Protective effect of a nebulized β2-adrenoreceptor agonist in warm ischemic-reperfused rat lungs
Protective effect of a nebulized β2-adrenoreceptor agonist in warm ischemic-reperfused rat lungs
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DOI：
10.1016/j.athoracsur.2006.01.010
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发表时间：
2006-08-01
影响因子：
4.6
通讯作者：
Fukuse, Tatsuo
中科院分区：
文献类型：
--
作者：
Chen, Fengshi;Nakamura, Takayuki;Fukuse, Tatsuo
背景资料。为了解决临床肺移植供者短缺的问题，非跳动心脏供体的应用似乎是不可避免的。热缺血再灌注损伤的控制是非停跳心脏供体处理的关键。我们假设在热缺血期间雾化吸入β(2)肾上腺素受体激动剂沙美特罗辛诺酯(SLM)会增加肺组织环磷酸腺苷(CAMP)水平，从而达到肺保护作用。进行了两项研究。首次采用大鼠隔离肺灌流模型，研究了肺缺血时雾化吸入SLM对肺缺血再灌注损伤的影响。切除心肺块，插入肺动脉和静脉，暴露在37℃下55分钟的缺血中，然后再灌流60分钟。在再灌流过程中测量几个参数。在第二项研究中，为了测量热缺血时肺组织cAMP水平的变化，在SLM雾化或不雾化两种情况下，取大鼠肺组织，暴露于热缺血60min的机械通气中。沙美特罗雾化吸入显著降低肺分流分数、气道阻力和肺血管阻力。在整个再灌注期内对肺水肿也有抑制作用。雾化吸入SLM可有效维持再灌流结束时肺组织cAMP。雾化吸入SLM可显著降低肺组织髓过氧化物酶活性。肺组织cAMP水平在热缺血60min内下降，但随SLM雾化吸入时间的延长而升高(p<；0.01)。我们的结果证实了热缺血时SLM雾化吸入维持肺组织cAMP水平，从而减轻肺热缺血再灌注损伤。
Background. It seems inevitable that non-beating-heart donors will be utilized to resolve the shortage of donors for clinical lung transplantation. The control of warm ischemia-reperfusion injury is crucial in manipulating non-beating-heart donors. We hypothesized that nebulization of a beta(2)-adrenoreceptor agonist, salmeterol xinafoate (SLM), during warm ischemia would increase lung tissue cyclic adenosine monophosphate (cAMP) levels, resulting in lung protection.Methods. Two studies were conducted. The first investigated the effect of SLM nebulization during ischemia on pulmonary ischemia-reperfusion injury, using an isolated rat lung-perfusion model. The heart-lung block was excised with cannulation of the pulmonary artery and vein, exposed to 55 minutes of ischemia at 37 degrees C, and subsequently reperfused for 60 minutes. Several parameters were measured during reperfusion. In the second study, to measure changes in lung tissue cAMP levels during warm ischemia with or without SLM nebulization, rat lungs were harvested and exposed to 60 minutes of warm ischemia with ventilation.Results. Salmeterol xinafoate nebulization significantly decreased the pulmonary shunt fraction, airway resistance, and pulmonary vascular resistance. It also inhibited pulmonary edema throughout the reperfusion period. Lung tissue cAMP was effectively maintained by SLM nebulization at the end of reperfusion. Myeloperoxidase activity in the lungs was decreased significantly by SLM nebulization. Lung tissue cAMP levels decreased during the 60 minutes of warm ischemia, but increased with SLM nebulization (p < 0.01).Conclusions. Our results confirmed that SLM nebulization during warm ischemia maintained lung tissue cAMP levels, resulting in the alleviation of pulmonary warm ischemia-reperfusion injury.