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在猪心肌梗死模型中,侵入性手术可减小梗死面积并保留心脏功能。

Invasive surgery reduces infarct size and preserves cardiac function in a porcine model of myocardial infarction.

作者信息

van Hout Gerardus P J, Teuben Michel P J, Heeres Marjolein, de Maat Steven, de Jong Renate, Maas Coen, Kouwenberg Lisanne H J A, Koenderman Leo, van Solinge Wouter W, de Jager Saskia C A, Pasterkamp Gerard, Hoefer Imo E

机构信息

Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.

Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

J Cell Mol Med. 2015 Nov;19(11):2655-63. doi: 10.1111/jcmm.12656. Epub 2015 Aug 18.

Abstract

Reperfusion injury following myocardial infarction (MI) increases infarct size (IS) and deteriorates cardiac function. Cardioprotective strategies in large animal MI models often failed in clinical trials, suggesting translational failure. Experimentally, MI is induced artificially and the effect of the experimental procedures may influence outcome and thus clinical applicability. The aim of this study was to investigate if invasive surgery, as in the common open chest MI model affects IS and cardiac function. Twenty female landrace pigs were subjected to MI by transluminal balloon occlusion. In 10 of 20 pigs, balloon occlusion was preceded by invasive surgery (medial sternotomy). After 72 hrs, pigs were subjected to echocardiography and Evans blue/triphenyl tetrazoliumchloride double staining to determine IS and area at risk. Quantification of IS showed a significant IS reduction in the open chest group compared to the closed chest group (IS versus area at risk: 50.9 ± 5.4% versus 69.9 ± 3.4%, P = 0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow-up differed significantly between both groups (51 ± 5 ml versus 65 ± 3 ml, P = 0.033; 47.5 ± 2.6% versus 38.8 ± 1.2%, P = 0.005). The inflammatory response in the damaged myocardium did not differ between groups. This study indicates that invasive surgery reduces IS and preserves cardiac function in a porcine MI model. Future studies need to elucidate the effect of infarct induction technique on the efficacy of pharmacological therapies in large animal cardioprotection studies.

摘要

心肌梗死(MI)后的再灌注损伤会增加梗死面积(IS)并使心功能恶化。大型动物MI模型中的心脏保护策略在临床试验中常常失败,这表明转化失败。在实验中,MI是人为诱导的,实验操作的效果可能会影响结果,进而影响临床适用性。本研究的目的是调查像常见的开胸MI模型中的侵入性手术是否会影响IS和心功能。20只雌性长白猪通过经腔球囊闭塞诱导MI。在20只猪中的10只中,球囊闭塞之前进行了侵入性手术(胸骨正中切开术)。72小时后,对猪进行超声心动图检查以及伊文思蓝/氯化三苯基四氮唑双重染色以确定IS和危险区域。IS的量化显示,与闭胸组相比,开胸组的IS显著降低(IS与危险区域之比:50.9±5.4%对69.9±3.4%,P = 0.007)。随访时通过超声心动图测量的左心室收缩末期容积和左心室射血分数在两组之间存在显著差异(51±5 ml对65±3 ml,P = 0.033;47.5±2.6%对38.8±1.2%,P = 0.005)。受损心肌中的炎症反应在两组之间没有差异。本研究表明,在猪MI模型中,侵入性手术可减少IS并保留心功能。未来的研究需要阐明梗死诱导技术对大型动物心脏保护研究中药理学疗法疗效的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1aa/4627570/27c4edcc7aa4/jcmm0019-2655-f1.jpg

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