| First Author | Westermann D | Year | 2006 |
| Journal | Eur J Heart Fail | Volume | 8 |
| Issue | 2 | Pages | 115-21 |
| PubMed ID | 16214409 | Mgi Jnum | J:308074 |
| Mgi Id | MGI:6725876 | Doi | 10.1016/j.ejheart.2005.07.012 |
| Citation | Westermann D, et al. (2006) Diltiazem treatment prevents diastolic heart failure in mice with familial hypertrophic cardiomyopathy. Eur J Heart Fail 8(2):115-21 |
| abstractText | BACKGROUND: The cardiac troponin T I79N mutation, linked to familial hypertrophic cardiomyopathy, carries a high risk of sudden cardiac death even in the absence of significant cardiac hypertrophy. The pathology underlying this mechanism has not yet been identified. AIMS: To study the underlying mechanism of this phenomenon we characterized the left ventricular (LV) performance of transgenic mice carrying the human troponin T mutation I79N under basal and isoproterenol-induced stress conditions. METHODS AND RESULTS: LV function was analyzed by recording pressure-volume loops using a microconductance catheter. Despite a hypercontractile systolic function under basal conditions TnT-I79N mice showed a diastolic dysfunction indicated by an increase in end-diastolic pressure-volume relationship (EDPVR), a load-independent factor of LV stiffness (0.06+/-0.01 vs. 0.02+/-0.01; P<0.05), when compared to mice expressing human wild-type troponin T (TnT-WT). TnT-I79N mutants developed severe diastolic heart failure and cardiac sudden death under isoproterenol stress. This was prevented after pretreatment with the L-type Ca2+ channel inhibitor diltiazem. CONCLUSIONS: Diastolic dysfunction due to increased LV stiffness in TnT-I79N mice leads to severe primary diastolic heart failure and finally to cardiac sudden death, which can be prevented by diltiazem. |
