Novel assessment of haemodynamic kinetics with acute exercise in a rat model of pulmonary arterial hypertension

Mary Beth Brown, Tsungai J. Chingombe, Abigail B. Zinn, Jagadeshwar G. Reddy, Rachel A. Novack, Sean A. Cooney, Amanda J. Fisher, Robert Presson, Tim Lahm, Irina Petrache

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Abstract

New Findings: What is the central question of this study? The acute effect of exercise at moderately high intensity on already-elevated pulmonary arterial pressures and right ventricular wall stress in a rat model of pulmonary arterial hypertension (PAH) is unknown. What is the main finding and its importance? We show, for the first time, that in a rat model of PAH, exercise induces an acute reduction in pulmonary artery pressure associated with lung endothelial nitric oxide synthase activation, without evidence of acute right ventricular inflammation or myocyte apoptosis. Haemodynamic measures obtained with traditional invasive methodology as well as novel implantable telemetry reveal an exercise-induced 'window' of pulmonary hypertension alleviation, supporting future investigations of individualized exercise as therapy in PAH. Exercise improves outcomes of multiple chronic conditions, but controversial results, including increased pulmonary artery (PA) pressure, have prevented its routine implementation in pulmonary arterial hypertension (PAH), an incurable disease that drastically reduces exercise tolerance. Individualized, optimized exercise prescription for PAH requires a better understanding of disease-specific exercise responses. We investigated the acute impact of exercise on already-elevated PA pressure and right ventricular (RV) wall stress and inflammation in a rat model of PAH (PAH group, n = 12) induced once by monocrotaline (50 mg kg<sup>-1</sup>, i.p.; 2 weeks), compared with healthy control animals (n = 8). Single bouts of exercise consisted of a 45 min treadmill run at 75% of individually determined aerobic capacity (V˙O2max). Immediately after exercise, measurements of RV systolic pressure and systemic pressure were made via jugular and carotid cannulation, and were followed by tissue collection. Monocrotaline induced moderate PAH, evidenced by RV hypertrophy, decreased V˙O2max, PA muscularization, and RV and skeletal muscle cytoplasmic glycolysis detected by increased expression of glucose transporter-1. Acute exercise normalized the monocrotaline-induced elevation in RV systolic pressure and augmented pulmonary endothelial nitric oxide synthase activation, without evidence of increased RV inflammation or apoptosis. Real-time recordings of pulmonary and systemic pressures during and after single bouts of exercise made using novel implantable telemetry in the same animal for up to 11 weeks after monocrotaline (40 mg kg<sup>-1</sup>) corroborated the finding of acute PA pressure decreases with exercise in PAH. The PA pressure-lowering effects of individualized exercise associated with RV-neutral effects and increases in vasorelaxor signalling encourage further development of optimized exercise regimens as adjunctive PAH therapy.

Original languageEnglish
Pages (from-to)742-754
Number of pages13
JournalExperimental Physiology
Volume100
Issue number6
DOIs
StatePublished - Jun 1 2015

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Pulmonary Hypertension
Hemodynamics
Exercise
Monocrotaline
Pulmonary Artery
Pressure
Ventricular Pressure
Lung
Telemetry
Nitric Oxide Synthase Type III
Inflammation
Apoptosis
Blood Pressure
Right Ventricular Hypertrophy
Exercise Therapy
Exercise Tolerance
Facilitative Glucose Transport Proteins
Glycolysis
Catheterization
Muscle Cells

ASJC Scopus subject areas

  • Physiology

Cite this

Novel assessment of haemodynamic kinetics with acute exercise in a rat model of pulmonary arterial hypertension. / Brown, Mary Beth; Chingombe, Tsungai J.; Zinn, Abigail B.; Reddy, Jagadeshwar G.; Novack, Rachel A.; Cooney, Sean A.; Fisher, Amanda J.; Presson, Robert; Lahm, Tim; Petrache, Irina.

In: Experimental Physiology, Vol. 100, No. 6, 01.06.2015, p. 742-754.

Research output: Contribution to journalArticle

Brown, Mary Beth ; Chingombe, Tsungai J. ; Zinn, Abigail B. ; Reddy, Jagadeshwar G. ; Novack, Rachel A. ; Cooney, Sean A. ; Fisher, Amanda J. ; Presson, Robert ; Lahm, Tim ; Petrache, Irina. / Novel assessment of haemodynamic kinetics with acute exercise in a rat model of pulmonary arterial hypertension. In: Experimental Physiology. 2015 ; Vol. 100, No. 6. pp. 742-754.
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