Intestinal and hemodynamic impairment following mesenteric ischemia/reperfusion.
BACKGROUND
Clinical intestinal ischemia/reperfusion (I/R) injury results in local and systemic dysfunction. A rat model of transient mesenteric occlusion has been used to study this phenomenon. However, a systematic analysis of the rat model with respect to intestinal permeability and hemodynamics has not been carried out.


METHODS
In anesthetized rats, the superior mesenteric artery was occluded for 60 min, followed by reperfusion for 4 h. Intestinal impairment was evaluated via histological examination and by measuring ex vivo apparent permeability coefficients (Papp) of mannitol (0.18 kDa), inulin (5 kDa), and dextran (70 kDa). Hemodynamic effects of intestinal I/R were determined by monitoring mean arterial pressure (MAP) and heart rate (HR) via a catheter placed in the femoral artery.


RESULTS
The animal model was associated with increased ex vivo Papp for mannitol and inulin. Although I/R injury was accompanied by significant histological disruption, there was no observable alteration in dextran permeability, suggesting that the loss in normal barrier function was limited to low-molecular-weight compounds. Hemodynamic measurements indicated that reperfusion induced a precipitous and sustained fall in MAP. HR values fell sharply following reperfusion but gradually increased and eventually "overshot" to values greater than baseline.


CONCLUSIONS
Our findings demonstrate the selective loss of barrier function of the small bowel following intestinal I/R. Furthermore, these results also illustrate the importance of selecting appropriate permeability markers for the evaluation of intestinal damage. In light of the significant hemodynamic disruption accompanying the animal model, our investigation also points toward the need for developing therapeutic strategies that mitigate the local and systemic effects of intestinal I/R injury.
Khanna
A
A
Department of Pharmaceutics, University at Buffalo, Amherst, New York 14260, USA. ashish.khanna@bms.com
Rossman
J E
JE
Fung
H L
HL
Caty
M G
MG
D000818:Animals; D006439:Hemodynamics; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology / Q000503:physiopathology*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D013152:Splanchnic Circulation