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Acute and chronic exercise in patients with HFrEF: Evidence of structural and functional plasticity and intact angiogenic signaling in skeletal muscle.

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Acute and chronic exercise in patients with HFrEF: Evidence of structural and functional plasticity and intact angiogenic signaling in skeletal muscle.

J Physiol. 2018 Sep 07;:

Authors: Esposito F, Mathieu-Costello O, Wagner PD, Richardson RS

Abstract
KEY POINTS: The vascular endothelial growth factor (VEGF) response to acute submaximal exercise and training effects in patients with heart failure with reduced ejection fraction (HFrEF) were investigated. Six patients and six healthy matched-controls performed knee-extensor exercise (KE) at 50% of maximum work-rate before and after (only patients) KE training. Muscle biopsies were taken to assess skeletal muscle structure and the angiogenic response. Pre-training, during this submaximal KE exercise, HFrEF exhibited higher leg vascular resistance and greater norepinephrine spillover. Skeletal muscle structure and VEGF response were mostly not different between groups. Post-training, resistance was no longer elevated and norepinephrine spillover was curtailed in the patients. Although, in the trained state, VEGF did not respond to acute exercise, capillarity was augmented. Muscle fiber cross sectional area and %area of type I fibers increased and mitochondrial volume density exceeded that of controls. Structural/functional plasticity and appropriate angiogenic signaling were observed in skeletal muscle of patients with HFrEF.
ABSTRACT: Objectives This study examined the response to acute submaximal exercise and the effect of training in patients with heart failure with reduced ejection fraction (HFrEF). Background The acute angiogenic response to submaximal exercise in HFrEF after small muscle mass training is debated. Methods The direct Fick method, with vascular pressures, was performed across the leg during knee-extensor exercise (KE) at 50% of maximum work-rate (WRmax ) in patients (n = 6) and controls (n = 6) and then post-KE training in patients. Muscle biopsies facilitated the assessment of skeletal muscle structure and vascular endothelial growth factor (VEGF) mRNA levels. Results Pre-training, HFrEF exhibited significantly higher leg vascular resistance (LVR) (≈15%) and significantly greater norepinephrine (Ne) spillover (≈385%). Apart from mitochondrial volume density, which was significantly lower (≈22%) in HFrEF, initial skeletal muscle structure, including capillarity, were not different between groups. Resting VEGF mRNA levels, and the increase with exercise, was not different between patients and controls. Post-training LVR was no longer elevated and Ne spillover was curtailed. Skeletal muscle capillarity increased with training, as assessed by capillary-to-fiber ratio (≈13%) and number of capillaries around a fiber (NCAF )(≈19%). VEGF mRNA was now not significantly increased by acute exercise. Muscle fiber cross sectional area and % area of type I fibers both increased significantly with training (≈18% and ≈21%, respectively), while the %area of type II fibers fell significantly (≈11%), and mitochondrial volume density now exceeded that of controls. Conclusions These data reveal structural and functional plasticity and appropriate angiogenic signaling in skeletal muscle of HFrEF patients. This article is protected by copyright. All rights reserved.

PMID: 30192995 [PubMed – as supplied by publisher]

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