The effect of hypoxia, reoxygenation, ischemia, and reperfusion on hydraulic permeability in rat mesenteric venules

Little is known regarding the effects of l/R on hydraulic permeability (L _p). We sought to compare the individual influences of hypoxia, ischemia, reoxygenation, and reperfusion on L _p. We hypothesized that (1) hypoxia increases L _p; (2) reoxygenation further increases L _p; (3) ischemia results in greater increases in L _p compared with hypoxia; (4) reperfusion causes additional increases in L _p compared with hypoxia, ischemia, and reoxygenation; and (5) xanthine oxidase (XO) and white blood cell adherence play important roles in hypoxia, ischemia, and reperfusion. Hydraulic permeability was measured by an in vivo microcannulation technique during hypoxia, reoxygenation, ischemia, and reperfusion in rat mesenteric postcapillary venules. Additional rats were fed a Tungsten-enriched diet to inhibit XO activity, and the studies were repeated. White blood cell adherence was also documented. Hypoxia and ischemia both increased L _p 2-fold from baseline levels (P < 0.001). Reoxygenation did not alter L _p compared with 15 min of hypoxia alone (P > 0.07). Reperfusion after hypoxia increased L _p 6-fold (P < 0.001). Reperfusion after ischemia also increased L _p 6-fold (P < 0.001). Inhibition of XO had no effect on the increase in L _p after both hypoxia and ischemia. However, inhibition of XO attenuated the 6-fold increase in L _p observed during reperfusion after both hypoxia and ischemia by approximately 50% (P < 0.001). White blood cell adherence increased during reperfusion but not hypoxia or ischemia. The complexity of l/R injury makes it a difficult clinical scenario to model for research. We have demonstrated in an in vivo model that hypoxia and ischemia increase L _p similarly, and that reperfusion has a profound deleterious effect on L _p. These changes in L _p seem to be XO and white blood cell dependent.