Stowe D F, Fujita S, An J, Paulsen R A, Varadarajan S G, Smart S C
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Am J Physiol. 1999 Dec;277(6):H2321-32. doi: 10.1152/ajpheart.1999.277.6.H2321.
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+.
心脏低温会改变心肌收缩力和细胞内钙离子浓度([Ca2+]i)的稳态。我们研究了在37℃、27℃和17℃下对离体的、有起搏的豚鼠心脏进行灌注时,在一系列细胞外氯化钙浓度([CaCl2]e)范围内,左心室压力(LVP)如何随胞质[Ca2+]i的变化而改变。使用钙离子指示剂indo 1测量跨壁左心室的阶段性[Ca2+],并在对自发荧光、温度和非胞质钙离子进行校正后进行校准(以纳摩尔为单位)。将非胞质[Ca2+]i、胞质舒张期和收缩期[Ca2+]i、阶段性[Ca2+]i以及每搏释放的收缩期钙离子(钙离子面积)绘制为0.3 - 4.5 mM [CaCl2]e的函数,并且将收缩性指标[LVP、LVP发展的最大速率(+dLVP/dt)和舒张速率(-dLVP/dt)以及每搏LVP曲线的积分(LVP面积)]绘制为[Ca2+]i的函数。低温增加了收缩期[Ca2+]i,轻微改变了收缩期LVP,但增加了舒张期LVP和[Ca2+]i。在17℃和27℃时,舒张期和非胞质[Ca2+]与[CaCl2]e的关系向上移动,而阶段性[Ca2+]与[CaCl2]e的关系在17℃时向上移动,但在27℃时未移动。低温逐渐降低了阶段性[Ca2+]i与发展的LVP、+dLVP/dt和LVP面积之间的关系,从而使最大钙离子激活的LVP降低,并且心脏对钙离子脱敏。因此,轻度低温适度增加舒张期和非胞质钙离子,对收缩期钙离子或释放的(面积)钙离子影响很小,而中度低温则显著增加舒张期、非胞质、收缩期峰值和释放的钙离子,并导致最大钙离子激活的LVP降低以及心肌对收缩期钙离子的敏感性降低。