Inhibition of Constitutive Nitric Oxide Synthase Does Not Influence Ventilation-Perfusion Matching in Normal Prone Adult Sheep With Mechanical Ventilation.
Local formation of nitric oxide in the lung induces vasodilation in proportion to ventilation and is a putative mechanism behind ventilation-perfusion matching. We hypothesized that regional ventilation-perfusion matching occurs in part due to local constitutive nitric oxide formation.



Ventilation and perfusion were analyzed in lung regions (≈1.5 cm) before and after inhibition of constitutive nitric oxide synthase with N-nitro-L-arginine methyl ester (L-NAME) (25 mg/kg) in 7 prone sheep ventilated with 10 cm H2O positive end-expiratory pressure. Ventilation and perfusion were measured by the use of aerosolized fluorescent and infused radiolabeled microspheres, respectively. The animals were exsanguinated while deeply anesthetized; then, lungs were excised, dried at total lung capacity, and divided into cube units. The spatial location for each cube was tracked and fluorescence and radioactivity per unit weight determined.



After administration of L-NAME, pulmonary artery pressure increased from a mean of 16.6-23.6 mm Hg, P = .007 but PaO2, PaCO2, and SD log(V/Q) did not change. Distribution of ventilation was not influenced by L-NAME, but a small redistribution of perfusion from ventral to dorsal lung regions was observed. Perfusion to regions with the highest ventilation (fifth quintile of the ventilation distribution) remained unchanged after L-NAME.



We found minimal or no influence of constitutive nitric oxide synthase inhibition by L-NAME on the distributions of ventilation and perfusion, and ventilation-perfusion in prone, anesthetized, ventilated, and healthy adult sheep with normal gas exchange.
From the *Department of Cardiothoracic Anesthesia and Intensive Care; †Division of Cardiovascular Medicine, Department of Medical and Health Sciences; ‡Department of Cardiothoracic Surgery, Linköping University Hospital, Linköping, Sweden; and §Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Mats J
MJ
Johansson
John-Peder Escobar
JP
Kvitting
Torun
T
Flatebø
Anne
A
Nicolaysen
Gunnar
G
Nicolaysen
Sten M
SM
Walther
D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011175:Positive-Pressure Respiration; D016684:Prone Position; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology; D011652:Pulmonary Circulation / Q000187:drug effects*; D034561:Sheep, Domestic; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester