High Intensity Interval Training is Superior to Continuous Training in a Pulmonary Hypertension Rat Model

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Exercise appears to have overall benefit in pulmonary arterial hypertension (PAH); however, studies to date indicate little effect on the elevated pulmonary artery pressure (PAP) or RV hypertrophy (RVH) and dysfunction associated with the disease. We investigated if the greater endothelial stimulation of high intensity interval training (HIIT) would provide superior benefit over the more customary prolonged continuous exercise training (CExT) protocol in a rat model of PAH. We further sought to characterize acute PAP responses to HIIT and CExT in a PAH rat. METHODS: Six wks of treadmill training was performed 5x/wk in male Sprague-Dawley rats (250-300g) with monocrotaline- (MCT, 40 mg/kg) induced mild PAH. Training sessions were either HIIT (2 min at ~90% VO2 reserve [VO2R] + 3 min at 30% VO2R, for 5 cycles; n=8), or low intensity CExT (60 min at 50% VO2R; n=7). In an additional rat, telemetric recording of simultaneous PAP and systemic pressures were obtained during HIIT and CExT running, serially at pre- and 2, 4, 6, and 8 wks post-MCT. Values are means±SE. RESULTS: MCT-induced decrement in VO2max was ameliorated by both HIIT and CExT (p≤0.01 vs. sedentary MCT rats, MCT-SED, n=6), and were similar to healthy sedentary controls (CON, n=6). Most importantly, RV systolic pressure (in mmHg) and RVH (ratio of RV to LV+S mass) were lowered (p<0.05) only by HIIT (28.7±2, and 0.32±0.02) and not by CExT (44.1±3, and 0.43±0.01) vs. MCT-SED (40.2±3.2, and 0.41±0.02). Echocardiography performed pre- and post-HIIT also indicated reduced RVH ([INCREMENT] wall thickness 0.11±8 mm) and improved RV function ([INCREMENT] cardiac output 117±28 μl) vs. MCT-SED (0.79±8 mm, and 6±42 μl, p<0.05). RV fibrosis was less only for HIIT (p<0.05 vs. MCT-SED), and no training effect was observed on RV inflammation and apoptosis or pulmonary vascular remodeling. Pulmonary endothelial nitric oxide synthase was increased (p<0.05) only with HIIT, consistent with enhanced endothelial stimulation. Implantable telemetry revealed repeated ‘surging’ of PAP during HIIT running, followed by more pronounced PAP reduction during recovery. CONCLUSIONS: HIIT may be superior to CExT for improving hemodynamics and RV dysfunction in PAH and may be explained by greater sheer-stress mediated vascular endothelial adaptation to HIIT stimulus. Funding: Amer. Heart Assoc. SDG to Brown.