Effects of growth hormone following chronic angiotensin-converting enzyme inhibition in chronic heart failure: Their relation to infarct size

Growth hormone (GH) has been attracted as a possible adjunctive treatment f or severe heart failure. However, its treatment effects have been still con troversial. To assess severity of basal cardiac disease states in which GH might be effective, we analyzed the relation of treatment effects of GH fol lowing chronic angiotensin-converting enzyme (ACE) inhibition on cardiac fu nction and structures to infarct size in rat model of chronic heart failure after myocardial infarction. One day after coronary occlusion, rats were r andomized to either an ACE inhibitor, temocapril (T) (80 mg/L in drinking w ater) or placebo for 12 weeks. The animals received concomitant recombinant human (rh) GH (2 mg/kg/day, SC) (T + GH) or vehicle during the final 2 wee ks. Compared with the T group, the T + GH group with large MI had smaller i ncrements of left ventricular (LV) dP/dt(m)ax (0 vs 17%) and cardiac output (9 vs 49%), less improvement of LV relaxation (tau) (-3 vs 29%) and system ic vascular resistance (8 vs 29%), and a greater increase in LV end-diastol ic pressure (123 vs -5%) than did the T + GH group with moderate MI. In the T + GH group when compared with the T group, these functional alterations were associated with a 12% reduction in the LV capillary density and a 21% increase in hydroxyproline contents in rats with large MI, whereas a 12% in crease in the density and similar collagen contents were found in rats with moderate MI. Thus, prominent beneficial cardiovascular effects of the addi tive short-term, high-dose GH to chronic high-dose ACE inhibition were obta ined in rats with moderate MI, whereas little additional benefit or even de trimental effects of GH were found in rats with large MI. The present study may provide an insight into the therapeutic strategy of GH given late afte r MI in the presence of chronic ACE inhibition in congestive heart failure.