PROTECTIVE EFFECTS OF INTRAVASCULAR PRESSURE AND NITRIC-OXIDE IN ISCHEMIC LUNG INJURY

Cessation of blood flow during ischemia will decrease both distending and shear forces exerted on endothelium and may worsen ischemic lung i njury by decreasing production of nitric oxide (NO), which influences vascular barrier function. We hypothesized that increased intravascula r pressure (Piv) during ventilated ischemia might maintain NO producti on by increasing endothelial stretch or shear forces, thereby attenuat ing ischemic lung injury. Injury was assessed by measuring the filtrat ion coefficient (K-f) and the osmotic reflection coefficient for album in (sigma(alb)) after 3 h of ventilated (95% O-2-5% CO2; expiratory pr essure 3 mmHg) ischemia. Lungs were flushed with physiological salt so lution, and then Piv was adjusted to achieve High Piv (mean 6.7 +/- 0. 4 mmHg, n = 15) or Low Piv (mean 0.83 +/- 0.4 mmHg, n = 10). N-G-nitro -L-arginine methyl ester (L-NAME; 10(-5) M, n = 10), N-G-nitro-D-argin ine methyl ester (D-NAME; 10(-5) M, n = 11), or LNAME (10(-5) M)+L-arg inine (5 x 10(-4) M, n = 6) was added at the start of ischemia in thre e additional groups of lungs with High Piv. High Piv attenuated ischem ic injury compared with Low Piv (sigma(alb) 0.67 +/- 0.04 vs. 0.35 +/- 0.04, P < 0.05). The protective effect of High Piv was abolished by L -NAME (sigma(alb) 0.37 +/- 0.04, P < 0.05) but not by D-NAME (sigma(al b) 0.63 +/- 0.07). The effects of L-NAME were overcome by an excess of L-arginine (sigma(alb) 0.56 +/- 0.05, P < 0.05). K-f did not differ s ignificantly among groups. These results suggest that Piv modulates is chemia-induced barrier dysfunction in the lung, and these effects may be mediated by NO.