title: Sensitization of reperfused myocardium to subsequent coronary flow reductions. An extension of the concept of myocardial stunning.
abstract: The purpose of the present study was to evaluate the response of briefly ischemic and reperfused myocardium to subsequent moderate reductions of coronary arterial flow. In mongrel dogs, a carotid to left anterior descending coronary shunt was constricted to produce moderate coronary flow reductions (50-60% of control) and to thereby reduce regional systolic thickening (measured by echocardiography or sonomicrometry). First, we demonstrated an abnormal response of reperfused myocardium to subsequent flow reductions. We performed two episodes of coronary shunt stenosis, with an intervening 5-minute complete coronary shunt occlusion followed by 30 minutes of reperfusion. In a control group, the same two shunt stenoses were done, but no intervening shunt occlusion was performed. In the control dogs, repeated coronary shunt stenosis that produced equivalent perfusion reductions also produced equivalent declines in regional wall thickening. In contrast, in the intervention group (animals undergoing the intervening occlusion-reperfusion sequence between two shunt stenoses), the second coronary shunt stenosis produced an exaggerated decline in regional systolic thickening, even though the decline in myocardial perfusion was similar to the first stenosis. Second, we sought to demonstrate the mechanism of the exaggerated decline of the reperfused myocardium to subsequent moderate flow reductions. Again, two groups of animals were studied. Each group underwent two episodes of coronary shunt stenosis with an intervening sequence of 5 minutes of complete shunt occlusion and 30 minutes of reperfusion. In addition, one of the groups received an infusion of the oxygen free radical scavengers superoxide dismutase and catalase during the occlusion-reperfusion sequence. In the superoxide dismutase and catalase-treated animals, the decline in regional systolic function during the postreperfusion shunt stenosis was similar to the preocclusion stenosis. Thus, oxygen free radical scavengers blocked the exaggerated contraction decline in response to the postreperfusion flow reduction. We conclude that briefly ischemic and reperfused myocardium displays an exaggerated response to subsequent coronary arterial flow reductions and that this response is a subtle manifestation of postischemic ventricular dyskinesis, or "stunning." The mechanism is probably oxygen free radical toxicity.
authors.affiliation: Cardiovascular Center, University of Iowa, Iowa City.
authors.forename: E S
authors.initials: ES
authors.lastname: Schröder
authors.forename: S J
authors.initials: SJ
authors.lastname: Sirna
authors.forename: R A
authors.initials: RA
authors.lastname: Kieso
authors.forename: R E
authors.initials: RE
authors.lastname: Kerber
mesh_terms: D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003326:Coronary Circulation; D003327:Coronary Disease / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D012146:Rest; D013482:Superoxide Dismutase / Q000494:pharmacology; D013599:Systole
chemical_list: D002374:Catalase; D013482:Superoxide Dismutase