ACUTE CARDIOVASCULAR EFFECTS OF INSULIN-LIKE-GROWTH-FACTOR-I IN PATIENTS WITH CHRONIC HEART-FAILURE

Insulin-like growth factor I(IGF-I) enhances myofibrillar development in cardiomyocytes of rats in culture and in vivo. In addition, IGF-I h as vasodilatory effects and improves cardiac function in healthy volun teers. This study was conducted to evaluate the acute hemodynamic effe cts of IGF-I in patients with chronic heart failure. Eight patients wi th chronic heart failure were randomized to receive recombinant human IGF-I (60 mu g/kg) or placebo, iv, over 4 h in a cross-over, double bl ind study on 2 consecutive days. Electrocardiogram as well as systemic hemodynamics were continuously monitored over 7 h by flow-guided ther modilution and radial artery catheters. IGF-I was well tolerated by al l patients, and no pathological changes on electrocardiogram were reco rded. Compared with placebo, IGF-I increased the cardiac index by 27 /- 3.7% (+/-SE; P < 0.0005) and the stroke volume index by 21 +/- 5.6% (P < 0.05), and decreased systemic vascular resistance by 28 +/- 4.4% (P < 0.0002), right atrial pressure by 33 +/- 9.0% (P < 0.003), and p ulmonary artery wedge pressure by 25 +/- 6.1% (P < 0.03). Mean systemi c and pulmonary artery pressure as well as heart rate and pulmonary va scular resistance were not significantly influenced by IGF-I treatment . Insulin and C peptide levels were decreased by IGF-I, whereas glucos e and electrolyte levels remained unchanged. Urinary levels of norepin ephrine decreased significantly (P < 0.05) during IGF-I infusion. Thus , acute administration of IGF-I in patients with chronic heart failure is safe and improves cardiac performance by afterload reduction and p ossibly by positive inotropic effects. Further investigations to estab lish whether the observed acute effects of IGF-I are maintained during chronic therapy appear to be warranted.