The effect of cyclosporine in gut ischemic injury: a computerized morphometric and enzymatic analysis.
OBJECTIVE
Gut ischemia has been implicated in the pathogenesis of necrotizing enterocolitis. Cyclosporine A (CSA), a potent immunosuppressant, attenuates immune/inflammatory cellular reactions. CSA also might be useful for inhibiting cellular immune responses involved in tissue ischemia/reperfusion injury. The authors hypothesized that CSA would attenuate inflammatory cellular changes associated with gut ischemic injury and that these effects could be quantified by computerized morphometry.


METHODS
Twenty Sprague-Dawley rats underwent 60 minutes of gut ischemia by vascular occlusion of the superior mesenteric vessels. After 1 hour of reperfusion, the ischemic small bowel was harvested for histopathological examination and computerized morphometry, as well as xanthine oxidase (XO, U/mg protein) and maltase (MALT, mmol/L substrate degraded/min/mg protein) assays. CSA (5 mg/kg/d subcutaneously) was given to experimental animals (CSA, n = 10) for 5 days before ischemia, and vehicle was given to controls (CON, n = 10). The computer morphometric parameters studied were: surface index (SI, mucosal surface length per linear unit of intestine), average villous thickness (AVT), and average villous height (AVH).


RESULTS
Results are provided in Table 1.


CONCLUSIONS
The results of this study show that CSA may play a role in attenuating ischemia/reperfusion injury in the gut. Enzymatic analysis showed a beneficial role in the preservation of mucosal cell function after gut ischemia/reperfusion injury, as demonstrated by an elevated maltose level. Computerized morphometry demonstrated significant differences in all parameters in the experimental group, showing that CSA does confer gut mucosal protection during ischemia.
Puglisi
R N
RN
Division of Pediatric Surgery, Cooper Hospital, Camden, NJ, USA.
Strande
L
L
Santos
M
M
Doolin
E J
EJ
Hewitt
C W
CW
Whalen
T V
TV
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000503:physiopathology; D007090:Image Interpretation, Computer-Assisted; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D014969:Xanthine Oxidase / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014969:Xanthine Oxidase; D000520:alpha-Glucosidases