Madelyn Blake

A Ketogenic Diet Enhances Right Ventricular Function in Rodent Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a rare, but lethal condition characterized by elevated pressures in the pulmonary circulation. Increased right ventricular (RV) afterload leads to RV dysfunction and ultimately death, and currently we do not have any efficacious interventions to augment RV function. Ketones are an efficiently metabolized carbon source for the heart, and induction of ketosis with a ketogenic diet can be readily achieved. However, the effects of dietary ketosis on RV function in rodent PAH are unknown. Methods: Male Sprague Dawley rats were randomly assigned to 3 groups: control (phosphate buffered saline injection), monocrotaline (MCT) given a standard chow diet (caloric breakdown of 58% carbohydrates, 18% fat, and 24% protein), and monocrotaline given a ketogenic diet diet (caloric breakdown of 0% carbohydrates, 90.5% fat, and 9.5% protein) starting two weeks after MCT injection to improve translational value. Results: MCT rats given a ketogenic diet gained slightly less weight during study duration compared to MCT standard diet. The severity of PAH and degree of RV hypertrophy was not significantly altered by a ketogenic diet. However, dietary ketosis resulted in augmented RV function as demonstrated by a significant increase in tricuspid plane systolic excursion, RV free wall thickening, and cardiac output. Dietary ketosis also resulted in decreased RV fibrosis. Conclusions: Ketogenic diet did not alter PAH severity or RVH, but it augmented RV function in rodent PAH. These results suggest therapeutic ketosis via a ketogenic diet may be a non-pharmaceutical approach to combat RV dysfunction in PAH.