Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs

Ventilation during ischemia attenuates ischemia-reperfusion lung injury, bu t the mechanism is unknown. Increasing tissue cyclic nucleotide levels has been shown to attenuate lung ischemia-reperfusion injury. We hypothesized t hat ventilation prevented increased pulmonary vascular permeability duping ischemia by increasing lung cyclic nucleotide concentrations. To test this hypothesis, we measured vascular permeability and cGMP and cAMP concentrati ons in ischemic (75 min) sheep lungs that were ventilated (12 ml/kg tidal v olume) or statically inflated with the same positive end-expiratory pressur e (5 Torr). The reflection coefficient for albumin (sigma(alb)) was 0.54 +/ - 0.07 and 0.74 +/- 0.02 (SE) in nonventilated and ventilated lungs, respec tively (n = 5, P < 0.05). Filtration coefficients and capillary blood gas t ensions were not different. The effect of ventilation was not mediated by c yclic compression of alveolar capillaries, because negative-pressure ventil ation (n = 4) also was protective (sigma(alb) = 0.78 +/- 0.09). The final c GMP concentration was less in nonventilated than in ventilated lungs (0.02 +/- 0.02 and 0.49 +/- 0.18 nmol/g blood-free dry wt, respectively, n = 5, P < 0.05). cAMP concentrations were not different between groups or over tim e. Sodium nitroprusside increased cGMP (1.97 +/- 0.35 nmol/g blood-free dry wt) and sigma(alb) (0.81 +/- 0.09) in nonventilated lungs (n = 5, P < 0.05 ). Isoproterenol increased cAMP in nonventilated lungs (n = 4, P < 0.05) bu t had no effect on sigma(alb). The nitric oxide synthase inhibitor N-G-nitr o-L-arginine methyl ester had no effect on lung cGMP (n = 9) or sigma(alb) (n = 16) in ventilated lungs but did increase pulmonary vascular resistance threefold (P < 0.05) in perfused sheep lungs (n = 3). These results sugges t that ventilation during ischemia prevented an increase in pulmonary vascu lar protein permeability, possibly through maintenance of lung cGMP by a ni tric oxide-independent mechanism.