Background
Recent in vitro studies on failing human heart muscle has suggested that ranolazine (RAN), a novel antianginal drug known to inhibit late sodium current, may improve diastolic dysfunction (DD) caused by hypertension (HTN)-induced oxidative stress. By improving DD, RAN can improve heart failure with preserved ejection fraction (HFPEF).
Methods
A mouse model of DD was developed by inducing mild HTN by unilateral nephrectomy, deoxycorticosterone acetate (DOCA) pellet implantation, and substituting drinking water with 1% NaCl. Control animals underwent sham operation and drank regular tap water. RAN 50 (mg/kg) was given orally twice a day. Weekly blood pressures (BPs) and heart rates (HRs) were measured using tail-cuff plethysmography. Cardiac function and left ventricular posterior wall thickness (LVPWd) were measured by echocardiogram under light anesthesia using isoflurane. Treatment duration was for 3 weeks and 7 weeks. Pulmonary congestion was assessed by lung to body weight (L/BW) ratio.
Methods
A mouse model of DD was developed by inducing mild HTN by unilateral nephrectomy, deoxycorticosterone acetate (DOCA) pellet implantation, and substituting drinking water with 1% NaCl. Control animals underwent sham operation and drank regular tap water. RAN 50 (mg/kg) was given orally twice a day. Weekly blood pressures (BPs) and heart rates (HRs) were measured using tail-cuff plethysmography. Cardiac function and left ventricular posterior wall thickness (LVPWd) were measured by echocardiogram under light anesthesia using isoflurane. Treatment duration was for 3 weeks and 7 weeks. Pulmonary congestion was assessed by lung to body weight (L/BW) ratio.
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