(Circulation. 2000;101:2874.)
© 2000 American Heart Association, Inc.
Editorial |
Myocardial Cell Protection
A Challenging Time for Action and a Challenging Time for Clinical Research
From the Department of Medicine, Montreal Heart Institute and University of Montreal, Quebec, Canada.
Key Words: Editorials • myocardial infarction • cariporide • reperfusion
Left ventricular dysfunction, most often the consequence of coronary artery disease and acute myocardial infarction (MI) in our society, is the primary determinant of prognosis in coronary artery disease and the major cause of cardiac disability. The principles for cell protection have long been established: on one hand, metabolic preservation; on the other, restoration of flow. Reperfusion therapy led most progress in the past 2 decades, leaving in the shadow other means of cell protection. The success of reperfusion therapy is measured in clinical trials in terms of lives saved. The more subtle benefits of direct cell intervention are difficult to assess in humans, given the large interindividual variability in infarct size, the small to moderate benefit expected from interventions, and the lack of a sensitive method to quantify exactly the area of necrosis versus the area at risk. Meanwhile, mechanisms involved in the progression of ischemia to necrosis have become better defined, opening new therapeutic perspectives. Some of the new or renewed concepts are ischemic insult, reperfusion damage, no-reflow, stunning, hibernation, and ischemic preconditioning.
Cell necrosis involves multiple mechanisms, including metabolic changes, ionic shifts, complement activation and generation of cytotoxic substances, inflammation, tissue edema, apoptosis, and matrix degradation. The respective roles of these mechanisms differ at various stages of ischemia and reperfusion and are cumulative. Unless interrupted, the process leads to irreversible damage. Early interventions will profit more and late interventions less; multiple interventions acting at different levels will probably be more successful.
The time constraints of 15 minutes
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