Efficacy of a growth hormone-releasing peptide mimetic in cardiac ischemia/reperfusion injury.
The cardioprotective efficacy of the pyrazolinone-piperidine dipeptide growth hormone secretagogue (GHS) CP-424,391 was studied in an in vivo rabbit model of ischemia and reperfusion. CP-424,391 was administered at 25 mg/kg p.o. x 7 days. Ischemia was induced by left coronary artery occlusion for 30 min, after which the heart was reperfused for 2 h. At the end of reperfusion, animals were euthanized and the infarct size was determined. The area at risk of infarct was not different between the control (45.8+/-3.7%, n=6) and CP-424,391-treated groups (36.9+/-4.3%, n=11). The infarct size of the control animals was 49.5+/-7.1% and was significantly (P<0.05) lower in the CP-424,391-treated group (infarct size=17.3+/-3.0). There was a trend, albeit not significant, for the left ventricular function to recover to a greater extent in CP-424,391-treated rabbits. Thus, the treatment of rabbits for 7 days with CP-424,391 was cardioprotective against ischemia/reperfusion injury.
MacAndrew
J T
JT
Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.
Ellery
S S
SS
Parry
M A
MA
Pan
L C
LC
Black
S C
SC
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000097:blood; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000150:complications*; D013997:Time Factors; D016896:Treatment Outcome
C433143:CP 424391; D010880:Piperidines; D011720:Pyrazoles; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone