Effect of intravenous glucagon on intestinal viability after segmental mesenteric ischemia.
OBJECTIVE
We have previously shown that intravenous glucagon significantly improves rat survival if given after release of superior mesenteric artery occlusion. The purpose of this study was to isolate the effects of glucagon on the intestine by creating a rat model of segmental mesenteric ischemia that avoids the systemic shock associated with total superior mesenteric artery occlusion and reperfusion.


METHODS
In 18 anesthetized Sprague-Dawley rats, an 8 cm segment of midileum was made totally ischemic for 110 minutes by occluding its vascular arcades and the bowel ends with microvascular clamps. Control animals (n = 8) received normal saline solution (10 ml/kg/hr intravenously) during ischemia and for 2 hours after declamping. Ten animals also received glucagon (1 microgram/kg/min intravenously) during 2 hours after declamping. After a 24-hour recovery, the ischemic bowel segment, plus nonischemic proximal ileum, was examined histologically by computerized planimetry to measure wall thickness (muscularis, mucosa, and transmural), percent epithelial coverage, and villar surface ratio (villar surface length/bowel circumference). All observations were blinded. Comparisons were made by Student's t test.


RESULTS
Compared with nonischemic ileum, the ischemic segment in control animals showed severe mucosal injury with a reduction in mucosal thickness to 25%, epithelial coverage to 23%, and villar surface ratio to 33% of that seen in nonischemic ileum (p < 0.01). Substantial preservation of ileal mucosal viability was seen in glucagon-treated animals. Mucosal thickness and epithelial coverage were twice as well preserved in glucagon-treated rats compared with control rats (p < 0.05), and villar surface ratio was also increased significantly (p < 0.05). The muscularis was not significantly injured in this model.


CONCLUSIONS
By use of quantitative histologic measurements, we found that intravenous glucagon significantly improved ileal mucosal viability when given early during reperfusion after segmental ischemia. The mechanism of this effect and its potential clinical application merit further study.
Gangadharan
S P
SP
Section of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Wagner
R J
RJ
Cronenwett
J L
JL
D000818:Animals; D005934:Glucagon / Q000008:administration & dosage*; D007082:Ileum / Q000098:blood supply / Q000473:pathology*; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000098:blood supply / Q000473:pathology; D007511:Ischemia / Q000473:pathology*; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014022:Tissue Survival / Q000187:drug effects
D005934:Glucagon