HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Min, J.-Y. Articles by Morgan, J. P. Search for Related Content PubMed PubMed Citation Articles by Min, J.-Y. Articles by Morgan, J. P.

---

ORIGINAL ARTICLE

Genistein Attenuates Postischemic Depressed Myocardial Function by Increasing Myofilament Ca²⁺ Sensitivity in Rat Myocardium¹

The Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215

The present study investigated whether genistein, a broad-spectrum tyrosine kinase inhibitor, could increase the myofilament Ca²⁺ sensitivity and partially reverse postischemic depressed myocardial function. Left ventricular papillary muscles were isolated from adult Wistar rats and loaded with the Ca²⁺ indicator, aequorin. The use of fluorocarbon immersion with hypoxia simulated a model of ischemia. Myofilament responsiveness to Ca²⁺ was evaluated from force-[Ca²⁺]_i relationship recorded during tetani in papillary muscles. Protein levels of troponin I (TnI) were measured in postischemic papillary muscles with the Western blot technique. Isometric contraction was depressed during the period of ischemia and remained low after 60 min of reoxygenation without a corresponding significant change of peak [Ca²⁺]_i in the control group (n = 7). In contrast, the depression of isometric contraction was ameliorated during ischemia in muscle preparations in the presence of genistein (2 µM; n = 8), and postischemic depressed myocardial contractility partially recovered after a 60-min reperfusion. The myofilament Ca²⁺ responsiveness was significantly increased in papillary muscles in the presence of genistein. Protein levels of TnI were reduced in postischemic papillary muscles, whereas genistein partially restored decreased protein levels of TnI. Our results reveal that genistein produces an effective attenuation of postischemic depressed myocardial function and improves myofibrillar Ca²⁺ responsiveness in rat myocardium.

Key Words: genistein • intracellular Ca²⁺ • ischemia • troponin I