Diabetic hyperglycemia: a facilitating factor in systemic capillary leak.
BACKGROUND
Diabetes is a known risk factor for increased morbidity and mortality following trauma and serious injuries. The current studies were designed to investigate the effects of diabetes on both local and systemic injury following mesenteric ischemia-reperfusion in rats.


METHODS
Rats received streptozotocin (65 mg/kg ip) to induce diabetes or vehicle and were studied 8 weeks later. In another group of normal rats, hyperglycemia (blood sugar >200 mg/dl) was induced by intravenous infusion of a glucose solution. Rats were subjected to 10 or 30 min of superior mesenteric artery occlusion followed by 1 or 4 h of reperfusion or a sham operation. Intestinal mucosal injury, neutrophil infiltration, and changes in capillary leak were determined. Flow cytometry was used to assess neutrophil "priming state."


RESULTS
Euglycemic and acutely hyperglycemic rats exhibited no mucosal injury after 10 min of ischemia, but did show significant damage after 30 min of ischemia followed by 1 h of reperfusion. Euglycemic rats had significant capillary leak following 30 min of ischemia and 4 h of reperfusion that was associated with an increase in the neutrophil priming state. In acute hyperglycemia, leak occurred after 30 min of ischemia and only 1 h of reperfusion. Diabetic rats exhibited significant mucosal injury after 10 min of ischemia and 1 h of reperfusion that was associated with significant capillary leak and increased neutrophil priming state.


CONCLUSIONS
Altered neutrophil activity contributes to the increased susceptibility to local intestinal and systemic injury in diabetes.
Lawson
Stephen
S
Department of Surgery, Walter Reed Army Medical Center, Washington, DC 20307, USA.
Ward
David T
DT
Conner
Chance
C
Gallagher
Christopher
C
Tsokos
George
G
Shea-Donohue
Terez
T
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D006943:Hyperglycemia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000473:pathology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D013152:Splanchnic Circulation