Free radical-mediated vascular injury in lungs preserved at moderate hypothermia.

BACKGROUND: Early allograft dysfunction remains a frequently encountered problem in clinical lung transplantation. Lung ischemia-reperfusion injury is associated with increased vascular permeability, which may be due in part to oxygen (O2) free radicals. However, it is not clear whether O2 free radicals are produced during ischemia under storage conditions in clinical lung transplantation. METHODS: Using an isolated ex vivo rabbit lung model, we studied the effects of preservation temperature on pulmonary capillary filtration coefficient (Kf) and lipid peroxidation in rabbit lungs inflated with 100% O2 after preservation with or without the O2 free radical scavenger dimethylthiourea. New Zealand white rabbits weighing 2.7 to 3.1 kg were intubated and ventilated with room air or 100% O2 (tidal volume = 25 mL). After heparinization and sternotomy, the pulmonary artery was flushed with low-potassium-dextran-1% glucose solution (200 mL). The heart-lung block was excised, submerged, and stored for 24 hours at 1 degree or 10 degrees C. After 24-hour preservation, the heart-lung block was suspended from a strain-gauge force transducer and ventilated with room air. The pulmonary artery cannula was connected to a reservoir of hetastarch solution. The lungs were flushed briefly with the hetastarch solution, and the reservoir was raised sequentially at 8-minute intervals to achieve 1.0 to 1.5 mm Hg increments in pulmonary artery pressure. Lung weight gain, airway pressure, pulmonary artery pressure, and left atrial pressure were measured continuously. The slope of steady-state lung weight gain was used to determine Kf (g.min-1.cm H2O-1 x 100 g-1 wet weight). RESULTS: Twenty-four-hour lung preservation at both 1 degree and 10 degrees C increased Kf. A similar increase in Kf was observed in lungs stored at 1 degree C while inflated with 100% O2. However, a significant increase in Kf was observed when lungs inflated with 100% O2 were stored at 10 degrees C. This increase in Kf was ameliorated by dimethylthiourea. Thiobarbituric acid-reactive substance levels were increased in lungs stored at 10 degrees C while inflated with 100% O2. This finding was eliminated by dimethylthiourea. CONCLUSIONS: These results indicate that free radical injury occurs during the ischemic phase when lungs are stored at moderate hypothermia while inflated with 100% O2.

Metabolic efficacy of enteral feeding in malnourished cancer and noncancer patients.

Total parenteral nutrition and enteral nutrition are the two available methods for supplementary nutritional support of malnourished patients. Although supplemental alimentation is beneficial in malnourished patients, it is unclear whether malnourished cancer bearing patients are successfully replenished with similar nutritional support. We studied the efficacy of 2 weeks of enteral nutrition on intermediary glucose and protein metabolism in malnourished tumor-bearing (TB) and non-tumor bearing (NTB) patients. Both TB and NTB patients showed equivalent suppression of endogenous glucose production (2.13 +/- 0.23 to 0.35 +/- 0.16 mg/kg/min and 2.35 +/- 0.18 to 0 mg/kg/min), suppression of alanine to glucose conversion (43.8 +/- 10.6% to 0.75 +/- 0.41% and 37.0 +/- 10.7% to 0.11 +/- 0.09%), attainment of positive nitrogen balance (-2.15 +/- 1.18 to 4.26 +/- 1.37 gN/d and -2.25 +/- 0.63 to 4.32 +/- 0.44 gN/d) and suppression of protein catabolism (2.39 +/- 0.13 to 1.10 +/- 0.27 gP/kg/d and 2.23 +/- 0.04 to 1.34 +/- 0.22 gP/kg/d). Following 2 weeks of enteral support, the TB patients differed from the NTB group with significantly elevated lactate levels (80 +/- 8 v 48 +/- 7 mg/L) and depressed plasma glycine levels (264 +/- 12 v 356 +/- 27 mumol/L plasma) and inability to replenish fat stores (triceps skin fold, 7.6 +/- 1.5 to 7.1 +/- 1.5 mm in TB v 5.9 +/- 0.7 to 8.0 +/- 1.2 mm in NTB). A significant reduction in whole body protein synthesis (2.08 +/- 0.19 to 1.84 +/- 0.18 gP/kg/d) in TB patients was obtained while NTB showed no significant change (1.86 +/- 1.3 to 1.91 +/- 0.26 gP/kg/d).(ABSTRACT TRUNCATED AT 250 WORDS)