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CLINICAL STUDIES: MYOCARDIAL INFARCTION

Enhanced secretion of cardiac hepatocyte growth factor from an infarct region is associated with less severe ventricular enlargement and improved cardiac function

^a Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Osaka, Japan

Manuscript received February 1, 1999; revised manuscript received January 17, 2000, accepted March 6, 2000.

Reprint requests and correspondence: Dr. Satoshi Yasuda, Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan
syasuda{at}hsp.ncvc.go.jp

OBJECTIVES

We hypothesized that the hepatocyte growth factor (HGF) may play a cardioprotective role in human myocardial infarction (MI).

BACKGROUND

The HGF is a novel, multifunctional growth factor implicated in wound healing, angiogenesis and promotion of cell survival. Recent animal studies have demonstrated the existence of an HGF system in the heart, where it is activated in response to myocardial ischemia and reperfusion.

METHODS

We studied 40 patients with acute myocardial infarction (AMI), who underwent coronary reperfusion therapy upon admission. Approximately four weeks later, left ventricular (LV) catheterization was repeated to determine the LV ejection fraction (EF), end-diastolic volume index (EDVI) and pressure (EDP). The levels of HGF and brain natriuretic peptide (BNP) were measured by collecting blood samples from cardiac veins draining the infarcted region (MI region) and those draining the noninfarcted region (non-MI region). The ratio of the HGF level in the MI region to that in the non-MI region (= MI/non-MI ratio) was calculated in each patient as an index of the MI-related HGF secretion. The MI/non-MI ratio for BNP was also calculated.

RESULTS

The MI/non-MI ratio for HGF correlated inversely with LVEDP (r = –0.644, p < 0.0001) and LVEDVI (r = –0.843, p < 0.0001) and positively with LVEF (r = 0.763, p < 0.0001). These correlations were completely opposite in direction from those for BNP and LVEDP (r = 0.678, p < 0.0001), LVEDVI (r = 0.783, p < 0.0001) and LVEF (r = –0.805, p < 0.0001). These findings indicate that cardiac HGF acts in contrast to BNP, a biochemical marker for the development of LV remodeling.

CONCLUSIONS

Enhanced secretion of cardiac HGF from the MI region is associated with an attenuation of ventricular enlargement and an improvement in cardiac function. The HGF system may modulate the process of ventricular remodeling and thus have important clinical implications.

Abbreviations and Acronyms   ACE-I = angiotensin-converting enzyme inhibitors   AIV = anterior interventricular vein   AMI = acute myocardial infarction   BNP = brain natriuretic peptide   CS = coronary sinus   EDP = end-diastolic pressure   EDVI = end-diastolic volume index   EF = ejection fraction   HGF = hepatocyte growth factor   LV = left ventricular   MI = myocardial infarction   VEGF = vascular endothelial growth factor

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