Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction.
Therapies aimed at enhancing cardiomyocyte survival following myocardial injury are urgently required. As GHRP6 [GH (growth hormone)-releasing peptide 6] has been shown to stimulate GH secretion and has beneficial cardiovascular effects, the aim of the present study was to determine whether GHRP6 administration reduces myocardial infarct size following acute coronary occlusion in vivo. Female Cuban Creole pigs were anaesthetized, monitored and instrumented to ensure a complete sudden left circumflex artery occlusion for 1 h, followed by a 72 h reperfusion/survival period. Animals were screened clinically before surgery and assigned randomly to receive either GHRP6 (400 microg/kg of body weight) or normal saline. Hearts were processed, and the area at risk and the infarct size were determined. CK-MB (creatine kinase MB) and CRP (C-reactive protein) levels and pathological Q-wave-affected leads were analysed and compared. Evaluation of the myocardial effect of GHRP6 also included quantitative histopathology, local IGF-I (insulin-growth factor-I) expression and oxidative stress markers. GHRP6 treatment did not have any influence on mortality during surgery associated with rhythm and conductance disturbances during ischaemia. Infarct mass and thickness were reduced by 78% and 50% respectively, by GHRP6 compared with saline (P<0.01). More than 50% of the GHRP6-treated pigs did not exhibit pathogological Q waves in any of the ECG leads. Quantitative histopathology and CK-MB and CRP serum levels confirmed the reduction in GHRP6-mediated necrosis (all P<0.05). Levels of oxidative stress markers suggested that GHRP6 prevented myocardial injury via a decrease in reactive oxygen species and by the preservation of antioxidant defence systems (all P<0.05). Myocardial IGF-I transcription was not amplified by GHRP6 treatment compared with the increase induced by the ischaemic episode in relation to expression in intact hearts (P<0.01). In conclusion, GHRP6 exhibits antioxidant effects which may partially contribute to reduce myocardial ischaemic damage.
Berlanga
Jorge
J
Center for Genetic Engineering and Biotechnology, Ave. 31 e/ 158 and 190, P.O. Box 6162, Cubanacán, Playa, Havana, Cuba. jorge.berlanga@cigb.edu.cu
Cibrian
Danay
D
Guevara
Luis
L
Dominguez
Heberto
H
Alba
Jose S
JS
Seralena
Alina
A
Guillén
Gerardo
G
López-Mola
Ernesto
E
López-Saura
Pedro
P
Rodriguez
Alberto
A
Perez
Brumny
B
Garcia
Diana
D
Vispo
Nelson S
NS
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D002097:C-Reactive Protein / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D052279:Creatine Kinase, MB Form / Q000097:blood; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis / Q000517:prevention & control; D009842:Oligopeptides / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D013552:Swine
D000975:Antioxidants; D002316:Cardiotonic Agents; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D007334:Insulin-Like Growth Factor I; D002097:C-Reactive Protein; D052279:Creatine Kinase, MB Form