Kimura S, Bassett A L, Furukawa T, Furukawa N, Myerburg R J
Department of Medicine (Division of Cardiology), University of Miami School of Medicine 33101.
Am J Physiol. 1990 Oct;259(4 Pt 2):H1044-9. doi: 10.1152/ajpheart.1990.259.4.H1044.
Hypertrophied hearts have enhanced susceptibility to ischemia-induced contractile dysfunction. To explore the mechanisms of this phenomenon, we studied the effect of acidosis on the Ca2+ sensitivity of the contractile proteins and on Ca2+ accumulation by the sarcoplasmic reticulum (SR) in chemically (saponin) skinned cardiac fibers obtained from normal and pressure-overloaded hypertrophied rat left ventricles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta 6-8 wk before study. Age- and weight-matched normal rats served as controls. Pressure overload increased the left ventricular weight-to-body weight ratio by 48%. Reduction in pH shifted the pCa-tension curve to the right similarly in normal and hypertrophied preparations, and there was no difference in pCa-tension relationship at pH 7.0 or 6.5 between the two groups. However, reducing the pH of 1 microM Ca2(+)-loading solution from 7.0 to 6.5 decreased the amount of Ca2+ accumulated in the SR to 66.2 +/- 3.0% in normal fibers and 43.2 +/- 4.0% in hypertrophied fibers (P less than 0.01). We conclude that the enhanced susceptibility of hypertrophied hearts to ischemia-induced diastolic dysfunction may be partly explained by the greater depressing effect of acidosis on Ca2+ accumulation by the SR.
肥厚的心脏对缺血诱导的收缩功能障碍易感性增强。为了探究这一现象的机制，我们研究了酸中毒对正常和压力超负荷肥厚大鼠左心室化学（皂角苷）去皮心肌纤维中收缩蛋白的Ca2+敏感性以及肌浆网（SR）钙蓄积的影响。在研究前6 - 8周通过部分结扎腹主动脉诱导左心室压力超负荷。年龄和体重匹配的正常大鼠作为对照。压力超负荷使左心室重量与体重之比增加了48%。pH降低使正常和肥厚标本中的pCa-张力曲线同样右移，两组在pH 7.0或6.5时的pCa-张力关系无差异。然而，将1 microM Ca2(+)加载溶液的pH从7.0降至6.5时，正常纤维中SR蓄积的Ca2+量降至66.2 +/- 3.0%，肥厚纤维中降至43.2 +/- 4.0%（P < 0.01）。我们得出结论，肥厚心脏对缺血诱导的舒张功能障碍易感性增强可能部分是由于酸中毒对SR钙蓄积的更大抑制作用。
