Protective effects of intravascular pressure and nitric oxide in ischemic lung injury

Patrice M. Becker, Wendy Buchanan, J. T. Sylvester

Research output: Contribution to journalArticlepeer-review

Abstract

Cessation of blood flow during ischemia will decrease both distending and shear forces exerted on endothelium and may worsen ischemic lung injury by decreasing production of nitric oxide (NO), which influences vascular barrier function. We hypothesized that increased intravascular pressure (Piv) during ventilated ischemia might maintain NO production by increasing endothelial stretch or shear forces, thereby attenuating ischemic lung injury. Injury was assessed by measuring the filtration coefficient (K(f)) and the osmotic reflection coefficient for albumin (σ(alb)) after 3 h of ventilated (95% O2-5% CO2; expiratory pressure 3 mmHg) ischemia. Lungs were flushed with physiological salt solution, 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-arginine methyl ester (D-NAME; 10-5 M, n = 11), or L-NAME (10-5 M)+L-arginine (5 x 10-4 M, n = 6) was added at the start of ischemia in three additional groups of lungs with High Piv. High Piv attenuated ischemic injury compared with Low Piv (σ(alb) 0.67 ± 0.04 vs. 0.35 ± 0.04, P < 0.05). The protective effect of High Piv was abolished by L-NAME (σ(alb) 0.37 ± 0.04, P < 0.05) but not by D-NAME (σ(alb) 0.63 ± 0.07). The effects of L-NAME were overcome by an excess of L-arginine (σ(alb) 0.56 ± 0.05, P < 0.05). K(f) did not differ significantly among groups. These results suggest that Piv modulates ischemia-induced barrier dysfunction in the lung, and these effects may be mediated by NO.

Original languageEnglish (US)
Pages (from-to)803-808
Number of pages6
JournalJournal of applied physiology
Volume84
Issue number3
DOIs
StatePublished - Mar 1998

Keywords

  • Acute lung injury
  • Osmotic reflection coefficient
  • Vascular permeability

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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