Sildenafil is a selective pulmonary vasodilator in an ovine model of acute pulmonary hypertension. Sildenafil induces pulmonary vasodilation via a NO-dependent mechanism. In contrast to zaprinast, sildenafil did not prolong the pulmonary vasodilator action of inhaled NO.

Nebulized sildenafil is a selective pulmonary vasodilator that can potentiate the pulmonary vasodilating effects of inhaled NO.

In this model of acute respiratory distress syndrome, optimal Paw during HFO is equal to P(CL) + 6, which correlates with the PMC.

Breathing NO produced a rapid, protective effect to severe hypoxic stress in SAD mice. There appears to be a required loading period between NO breathing and its beneficial effect during hypoxic stress, possibly because of the total amount of NO delivered to SAD hemoglobin, blood cell components, and endothelium. NO breathing may be beneficial as a therapeutic intervention in SCD.

Nitric oxide (NO) is produced in the nasal cavities, airways, and lungs and is exhaled by normal animals and humans. Although increased exhaled NO concentrations in airway inflammation have been associated with increased airway expression of nitric oxide synthase 2 (NOS 2), it is uncertain which NOS isoform is responsible for baseline levels of exhaled NO. We therefore studied wild-type mice and mice with a congenital deficiency of NOS 1, NOS 2, or NOS 3. By studying a closed chamber in which the exhaled gas of a group of mice was collected, gaseous NO production rates were measured. Wild-type mice exhaled 362 +/- 35 x 10(-15) mol g(-1) min(-1) NO (mean +/- SE, n = 16 groups of five mice), NOS 1-deficient mice exhaled 592 +/- 74 x 10(-15) mol g(-1) min(-1) NO (n = 15 groups, p < 0.05 versus wild-type and NOS 2-deficient mice), NOS 2-deficient mice 330 +/- 74 x 10(-15) mol g(-1) min(-1) NO (n = 14 groups) and NOS 3-deficient mice 766 +/- 101 x 10(-15) mol g(-1) min(-1) NO (n = 16 groups, p < 0.001 versus wild-type and NOS 2-deficient mice). Pharmacological NOS inhibition with L-NAME decreased (p < 0.05) the exhaled NO production rate of wild-type and NOS 3-deficient but not of NOS 2-deficient mice. L-Arginine administration increased exhaled NO production rate in all but NOS 2-deficient mice. Absence of NOS 1 or 3 is associated with increased murine exhaled NO production rates. Since NOS 2-deficient mice were the only genotype to lack substrate- and inhibitor-regulated changes of NO exhalation, we suggest that NOS 2 is an important isoform contributing to exhaled NO exhalation in healthy mice.

Partial liquid ventilation (PLV) improves oxygenation in several models of lung injury. However, PLV has only been compared with conventional gas ventilation (GV) with low PEEP. Both PLV and GV can markedly improve oxygenation when PEEP is set above the lower corner pressure (Plc) on the inspiratory pressure-volume (P-V) curve of the total respiratory system. We questioned if the use of PEEP set above the Plc during PLV and GV would result in similar gas exchange. Lung injury was induced in 12 sheep by saline lavage before randomization to PLV (n = 6) or GV (n = 6). Animals in the PLV group were filled with perflubron (22 ml/kg) until a meniscus at the teeth was observed. Both groups were then ventilated with pressure control (FI(O(2)), 1.0; rate, 20/min; I:E, 1:1) and PEEP (1 cm H(2)O above the Plc on the inspiratory P-V curve). Peak inspiratory pressure (PIP) was limited to 35 cm H(2)O. Animals were ventilated for 5 h and then killed for histologic examinations. All 12 animals survived the 5-h ventilation period. After increasing PEEP above Plc, Pa(O(2)) increased significantly (p < 0.01) in both the GV and the PLV groups, but it did not differ significantly between groups (p = 0.86) at any time during the experiment. Pa(CO(2)) and VD/VT in GV increased markedly throughout the experiment after increasing PEEP (p < 0.001), but there was no significant change in Pa(CO(2)) in PLV (p = 0.13). Mean arterial blood pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, and central venous pressure, increased and SVR decreased in GV (p < 0.05). The extent and the severity of lung injury in the dependent regions was greater in the GV group (p < 0.05). Both PLV and GV improved oxygenation, but PLV resulted in better ventilation than GV while preserving lung structure when PEEP was set 1 cm H(2)O above the Plc and PIP limited to 35 cm H(2)O.

Although tracheal gas insufflation (TGI) has proved to be a useful adjunct to mechanical ventilation, end-inspiratory as well as end-expiratory pressures may increase. We investigated the ability of continuous-flow TGI to maintain eucapnia while reducing airway pressure (Paw) and tidal volume (VT). Seven sheep (36 +/- 2 kg) were ventilated using the Dräger Evita 4 in the pressure control plus mode where flow is released via the expiratory valve to maintain constant inspiratory pressure. To avoid TGI-generated positive end-expiratory pressure (PEEP), a prototype reverse flow TGI tube was used. Two TGI flows (5 and 10 L/min) were investigated pre- and postsaline lavage-induced lung injury. Inspiratory pressures and VT were significantly reduced as TGI flow increased. At 10 L/min TGI flow the carinal pressures (Pcar) and VT were reduced pre- and postinjury by 15% and 20%, and by 28% and 34%, respectively. Tidal volume to dead space ratio (VD/VT) decreased preinjury from 0.49 +/- 0.1 to 0.18 +/- 0.2 and postinjury from 0.62 +/- 0.1 to 0.33 +/- 0.1 at a TGI flow of 10 L/min. The combination of the reverse flow TGI tube and a ventilator with an inspiratory pressure relief mechanism kept set end-inspiratory and end-expiratory pressures constant. This TGI system effectively reduced set Paw and VT while maintaining eucapnia.

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