Preventive Effect of Inhaled Nitric Oxide and Pentoxifylline on Ischemia/Reperfusion Injury After Lung Transplantation

Thabut, Gabriel; Brugière, Olivier; Lesèche, Guy; Stern, Jean Baptiste; Fradj, K; Hervé, Philippe; Jébrak, G.; Marty, J; Fournier, Michel; Mal, Hervé

doi:10.1097/00007890-200105150-00019

Cited by 68 publications

(35 citation statements)

References 23 publications

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“…16 In patients with sickle cell disease, inhaled NO (80 ppm) does not modify the erythrocyte oxygen affinity, even when associated with a modest increase in methemoglobin. 32,33 Here, we found that inhaled NO (40 ppm) ameliorates red blood cell dehydration in SAD mice exposed to 46 hours of hypoxia, with an increase in red blood cell K ϩ content. We previously reported that hypoxia-induced red blood cell dehydration in SAD mice is mostly mediated by the Ca 2ϩ -activated K ϩ channel and prevented by its specific inhibitor, clotrimazole.…”

Section: Discussionmentioning

confidence: 73%

“…Gene expression profiling of lung tissue pointed to the specific induction of genes involved in the response to ischemic stress and microcirculation remodeling. Because NO is a potent vasodilator and inhibitor of vascular remodeling and also affects the multistep cascade events involved in leukocyte, platelets, and endothelial activation, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] we have investigated whether inhaled NO, which diffuses directly from alveoli to pulmonary vascular smooth muscle, could prevent lung injury consecutive to pulmonary ischemic/reperfusion damage and studied its mechanism(s) of action.…”

Section: Introductionmentioning

confidence: 99%

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Inhaled nitric oxide protects transgenic SAD mice from sickle cell disease-specific lung injury induced by hypoxia/reoxygenation

Franceschi

Scarpa

et al. 2003

Blood

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Central to the pathophysiology of sickle cell disease are the vaso-occlusive events that lead to tissue damages and lifethreatening complications. Lungs are particularly vulnerable to vaso-occlusion because of their specific vasculature. We developed a mouse model of hypoxia/ reoxygenation lung injury closely mimicking the lung pathology of patients with sickle cell disease. This model involves the exposure of transgenic sickle cell (SAD) mice to hypoxia (8% oxygen) for 4, 10, and 46 hours followed by 2 hours of reoxygenation. Gene expression profiling of SAD lung tissue pointed to the specific induction of genes involved in the response to ischemic stress and microcir-

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Inhaled nitric oxide protects transgenic SAD mice from sickle cell disease-specific lung injury induced by hypoxia/reoxygenation

Franceschi

Scarpa

et al. 2003

Blood

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“…Aprotinin's effects are especially beneficial in light of a retrospective study of 180 lung transplant patients, which demonstrated a significant decrease of severe posttransplant LIRI, largely through the attenuation of neutrophil activity (24). Thabut et al (198) found a marked decrease in the incidence of allograft dysfunction (by mortality, pulmonary edema, lung function, and duration of mechanical ventilation) after lung transplantation when administrating pentoxyfilline and inhaled NO before and during perfusion compared with historical controls.…”

