Raake Philip W J, Barthelmes Jens, Krautz Birgit, Buss Sebastian, Huditz Regina, Schlegel Philipp, Weber Christophe, Stangassinger Manfred, Haberkorn Uwe, Katus Hugo A, Most Patrick, Pleger Sven T
Department of Internal Medicine III, Cardiology, University of Heidelberg, Heidelberg, Germany.
Department of Internal Medicine III, University Hospital Heidelberg, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
Int J Cardiovasc Imaging. 2019 Sep;35(9):1691-1699. doi: 10.1007/s10554-019-01610-z. Epub 2019 May 5.
Large animal ischemic cardiomyopathy models are widely used for preclinical testing of promising novel therapeutic approaches. Pressure volume (PV) loop analysis and cardiac magnetic resonance imaging (CMRI) allow functional and morphological phenotyping. In this study we performed a comparative analysis of both methods highlighting the strength of each and their synergistic potential. Myocardial infarction (MI) was created in German farm pigs (German Landrace) by 2 h LCX occlusion (n = 11) and subsequent reperfusion. Cardiac function was assessed by PV-loops and CMRI 56 and 112 days post-MI. Two hours occlusion of the LCX led to mid-size left ventricular (LV) MI represented by high-sensitive troponin T (hsTnT) 3 days post-MI, correlating well with cardiac CMRI late enhancement. CMRI determined end-diastolic and end-systolic volumes significantly increased post-MI, while ejection fraction was reduced in infarcted animals compared to the sham group (n = 6). PV-loop derived preload-insensitive parameters of systolic and diastolic function were diminished post-MI compared to sham animals while preload-dependent parameters only deteriorated in advanced HF. PV-loop analysis significantly correlates with CMRI analysis of cardiac function in pig post-MI ischemic cardiomyopathy. PV-Loop analysis accurately quantifies LV volumetry and function in post-MI HF, and thus eccentric LV morphology. PV-loop analysis correlates well to cardiac MRI. Preload-insensitive parameters show high sensitivity to quantify HF while preload-sensitive parameters are not able to quantify early-stages of LV HF.
大型动物缺血性心肌病模型被广泛用于对有前景的新型治疗方法进行临床前测试。压力容积(PV)环分析和心脏磁共振成像(CMRI)可实现功能和形态表型分析。在本研究中,我们对这两种方法进行了比较分析,突出了每种方法的优势及其协同潜力。通过结扎左冠状动脉回旋支(LCX)2小时(n = 11)并随后再灌注,在德国农场猪(德国长白猪)中制造心肌梗死(MI)。在心肌梗死后56天和112天通过PV环和CMRI评估心脏功能。结扎LCX 2小时导致中等大小的左心室(LV)心肌梗死,在心肌梗死后3天通过高敏肌钙蛋白T(hsTnT)表现出来,与心脏CMRI延迟强化密切相关。CMRI测定的舒张末期和收缩末期容积在心肌梗死后显著增加,而与假手术组(n = 6)相比,梗死动物的射血分数降低。与假手术动物相比,PV环得出的收缩和舒张功能的前负荷不敏感参数在心肌梗死后降低,而前负荷依赖参数仅在晚期心力衰竭中恶化。在猪心肌梗死后缺血性心肌病中,PV环分析与心脏功能的CMRI分析显著相关。PV环分析准确地量化了心肌梗死后心力衰竭时的左心室容积和功能,从而量化了左心室的偏心形态。PV环分析与心脏MRI相关性良好。前负荷不敏感参数在量化心力衰竭方面具有高敏感性,而前负荷敏感参数无法量化左心室心力衰竭的早期阶段。