Effects of inhaled nitric oxide on lung injury after intestinal ischemia-reperfusion in rats.
Splanchnic ischemia/reperfusion (I/R) induces a systemic inflammatory response with acute lung injury. Impaired production of endothelial nitric oxide (NO) plays a key role in this process. We evaluated the effects of early treatment with inhaled NO (iNO) on lung microcirculatory inflammatory changes during splanchnic I/R. I/R was induced in rats by occlusion of the superior mesenteric artery (SMA; 40 min) and reperfusion (90 min). Four groups were studied: Control, anesthesia only; Sham, all surgical procedures without I/R, ventilated with air; Air, SMA I/R, ventilation with air; and NO, SMA I/R, ventilation with NO (20 ppm) starting 10 min before reperfusion. Intravital video microscopy was used to monitor pulmonary macromolecular flux and capillary flow velocity (CFV). Leukocyte infiltration was determined by morphometry. SMA I/R decreased mean arterial blood pressure, capillary CFV (P < 0.01), and shear rate (P < 0.01), and increased pulmonary macromolecular leak by 138% +/- 8% (P < 0.001). iNO markedly attenuated the increase in macromolecular leak (P < 0.01), blunted the decrease in capillary CFV (P < 0.05) and shear rate (P < 0.05), and prevented the increase in leukocyte infiltration of the lungs after SMA I/R (P < 0.05). The direct, real-time, in vivo data suggest that early institution of low-dose iNO therapy effectively ameliorates the acute remote pulmonary inflammatory response after splanchnic I/R.
Waisman
Dan
D
Department of Neonatology, Carmel Medical Center, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 34362 Haifa, Israel.
Brod
Vera
V
Dickstein
Ronit
R
Abramovich
Amir
A
Rotschild
Avi
A
Bitterman
Haim
H
D000280:Administration, Inhalation; D000388:Air; D000818:Animals; D001794:Blood Pressure; D007150:Immunohistochemistry; D007249:Inflammation; D007422:Intestines / Q000473:pathology*; D007511:Ischemia; D007962:Leukocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000473:pathology; D055370:Lung Injury; D008297:Male; D008833:Microcirculation; D018715:Microscopy, Video; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury; D013997:Time Factors
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat