Positive inotropism in hypothermia partially depends on an increase in maximal Ca(2+)-activated force

Abstract

We investigated the contribution of maximal Ca(2+)-activated force to the positive inotropism induced by mild hypothermia. Phosphorus-31 nuclear magnetic resonance spectroscopy revealed that neither energy-related phosphorus compounds in myocardium nor intracellular pH was responsible for the change in contractility. Maximal Ca(2+)-activated pressure (MCAP), the intact-heart correlate of maximal Ca(2+)-activated force, was determined in isolated perfused rabbit hearts by measuring isovolumic left ventricular pressure during tetani at extracellular Ca2+ concentrations greater than or equal to 10 mM. Tetani were elicited by rapid pacing after exposure to ryanodine. MCAP increased by 2.17 +/- 0.28% (mean +/- SE, P less than 0.001, n = 19) for each degree of myocardial cooling between 30 and 38 degrees C. Our results indicate that a primary change in myofilament Ca2+ responsiveness underlies the positive inotropism in hypothermia. The increase in maximal Ca(2+)-activated force may explain the observation of positive inotropism without an upward shift in the relation between oxygen consumption and pressure-volume area, as previously reported for cooled whole hearts.

Hypothermia increases the gain of excitation-contraction coupling in guinea pig ventricular myocytes

“…The observation that hypothermia caused a marked increase in contraction amplitude is supported by many other studies (32,34,36). Some investigators have suggested that an increase in myofilament Ca 2ϩ sensitivity is responsible, at least in part, for the increase in contraction amplitude associated with hypothermia (26,30). However, we found that the hypothermia-induced increase in contractions was accompanied by a proportional increase in the size of Ca 2ϩ transients.…”

“…Interestingly, cooling reduces the activity of the SR Ca 2ϩ -ATPase but increases SR Ca 2ϩ load in rabbit, ferret, and cat myocytes (32). Myofilament Ca 2ϩ sensitivity increases in response to cooling in intact rabbit hearts (26,31) but declines with cooling in chemically skinned rabbit ventricular muscle (21,22). Thus temperature has a marked influence on many components of the EC-coupling pathway in the mammalian heart.…”

Temperature-dependent postextrasystolic potentiation and Ca2+ recirculation fraction in canine hearts

“…The slowed Ca 2ϩ handling not only decelerates but also prolongs contraction (Q 10 around 3) (4,22). Cooling enhances the Ca 2ϩ responsiveness so that contractile force increases for a given sarcoplasmic Ca 2ϩ concentration (12). Cooling suppresses myosin ATPase and hence cross-bridge cycling, leading to a slower contraction and relaxation (4)(5)(6)14).…”

Reduced Cytosolic Ca 2+ Loading and Improved Cardiac Function After Cardioplegic Cold Storage of Guinea Pig Isolated Hearts

“…22 Interrelated ionic disturbances underlie hypothermiainduced Ca 2ϩ loading during HS and dysfunction associated with Ca 2ϩ overloading on reperfusion. [25][26][27][28][29][30][31][32][33] Hypothermia most likely prolongs Ca 2ϩ channel influx and alters ion exchangers that trigger enhanced SR Ca 2ϩ -induced Ca 2ϩ release. During hypothermia, depressed Ca and Na pump activities may lead to Na and Ca overload via Na-H exchange and reversed Na-Ca exchange.…”