Pharmacologic treatment of occlusive mesenteric ischemia in rats.
This study assessed the contribution of angiotensin II, oxygen-free radicals, and vasopressin to the mortality of acute mesenteric ischemia in rats. Rats received saline replacement (16 ml/kg/hr) for 3 hr during and after 85 min of superior mesenteric artery (SMA) occlusion. Only 21% of rats that received saline alone (n = 14, control) survived 48 hr, significantly less than the 100% survival of sham-operated rats (no SMA occlusion, n = 5, P less than 0.01). Neither teprotide (an angiotensin converting-enzyme inhibitor), allopurinol (to reduce oxygen-free radical formation), nor a specific vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethyleneproprionic acid), 2-(O-methyl) tyrosine arginine-vasopressin] improved 48-hr survival, which was 17% in each group (n = 6, each). Survival improved significantly to 86% (n = 7, P less than 0.001) when intravenous glucagon (1.6 micrograms/kg/min) was given for 2 hr after SMA reperfusion. Survival after dopamine infusion (12 micrograms/kg/min iv) was 67% at 48 hr, a nearly significant improvement (n = 9, P less than 0.06). These results suggest that angiotensin II, oxygen-free radicals, and vasopressin do not contribute significantly to the high mortality observed after acute intestinal ischemia in this rat model, but that glucagon, and to a lesser extent, dopamine, are potentially therapeutic.
Boorstein
J M
JM
Section of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire 03756.
Dacey
L J
LJ
Cronenwett
J L
JL
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000401:mortality; D004298:Dopamine / Q000627:therapeutic use*; D005934:Glucagon / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries; D051381:Rats; D011919:Rats, Inbred Strains; D013722:Teprotide / Q000627:therapeutic use
D000493:Allopurinol; D005934:Glucagon; D013722:Teprotide; D004298:Dopamine