Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction
Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction
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DOI：
10.1093/eurheartj/ehn337
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发表时间：
2008-09-01
影响因子：
39.3
通讯作者：
Schulz, Rainer
中科院分区：
文献类型：
--
作者：
Heusch, Gerd;Skyschally, Andreas;Schulz, Rainer
目的在猪心肌缺血/再灌注模型中研究缓速剂伊伐布雷定对局部血流量、收缩功能和梗死面积的影响。β -阻滞剂的心率降低与负性肌力变性和暴露的α -肾上腺素能性冠状动脉收缩有关。伊伐布雷定是临床唯一可用的心动过缓药物。方法和结果麻醉猪90 min控制性冠状动脉左前降支低灌注和120 min再灌注。用微球法测定局部血流，用声速测定法测定局部功能，用三苯四氮氯化染色法测定梗死面积。猪在缺血前、缺血中或再灌注前分别接受安慰剂或伊伐布雷定（0.6 mg/kg静脉注射）。伊伐布雷定预处理将梗死面积从35 +/- 4% （SEM）降低到19 +/- 4% （AAR）。伊伐布雷定在缺血后15-20 min使局部心肌血流量从2.12 +/- 0.31 μ L/beat/g增加到3.55 +/- 0.56 μ L/beat/g，收缩壁增厚从6.7 +/- 1.0增加到16.3 +/- 3.0%；梗死面积从12% +/- 4%减小到2% +/- 1%。伊伐布雷定在再灌注前5分钟仍可将梗死面积从36% +/- 4%降低至21% +/- 5%。依瓦布雷定对血流和功能的益处被心房起搏消除了，但依瓦布雷定对梗死面积的部分减少却没有。结论伊伐布雷定的保护作用不仅仅是降低心率。
Aims Effects of the bradycardic agent ivabradine on regional blood flow, contractile function, and infarct size were studied in a pig model of myocardial ischaemia/reperfusion. Heart rate reduction by beta-blockade is associated with negative inotropism and unmasked alpha-adrenergic coronary vasoconstriction. Ivabradine is the only available bradycardic agent for clinical use.Methods and results Anaesthetized pigs were subjected to 90 min controlled left anterior descending coronary artery hypoperfusion and 120 min reperfusion. Regional blood flow was measured with microspheres, regional function with sonomicrometry, and infarct size with triphenyl tetrazolium chloride staining. Pigs received placebo or ivabradine (0.6 mg/kg i.v.) before or during ischaemia or before reperfusion, respectively.Pre-treatment with ivabradine reduced infarct size from 35 +/- 4 (SEM) to 19 +/- 4% of area at risk (AAR). Ivabradine 15-20 min after the onset of ischaemia increased regional myocardial blood flow from 2.12 +/- 0.31 to 3.55 +/- 0.56 mu L/beat/g and systolic wall thickening from 6.7 +/- 1.0 to 16.3 +/- 3.0%; infarct size was reduced from 12 +/- 4 to 2 +/- 1% of AAR. Ivabradine 5 min before reperfusion still reduced infarct size from 36 +/- 4 to 21 +/- 5% of AAR. The benefit of ivabradine on flow and function was eliminated by atrial pacing, but part of the reduction of infarct size by ivabradine was not.Conclusion Ivabradine's protection goes beyond heart rate reduction.