Molecular mechanisms in "stunned" myocardium.
In a recent overview on stunning, Bolli listed the three pillars on which theories on stunning rest: its causation by oxygen radicals, the amplification of damage by Ca2+ overload, and the resulting excitation contraction uncoupling. Our own experiments with SOD and catalase do not convince us that stunning is caused by free radicals, because we and others were unable to show improvement. An important pathway of radical generation, i.e., xanthine oxidase, does not exist in the hearts of several families of mammals, but stunning can of course be produced in these species. We agree with Bolli that stunning represents a disturbance of electromechanical coupling, but we acknowledge the controversy that exists with regard to the subcellular seat of the defect. Our results would support hypotheses that pinpoint the defect to the sarcoplasmic reticulum. However, the possibility of multiple defects should also be considered: Our finding of altered Ca2+ ATPase expression and Kusuoka's finding of altered myofibrillar Ca2+ sensitivity are not necessarily mutually exclusive but may be complementary, or may represent different stages of ischemic damage. Our finding of decreased myosin expression may help to explain the long persistence of the contractile defect. From the available evidence, the hypothetial possibility evolves that stunning is not just an injury, but rather the unmasking of a regulatory mechanism to protect the heart against premature or further damage. The observation that coronary occlusion causes both stunning and preconditioning by a parallel, and not by a sequential, mechanism and that a multitude of genes alter their expression in order to protect the myocyte argue for a regulatory change.
Schaper
W
W
Max-Planck-Institute, Department of Experimental Cardiology, Bad Nauheim, FRG.
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D003327:Coronary Disease / Q000209:etiology* / Q000378:metabolism; D015536:Down-Regulation; D005609:Free Radicals / Q000378:metabolism; D015870:Gene Expression; D010101:Oxygen Consumption
D005609:Free Radicals; D002118:Calcium