Diet Modification Reverses Diastolic Dysfunction in Rats with Heart Failure and Preserved Ejection Fraction

Abstract

Dahl Salt-Sensitive (DSS) rats develop heart failure and preserved ejection fraction (HFpEF) when fed a high-salt (8% NaCl) diet. Hypertension-induced inflammation and subsequent ventricular fibrosis are believed to underlie the development of HFpEF. We investigated the role of diet modification in the progression of HFpEF using DSS rats, fed either a high-salt diet from 7 weeks of age to induce HFpEF, or a normal-salt (0.3% NaCl) diet as controls. After echocardiographic confirmation of diastolic dysfunction at 14-15 weeks of age along with HF manifestations, the HFpEF rats were randomly assigned to either continue a high-salt diet or switch to a normal-salt diet for an additional 4 weeks. HFpEF rats with diet modification showed improved diastolic function (reduced E/E’ ratio in echocardiogram), increased functional capacity (increased treadmill exercise distance), and reduced pulmonary congestions (lung/body weight ratio), compared to high-salt-fed HFpEF rats. Systolic blood pressure remained high (~200 mmHg), and ventricular hypertrophy remained unchanged. Ventricular arrhythmia inducibility (100% inducible) and corrected QT interval (on ECG) did not change in HFpEF rats after diet modification. HFpEF rats with diet modification showed prolonged survival and reduced ventricular fibrosis (Masson’s trichrome staining) compared to high-salt-fed HFpEF rats. Our experiments implicate that a high-salt diet is an important trigger for HFpEF, not the high blood pressure or hypertrophy. A high-salt diet-induced ventricular fibrosis is the main culprit that causes the HFpEF pathology.

Note:

Funding Information: This research was supported by NIH R01HL147570 (EC).

Declaration of Interests: None.

Ethics Approval Statement: All the rodent protocols and experiments were approved by the Cedars-Sinai Medical Center Institutional Animal Care and Use Committee

Keywords: heart failure with preserved ejection fraction, diet, blood pressure, diastolic function, hypertension, ventricular arrhythmias