Two new peptides to improve post-operative gastric ileus in dog

Peptides can influence gastrointestinal motility, and from data obtained earlier in rats, we hypothesized that MTL-RP/Ghrelin, as well as CGRP receptor antagonist 8-37, could improve gastric post-operative ileus in dog. Dogs submitted to laparotomy were perfused with or saline or CGRP 8-37 or MTL-RP/Ghrelin on days 1-4 post-operatively while gastric emptying was estimated by measuring the postprandial increase in plasma acetaminophen ingested with a meal. As expected, in saline-treated animals the gastric emptying function was impaired post-operatively. The total amount of acetaminophen emptied (AUC over 150 min) on post-operative days 1-4 reached respectively 31 +/- 5%, 65 +/- 8%, 60 +/- 8% and 62 +/- 8% of the normal emptying capacity. CGRP antagonist increased the total emptying of acetaminophen to 52 +/- 5% on day 1,95 +/- 2% on day 2 and 103 +/- 3% (P < 0.05) on day 3. The delayed emptying of acetaminophen seen post-operatively in saline-treated animals could be completely reversed by MTL-RP/Ghrelin (P < 0.01) whether it was given at 100 mug/kg on day 2 (102 +/- 7% of the normal emptying capacity), 4 mug/kg on day 3 (106 +/- 7%) or 20 mug/kg on day 4 (132 +/- 8%). As found earlier in rodents, CGRP receptor antagonist 8-37 as well as MTL-RP/Ghrelin are potent prokinetics to improve post-operative gastric ileus in dog. (C) 2003 Elsevier Science Inc. All rights reserved.