Effects of glucagon and prostacyclin in acute occlusive and postocclusive canine mesenteric ischemia.
Effects of glucagon and prostacyclin (PGI2) were studied in anesthetized dogs during sequential occlusive and postocclusive mesenteric ischemia induced by 90 min of tourniquet stenosis of the superior mesenteric artery (SMA). After 30 min of SMA stenosis, glucagon (1 microgram/kg/min, n = 7), PGI2 (30 ng/kg/min, n = 7), or saline (1 ml/min, n = 3) was infused intravenously for 30 min, followed by 30 min of continued ischemia. SMA flow and distal SMA pressure ( SMAP ) decreased 76% with SMA stenosis (P less than 0.01). Ileal wall flow measured by radiolabeled microspheres decreased from 45 to 13 ml/min/100 g (P less than 0.01); mesenteric AV O2 difference ( AVDO2 ) increased from 5.1 to 10.1 ml/dl (P less than 0.01); and mesenteric O2 consumption (VO2) decreased by 48% (P less than 0.05). Glucagon infusion caused a further decrease in ileal wall flow, to 10 ml/min/100 g (P less than 0.05), and an increase in AVDO2 to 11 ml/dl (P less than 0.05), despite a 22% increase in cardiac output. PGI2 caused a similar decrease in ileal wall flow and an increase in AVDO2 , although these were not statistically significant. Saline infusion caused no change in measured variables. In the second phase of this study, SMA blood flow was restored by tourniquet release. After animals had stabilized for 30 min, a repeat 30-min drug infusion was studied. In this postocclusive period, persistent gut ischemia was indicated by a reduction in VO2 to 76% of original baseline, associated with a 50% decrease in both CO and SMAQ . Intravenous infusion of glucagon at this time increased SMAQ by 195% (P less than 0.05) and resulted in a return of VO2 to its original baseline level. PGI2 infusion caused a 21% increase in SMAQ and a 16% decrease in AVDO2 (NS), but had no significant effect on VO2. Glucagon was effective in the management of postocclusive mesenteric ischemia but appeared to have a detrimental effect on ileal blood flow in severe occlusive ischemia.
D000208:Acute Disease; D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D011464:Epoprostenol / Q000627:therapeutic use*; D005934:Glucagon / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008638:Mesenteric Arteries; D008641:Mesenteric Vascular Occlusion / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use
D014665:Vasodilator Agents; D005934:Glucagon; D011464:Epoprostenol