Cardiopulmonary bypass (CPB) induced systemic
inflammation significantly contributes to the development of postoperative complications, including
respiratory failure, myocardial, renal and neurological dysfunction and ultimately can lead to failure of multiple organs.
Ghrelin is a small endogenous
peptide with wide ranging physiological effects on metabolism and cardiovascular regulation. Herein, we investigated the protective effects of
ghrelin against CPB-induced inflammatory reactions, oxidative stress and acute organ damage. Adult male Sprague Dawley rats randomly received vehicle (n = 5) or a bolus of
ghrelin (150 μg/kg, sc, n = 5) and were subjected to CPB for 4 h (protocol 1). In separate rats,
ghrelin pre-treatment (protocol 2) was compared to two doses of
ghrelin (protocol 3) before and after CPB for 2 h followed by recovery for 2 h. Blood samples were taken prior to CPB, and following CPB at 2 h and 4 h. Organ nitrosative stress (3-nitrotyrosine) was measured by Western blotting. CPB induced
leukocytosis with increased plasma levels of
tumor necrosis factor-α and
interleukin-6 indicating a potent inflammatory response.
Ghrelin treatment significantly reduced plasma organ damage markers (
lactate dehydrogenase,
aspartate aminotransferase,
alanine aminotransferase) and
protein levels of
3-nitrotyrosine, particularly in the brain, lung and liver, but only partly suppressed inflammatory cell invasion and did not reduce proinflammatory
cytokine production.
Ghrelin partially attenuated the CPB-induced elevation of
epinephrine and to a lesser extent
norepinephrine when compared to the CPB saline group, while
dopamine levels were completely suppressed.
Ghrelin treatment sustained plasma levels of
reduced glutathione and decreased
glutathione disulphide when compared to CPB saline rats. These 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. Pre-treatment with
ghrelin might provide an effective adjunct
therapy for preventing widespread CPB induced organ injury.