Bolus ghrelin administration ameliorates the inflamatory response and oxidative stress during precutaneous cardiopulmonary support in a rat model

Abstract

BackgroundPercutaneous cardiopulmonary support (PCPS) 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 PCPS‐induced inflammatory reactions, oxidative stress and acute organ damage.MethodsAdult male Sprague Dawley rats were subjected to PCPS for 4 hours and randomly received vehicle (n=6) or a bolus of ghrelin (150μg/kg, sc, n=6). Rats were euthanized and heart, lung, kidney and brain samples were harvested for further histopathological analysis. Blood samples were taken before starting, after 2 hrs and 4 hrs of PCPS. We measured the plasma cytokine levels of (tumor necrosis factor (TNF)‐α and interleukin (IL)‐6), catecholamines (norepinephrine, epinephrine and dopamine) and organ damage markers (lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Oxidative stress markers (3‐nitrotyrosine) were measured by western blot.ResultsPCPS‐induced leucocytosis and increased plasma levels of TNF‐α, IL‐6 indicating an inflammatory response. In addition, organ damage markers and catecholamines were also elevated. Ghrelin treatment attenuated the inflammatory response, as evidenced by reduced inflammatory cytokines, organ damage markers and protein levels of 3‐nitrotyrosin. Importantly, ghrelin dramatically suppressed the plasma catecholamines concentration when compared to the PCPS group.ConclusionsThese results suggest that ghrelin inhibits the inflammatory response and oxidative stress. One bolus of ghrelin might provide an effective approach for reducing widespread PCPS‐induced organ injury.Support or Funding InformationJapan society for the promotion of science