by Holly R. Middlekauff Circ Heart Fail Volume 3(4): July 20, 2010

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Presentation transcript:

Making the Case for Skeletal Myopathy as the Major Limitation of Exercise Capacity in Heart Failure by Holly R. Middlekauff Circ Heart Fail Volume 3(4):537-546 July 20, 2010 Copyright © American Heart Association, Inc. All rights reserved.

A, Fiber type shift correlates with decreased exercise capacity. A, Fiber type shift correlates with decreased exercise capacity. Morphometric analyses of muscle biopsies from HF patients have revealed a shift in fiber type, from slow-twitch, oxidative type I fibers to fast-twitch, glycolytic type IIb fibers. The shift in fiber type correlates with diminished exercise capacity as estimated by peak oxygen consumption. B, Decreased mitochondrial density correlates with decreased exercise capacity. Quantified by electron microscopy, volume density of the mitochondrial in HF is significantly diminished compared with control subjects. See text for discussion. Filled squares indicate HF and open squares, control subjects. Reprinted with permission from Woltersk Kluwer/Lippincott Williams & Wilkins.9 Holly R. Middlekauff Circ Heart Fail. 2010;3:537-546 Copyright © American Heart Association, Inc. All rights reserved.

Correlation between exercise capacity and muscle oxidative capacity. Correlation between exercise capacity and muscle oxidative capacity. HF patients have lower exercise capacity but similar muscle oxidative capacity compared with sedentary control subjects; both exercise capacity and muscle oxidative capacity are lower in these groups compared with active control subjects. The decreased exercise capacity in HF, therefore, cannot be entirely attributed to decreased muscle oxidative capacity. Open circles indicate HF; open triangles, sedentary control subjects; and closed triangles, active control subjects. Modified from Reference 16. Holly R. Middlekauff Circ Heart Fail. 2010;3:537-546 Copyright © American Heart Association, Inc. All rights reserved.

Abnormal E-C coupling in HF. See text for discussion. Abnormal E-C coupling in HF. See text for discussion. Modified from Reference 19. Holly R. Middlekauff Circ Heart Fail. 2010;3:537-546 Copyright © American Heart Association, Inc. All rights reserved.

RyR1 phosphorylation and muscle fatigue. RyR1 phosphorylation and muscle fatigue. Time to fatigue was directly correlated to RyR1 PKA phosphorylation in rat skeletal muscle from sham-operated (open squares) and HF(closed squares) animals. Reprinted with permission from Reiken et al.20 Holly R. Middlekauff Circ Heart Fail. 2010;3:537-546 Copyright © American Heart Association, Inc. All rights reserved.

Coordinated adaptation in oxygen transport. Coordinated adaptation in oxygen transport. Arrow size indicates capacity; shaded arrows indicate sites of greatest limitation. The number of plus signs indicates the effect of changing capacity on changing maximal oxygen flux. The athlete has matched capacities at all steps. The untrained person is limited by cardiovascular delivery and muscle extraction. The patient with chronic lung disease is limited by pulmonary diffusion. In chronic HF, the limited maximal cardiac output leads to downregulation of muscle oxygen extraction and mitochondrial utilization. Modified from Reference 6. Holly R. Middlekauff Circ Heart Fail. 2010;3:537-546 Copyright © American Heart Association, Inc. All rights reserved.

Mechanisms by which SNA may contribute to the skeletal myopathy of HF Mechanisms by which SNA may contribute to the skeletal myopathy of HF. See text for discussion. Mechanisms by which SNA may contribute to the skeletal myopathy of HF. See text for discussion. Holly R. Middlekauff Circ Heart Fail. 2010;3:537-546 Copyright © American Heart Association, Inc. All rights reserved.

Benefits of exercise. Benefits of exercise. Exercise training decreases resting SNA, decreases inflammation, reverses morphometric and histochemical features of skeletal myopathy, leads to improved blood flow, and increases quality of life (QOL) and overall exercise capacity. Holly R. Middlekauff Circ Heart Fail. 2010;3:537-546 Copyright © American Heart Association, Inc. All rights reserved.

Sympathetic nerve recordings before and after exercise training period (A) or sedentary period (B). Sympathetic nerve recordings before and after exercise training period (A) or sedentary period (B). In pretraining patients and presedentary control patients, SNA is markedly increased. After the training period but not the sedentary period, SNA is significantly reduced. Reproduced with permission from Elsevier.68 Holly R. Middlekauff Circ Heart Fail. 2010;3:537-546 Copyright © American Heart Association, Inc. All rights reserved.