Inhaled Nitric Oxide Pretreatment But Not Post-treatment Attenuates Ischemia-Reperfusion-induced Pulmonary Microvascular Leak 

Abstract

Inhaled NO attenuates I/R-induced pulmonary microvascular leak, which requires sGC activation and may involve a mechanism independent of inhibition of leukocyte-endothelial cell interactions. In addition, INO is ineffective in reversing I/R-induced microvascular leak.

Aerosolized PGE1, PGI2and nitroprusside protect against vascular leakage in lung ischaemia-reperfusion

“…Adding 8-Br-cGMP to the preservation solution improved lung function and recipient survival in this model [30]. Similarly, inhalation of NO upon reperfusion attenuated I-Rinduced increases of capillary filtration via activation of guanylate cyclase [5].…”

“…Along this line, maintenance of ventilation with an ongoing oxygen supply during ischaemia was demonstrated to attenuate I-R injury in previous studies [10,11]. Moreover, ongoing delivery of nitric oxide (NO) to the lung parenchyma, via admixture of this gaseous agent to the inhaled gas, was found to reduce lung oedema formation upon reperfusion and to improve ventilation-perfusion matching in experimental I-R injury [5,12]. Next to the vasomotor effects of NO, i.e.…”

“…Comparable pathogenetic sequelae are suggested to be operative in pulmonary thromboendarterectomy, re-expansion of collapsed lungs, or fibrinolysis after lung embolism [2,3]. Besides enhanced microvascular pressure that may arise upon onset of reperfusion, increased permeability of the pulmonary capillary endothelial barrier is known to be a major contributor to the oedema formation in reperfused lung areas [4,5].…”

Anti-inflammatory effects of inhaled nitric oxide are optimized at lower oxygen concentration in experimental Klebsiella pneumoniae pneumonia

“…Neutrophils infi ltrated in the lungs release reactive oxygen species and proteolytic enzymes, provoke proinfl ammatory cytokine activity, and the endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1) [10]. NO administration before the establishment of lung injury has been suggested to protect against ALI by decreasing oxygen radicals as well as modulating interaction between the vascular endothelium and infl ammatory cells [16].…”

Endogenous Nitric Oxide Synthesis and Vascular Leakage in Ischemic-Reperfused Rabbit Lungs

“…In I/R injury following clinical lung transplantation, with respiratory failure caused by noncardiogenic, highpermeability edema and increased pulmonary vascular resistance, the exogenous supply of NO by inhalation of NO has been recommended (15), on the assumption of impaired endogenous synthesis of this vasoactive agent in the reperfused lungs (16). This view is further supported by several experimental studies showing that inhalation of NO upon reperfusion attenuates microvascular leakage (17)(18)(19)(20), an effect that is related to the nonvasodilatory, antiinflammatory properties of this agent (21), and which depends on release of cyclic guanosine monophosphate (cGMP) (18). However, in one model addressing NO inhalation in I/R injury, NO was noted to be ineffective, whereas a cGMP analogue reduced the reperfusion injury (16,22), thus pointing to possibly disadvantageous (peroxynitriterelated?)…”