Faculty Collaboration Database

Evidence for a role of iron-catalyzed oxidants in functional and metabolic stunning in the canine heart. Circ Res 1988 Aug;63(2):351-60

Date

08/01/1988

Pubmed ID

3396156

DOI

10.1161/01.res.63.2.351

Scopus ID

2-s2.0-0023694445 (requires institutional sign-in at Scopus site)   109 Citations

Abstract

Brief (15-minute) coronary occlusion and subsequent reperfusion lead to prolonged functional and metabolic abnormalities (stunned myocardium). Previous work suggests that one factor responsible for this phenomenon is oxygen-derived free radicals. The formation of the highly reactive hydroxyl radical requires the presence of metal ions, most importantly iron. In the present study, the effect of the iron-chelator deferoxamine on the recovery of segment shortening (%SS) in the stunned myocardium was compared with a control group in barbital anesthetized dogs. Deferoxamine (500 mg intra-atrially) was administered 15 minutes prior to and throughout 15 minutes of coronary occlusion. %SS, regional myocardial blood flow, hemodynamics, and myocardial high-energy phosphates were measured. Areas at risk, collateral blood flow, and all hemodynamic parameters were similar between control and deferoxamine-treated animals. While deferoxamine did not prevent the loss of systolic wall function that occurred during ischemia, deferoxamine significantly improved the recovery of %SS at all times throughout reperfusion (3-hour %SS of pretreatment: control, 12 +/- 11; deferoxamine, 65 +/- 12), normalized endocardial ATP (percent of nonischemic area: control, 79 +/- 3%, deferoxamine, 93 +/- 6%), attenuated the reperfusion-induced rebound increase in phosphocreatine and prevented the increase in tissue edema at 3 hours after reperfusion. Thus, deferoxamine exhibited a cardioprotective action both metabolically and functionally in the stunned myocardium presumably by decreasing the redox cycling, and hence, the availability of catalytic iron for use in hydroxyl radical formation and for the initiation of lipid peroxidation. These data suggest a possible role for the hydroxyl radical as a mediator of postischemic abnormalities in reversibly injured tissue.

Author List

Farber NE, Vercellotti GM, Jacob HS, Pieper GM, Gross GJ

MESH terms used to index this publication - Major topics in bold

Animals
Cardiomyopathies
Coronary Circulation
Deferoxamine
Dogs
Energy Metabolism
Female
Free Radicals
Heart
Heart Diseases
Hemodynamics
Iron
Male
Myocardial Contraction
Myocardium
Oxygen
Phosphates