Terry J. Chong

Ischemia-reperfusion injury in rats affects hydraulic conductivity in two phases that are temporally and mechanistically separate

Ischemia-reperfusion (IR) injury is a major insult to postcapillary venules. We hypothesized that IR increases postcapillary venular hydraulic conductivity and that IR-mediated changes in hydraulic conductivity result from temporally and mechanistically separate processes. A microcannulation technique was used to determine hydraulic conductivity (Lp) in rat mesenteric postcapillary venules serially throughout ischemia (45 min) and reperfusion (5 h) induced by superior mesenteric artery occlusion and release. Mesenteric IR resulted in a biphasic increase in Lp. White blood cell (WBC) adhesion slowly increased with maximal adhesion corresponding to the second peak (P < 0.005). After IR, tissue was harvested for RT-PCR analysis of ICAM-1, E-selectin, and P-selectin mRNA. Intercellular adhesion molecule-1 (ICAM-1) mRNA in the gut showed the most significant upregulation. Quantitative real-time PCR revealed that ICAM-1 mRNA was upregulated 60-fold in the gut. An ICAM-1 antibody was therefore used to determine the effect of WBC adhesion on Lp during IR. ICAM-1 inhibition attenuated Lp during the first peak and completely blocked the second peak (P < 0.005). When rats were fed a tungsten diet to inhibit xanthine oxidase and then underwent IR, Lp was dramatically attenuated during the first peak and mildly decreased the second peak (P < 0.005). Inhibition of xanthine oxidase by oxypurinol decreased Lp during IR by over 60% (P < 0.002). Tempol, a superoxide dismutase mimetic, decreased Lp during IR by over 30% (P < 0.01). We conclude that IR induces a biphasic increase in postcapillary hydraulic conductivity. Reactive oxygen species impact both the first transient peak and the sustained second peak. However, the second peak is also dependent on WBC-endothelial cell adhesion. These serial measurements of postcapillary hydraulic conductivity may lead the way for optimal timing of pharmaceutical therapies in IR injury.

Endothelin 1 and prostacyclin attenuate increases in hydraulic permeability caused by platelet-activating factor in rats.

We have previously documented that endothelin 1 (ET-1) and prostacyclin (PGI2) decrease basal state hydraulic permeability (Lp). The aim of this study was to investigate the ability of ET-1 and PGI2 to modulate transendothelial fluid flux during situations in which Lp was artificially elevated with platelet-activating factor (PAF). We hypothesized that ET-1 and PGI2 administration before PAF exposure would prevent the increase in Lp secondary to PAF. In addition, in a potentially more clinically relevant situation, we also hypothesized that ET-1 and PGI2 administration after PAF exposure would attenuate the increase in Lp secondary to PAF. Microvascular Lp was measured in rat mesenteric postcapillary venules. Exposure to 10 nM PAF increased Lp 4-fold (P < 0.001). If the administration of 80 pM ET-1 or 10 &mgr;M PGI2 was completed before PAF exposure, no PAF-associated increase in Lp was observed (P < 0.001). The administration of ET-1 or PGI2 after PAF exposure attenuated the peak increase in Lp caused by PAF alone by 55% and 57%, respectively (P < 0.001). We conclude that ET-1 and PGI2 administration before PAF exposure prevents PAF-induced elevations in Lp, and in a more clinically relevant situation, ET-1 and PGI2 administered after PAF exposure attenuate the PAF-induced increase in Lp. Endothelin 1 and PGI2 receptors may provide important therapeutic targets for decreasing the microvascular fluid leak-associated morbidity resulting from shock and sepsis.

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

Little is known regarding the effects of I/R on hydraulic permeability (Lp). We sought to compare the individual influences of hypoxia, ischemia, reoxygenation, and reperfusion on Lp. We hypothesized that (1) hypoxia increases Lp; (2) reoxygenation further increases Lp; (3) ischemia results in greater increases in Lp compared with hypoxia; (4) reperfusion causes additional increases in Lp 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 Lp 2-fold from baseline levels (P < 0.001). Reoxygenation did not alter Lp compared with 15 min of hypoxia alone (P > 0.07). Reperfusion after hypoxia increased Lp 6-fold (P < 0.001). Reperfusion after ischemia also increased Lp 6-fold (P < 0.001). Inhibition of XO had no effect on the increase in Lp after both hypoxia and ischemia. However, inhibition of XO attenuated the 6-fold increase in Lp 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 I/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 Lp similarly, and that reperfusion has a profound deleterious effect on Lp. These changes in Lp seem to be XO and white blood cell dependent.

CT diagnosis of postoperative intussusception after penetrating abdominal trauma

A 17-year-old male patient was seen in the emergency room after sustaining a gunshot wound to the right buttock. He complained of abdominal pain and had a tender abdomen on physical examination. The patient underwent an exploratory laparotomy, which revealed 10 small bowel perforating injuries. Four of the injuries were repaired primarily, whereas the remaining six injuries required two separate segmental resections and stapled end-to-end anastomoses. On postoperative day 6, the patient’s postoperative course was complicated by several episodes of emesis. Abdominal x-ray films showed dilated loops of small