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Impaired skeletal muscle performance as a consequence of random functional capillary rarefaction can be restored with overload-dependent angiogenesis.

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Abstract:

KEY POINTS:Loss of skeletal muscle capillaries is thought to contribute to a reduction in exercise tolerance but the relative contribution of a compromised microcirculation with disease, in isolation of co-morbidities, to impaired muscle function is unknown. We have therefore developed a novel method to randomly occlude capillaries in the rat hindlimb to mimic the capillary rarefaction observed in many conditions. We demonstrate that muscle fatigue resistance is closely coupled with functional microvascular density, independent of arterial blood flow while, disturbance of the microcirculation leads to long-term impairment of muscle function if left untreated. Mechanical stretch due to muscle overload causes a restoration of fatigue resistance via angiogenic remodelling. These observations highlight the importance of a healthy microcirculation and suggest that restoring impaired microvascular supply, regardless of disease co-morbidities, will assist recovery of exercise tolerance in a variety of conditions that limit quality of life. ABSTRACT:To what extent microvascular rarefaction contributes to impaired skeletal muscle function remains unknown. Our understanding of whether pathological changes in the microcirculation can be reversed remains limited by a lack of basic physiological data in otherwise healthy tissue. Principal objectives were: 1) quantify the effect of random microvascular rarefaction on limb perfusion and muscle performance; 2) determine if these changes could be reversed. We developed a novel protocol in rats whereby microspheres injected into the femoral artery allowed a unilateral reduction in functional capillary density in the extensor digitorum longus (EDL), and assessed acute and chronic effects on muscle function. Simultaneous bilateral EDL force and hindlimb blood flow measurements were made during electrical stimulation. Following functional capillary rarefaction there was an acute microsphere dose-dependent reduction in muscle fatigue resistance (P < 0.001), despite preserved femoral artery perfusion. Histological analysis of EDL samples taken from injected animals confirmed a positive correlation between the proportion of functional capillaries and fatigue resistance (P = 0.002). Such impaired performance persisted for at least 2 weeks (P = 0.016). Concomitant mechanical overload improved both perfused capillary density and fatigue resistance (P < 0.05), confirming that the capacity for muscle remodelling was retained following chronic distributed ischaemia, and that the impact of capillary rarefaction could be alleviated. These results demonstrate that loss of functional capillaries is detrimental to muscle function, even in otherwise healthy tissue, independent of arterial perfusion. Restoration of muscle performance following a mechanical overload stimulus indicates that angiogenic treatments to alleviate microvascular rarefaction may be key to restoring exercise tolerance. This article is protected by copyright. All rights reserved.

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JOURNAL OF PHYSIOLOGY-LONDON

J PHYSIOL-LONDON
最新影响因子:5.182 期刊ISSN:0022-3751 CiteScore:
出版周期:Semimonthly 是否OA:YES 出版年份:1878

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自引率:8.80% 研究方向:医学-神经科学
出版地区:ENGLAND

SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)

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JOURNAL OF PHYSIOLOGY-LONDON 期刊简介

英文简介:

Published by Cambridge University Press. ISSN (printed): 0022-3751. ISSN (electronic): 1469-7793. Published for The Physiological Society The policy of The Journal of Physiology

中文简介:(来自Google、百度翻译)

由剑桥大学出版社出版。ISSN(印刷):0022-3751。ISSN(电子):1469-7793。 为生理学会出版的《生理学杂志》政策

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(由下方点评分析获得,2人参与,1849人阅读)

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  • avatar

    liting7111

    研究方向:医药科学 神经系统 精神疾病 认知功能障碍

    审稿时间: 2个月内

    投稿两个月不到被拒,回复速度太慢了,不建议大家投,我是老板要求我投,没办法才投的。
    2020-06-20
  • avatar

    liting7111

    研究方向:医药科学 神经系统 精神疾病 躯体感觉、疼痛与镇痛

    审稿时间: 1个月内

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    2020-01-23

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