Browsing by Author "Graber, Jeremy"

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    High Intensity Interval Training Benefits Right Heart Function in a Rat Model of Pulmonary Arterial Hypertension
    (Office of the Vice Chancellor for Research, 2016-04-08) Troutman, Ashley; Brown, Mary Beth; Johnson, Breann; Neves, Evandro; Fisher, Amanda; Graber, Jeremy; Gladish, Brett; Presson, Robert; Petrache, Irina; Kline, Jeffrey A.; Lahm, Tim
    Pulmonary Arterial Hypertension (PAH) is a disease of progressive remodeling in pulmonary arteries that elevates pulmonary pressures and eventually leads to right ventricular (RV) failure and death. The purpose of this study was to examine the benefit and detriment of high intensity interval training (HIIT) to the RV in a monocrotaline (MCT) PAH rat model. It is hypothesized that HIIT will improve indicators of RV function without increasing myocardial inflammation or apoptosis. Male Sprague Dawley rats were injected with either MCT (40 mg/kg, n=14)) to induce mild PAH or saline for healthy controls (CON, n=9). A subgroup of MCT (n= 8) and CON rats (n=6) performed a 6 week treadmill HIIT program 5x/week using short bouts of alternating high intensity (2 min, 85-90%VO2max) and low intensity (3 min, ~30%VO2max) running for 30 min/session. Histochemistry/immunohistochemistry was performed on cryofixed or formalin-fixed/paraffin-embedded RV sections to assess indicators of inflammation (CD45+ cells), apoptosis (TUNEL), fibrosis (trichrome) and was imaged using epifluorescence or brightfield microscopy. Image quantification was performed using ImageJ. For the HIIT rats, a reduction in MCTinduced RV hypertrophy was observed, as measured echocardiographically, and by the calculated ratio of RV mass relative to LV+Septum mass. RV function was better preserved for HIIT vs. sedentary MCT, as indicated by stroke volume and cardiac index (cardiac output normalized by body weight) in echocardiography. MCT-induced RV fibrosis as measured by trichrome staining was lower for HIIT, also indicating a healthier myocardium. HIIT did not prompt greater counts per field of CD45+ cells and TUNEL+ cells in HIIT vs. sedentary MCT RV myocardium. In conclusion, in the monocrotaline rat model of PAH, HIIT appears to be a beneficial exercise approach that improves RV function without exacerbating RV inflammation or apoptosis. Future work will examine effects in other PAH models and ultimately in patients with disease.
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    High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension
    (APS, 2017) Brown, Mary Beth; Neves, Evandro; Long, Gary; Graber, Jeremy; Gladish, Brett; Wiseman, Andrew; Owens, Matthew; Fisher, Amanda J.; Presson, Robert G.; Petrache, Irina; Kline, Jeffrey A.; Lahm, Tim; Department of Physical Therapy, School of Health and Rehabilitation Sciences
    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.
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    Investigating Skeletal Muscle Metabolic Adaptations underlying Aerobic Fitness Gains following High Intensity Interval Training in a Rat Model of Pulmonary Arterial Hypertension
    (Office of the Vice Chancellor for Research, 2016-04-08) Talley, Mary; Troutman, Ashley; Neves, Evandro; Fisher, Amanda; Graber, Jeremy; Gladish, Brett; Presson, Robert; Petrache, Irina; Kline, Jeffrey A.; Lahm, Tim
    Rationale: In patients with pulmonary arterial hypertension (PAH) a shift from oxidative to a less efficient non-oxidative (glycolytic) metabolism in skeletal muscle is believed to contribute to the reduced exercise tolerance hallmark of the disease. As seen for other cardiopulmonary diseases, exercise training (ExT) may ameliorate this “glycolytic switch” in PAH and improve exercise capacity. Previous studies in this lab showed an improved metabolic profile of skeletal muscle in PAH rats following an ExT protocol of continuous running at moderate relative intensity, 60 minutes at 75% of maximal aerobic capacity (VO2 Max). This study tests the hypothesis in a PAH rat model that HIIT will also result in preserved aerobic capacity and attenuation of skeletal muscle glycolytic shift. Methods: Male Sprague-Dawley rats received either monocrotaline (MCT, 40 mg/kg) to induce mild PAH (n= 14), or saline, for healthy controls (n=9). After 2 wks, a 6 wkprogram of treadmill HIIT was initiated for a subset of PAH (n= 8) and healthy controls (n=6). The 30 min HIIT sessions alternated between 2 minutes at 85% VO2 max and 3 minutes at ~30% VO2 max. VO2 max was assessed at baseline, and in pre-training and post-training via analysis of expired gases. Preliminary results: MCT-induced decrement in VO2 max was attenuated by HIIT (p<0.05). Soleus muscle hypertrophy (soleus mass relative to body mass) tended to be higher (p=0.07) in HIIT vs. SED MCT. Membrane glucose transporter Glut-1, a marker of glycolytic metabolism, was evaluated in soleus cryosections with immunofluorescent staining and abundance was similar between sedentary and HIIT MCT rats (p>0.05). Western blotting of soleus homogenates for cytochromes I-V of the electron transport chain (OXPHOS), and for PGC1α, a potent stimulus for mitochondrial biogenesis, is being performed at present to further investigate potential training-induced adaptations in skeletal muscle metabolism