Lack of beneficial effects of growth hormone treatment in conscious dogs during development of heart failure

The effects of chronic treatment with growth hormone !porcine GH, 0.56 mg.kg(-1).day(-1) sc) were examined in dogs with heart failure induced by rapid ventricular pacing (240 beats/min) for 4 wk. Fourteen conscious dogs were studied 2-3 wk after surgical instrumentation with catheters in the descending aorta and left atrium, a pressure gauge in the left ventricle (LV), a flow probe around the ascending aorta, pacing leads on the ventricular free wall and left atrium, and ultrasonic crystals on the opposing anterior and posterior endomyocardium of the LV. GH treatment for 4 wk significantly increased both body weight and plasma insulin-like growth factor 1 (TGF-1) compared with vehicle treated dogs (P < 0.01, +2.0 +/- 0.5 vs. +0.3 +/- 1.1kg; 1,043 +/- 218 vs. 241 +/- 64 ng/ml, respectively). However, the changes in resting LV systolic (i.e., both isovolumic and ejection phases) and diastolic function (i.e., isovolumic relaxation time constant tau and the systemic vascular resistance were similar for the GH-and vehicle-treated groups during the development of heart failure. LV contractile reserve, assessed with step infusion of isoproter enol or dobutamine challenge, was markedly attenuated after heart failure, but there were no differences between the GH-and vehicle-treated groups. During the progression of heart failure, the increases in plasma atrial natriuretic peptide correlated (P < 0.01) directly with left atrial pressure and inversely with LV circumferential fiber shortening. However, GH- treatment did not. substantially modify these relationships. Tn addition, renal function and myocardial ultrastructure at the advanced stage of heart failure also showed similar changes for the GH-and PBS vehicle-treated groups. We conclude that in conscious dogs during the development of congestive heart failure produced by rapid ventricular pacing, GH at a dose that increases body weight and plasma IGF-1 levels does not affect LV performance or systemic vascular dynamics.