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在有氧能力较差的转甲状腺素蛋白心脏淀粉样变患者中,肌肉代谢反射的通气成分受到过度刺激。

The ventilatory component of the muscle metaboreflex is overstimulated in transthyretin cardiac amyloidosis patients with poor aerobic capacity.

作者信息

Monfort Astrid, Thevenet Eugenie, Enette Lievyn, Fagour Cedric, Inamo Jocelyn, Neviere Remi

机构信息

Department of Cardiology, CHU Martinique (University Hospital of Martinique), Fort de France, France.

Cardiovascular Research Team EA7525, Université des Antilles, Fort de France, France.

出版信息

Front Physiol. 2023 May 15;14:1174645. doi: 10.3389/fphys.2023.1174645. eCollection 2023.

Abstract

The exercise pressor reflex, i.e., metabo- and mechano-reflex, partially regulates the control of ventilation and cardiovascular function during exercise. Abnormal exercise pressor reflex response has been associated with exaggerated ventilatory drive, sympathovagal imbalance and exercise limitation in chronic heart failure patients. Whether metaboreflex is over-activated and participate to poor aerobic capacity in patients with hereditary transthyretin cardiac amyloidosis (CA-TTR) is unknown. Twenty-two CA-TTR patients (aged 76 ± 7, 68% male) with the V122I (p.Val142Ile) transthyretin underwent a thorough evaluation including heart rate variability metrics, electrochemical skin conductance (ESC), physical function cardiopulmonary exercise testing, and muscle metaboreflex assessment. Eleven control subjects were chosen for muscle metaboreflex assessment. Age-matched controls ( = 11) and CA-TTR patients ( = 22) had similar metaboreflex sensitivity for heart rate, stroke volume, cardiac index and mean systemic arterial pressure. Compared with age-matched controls, metaboreflex sensitivity for systemic vascular resistance (-18.64% ± 6.91% vs 3.14% ± 23.35%) and minute-ventilation responses (-9.65% ± 14.83% vs 11.84% ± 23.1%) was markedly increased in CA-TTR patients. Values of ESC displayed positive correlations with stroke volume ( = 0.53, = 0.011) and cardiac index ( = 0.51, = 0.015) components of metaboreflex sensitivity, an inverse correlation with systemic vascular resistance ( = -0.55, = 0.008) and a trend with mean arterial ( = -0.42, = 0.052) components of metaboreflex sensitivity. Peak aerobic capacity (peak VO%) displayed an inverse correlation with the ventilation component of metaboreflex sensitivity ( = -0.62, = 0.015). Consistent with the "muscle hypothesis" in heart failure, it is proposed that deterioration of skeletal muscle function in hereditary CA-TTR patients may activate muscle metaboreflex, leading to an increase in ventilation and sensation of breathlessness, the perception of fatigue, and overall sympathetic activation.

摘要

运动升压反射,即代谢性和机械性反射,在运动过程中部分调节通气和心血管功能的控制。慢性心力衰竭患者运动升压反射反应异常与通气驱动增强、交感迷走神经失衡及运动受限有关。遗传性转甲状腺素蛋白心脏淀粉样变性(CA-TTR)患者的代谢反射是否过度激活并参与有氧运动能力下降尚不清楚。22例携带V122I(p.Val142Ile)转甲状腺素蛋白的CA-TTR患者(年龄76±7岁,68%为男性)接受了全面评估,包括心率变异性指标、电化学皮肤电导(ESC)、身体功能心肺运动试验和肌肉代谢反射评估。选择11名对照受试者进行肌肉代谢反射评估。年龄匹配的对照组(n = 11)和CA-TTR患者(n = 22)在心率、每搏输出量、心脏指数和平均体循环动脉压方面具有相似的代谢反射敏感性。与年龄匹配的对照组相比,CA-TTR患者对体循环血管阻力的代谢反射敏感性(-18.64%±6.91% vs 3.14%±23.35%)和分钟通气反应(-9.65%±14.83% vs 11.84%±23.1%)明显增加。ESC值与代谢反射敏感性的每搏输出量(r = 0.53,P = 0.011)和心脏指数(r = 0.51,P = 0.015)成分呈正相关,与体循环血管阻力(r = -0.55,P = 0.008)呈负相关,与代谢反射敏感性的平均动脉(r = -0.42,P = 0.052)成分呈趋势相关。最大有氧能力(峰值VO₂%)与代谢反射敏感性的通气成分呈负相关(r = -0.62,P = 0.015)。与心力衰竭中的“肌肉假说”一致,有人提出遗传性CA-TTR患者骨骼肌功能的恶化可能激活肌肉代谢反射,导致通气增加、呼吸困难感、疲劳感和整体交感神经激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7d6/10225564/01feb39afad2/fphys-14-1174645-g001.jpg

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