Postischemic stunning: the two-phase model for the role of calcium as pathogen.
The hypothesis proposed is that postischemic stunning occurs in two phases. The first and causative phase occurs very rapidly after the onset of reperfusion and is associated with cytosolic calcium overload with transiently normal mechanical function. If agents enhancing calcium influx are given at this early stage, they worsen subsequent stunning. Conversely, agents inhibiting calcium influx such as nisoldipine may lessen the extent of stunning. In the second phase (established stunning), there is hypocontractility and calcium antagonists given to isolated hearts can further impair mechanical function. Logically, agents enhancing calcium influx improve mechanical function. Unexpectedly, calcium antagonists given to large animal hearts in situ can improve established stunning, through mechanisms that are not well understood. The harmful effects of free radicals are not discounted but can be explained by early membrane damage with a consequent rise in cytosolic calcium during the early first phase of reperfusion.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D017202:Myocardial Ischemia / Q000150:complications; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology
D002121:Calcium Channel Blockers; D005609:Free Radicals; D002118:Calcium