Ghrelin is a small endogenous peptide principally produced and secreted by the gastric mucosa, with a major role in appetite and metabolism regulation. We hypothesized that anti-inflammatory therapy, as produced by exogenous administration of ghrelin, would decrease the myocardial inflammatory response to global hypothermia I/R, thereby affording myocardial protection. Heterotopic cervical heart transplantation that allows to subject donor hearts to global hypothermic ischemia and blood reperfusion, which very closely stimulates I/R conditions associated with cardiac surgical operations. Ghrelin administration prior to blood reperfusion significantly decreased serum concentrations of cTn-I versus animals subjected I/R alone, with a significantly attenuated VCAM-1 expression in I/R animals pre-treated with ghrelin. The tissue concentrations of pro-inflammatory cytokines (IL-6, IL-1β, and MCP-1) were ameliorated by the administration of ghrelin prior to reperfusion versus the concentrations observed in animals subjected to I/R alone. Significantly fewer monocytes in the tissue sections of I/R+ghrelin animals versus those subjected to I/R alone. Exogenous ghrelin administration prior to reperfusion of an ischemic heart resulted in a significant reduction in myocardial injury as measured by cTn-I. The reduced myocardial injury was accompanied by an attenuated tissue expression of several pro-inflammatory mediators, including VCAM-1, IL-6, IL-1β, and MCP-1.
Key Words: Global ischemia/reperfusion; Ghrelin; cTn-I; Pro-inflammatory cytokines; VCAM-1
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American Journal of BioMedicine Volume 1, Issue 2, pages 38-48
Received September 21, 2013; accepted November 20, 2013; published December 11, 2013
How to cite this article
Austin EW, Yousif NG, Ao L, Cleveland JC, Fullerton DA, Meng X. Ghrelin reduces myocardial injury following global ischemia and reperfusion via suppression of myocardial inflammatory response. American Journal of BioMedicine 2013;1(2):38-48.
4. Method and Materials