2+]i, and systolic Ca2+released per beat (area Ca2+) were plotted as a function of 0.3–4.5 mM [CaCl2]e, and indexes of contractility [LVP, maximal rates of LVP development (+dLVP/d t) and relaxation (−dLVP/d t), and the integral of the LVP curve per beat (LVParea)] were plotted as a function of [Ca2+]i. Hypothermia increased systolic [Ca2+]iand slightly changed systolic LVP but increased diastolic LVP and [Ca2+]i. The relationship of diastolic and noncytosolic [Ca2+] to [CaCl2]ewas shifted upward at 17°C and 27°C, whereas that of phasic [Ca2+]ito [CaCl2]ewas shifted upward at 17°C but not at 27°C. The relationships of phasic [Ca2+]ito developed LVP, +dLVP/d t, and LVPareawere progressively reduced by hypothermia so that maximal Ca2+-activated LVP decreased and hearts were desensitized to Ca2+. Thus mild hypothermia modestly increases diastolic and noncytosolic Ca2+with little effect on systolic Ca2+or released (area) Ca2+, whereas moderate hypothermia markedly increases diastolic, noncytosolic, peak systolic, and released Ca2+and results in reduced maximal Ca2+-activated LVP and myocardial sensitivity to systolic Ca2+.