Cardioprotective effect of ghrelin in cardiopulmonary bypass involves a reduction in inflammatory response.
BACKGROUND
Ghrelin has been reported to protect the cardiovascular system; however, the cardioprotective effect of ghrelin against cardiopulmonary bypass (CPB) induced myocardial injury are unclear. In this study, the protective effect of ghrelin on CPB induced myocardial injury and the underlying mechanisms were investigated.


RESULTS
Adult male rats were subjected to CPB and randomly to receive vehicle (n = 8), ghrelin (n = 8), ghrelin plus [D-Lys3]-GHRP-6, a GHSR-1a inhibitor (n = 8), or ghrelin plus wortmannin, a phosphoinositide 3'-kinase (PI3K) inhibitor (n = 8). In vitro study was performed on cultured cardiomyocytes subjected to simulated cardiopulmonary bypass (SCPB). Ghrelin attenuated the inﬂammatory response, as evidenced by reduced induction of TNF-α, IL-6 and myocardial myeloperoxidase activity and concurrent reduction in apoptosis, oxidative stress, and levels of myocardial injury markers following CPB. Moreover, ghrelin significantly increased cardiac function after CPB. In cultured cardiomyocytes subjected to simulated CPB, ghrelin increased cell viability and decreased the percentage of apoptotic myocytes. Inhibition of ghrelin downstream signaling blocked the cardioprotective effects both in vivo and vitro.


CONCLUSIONS
Ghrelin could provide an effective approach to the attenuation of CPB induced myocardial injury. The cardioprotective effects elicited by ghrelin may contribute to the inhibition of inflammatory response through the Akt-activated pathway.
Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Yukun
Y
Cao
Jun
J
Tang
Ting
T
Yang
Heng
H
Ma
Dinghua
D
Yi
Chunhu
C
Gu
Shiqiang
S
Yu
D000818:Animals; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D054439:Ghrelin / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D054439:Ghrelin; D019869:Phosphatidylinositol 3-Kinases