Protective effects of hyperbaric oxygen and iloprost on ischemia/reperfusion-induced lung injury in a rabbit model

Because both the biosynthesis of nitric oxide (NO.) and its metabolic fate are related to molecular O2, we hypothesized that hypoxia would alter the effects of NO. during ischemia-reperfusion (IR) in the lung. In this study, buffer-perfused lungs from rabbits underwent either normoxic IR (AI), in which lungs were ventilated with 21% O2 during ischemia and reperfusion, or hypoxic IR (NI), in which lungs were ventilated with 95% N2 during ischemia followed by reoxygenation with 21% O2. Lung weight gain (WG) and pulmonary artery pressure (Ppa) were monitored continuously, and microvascular pressure (Pmv) was measured after reperfusion to calculate pulmonary vascular resistance. We found that both AI and NI produced acute lung injury, as shown by increased WG and Ppa during reperfusion. In AI, where perfusate PO2 was > 100 mmHg, the administration of the NO. synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) before ischemia worsened WG and Ppa. Pmv also increased, suggesting a hydrostatic mechanism involved in edema formation. The effects of L-NAME could be attenuated by giving L-arginine and exogenous NO. donors before ischemia or before reperfusion. Partial protection was also provided by superoxide dismutase. In contrast, lung injury in NI at perfusate PO2 of 25-30 mmHg was attenuated by L-NAME; this effect could be reversed by L-arginine. Exogenous NO. donors given either before ischemia or before reperfusion, however, did not increase lung injury. NO. production was measured by quantifying the total nitrogen oxides (NOx) accumulating in the perfusate. The average rate of NOx accumulation was greater in AI than in NI. We conclude that hypoxia prevented the protective effects of NO on AI lung injury. The effects of hypoxia may be related to lower NO. production relative to oxidant stress during IR and/or altered metabolic fates of NO.-mediated production of peroxynitrite by hypoxic ischemia.

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Protective Effects of Embelin on Myocardial Ischemia–Reperfusion Injury Following Cardiac Arrest in a Rabbit Model

Inflammation ◽

10.1007/s10753-014-9959-1 ◽

2014 ◽

Vol 38 (2) ◽

pp. 527-533 ◽

Cited By ~ 16

Author(s):

Zhi-Gang Zhao ◽

Zhong-Zhi Tang ◽

Wen-Kai Zhang ◽

Jian-Guo Li

Keyword(s):

Cardiac Arrest ◽

Myocardial Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Rabbit Model ◽

Protective Effects ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

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Protective Effects of Neural Crest-Derived Stem Cell-Conditioned Media against Ischemia-Reperfusion-Induced Lung Injury in Rats

Inflammation ◽

10.1007/s10753-017-0594-5 ◽

2017 ◽

Vol 40 (5) ◽

pp. 1532-1542 ◽

Cited By ~ 4

Author(s):

Chung-Kan Peng ◽

Shu-Yu Wu ◽

Shih-En Tang ◽

Min-Hui Li ◽

Shih-Shiuan Lin ◽

...

Keyword(s):

Stem Cell ◽

Lung Injury ◽

Neural Crest ◽

Ischemia Reperfusion ◽

Conditioned Media ◽

Protective Effects

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Therapeutic Applications of Carbon Monoxide

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/360815 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 20

Author(s):

Melissa Knauert ◽

Sandeep Vangala ◽

Maria Haslip ◽

Patty J. Lee

Keyword(s):

