Patten R D, Aronovitz M J, Deras-Mejia L, Pandian N G, Hanak G G, Smith J J, Mendelsohn M E, Konstam M A
Division of Cardiology, Molecular Cardiology Research Institute, New England Medical Center, Boston, Massachusetts, USA.
Am J Physiol. 1998 May;274(5):H1812-20. doi: 10.1152/ajpheart.1998.274.5.H1812.
We investigated the suitability of studying ventricular remodeling in a mouse model of myocardial infarction (MI). We performed left coronary ligation (n = 22) or a sham procedure (n = 21) on normal C57BL/6J mice. Six weeks later, animals underwent echocardiography and hemodynamic evaluation. Left ventricular (LV) volume at a common distending pressure was calculated from passive pressure-volume curves. The MI group exhibited lower systolic blood pressure (P < 0.05), higher LV end-diastolic pressure (P < 0.05), and lower peak first derivative of LV pressure (dP/dt, P < 0.05) than the sham group. Mice with moderate (< 40%, n = 11) and large (> or = 40%, n = 11) MIs displayed increased LV mass-to-body weight ratio (P < 0.02 and P < 0.01, respectively, vs. sham group), whereas only the large-MI group exhibited increased right ventricular mass-to-body weight ratio (P < 0.01). LV volumes were increased in the moderate-MI group (P = 0.059 vs. sham group) and to a much greater extent in the large-MI group (P < 0.0001 vs. sham group). The moderate- and large-MI groups also exhibited increases in LV end-diastolic diameter (P < 0.03 and P < 0.0001, respectively, vs. sham group) and LV end-systolic diameter (P < 0.01 and P < 0.0001, respectively, vs. sham group) with decreased fractional shortening (P < 0.01 for both). These data demonstrate ventricular remodeling in a mouse model of MI and confirm the feasibility of quantifying indexes of remodeling in vivo and postmortem. This model will be of particular usefulness when applied to transgenic strains.
我们研究了在心肌梗死(MI)小鼠模型中研究心室重构的适用性。我们对正常的C57BL/6J小鼠进行左冠状动脉结扎(n = 22)或假手术(n = 21)。六周后,对动物进行超声心动图和血流动力学评估。根据被动压力-容积曲线计算在共同扩张压力下的左心室(LV)容积。MI组的收缩压低于假手术组(P < 0.05),左心室舒张末期压力高于假手术组(P < 0.05),左心室压力的峰值一阶导数(dP/dt,P < 0.05)低于假手术组。中度(< 40%,n = 11)和大面积(>或 = 40%,n = 11)MI的小鼠左心室质量与体重比增加(分别与假手术组相比,P < 0.02和P < 0.01),而只有大面积MI组的右心室质量与体重比增加(P < 0.01)。中度MI组的左心室容积增加(与假手术组相比,P = 0.059),而大面积MI组增加的程度更大(与假手术组相比,P < 0.0001)。中度和大面积MI组的左心室舒张末期直径(分别与假手术组相比,P < 0.03和P < 0.0001)和左心室收缩末期直径(分别与假手术组相比,P < 0.01和P < 0.0001)也增加,而缩短分数降低(两者均P < 0.01)。这些数据证明了MI小鼠模型中的心室重构,并证实了在体内和死后量化重构指标的可行性。当应用于转基因品系时,该模型将特别有用。