Selective iNOS inhibition attenuates acetylcholine- and bradykinin-induced vasoconstriction in lipopolysaccharide-exposed rat lungs.

Background: Nonselective nitric oxide synthase (NOS) inhibition has detrimental effects in sepsis because of inhibition of the physiologically important endothelial NOS (eNOS). The authors hypothesized that selective inducible NOS (iNOS) inhibition would maintain eNOS vasodilation but prevent acetylcholine- and bradykinin-mediated vasoconstriction caused by lipopolysaccharide-induced endothelial dysfunction.

Methods: Rats were administered intraperitoneal lipopolysaccharide (15 mg/kg) with and without the selective iNOS inhibitors L-N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg), dexamethasone (1 mg/kg), or the nonselective NOS inhibitor Nomega-nitro-L-arginine methylester (L-NAME, 5 mg/kg).

Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency.

To test the hypotheses that perfluorochemical (PFC) liquid rescue after natural surfactant (SF) treatment would improve pulmonary function and histology and that this profile would be influenced by PFC dose or ventilator strategy, anesthetized preterm lambs (n = 31) with respiratory distress were studied using nonpreoxygenated perflubron. All animals received SF at 1 h and were randomized at 2 h as follows and studied to 4 h postnatal age: 1) conventional mechanical gas ventilation (n = 8), 2) 30 ml/kg perflubron with gas ventilation [partial liquid ventilation (PLV)] at 60 breaths/min (n = 8), 3) 10 ml/kg perflubron with PLV at 60 breaths/min (n = 7), and 4) 10 ml/kg perflubron with PLV at 30 breaths/min (n = 8). All animals tolerated instillation without additional cardiopulmonary instability.

Physiologic, biochemical, and histologic correlates associated with tidal liquid ventilation.

Tidal liquid ventilation (TLV) with perfluorochemical fluid (PFC) has been successfully used experimentally for up to 4 h. However, no studies of prolonged TLV have been reported. We hypothesized that full-term newborn lambs can safely and effectively be liquid-ventilated for up to 24 h.

Comparison of natural surfactant and brief liquid ventilation rescue treatment in very immature lambs. Clinical and physiological correlates.

We studied the effect of rescue therapy with modified porcine surfactant (Curosurf) or brief perfluorocarbon liquid ventilation on pulmonary gas exchange, mechanics and structure in very immature lambs. Both rescue strategies produced an improvement in arterial oxygenation and were able to support CO2 elimination. Histology showed unevenly inflated lungs in all but tidal-liquid-ventilated lambs.

Utility of a perfluorochemical liquid for pulmonary diagnostic imaging.

The use of neat perfluorochemical liquid (PFC) as an alternative respiratory medium has gained increasing attention for assessment and treatment of the immature or injured lung. In vitro and in vivo plain film and computed tomographic (CT) studies were performed on small and large animals to evaluate the use of perfluorooctylbromide (perflubron) as a bronchographic contrast agent and to quantitate the distribution and elimination of this fluid from the lung following total liquid ventilation or during gas breathing after tracheal instillation of small quantities of this liquid. The results demonstrate the utility of a highly radiopaque PFC liquid in combination with diagnostic imaging techniques to visualize small airways anatomy, identify regional and gravity dependent differences in distribution/elimination of the fluid, ventilation, and track PFC liquid following therapeutic application.