L. H. Taylor1, P. J. Matheson1,2, C. A. Ghazi1, J. L. Weaver1, C. D. Downard1,2, R. N. Garrison1,2, J. W. Smith1 1University Of Louisville,Department Of Surgery,Louisville, KENTUCKY, USA 2Robley Rex VAMC,Department Of Surgery,Louisville, KENTUCKY, USA
Introduction: ~~Deficient resuscitation in brain dead organ donors causes pulmonary cellular necrosis, leukocyte infiltration, organ edema, organ dysfunction, and organ failure. A new method of resuscitation, Direct Peritoneal Resuscitation (DPR), improves gut and hepatic perfusion, prevents vital organ edema, and down-regulates systemic inflammation, and thus, prevents gut-derived alarmins such as HMGB1 or LPS in the systemic circulation. Previous studies showed that DPR increased organs transplanted per donor (OTPD) due to increased suitability of lungs in human organ donors. We hypothesized that DPR benefits in gut and liver could improve lung function, in particular, decrease sICAM-1, as well as integrin-?L (i.e., CD11a or LFA-1) and integrin-?M (i.e., CD11b or MAC-1).
Methods: ~~Anesthetized male Sprague-Dawley rats (n=44 total) were randomized to groups: 1) ABD with minimal IV RES (Low IVF); 2) ABD + mid-range IV RES (Mid IVF); 3) ABD with aggressive IV RES (High IVF); or 4) ABD + IV RES + DPR (IVF+DPR). ABD was induced by inflation (1 mL/hr) of a supra-dural balloon catheter (4F angioplasty) until the loss of blink and withdrawal reflexes. Ventilation was started (TV=1.6mL, rate=80) with the onset of apnea. After the appearance of the characteristic Cushing response, IV fluid RES was started and mean arterial blood pressure (MAP) and heart rate (HR) were recorded. Serum and lung tissue were collected, snap frozen in liquid nitrogen, and stored until assays. Lung tissue was homogenized in ice cold PBS with protease and phosphatase inhibitors and ELISAs were performed.
Results: ~~DPR decreased soluble ICAM-1 levels compared to Low IVF or Mid IVF (see figure). Integrin-?L levels were decreased compared to Low IVF, Mid IVF, or High IVF alone groups, but integrin-?M levels were not different among groups.
Conclusion: ~~These data suggest that DPR prevents or minimizes alarmin signals from the gut and liver to the lung, and thus, decreases leukocyte extravasation in this slow onset model of acute brain death. This might partially explain the beneficial effects of DPR to maintain pulmonary function and prevent organ injury, which might improve suitability of lungs for organ transplantation in organ donors.
