Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.
Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.
复制标题
尽管使用β-阻滞剂，异丙肾上腺素仍可减少缺血再灌注肺损伤。
DOI：
10.1016/j.jss.2005.01.017
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Egan,ThomasM
中科院分区：
文献类型：
--
作者：
Takashima,Seiki;Schlidt,ScottA;Koukoulis,Giovanna;Sevala,Mayura;Egan,ThomasM
背景：如果能够从非心脏跳动供体（NHBDs）中提取肺，可以缓解用于移植的肺的短缺。NHBDs肺的使用与强制性热缺血间隔有关，这导致再灌注时缺血-再灌注损伤。在早期的一项研究中，从NHBDs中取出的死后2小时的大鼠肺在再灌注异丙肾上腺素（iso）时，通过过滤系数（Kfc）测量毛细血管泄漏减少，与肺组织中环AMP （cAMP）水平的增加有关。目的是确定肯德基的这种减少是由于β刺激，还是在β阻断的情况下仍会持续。材料与方法供体大鼠腹腔注射β-阻断剂（心得安或品多洛尔）或载体，处死，死后立即或死后2 h取肺。用或不用iso和β受体阻滞剂对肺进行再灌注。结局指标为Kfc、干湿比（W/D）、肺腺嘌呤核苷酸和cAMP水平。结果死亡后立即取出的肺中含有正常的Kfc和W/D。缺血2小时后，对照组（未给药）的Kfc和W/D明显升高，单独给β受体阻滞剂后肺再灌注。再灌注异丙肾上腺素可显著降低大鼠的Kfc和W/D （P < 0.01）。在没有β-阻断的情况下，肺cAMP水平仅随iso升高。结论在有β-阻断的情况下，iso对缺血再灌注损伤的减弱也会发生，而可能不是β刺激cAMP增加的结果。
BACKGROUNDIf lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of β-stimulation, or would persist despite β-blockade.MATERIALS AND METHODSDonor rats were treated intraperitoneally with β-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the β-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP.RESULTSLungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with β-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of β-blockade. Lung cAMP levels were increased only with iso in the absence of β-blockade.CONCLUSIONSThe attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of β-blockade, and may not be a result of β-stimulated increased cAMP.