Carbon Monoxide ◽

Lung Injury ◽

Ischemia Reperfusion ◽

Heme Oxygenase 1 ◽

Protective Effects ◽

Phase Ii Trials ◽

Therapeutic Implications ◽

Damage Models ◽

Therapeutic Benefits ◽

Stress States

Heme oxygenase-1 (HO-1) is a regulated enzyme induced in multiple stress states. Carbon monoxide (CO) is a product of HO catalysis of heme. In many circumstances, CO appears to functionally replace HO-1, and CO is known to have endogenous anti-inflammatory, anti-apoptotic, and antiproliferative effects. CO is well studied in anoxia-reoxygenation and ischemia-reperfusion models and has advanced to phase II trials for treatment of several clinical entities. In alternative injury models, laboratories have used sepsis, acute lung injury, and systemic inflammatory challenges to assess the ability of CO to rescue cells, organs, and organisms. Hopefully, the research supporting the protective effects of CO in animal models will translate into therapeutic benefits for patients. Preclinical studies of CO are now moving towards more complex damage models that reflect polymicrobial sepsis or two-step injuries, such as sepsis complicated by acute respiratory distress syndrome. Furthermore, co-treatment and post-treatment with CO are being explored in which the insult occurs before there is an opportunity to intervene therapeutically. The aim of this review is to discuss the potential therapeutic implications of CO with a focus on lung injury and sepsis-related models.

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The protective effects of paricalcitol on renal ischemia reperfusion induced lung injury

10.1183/13993003.congress-2018.pa4297 ◽

2018 ◽

Author(s):

Süreyya Yilmaz ◽

Zülfükar Yilmaz ◽

Ali Kemal Kadiroğlu ◽

Veysi Bahadır ◽

İbrahim Kaplan ◽

...

Keyword(s):

Lung Injury ◽

Ischemia Reperfusion ◽

Renal Ischemia ◽

Protective Effects

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PECAM-directed delivery of catalase to endothelium protects against pulmonary vascular oxidative stress

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00021.2003 ◽

2003 ◽

Vol 285 (2) ◽

pp. L283-L292 ◽

Cited By ~ 61

Author(s):

Melpo Christofidou-Solomidou ◽

Arnaud Scherpereel ◽

Rainer Wiewrodt ◽

Kimmie Ng ◽

Thomas Sweitzer ◽

...

Keyword(s):

Oxidative Stress ◽

Lung Injury ◽

Intravenous Injection ◽

Targeted Delivery ◽

Ischemia Reperfusion ◽

Therapeutic Interventions ◽

Protective Effects ◽

Stress Injury ◽

Pulmonary Endothelium

Targeted delivery of drugs to vascular endothelium promises more effective and specific therapies in many disease conditions, including acute lung injury (ALI). This study evaluates the therapeutic effect of drug targeting to PECAM (platelet/endothelial cell adhesion molecule-1) in vivo in the context of pulmonary oxidative stress. Endothelial injury by reactive oxygen species (e.g., H2O2) is involved in many disease conditions, including ALI/acute respiratory distress syndrome and ischemia-reperfusion. To optimize delivery of antioxidant therapeutics, we conjugated catalase with PECAM antibodies and tested properties of anti-PECAM/catalase conjugates in cell culture and mice. Anti-PECAM/catalase, but not an IgG/catalase counterpart, bound specifically to PECAM-expressing cells, augmented their H2O2-degrading capacity, and protected them against H2O2 toxicity. Anti-PECAM/catalase, but not IgG/catalase, rapidly accumulated in the lungs after intravenous injection in mice, where it was confined to the pulmonary endothelium. To test its protective effect, we employed a murine model of oxidative lung injury induced by glucose oxidase coupled with thrombomodulin antibody (anti-TM/GOX). After intravenous injection in mice, anti-TM/GOX binds to pulmonary endothelium and produces H2O2, which causes lung injury and 100% lethality within 7 h. Coinjection of anti-PECAM/catalase protected against anti-TM/GOX-induced pulmonary oxidative stress, injury, and lethality, whereas polyethylene glycol catalase or IgG/catalase conjugates afforded only marginal protective effects. This result validates vascular immunotargeting as a prospective strategy for therapeutic interventions aimed at immediate protective effects, e.g., for augmentation of antioxidant defense in the pulmonary endothelium and treatment of ALI.

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