Effect of mesenteric ischemia and reperfusion or hemorrhagic shock on intestinal mucosal permeability and ATP content in rats.
In a reductionist in vitro system, intestinal epithelial permeability appears to be dependent on cellular ATP content. In order to extend these prior observations, we used rat models of mesenteric ischemia/reperfusion (I/R) and pressure-controlled hemorrhagic shock to test the hypothesis that intestinal barrier function is directly proportional to tissue ATP content. I/R was induced by clamping the mesenteric vessels for 60 min followed by 60 min of reperfusion. Normal, ischemic, and reperfused ileal segments were prepared from each rat (n = 12). Hemorrhagic shock was induced by bleeding rats (n = 9) to a mean arterial pressure of 30 mmHg and maintaining this pressure for 4 h by infusing Ringer's lactate solution as necessary. Ileal segments were harvested before induction of hemorrhage and at 1 h intervals thereafter. Everted gut sacs were prepared to measure the mucosal-to-serosal passage of fluorescein-conjugated dextran (FD4; M.W. = 4 kDa). Tissue ATP levels were determined using a luciferase assay. FD4 clearance rates were plotted as a function of tissue ATP content. Linear regression analyses showed a strong inverse relationship between intestinal permeability and tissue ATP level in rats subjected to I/R (r2 = 0.78; P < 0.001) or hemorrhage (r2 = 0.82; P < 0.001). These data support the idea that ATP content is a determinant of intestinal epithelial barrier function in vivo.
Wattanasirichaigoon
S
S
Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Surgery, Boston, MA 02215, USA.
Menconi
M J
MJ
Delude
R L
RL
Fink
M P
MP
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002463:Cell Membrane Permeability; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D012771:Shock, Hemorrhagic / Q000378:metabolism*
D000255:Adenosine Triphosphate