Ashraf M, Suleiman J, Ahmad M
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Ohio.
Circ Res. 1994 Feb;74(2):360-7. doi: 10.1161/01.res.74.2.360.
Repeated Ca2+ depletion and repletion of short duration, termed Ca2+ preconditioning (CPC), is hypothesized to protect the heart from lethal injury after exposing it to the Ca2+ paradox (Ca2+ PD). Hearts were preconditioned with five cycles of Ca2+ depletion (1 minute) and Ca2+ repletion (5 minutes). These hearts were then subjected to Ca2+ PD, ie, one cycle of Ca2+ depletion (10 minutes) and Ca2+ repletion (10 minutes). Hearts subject to the Ca2+ PD underwent rapid necrosis, and myocytes were severely injured. CPC hearts showed a remarkable preservation of cell structure; ie, 65% of the cells were normal in CPC hearts compared with 0% in the Ca2+ PD hearts. LDH release was significantly reduced in CPC hearts compared with Ca2+ PD hearts (2.45 +/- 0.18 and 8.02 +/- 0.7 U.min-1 x g-1, respectively). ATP contents of CPC hearts were less depleted compared with the Ca2+ PD hearts (5.9 +/- 0.8 and 3.0 +/- 0.16 mumol/g dry weight, respectively). Addition of the adenosine A1 receptor agonist R-phenylisopropyl adenosine before and during Ca2+ PD provided protection similar to that in CPC hearts, whereas the nonselective adenosine A1 receptor antagonist, 8-(p-sulfophenyl)-theophylline, blocked the beneficial effects of CPC. CPC-mediated protection was aborted when hearts subjected to CPC were treated with pertussis toxin (the guanine nucleotide or G-protein inhibitor). The present study suggests that Ca2+ preconditioning confers significant protection against the lethal injury of Ca2+ PD in rat hearts. Cardioprotection appears to result from adenosine release during preconditioning and by Gi-protein-modulated mechanisms.
重复进行短时间的钙离子耗竭和再充盈，即钙离子预处理（CPC），据推测可保护心脏免受钙离子反常（Ca2+ PD）所致的致命性损伤。心脏先经过五个周期的钙离子耗竭（1分钟）和钙离子再充盈（5分钟）进行预处理。然后这些心脏接受钙离子PD，即一个周期的钙离子耗竭（10分钟）和钙离子再充盈（10分钟）。经历钙离子PD的心脏迅速发生坏死，心肌细胞严重受损。CPC处理的心脏显示出细胞结构的显著保存；也就是说，CPC处理的心脏中65%的细胞正常，而钙离子PD处理的心脏中这一比例为0%。与钙离子PD处理的心脏相比，CPC处理的心脏中乳酸脱氢酶（LDH）释放显著减少（分别为2.45±0.18和8.02±0.7 U.min-1 x g-1）。与钙离子PD处理的心脏相比，CPC处理的心脏中ATP含量消耗较少（分别为5.9±0.8和3.0±0.16 μmol/g干重）。在钙离子PD之前和期间添加腺苷A1受体激动剂R-苯异丙基腺苷可提供与CPC处理的心脏类似的保护，而非选择性腺苷A1受体拮抗剂8-（对磺基苯基）茶碱可阻断CPC的有益作用。当对接受CPC处理的心脏用百日咳毒素（鸟嘌呤核苷酸或G蛋白抑制剂）处理时，CPC介导的保护作用消失。本研究表明，钙离子预处理可对大鼠心脏免受钙离子PD的致命性损伤提供显著保护。心脏保护作用似乎源于预处理期间腺苷的释放以及Gi蛋白调节的机制。
