Calcium antagonists and experimental myocardial ischemia reperfusion injury.
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.
Ambrosio
G
G
Division of Cardiology, 2nd School of Medicine, University of Naples, Italy.
Villari
B
B
Chiariello
M
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D005609:Free Radicals; D006801:Humans; D017202:Myocardial Ischemia / Q000628:therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010100:Oxygen / Q000378:metabolism
D002121:Calcium Channel Blockers; D005609:Free Radicals; D010100:Oxygen