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Age‐Related Left Ventricular Systolic Dysfunction in a Mouse Model of Hypertrophic Cardiomyopathy
Author(s) -
Larson Robert A.,
Purnell Benton S.,
Davis Melissa K.,
Weiss Robert M.,
Cicha Michael Z.,
Sabharwal Rasna,
Chapleau Mark W.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb676
Subject(s) - medicine , hypertrophic cardiomyopathy , cardiology , diastole , ejection fraction , contractility , cardiomyopathy , heart failure , cardiac function curve , blood pressure
Familial hypertrophic cardiomyopathy (HCM) is a devastating disease caused by mutations in cardiac sarcomeric proteins that result in myocyte disarray, cardiac fibrosis and hypertrophy. A hallmark of HCM is cardiac diastolic dysfunction. Systolic function is generally preserved or even enhanced; however, some patients develop systolic dysfunction over time. In this study we tested the hypothesis that left ventricular (LV) systolic dysfunction increases with age in transgenic mice with cardiac‐specific expression of mutated alpha tropomyosin (Glu180Gly), an established model of human HCM. Cardiac function was assessed by echocardiography (Vevo 2100, Visualsonics) in HCM and control wild type (WT) mice over a wide range of age (3–47 weeks). Mice were lightly sedated with midazolam (0.15 mg, SC) to avoid anesthesia‐induced decreases in heart rate, myocardial contractility and sympathetic tone. LV end diastolic volume (EDV) was not significantly different in HCM vs. WT mice at any age (see Table). LV end systolic volume (ESV) and ejection fraction (EF) did not differ between very young, 3‐week old WT and HCM mice. In contrast, at 7 weeks of age, ESV was higher and EF was lower in HCM vs. WT mice (P<0.05). Systolic dysfunction was most pronounced in middle‐aged HCM mice between 36 and 47 weeks of age (Table, P<0.05). We conclude that alpha tropomyosin mutant mice with HCM exhibit age‐dependent LV systolic dysfunction. Support or Funding Information AAS‐Lundbeck Fellowship & HL143883 Weeks 7 Weeks 43±1 WeeksWT (n=8) HCM (n=9) WT (n=8) HCM (n=9) WT (n=5) HCM (n=12)EDV (μL) 24.2±2.4 28.8±2.0 37.4±4.8 45.4±4.3 41.6±7.3 54.0±3.7 ESV (μL) 6.7±1.1 9.5±0.9 9.1+1.5 18.0±2.8 * 10.1±2.0 21.3±1.7 * EF (%) 73±2 67±1 76±2 62±3 * 76±3 61±2 ** p<0.05 WT vs. HCM