A new porcine model of hypertensive cardiomyopathy: a helpful tool to explore the HFpEF mystique

摘要

heart failure with preserved ejection fraction (HFpEF) is a challenging clinical entity with a lack of clear diagnostic criteria and evidence for therapy (3, 5, 15). Most clinical studies have failed to demonstrate a benefit of drugs in HFpEF (7). Since HFpEF is heterogenous both in aetiology and patho-physiology and notable with multiple cardiac and noncardiac comorbidities (13), the "one size fits all" principle will probably not work. HFpEF may require an individualized, targeted therapy based on age, the underlying aetiology, comorbidities, and so on (4, 14).The underlying mechanisms of the HFpEF syndrome are not fully understood (3). Research animals may be tools for in-depth understanding of pathophysiology and the development of novel therapies. For HFpEF, only few animal models have been proposed. Doi et al. (2) placed Dahl salt-sensitive rats on 8% NaCl from the age of 6 to 7 wk; these hypertensive rats developed HFpEF after 18-21 wk and left ventricular (LV) hypertrophy, followed by transition to congestive heart failure with maintained LV fractional shortening and increased LV stiffness (2, 11). Regan et al. (9) showed that chronic infusion of low-dose angiotensin II results in a HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. Reil et al. (10) demonstrated that selective reduction of heart rate by If-inhibition improved vascular stiffness, LV contractility, and diastolic function in male leptin receptor-deficient C57BL/KsJleprdb/leprdb type 2 diabetic HFpEF mice.