Ambrosio G, Villari B, Chiariello M
Division of Cardiology, 2nd School of Medicine, University of Naples, Italy.
J Cardiovasc Pharmacol. 1992;20 Suppl 7:S26-9.
A number of previous studies have reported that administration of calcium antagonists reduces acute ischemic injury in a variety of experimental models. More recently, however, it has been suggested that the beneficial effects of reperfusing the ischemic myocardium might be blunted by the paradoxical occurrence of a specific form of reperfusion-mediated injury. Although the ultimate mechanisms responsible for this phenomenon have not been completely elucidated, it has been suggested that oxygen radical generation, neutrophil activation, and calcium overload, may all contribute to the development of myocardial damage in postischemic hearts. Several experimental studies suggest that, in addition to their well-known effects on ischemic injury, calcium antagonists may variably affect these mechanisms of reperfusion-mediated cell damage. In particular, evidence has been provided that suggests these drugs may inhibit oxygen radical-mediated peroxidation of membrane lipids and may also reduce activation of stimulated neutrophils. Furthermore, calcium-channel blockers might also prevent calcium overload in reperfused hearts, and they might interfere with reperfusion injury indirectly, secondary to a reduction in the severity of ischemia. From the experimental data available it can be speculated that calcium antagonists might contribute to reducing oxygen radical damage following reflow. At the same time, these drugs may allow the extension of the time window of reperfusion therapy, thus further expanding the benefits of thrombolysis.
此前的多项研究报告称，在多种实验模型中，给予钙拮抗剂可减轻急性缺血性损伤。然而，最近有观点认为，缺血心肌再灌注的有益作用可能会因一种特定形式的再灌注介导损伤的反常出现而减弱。尽管导致这种现象的最终机制尚未完全阐明，但有人提出，氧自由基生成、中性粒细胞活化和钙超载，可能都与缺血后心脏的心肌损伤发展有关。多项实验研究表明，钙拮抗剂除了对缺血性损伤有众所周知的作用外，还可能以不同方式影响这些再灌注介导的细胞损伤机制。特别是，已有证据表明这些药物可能抑制氧自由基介导的膜脂质过氧化，还可能减少受刺激中性粒细胞的活化。此外，钙通道阻滞剂可能还能防止再灌注心脏中的钙超载，并且它们可能间接干扰再灌注损伤，这是由于缺血严重程度降低所致。根据现有的实验数据可以推测，钙拮抗剂可能有助于减轻再灌注后的氧自由基损伤。同时，这些药物可能会延长再灌注治疗的时间窗，从而进一步扩大溶栓的益处。
