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Am J Physiol Heart Circ Physiol 277: H2321-H2332, 1999;
0363-6135/99 $5.00
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Vol. 277, Issue 6, H2321-H2332, December 1999

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

David F. Stowe, Satoshi Fujita, Jianzhong An, Richard A. Paulsen, Srinivasan G. Varadarajan, and Steven C. Smart

Anesthesiology Research Laboratory, Departments of Anesthesiology, Medicine (Cardiovascular Diseases), Physiology, and Pharmacology, and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee 53226; and Research Service, Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295

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+]i over a range of extracellular CaCl2 concentration ([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/dt) and relaxation (-dLVP/dt), and the integral of the LVP curve per beat (LVParea)] were plotted as a function of [Ca2+]i. Hypothermia increased systolic [Ca2+]i and slightly changed systolic LVP but increased diastolic LVP and [Ca2+]i. The relationship of diastolic and noncytosolic [Ca2+] to [CaCl2]e was shifted upward at 17°C and 27°C, whereas that of phasic [Ca2+]i to [CaCl2]e was shifted upward at 17°C but not at 27°C. The relationships of phasic [Ca2+]i to developed LVP, +dLVP/dt, and LVParea were 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+.

cardiac contractility; cardioplegia; cytosolic calcium; mitochondrial calcium; calcium sensitivity


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