RT Journal Article
SR Electronic
T1 A Growth Hormone Secretagogue Prevents Ischemic-Induced Mortality Independently of the Growth Hormone Pathway in Dogs with Chronic Dilated Cardiomyopathy
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 815
OP 820
DO 10.1124/jpet.103.050997
VO 306
IS 2
A1 You-Tang Shen
A1 Joseph J. Lynch
A1 Richard J. Hargreaves
A1 Robert J. Gould
YR 2003
UL http://jpet.aspetjournals.org/content/306/2/815.abstract
AB To determine the functional role of growth hormone (GH) secretagogue in myocardium with ischemia, left ventricular (LV) pressure gauge, wall thickness crystals, coronary occluder, pacers, and catheters were implanted in 26 dogs. Beginning 1 week after ventricular pacing (240 beats/min) was initiated, dogs were treated (s.c.) with GH releasing peptide-6 (GHRP-6, n = 8, 0.2 mg/kg/day), GH (n = 7, 0.06 mg/kg/day), or vehicle (n = 11). Two weeks of pacing was associated with similar decreases in LV pressure, rate of change of LV pressure, systolic wall thickening (WT), and an increase in left atrial pressure in all groups. Coronary artery occlusion (CAO) resulted in a similar loss of WT in ischemic regions, which did not recover during reperfusion period in all groups. WT in nonischemic regions, however, was enhanced in the GHRP-6 group compared with the GH and vehicle groups, e.g., increase of WT after 1 h of reperfusion was greater (p <0.05) in the GHRP-6 (+53 ± 8%) than in the GH (+14 ± 12%) or (+14 ± 6%). There were no differences in myocardial blood flow, hemodynamics, or arrhythmic beats among all groups during CAO and reperfusion periods. Strikingly, no dogs in the GHRP-6 group died during CAO, whereas the survival rates for GH and vehicle groups were 57 and 55%, respectively. Our data demonstrate, for the first time, that chronic therapy with a GH secretagogue prevents sudden death in dogs with dilated cardiomyopathy subjected to acute ischemia. This seems to be related to an enhanced nonischemic compensatory mechanism mediated by the GH secretagogue receptors rather than via the GH/insulin growth factor-1 pathway. The American Society for Pharmacology and Experimental Therapeutics