Section: Therapeutic Possibilitiesmentioning

confidence: 99%

Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process

Hengst

Gielis

Lin

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

316

280

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Lung ischemia-reperfusion injury remains one of the major complications after cardiac bypass surgery and lung transplantation. Due to its dual blood supply system and the availability of oxygen from alveolar ventilation, the pathogenetic mechanisms of ischemia-reperfusion injury in the lungs are more complicated than in other organs, where loss of blood flow automatically leads to hypoxia. In this review, an extensive overview is given of the molecular and cellular mechanisms that are involved in the pathogenesis of lung ischemia-reperfusion injury and the possible therapeutic strategies to reduce or prevent it. In addition, the roles of neutrophils, alveolar macrophages, cytokines, and chemokines, as well as the alterations in the cell-death related pathways, are described in detail. pulmonary; lung transplantation; ventilated ischemia IN THE PAST, THE LUNG WAS thought to be relatively resistant to ischemia because of its dual circulation and the availability of oxygen from alveolar ventilation. However, the depletion of lung oxygenation by stopping the ventilation leads to the same degree of lung impairment as a decrease in mechanotransduction by loss of blood flow, as determined by increases in vascular pressure and permeability (11), indicating that any deficiency from oxygenation or mechanotransduction can have significant repercussions (149).Reperfusion of the ischemic lung is a double-edged sword. Reestablishing the perfusion of the ischemic lung is absolutely required to maintain the viability of the lung, but reperfusion itself can trigger a complex cascade of events, the so-called pulmonary ischemia-reperfusion injury (LIRI) (48), characterized by increased microvascular permeability (Pvasc), increased pulmonary vascular resistance (PVR), pulmonary edema, impaired oxygenation, and pulmonary hypertension. Ischemia of the lung, without loss of ventilation, results in a complex pathophysiological situation and, therefore, is not comparable with ischemia in other organs. During ventilated ischemia, for example, the adenosine triphosphate (ATP) levels remain normal while reactive oxygen species (ROS) are formed (70), illustrating aspects of complexity of the pathophysiology of ventilated and anoxic lung ischemia. Therefore, a distinction should be made between ventilated ischemia, meaning a loss of blood flow, and anoxia/reoxygenation, indicating the loss of oxygenation and/or perfusion. In this review, the terms anoxia/reoxygenation and ventilated ischemia will be used, if the specific model is known and/or the mechanism is suggested to be model specific. Ischemia alone will be used, if it applies for both mechanisms, if the specific model is not known, or the research involves other organs.Complete and prolonged lung anoxia for up to several hours is unavoidable during lung transplantation, with dire consequences. Reperfusion of the transplanted lung can lead to nonspecific alveolar damage, pulmonary edema, and hypoxemia within 72 h after lung transplantation. Even with the advancements in lung preservati...

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“…Studies of the anti-inflammatory effects of PTX in vivo have focused attention on tissue injury after ischemia. Thus, in vivo PTX treatment reduced ischemia-reperfusion injury in the lung (Thabut et al, 2001), intestine (Sener et al, 2001), liver (Iwamoto et al, 2002), kidney (Kim et al, 2001), spinal cord (Savas et al, 2002), and brain of different animal species including rats, mice, and dogs (Toung et al, 1994;Sirin et al, 1998;Eun et al, 2000). Inflammatory processes accompany tissue injury regardless of the organ system involved, and chronic inflammation may predispose to ischemia in peripheral organs and to brain damage (Lindsberg and Grau, 2003).…”

mentioning

confidence: 99%

Pentoxifylline Prevents Spontaneous Brain Ischemia in Stroke-Prone Rats

Banfi¹,

Sironi²,

Simoni³

et al. 2004

J Pharmacol Exp Ther

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Anti-inflammatory properties of pentoxifylline (PTX) have recently been described. Spontaneously hypertensive strokeprone rats (SHRSP) constitute an animal model that develops an inflammatory condition that precedes the appearance of brain abnormalities. The aim of the present investigation was to assess: 1) the efficacy of PTX treatment in protecting the neural system in SHRSP, and 2) how its anti-inflammatory properties might be involved in this effect. Male SHRSP fed with a permissive diet received no drug or PTX (100 or 200 mg/kg/day). Brain abnormalities detected by magnetic resonance imaging developed spontaneously in control rats after 42 Ϯ 3 days, whereas in rats treated with 100 mg/kg/day PTX, abnormalities developed in only 80% of the animals and only after 70 to 80 days. Treatment with a higher dose of PTX (200 mg/kg/day) completely protected the brain from abnormal development.

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Preventive Effect of Inhaled Nitric Oxide and Pentoxifylline on Ischemia/Reperfusion Injury After Lung Transplantation

Abstract: The marked decrease in the incidence of allograft dysfunction compared with two historical control groups suggests that PTX and inhaled NO given before and throughout reperfusion are protective against I/R injury in the setting of clinical transplantation.

Cited by 68 publications

References 23 publications

Inhaled nitric oxide protects transgenic SAD mice from sickle cell disease-specific lung injury induced by hypoxia/reoxygenation

Inhaled nitric oxide protects transgenic SAD mice from sickle cell disease-specific lung injury induced by hypoxia/reoxygenation

Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process

Pentoxifylline Prevents Spontaneous Brain Ischemia in Stroke-Prone Rats

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