Modulation of myocardial function and [Ca2+] sensitivity by moderate hypothermia in guinea pig isolated hearts.
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 degrees C, 27 degrees C, and 17 degrees 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 degrees C and 27 degrees C, whereas that of phasic [Ca2+]) 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 LVP(area) 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+.
Stowe
D F
DF
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA. dfstowe@mcw.edu
Fujita
S
S
An
J
J
Paulsen
R A
RA
Varadarajan
S G
SG
Smart
S C
SC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D002138:Calibration; D003326:Coronary Circulation; D003600:Cytosol / Q000378:metabolism; D003971:Diastole; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D007211:Indoles; D009200:Myocardial Contraction; D010477:Perfusion / Q000379:methods; D013696:Temperature; D016277:Ventricular Function, Left
D005456:Fluorescent Dyes; D007211:Indoles; D002122:Calcium Chloride; C048960:indo-1; D002118:Calcium