The role of leukocytes in mediating mucosal injury of intestinal ischemia/reperfusion.

The source of oxygen-free radicals in putative intestinal reperfusion injury is unknown. To define the role of the circulating leukocyte in this pathophysiology, we report a rat model of ex vivo intestinal perfusion that permits alteration of the intravascular perfusate. The validity of the model is proven by the degree of intestinal injury produced by reperfusion following occlusive ischemia. Severe damage was noted in the animals reperfused with normal blood; however, reperfusion with a white blood cell-free perfluorochemical significantly ameliorated this damage. The addition of leukocytes to the perfluorochemical negated the previously seen protection of the leukocyte-free perfusate. This study strongly suggests that the intravascular leukocyte is an important mediator of intestinal ischemia/reperfusion injury.

Intestinal ischemia: treatment by peritoneal lavage with oxygenated perfluorochemical.

Though the delivery of elemental oxygen to tissues ravaged by anaerobic infection may be useful, little data exists that suggests that such therapy may benefit ischemic tissue. We report the development of a model to test the question that peritoneal lavage with an oxygen containing solution may favorably influence occlusive intestinal ischemia. Adult Sprague-Dawley rats with Nembutal (sodium pentobarbital) anesthesia underwent midline laparotomy; a microvascular clamp was applied to the superior mesenteric artery (SMA); and an inflow and outflow lavage catheter was placed. Treatment groups included control rats undergoing SMA occlusion only without lavage, rats lavaged with albumin during SMA occlusion (medium control), and rats lavaged during SMA occlusion with oxygenated perfluorochemical FC-47 emulsified in albumin (O2-FC-47). The increase in serum L-lactate following occlusion was used as an index of intestinal injury whether the perfusate was maintained at room temperature (28 degrees C) or body temperature (37 degrees C). Beginning with time O, which corresponded to the time of unclamping, subsequent samples were collected at 15, 30, and 60 minutes after a 30-minute SMA occlusion. Sequential lactates in 13 control rats were 4.18, 4.10, 3.88, and 4.52 mmol/L. Albumin lavaged animals had values at 28 degrees C of 2.23, 1.35, 1.8, and 2.44 mmol/L and values at 37 degrees C of 2.22, 1.40, 2.07, and 3.21 mmol/L, respectively. With O2-FC-47 lavage the respective lactates were 1.89, 1.09, 1.32, and 1.44 mmol/L at 28 degrees C and 2.14, 2.19, 2.50, and 2.1 mmol/L at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuroblastoma and nutritional support: influence on the host-tumor relationship.

The nutritional sequelae of neuroblastoma are secondary to tumor burden, tumor-host influenced metabolism, and antitumor operative, pharmacologic, and radiation therapy. Nutritional support and its influence on the outcome of clinical cancer is confusing; but in a defined murine system, we hypothesized that whether or not nutritional repletion favors the host-tumor relationship is dependent on a nutritional augmentation of host antitumor immunity. C1300 murine neuroblastoma (NB) elicits a host antitumor immune response as determined by in vivo and in vitro testing; but the TBJ clone of the same tumor is nonimmunogenic. After receiving two weeks of either regular 24% protein or protein restricted 2.5% protein chow, normal and malnourished mice received either C1300-NB or TBJ-NB and were serially followed to animal death. The median survival time (MST) of TBJ recipients was shorter in this more aggressive tumor, but the MST of 27.5 days was equal for normal and malnourished mice. Contrasting with these data were an MST of 38 days for malnourished C1300 NB recipients and an MST of 64.5 days for normally nourished C1300 NB recipients, values that are significantly different (P less than 0.02). These data suggest that nutritional support influencing host antitumor immunity may be of benefit only in that circumstance where the tumor elicits an antitumor immune response.