急性心不全に対する補助循環治療成績を改善する新規グレリン皮下投与法の開発研究

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Cardiopulmonary bypass (CPB) induced inflammation significantly contributes to the development of postoperative complications, including respiratory failure, myocardial, renal and neurological dysfunction and ultimately leads to multiple organ failure. Ghrelin is a small endogenous peptide with wide ranging physiological effects on metabolism and cardiovascular regulation. We investigated the protective effects of ghrelin against the CPB-induced inflammatory reactions, oxidative stress and acute organ damage. Adult male rats were subjected to CPB for 4 hrs and randomly received vehicle (n=6) or a bolus of ghrelin (150 microgram/kg, sc, n=6). Rats were euthanized and heart, lung, liver, kidney and brain samples were harvested for histopathology. Blood samples were taken before CPB, after 2 hrs and 4 hrs of CPB. We measured the plasma levels of cytokines, catecholamines and organ damage markers and glutathione concentrations. CPB-induced leucocytosis with increased plasma levels of TNF-α, IL-6 indicating an inflammatory response. Our study results suggest that even though ghrelin only partially inhibited the large CPB induced increase in catecholamines and organ macrophage infiltration, it reduced oxidative stress and subsequent cell damage (Sukumaran et al., 2018). Administration of ghrelin might provide an effective co-treatment for reducing widespread CPB-induced organ injury.