Schaffer S W, Roy R S, McMcord J M
Eur Heart J. 1983 Dec;4 Suppl H:81-7. doi: 10.1093/eurheartj/4.suppl_h.81.
Several phenothiazines were found to provide significant protection against loss of tissue creatine phosphokinase caused by the calcium paradox. The concentration of phenothiazine required for protection lies within the range generally attributable to their calmodulin inhibition properties. Moreover, the order of effectiveness in protecting the calcium overloaded myocardium is consistent with their potency as calmodulin inhibitors (trifluoperazine greater than chloropromazine greater than promethazine). The most potent calmodulin inhibitor was shown to dramatically reduce the amount of creatine phosphokinase loss from calcium depleted hearts exposed to buffer containing calcium under anoxic conditions. On the other hand, the drug failed to alter the oxygen-dependent component of the calcium paradox. It also failed to prevent the proteolytic conversion of xanthine dehydrogenase to xanthine oxidase. The possibility that calmodulin activation promotes cellular damage by activating either directly or indirectly specific membrane cellular phospholipases is discussed. Also discussed is the hypothesis that oxygen-dependent damage may be linked to the generation of superoxide anion by the enzyme xanthine oxidase.
发现几种吩噻嗪能显著保护组织免受钙反常引起的肌酸磷酸激酶损失。提供保护所需的吩噻嗪浓度在通常归因于其钙调蛋白抑制特性的范围内。此外，保护钙超载心肌的有效性顺序与其作为钙调蛋白抑制剂的效力一致（三氟拉嗪大于氯丙嗪大于异丙嗪）。最有效的钙调蛋白抑制剂显示出能显著减少在缺氧条件下暴露于含钙缓冲液的钙耗竭心脏中肌酸磷酸激酶的损失量。另一方面，该药物未能改变钙反常的氧依赖性成分。它也未能阻止黄嘌呤脱氢酶向黄嘌呤氧化酶的蛋白水解转化。讨论了钙调蛋白激活通过直接或间接激活特定的膜细胞磷脂酶促进细胞损伤的可能性。还讨论了氧依赖性损伤可能与黄嘌呤氧化酶产生超氧阴离子有关的假说。
