Inhaled nitric oxide during partial liquid ventilation shifts pulmonary blood flow to the non-dependent lung regions

Background Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect. Methods Nitric oxide concentration was measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and without INO. Results Left lower lobar hypoxia increased exhaled NO from the LLL (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts per billion (ppb) (P < 0.001), and Ca2+-dependent NOS activity was higher in hypoxic than in hyperoxic lung tissue (197 [86] vs. 162 [96] pmol x g(-1) x min(-1), P < 0.05). INO to HL decreased the Ca2+-dependent NOS activity in hypoxic tissue to 49 [56] pmol x g(-1) x min(-1) (P < 0.01), and NO(E)LLL to 2.0 [0.8] ppb (P < 0.05). When open-chest pigs with LLL hypoxia received blood from closed-chest pigs with INO, NO(E)LLL decreased from 2.0 (0.6) to 1.5 (0.4) ppb (P < 0.001), and the Ca2+-dependent NOS activity in hypoxic tissue decreased from 152 (55) to 98 (34) pmol x g(-1) x min(-1) (P = 0.07). Pulmonary vascular resistance increased by 32 (21)% (P < 0.05), but more so in hypoxic (P < 0.01) than in hyperoxic (P < 0.05) lung regions, resulting in a further redistribution (P < 0.05) of pulmonary blood flow away from hypoxic to hyperoxic lung regions. Conclusions Inhaled nitric oxide downregulates endogenous NO production in other, predominantly hypoxic, lung regions. This distant effect is blood-mediated and causes vasoconstriction in lung regions that do not receive INO.

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Changes in Pulmonary Blood Flow during Gaseous and Partial Liquid Ventilation in Experimental Acute Lung Injury

Anesthesiology ◽

10.1097/00000542-200012000-00016 ◽

2000 ◽

Vol 93 (6) ◽

pp. 1437-1445 ◽

Cited By ~ 6

Author(s):

Martin Max ◽

Bernd Nowak ◽

Rolf Dembinski ◽

Gernot Schulz ◽

Ralf Kuhlen ◽

...

Keyword(s):

Blood Flow ◽

Acute Lung Injury ◽

Lung Injury ◽

Pulmonary Blood Flow ◽

Arterial Oxygen ◽

Pulmonary Vasculature ◽

Emission Computed Tomography ◽

Partial Liquid Ventilation ◽

Arterial Oxygenation ◽

Liquid Ventilation

Background It has been proposed that partial liquid ventilation (PLV) causes a compression of the pulmonary vasculature by the dense perfluorocarbons and a subsequent redistribution of pulmonary blood flow from dorsal to better-ventilated middle and ventral lung regions, thereby improving arterial oxygenation in situations of acute lung injury. Methods After induction of acute lung injury by repeated lung lavage with saline, 20 pigs were randomly assigned to partial liquid ventilation with two sequential doses of 15 ml/kg perfluorocarbon (PLV group, n = 10) or to continued gaseous ventilation (GV group, n = 10). Single-photon emission computed tomography was used to study regional pulmonary blood flow. Gas exchange, hemodynamics, and pulmonary blood flow were determined in both groups before and after the induction of acute lung injury and at corresponding time points 1 and 2 h after each instillation of perfluorocarbon in the PLV group. Results During partial liquid ventilation, there were no changes in pulmonary blood flow distribution when compared with values obtained after induction of acute lung injury in the PLV group or to the animals submitted to gaseous ventilation. Arterial oxygenation improved significantly in the PLV group after instillation of the second dose of perfluorocarbon. Conclusions In the surfactant washout animal model of acute lung injury, redistribution of pulmonary blood flow does not seem to be a major factor for the observed increase of arterial oxygen tension during partial liquid ventilation.

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