CHARACTERIZATION OF CARDIAC SARCOPLASMIC-RETICULUM DYSFUNCTION DURING SHORT-TERM, NORMOTHERMIC, GLOBAL-ISCHEMIA
CHARACTERIZATION OF CARDIAC SARCOPLASMIC-RETICULUM DYSFUNCTION DURING SHORT-TERM, NORMOTHERMIC, GLOBAL-ISCHEMIA
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DOI：
10.1161/01.res.55.2.176
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发表时间：
1984-01-01
影响因子：
20.1
通讯作者：
HESS, ML
中科院分区：
文献类型：
--
作者：
KRAUSE, S;HESS, ML
兴奋-收缩耦合系统的破坏显然在急性缺血过程中心肌功能障碍中起着关键作用。通过表征犬常温全身缺血 7.5、15 和 30 分钟后肌浆网在 pH 7.1 和 6.4 下的功能来检验这一假设。在 pH 7.1 时，全心匀浆肌浆网在缺血 7.5 分钟时显示草酸盐支持的 Ca 摄取降低 49%，在缺血 30 分钟时降低至 85%。在 pH 6.4 时，对照匀浆 Ca 吸收率显着降低，缺血组的情况进一步降低。分离的肌浆网 Ca 摄取反映了整个心脏匀浆的影响。 Ca 刺激的 Mg 依赖性 ATP 酶 (Ca-ATPase) 活性因缺血和酸中毒而显着降低，缺血 15 分钟和 30 分钟时偶联比 (μmol Ca/μmol ATP) 降低。酸中毒 (pH 6.4) 使肌浆网 pCa-ATPase 曲线显着向右移动，从 pCa 6.0-5.5 增加 50% 激活并降低最大速度 (pH 7.1 = 2.06 .+-. 0.14; pH 6.4 = 1.41 .+-. 0.05 .mu.mol Pi/mg/min; P < 0.01）。随着缺血，Ca-ATP酶的最大活化逐渐降低，Ca2+敏感性逐渐转变为更高浓度。在不存在草酸盐的情况下，在 pH 7.1 和 6.4 下缺血 7.5 分钟和 15 分钟后，稳态 Ca 吸收表现出类似的降低，与 Ca 被动渗透系数的显着增加相关。从 30 分钟缺血组中分离出的肌浆网不能支持稳态 Ca 摄取。在短期常温缺血期间，存在显着且进行性的肌浆网功能障碍，其在pH 6.4时放大，其特征是Ca摄取和ATP酶活性降低。 Ca 运输与 ATP 酶活性的解偶联也可能是肌质网膜 Ca 渗透性增加的部分结果。在原发性心肌缺血期间，肌浆网功能的破坏可能是细胞内钙超载的根源。
Breakdown of the excitation-contraction coupling system apparently plays a pivotal role in myocardial dysfunction during the course of acute ischemia. This hypothesis was tested by characterizing the function of the sarcoplasmic reticulum at pH 7.1 and 6.4 after 7.5, 15 and 30 min of canine normothermic global ischemia. At pH 7.1, whole heart homogenate sarcoplasmic reticulum demonstrated a 49% depression of oxalate-supported Ca uptake at 7.5 min of ischemia, which progressed to 85% at 30 min of ischemia. At pH 6.4, control homogenate Ca uptake rates were significantly depressed, accompanied by a further depression in the ischemic groups. Isolated sarcoplasmic reticulum Ca uptake mirrored the effects of the whole heart homogenate. Ca-stimulated Mg-dependent ATPase (Ca-ATPase) activity was significantly depressed by both ischemia and acidosis, with a decrease in the coupling ratio (.mu.mol Ca/.mu.mol ATP) at 15 and 30 minutes of ischemia. Acidosis (pH 6.4) significantly shifted the sarcoplasmic reticulum pCa-ATPase curve to the right, increasing 50% activation from pCa 6.0-5.5 and depressing the maximum velocity (pH 7.1 = 2.06 .+-. 0.14; pH 6.4 = 1.41 .+-. 0.05 .mu.mol Pi/mg/min; P < 0.01). With ischemia there was a progressive decrease in maximal activation of the Ca-ATPase enzyme and a progressive shift in Ca sensitivity to a higher concentration. Steady state Ca uptake, in the absence of oxalate, demonstrated a similar depression after 7.5 and 15 min of ischemia at pH 7.1 and 6.4, associated with a significant increase in the passive permeability coefficient for Ca. Sarcoplasmic reticulum isolated from the 30-min ischemic groups could not support steady state Ca uptake. During short-term normothermic ischemia, there is significant and progressive sarcoplasmic reticulum dysfunction which is magnified at pH 6.4, characterized by a decrease in Ca uptake and ATPase activity. There is also in uncoupling of Ca transport from ATPase activity which may be the result in part of an increase in the Ca permeability of the sarcoplasmic reticulum membrane. During primary myocardial ischemia, this breakdown in sarcoplasmic reticulum function may serve as the source of intracellular Ca overload.