title: High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension.
abstract: Exercise is beneficial in pulmonary arterial hypertension (PAH), although studies to date indicate little effect on the elevated pulmonary pressures or maladaptive right ventricle (RV) hypertrophy associated with the disease. For chronic left ventricle failure, high-intensity interval training (HIIT) promotes greater endothelial stimulation and superior benefit than customary continuous exercise training (CExT); however, HIIT has not been tested for PAH. Therefore, here we investigated acute and chronic responses to HIIT vs. CExT in a rat model of monocrotaline (MCT)-induced mild PAH. Six weeks of treadmill training (5 times/wk) were performed, as either 30 min HIIT or 60 min low-intensity CExT. To characterize acute hemodynamic responses to the two approaches, novel recordings of simultaneous pulmonary and systemic pressures during running were obtained at pre- and 2, 4, 6, and 8 wk post-MCT using long-term implantable telemetry. MCT-induced decrement in maximal aerobic capacity was ameliorated by both HIIT and CExT, with less pronounced pulmonary vascular remodeling and no increase in RV inflammation or apoptosis observed. Most importantly, only HIIT lowered RV systolic pressure, RV hypertrophy, and total pulmonary resistance, and prompted higher cardiac index that was complemented by a RV increase in the positive inotrope apelin and reduced fibrosis. HIIT prompted a markedly pulsatile pulmonary pressure during running and was associated with greater lung endothelial nitric oxide synthase after 6 wk. We conclude that HIIT may be superior to CExT for improving hemodynamics and maladaptive RV hypertrophy in PAH. HIIT's superior outcomes may be explained by more favorable pulmonary vascular endothelial adaptation to the pulsatile HIIT stimulus.
authors: Department of Physical Therapy, Indiana University School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana; brownmb@iu.edu.
authors: Mary Beth
authors: MB
authors: Brown
authors: Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors: Evandro
authors: E
authors: Neves
authors: Department of Physical Therapy, Indiana University School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana.
authors: Gary
authors: G
authors: Long
authors: Department of Physical Therapy, Indiana University School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana.
authors: Jeremy
authors: J
authors: Graber
authors: Department of Physical Therapy, Indiana University School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana.
authors: Brett
authors: B
authors: Gladish
authors: Department of Physical Therapy, Indiana University School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana.
authors: Andrew
authors: A
authors: Wiseman
authors: Department of Physical Therapy, Indiana University School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana.
authors: Matthew
authors: M
authors: Owens
authors: Department of Physical Therapy, Indiana University School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana.
authors: Amanda J
authors: AJ
authors: Fisher
authors: Department of Anesthesia, Indiana University School of Medicine, Indianapolis, Indiana.
authors: Robert G
authors: RG
authors: Presson
authors: Department of Pulmonary and Critical Care, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; and.|Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors: Irina
authors: I
authors: Petrache
authors: Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors: Jeffrey
authors: J
authors: Kline
authors: Department of Pulmonary and Critical Care, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; and.|Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors: Tim
authors: T
authors: Lahm
mesh_terms: D000818:Animals; D000072696:High-Intensity Interval Training / Q000379:methods*; D006976:Hypertension, Pulmonary / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D010805:Physical Conditioning, Animal / Q000379:methods; D010807:Physical Endurance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D018497:Ventricular Dysfunction, Right / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*
keywords: apelin; endothelial nitric oxide synthase