Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs
Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs
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DOI：
10.1016/j.yjmcc.2006.02.001
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发表时间：
2006-05-01
影响因子：
5
通讯作者：
Kitakaze, Masafumi
中科院分区：
文献类型：
--
作者：
Asanuma, Hiroshi;Minamino, Tetsuo;Kitakaze, Masafumi
我们以前曾报道组胺H-2受体阻滞剂可能对慢性心力衰竭患者具有心脏保护作用。由于内源性组胺和组胺H-2受体都存在于心脏组织中，我们测试了组胺H-2受体的阻断介导对可逆或不可逆缺血和再灌注损伤的保护的假设。在开胸犬中，阻断冠状动脉左前降支90分钟，然后再灌注6小时。从闭塞前10分钟至再灌注后1小时给予法莫替丁和西咪替丁可减少损伤大小（分别为溶剂组的17.0 +/- 4.1%和17.8 +/- 2.9%对36.9 +/- 5.9%）仅在再灌注期间给予法莫替丁1小时也减小了梗死面积（22.5 +/- 3.5%）。各组之间的风险区域或侧支血流均无差异。在另一组实验中，我们降低了狗的冠状动脉灌注压，使冠状动脉血流量下降到非缺血水平的50%。在这种情况下，我们观察到组胺释放与非缺血性条件相比增加（0.04 +/-0.03至0.28 +/-0.13ng/ml，p < 0.05）。法莫替丁改善心肌无氧代谢的乳酸提取率和心肌耗氧量。我们的结论是，组胺H1受体的阻断介导的改善无氧心肌代谢，从而防止缺血和再灌注损伤。(c)2006爱思唯尔有限公司保留所有权利。
We have previously reported that histamine H-2 blockers may be cardioprotective in patients with chronic heart failure. Since both endogenous histamine and histamine H-2 receptors are present in heart tissue, we tested the hypothesis that the blockade of histamine H-2 receptors mediates protection against reversible or irreversible ischemia and reperfusion injury. In open-chest dogs, the left anterior descending coronary artery was occluded for 90 minutes, followed by reperfusion for 6 hours. Administration of famotidine and cimetidine from 10 minutes before occlusion until after 1 hour of reperfusion reduced inflict size (17.0 +/- 4.1% and 17.8 +/- 2.9% vs. 36.9 +/- 5.9% of the solvent group, respectively) Famotidine administration only during the reperfusion period for 1 hour also attenuated infarct size (22.5 +/- 3.5%). There were no differences in either area at risk or collateral flow among the groups. In another set of experiments, we decreased coronary perfusion pressure in dogs so that the coronary blood flow decreased to 50% of the non-ischemic level. In such conditions, we observed the increases in histamine release compared with non-ischemic conditions (0.04 +/- 0.03 to 0.28 +/- 0.13 ng/ml, p < 0.05). Famotidine improved anaerobic myocardial metabolism gauged by both lactate extraction ratio and myocardial oxygen consumption. We conclude that the blockade of histamine H, receptors mediates improvements in the anaerobic myocardial metabolism, and thus protects against ischemia and reperfusion injury. (c) 2006 Elsevier Ltd. All rights reserved.