title: Early treatment with hepatocyte growth factor improves cardiac function in experimental heart failure induced by myocardial infarction.
abstract: Plasma levels of hepatocyte growth factor (HGF) are increased within hours of cardiac ischemia/reperfusion in rats, and HGF has been shown to be cardioprotective toward acute ischemic injury. Myocardial levels of HGF mRNA and protein are increased for several days after myocardial infarction (MI), however, indicating a possible additional protective effect of HGF toward the progression of MI to heart failure. The purpose of this study was to determine whether HGF administration during the time course of endogenous cardiac HGF induction would lead to long-term improvement in cardiac function in rats with MI. MI was induced by 2-h occlusion of the left coronary artery, followed by reperfusion. HGF was given by intravenous infusion at 0.45 mg/kg/day for 6 days beginning on the day after surgery. Cardiac function and hemodynamic parameters were measured by using indwelling catheters and perivascular flow probes in conscious animals 8 weeks post-MI. Myocardial infarcts were approximately 30% of the left ventricle, and there was no difference in infarct size between the vehicle-treated and HGF-treated groups. Compared with untreated sham-operated rats, vehicle-treated MI animals had significantly lower cardiac index and stroke volume index and higher systemic vascular resistance, indicating heart failure developed. Treatment with HGF caused a significant increase in cardiac index and stroke volume index and a reduction in systemic vascular resistance in rats with MI, restoring these parameters close to those observed in sham-operated control animals. These results provide direct evidence that HGF may be of benefit to cardiovascular function in ischemic cardiomyopathy.
authors.affiliation: Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080, USA. hkj@gene.com
authors.forename: Hongkui
authors.initials: H
authors.lastname: Jin
authors.forename: Renhui
authors.initials: R
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Annie K
authors.initials: AK
authors.lastname: Ogasawara
authors.forename: Ralph
authors.initials: R
authors.lastname: Schwall
authors.forename: David A
authors.initials: DA
authors.lastname: Eberhard
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.forename: David
authors.initials: D
authors.lastname: Kahn
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Paoni
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006334:Heart Function Tests / Q000187:drug effects / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor