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异丙肾上腺素作用于叙利亚心肌病仓鼠后,心肌性能改善且高能磷酸代谢产物未减少。

Improvement in myocardial performance without a decrease in high-energy phosphate metabolites after isoproterenol in Syrian cardiomyopathic hamsters.

作者信息

Camacho S A, Wikman-Coffelt J, Wu S T, Watters T A, Botvinick E H, Sievers R, James T L, Jasmin G, Parmley W W

机构信息

Department of Medicine (Cardiology), University of California, San Francisco 94143.

出版信息

Circulation. 1988 Mar;77(3):712-9. doi: 10.1161/01.cir.77.3.712.

DOI:10.1161/01.cir.77.3.712
PMID:3342496
Abstract

To determine the effect of isoproterenol on cardiac energetics and function in an animal preparation of cardiomyopathy, we studied Langendorff perfused hearts from Syrian cardiomyopathic hamsters. High-energy phosphate metabolites (phosphocreatine [PCr], ATP, inorganic phosphate [Pi]) and intracellular pH (pHi) were measured by 31P nuclear magnetic resonance spectroscopy and correlated with left ventricular developed pressure, coronary flow, and O2 consumption before and during a 10(-6)M infusion of isoproterenol. Total intracellular calcium was also determined by atomic absorption spectroscopy with the use of potassium ethylenediamine tetra-acetate cobaltate as a marker for extracellular space. In cardiomyopathic hamsters, isoproterenol infusion increased mean developed pressure by 300% (p less than .005 compared with control; n = 5), O2 consumption eightfold (p less than .0005), and PCr by 40% (p less than .05). PCr/Pi ratio, which is analogous to phosphorylation potential, improved 100% (p = .05). In normal hamsters, isoproterenol infusion resulted in an 83% increase in developed pressure (p less than .001) and a 25% increase in O2 consumption (NS). However, mean PCr and PCr/Pi decreased by 30% and 50%, respectively (p less than .05 for both), during isoproterenol infusion. pHi decreased in normal animals (p less than .01), but tended to improve in diseased animals (NS) during isoproterenol infusion. Freeze-clamp measurements of phosphate metabolites correlated well with the nuclear magnetic resonance data. Intracellular calcium increased from 0.0102 +/- 0.002 to 0.144 +/- 0.030 mumol/ml heart water in normal hamsters during isoproterenol infusion. Cardiomyopathic hamsters had a markedly elevated baseline calcium content of 60.82 +/- 5.85 mumol/ml heart water due to the presence of dystrophic calcification.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

为了确定异丙肾上腺素对心肌病动物模型中心脏能量代谢和功能的影响,我们研究了来自叙利亚心肌病仓鼠的Langendorff灌流心脏。通过31P核磁共振波谱法测量高能磷酸代谢物(磷酸肌酸[PCr]、三磷酸腺苷[ATP]、无机磷酸[Pi])和细胞内pH值(pHi),并将其与在输注10(-6)M异丙肾上腺素之前和期间的左心室舒张末压、冠状动脉血流量和耗氧量相关联。还使用乙二胺四乙酸钴酸钾作为细胞外空间标记物,通过原子吸收光谱法测定总细胞内钙。在心肌病仓鼠中,输注异丙肾上腺素使平均舒张末压增加300%(与对照组相比,p<0.005;n=5),耗氧量增加8倍(p<0.0005),PCr增加40%(p<0.05)。与磷酸化电位类似的PCr/Pi比值提高了100%(p=0.05)。在正常仓鼠中,输注异丙肾上腺素导致舒张末压增加83%(p<0.001),耗氧量增加25%(无显著性差异)。然而,在输注异丙肾上腺素期间,平均PCr和PCr/Pi分别下降了30%和50%(两者p<0.05)。在正常动物中pHi下降(p<0.01),但在患病动物中输注异丙肾上腺素期间pHi有改善趋势(无显著性差异)。磷酸盐代谢物的冷冻钳夹测量结果与核磁共振数据相关性良好。在正常仓鼠中,输注异丙肾上腺素期间细胞内钙从0.0102±0.002增加到0.144±0.030μmol/ml心肌水。由于存在营养不良性钙化,心肌病仓鼠的基线钙含量显著升高,为60.82±5.85μmol/ml心肌水。(摘要截断于250字)

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