Cholecystokinin octapeptide inhibits the inflammatory response and improves neurological outcome in a porcine model of cardiopulmonary resuscitation.

Abstract

Previous studies have demonstrated that cholecystokinin octapeptide (CCK8) induces hypothermia and inhibits the systemic inflammatory response in septic shock in rat and murine models. The present study aimed to ascertain whether CCK8 induced hypothermia and improved the neurological outcomes in a porcine model of cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced and left untreated for 10 min in 12 male Bama miniature pigs. Defibrillation was attempted after 5 min of CPR. At 5 min following resuscitation, the pigs were randomized and equally assigned into the CCK8 or the control group. CCK8 was continuously infused for 1 h at a dose of 44.4 µg/kg/h and a rate of 20 ml/h in the CCK8 group. Body temperature, hemodynamic measurements and post-resuscitation myocardial function were monitored in the first 4 h following CPR. Neuron specific enzyme (NSE), S100B protein, tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured at baseline and 4, 12 and 24 h following resuscitation. The neurological deficient score (NDS) was recorded and cerebral samples were collected for terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling assay and integrated optical density (IOD) analysis at 24 h following CPR. The results revealed that hypothermia was not induced by CCK8; however, post-resuscitation NSE, S100B, IL-6 and TNF-α were significantly decreased, and NDS and IOD were significantly improved in the CCK8 group compared with the control group (P<0.05). The present study revealed that in a porcine model of CPR, CCK8 does not induce hypothermia, but inhibits the inflammatory response and significantly improves neurological outcomes.