Heart failure and greater infarct expansion in middle-aged mice: a relevant model for postinfarction failure
Heart failure and greater infarct expansion in middle-aged mice: a relevant model for postinfarction failure
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DOI：
10.1152/ajpheart.00206.2001
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发表时间：
2002-02-01
影响因子：
4.8
通讯作者：
Entman, ML
中科院分区：
文献类型：
--
作者：
Gould, KE;Taffet, GE;Entman, ML
幼龄小鼠耐受冠状动脉结扎（CAL）后的心肌损失，无充血性心力衰竭（CHF）体征或死亡。我们预测了老年小鼠CAL后的CHF表型。左冠状动脉结扎造成永久性心肌梗死（MI）。雄性14月龄C57 BL/6 N小鼠（老年小鼠）的死亡率高于2月龄小鼠（年轻小鼠）（25只老年小鼠中有16只死亡，10只年轻小鼠中有0只死亡，P < 0.02）。8周后，出现啰音、体重减轻和嗜睡。Captopril（50 mg中心点/kg（-1）中心点/天（-1））增加了老龄小鼠的存活率（22只中有6只死亡，P < 0.02）。Captopril改善了收缩功能（峰值主动脉血流速度），从未治疗的老年小鼠基线的76 +/-6%提高到93 +/-8%（P < 0.036）。在24小时，MI占年轻小鼠左心室的28 +/-4%，令人惊讶地大于老年小鼠的MI（18 +/-2%，P < 0.011）。老年小鼠梗死瘢痕下的内皮细胞面积明显大于年轻小鼠。开搏通不能减少扩张，但能显著减少室间隔肥大。衰老降低了小鼠的代偿能力，尽管急性梗死较小。随着年龄的增长，心肌修复效率降低，梗死面积扩大，室间隔肥大。衰老是患者中MI后心力衰竭的更相关的鼠模型。
Young mice tolerate myocardial loss after coronary artery ligation (CAL) without congestive heart failure (CHF) signs or mortality. We predicted a CHF phenotype after CAL in aged mice. Left coronary artery ligation produced permanent myocardial infarcts (MI). Mortality was higher in male 14-mo-old C57BL/6N mice (Older mice) than in 2-mo-old mice (Young mice) (16 of 25 Older mice died vs. 0 of 10 Young mice, P < 0.02). After 8 wk, rales, weight loss, and lethargy preceded deaths. Captopril (50 mg center dot kg(-1)center dot day(-1)) increased Older mouse survival (6 of 22 died, P < 0.02). Captopril improved systolic function (peak aortic blood velocity) from 76 +/- 6% of baseline in untreated Older mice to 93 +/- 8% (P < 0.036). At 24 h, MI comprised 28 +/- 4% of the left ventricle in Young mice, surprisingly larger than that in Older mice (18 +/- 2%, P < 0.011). Endocardial area underlying the infarct scar was significantly larger in Older mice than in Young mice. Captopril did not reduce expansion but markedly reduced septal hypertrophy. Aging reduces compensatory ability in mice despite smaller acute infarcts. Less effective myocardial repair, greater infarct expansion, and septal hypertrophy are seen with aging. Aging is a more relevant murine model of post-MI heart failure in patients.