Mitochondrial Dysfunction Contributes to Sustained Muscle Loss After Cardiac Surgery: A Prospective Observational Study

IF 9.1 1区 医学 Q1 GERIATRICS & GERONTOLOGY
Ashley N. Thomas, Antonis Kalakoutas, Martin Yates, John Yap, Julie Sanders, Paul Kemp, Mark J. D. Griffiths
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引用次数: 0

Abstract

Background

As a major systemic insult, cardiac surgery can lead to significant muscle loss, which increases the time to recovery as well as being correlated with mortality. Highly variable loss of muscle mass (0%–40% rectus femoris cross-sectional area [RFcsa]) and strength in the week after surgery has aided understanding of mechanisms of sarcopenia after acute illness. To include muscle recovery, patients' muscle phenotype beyond the first week after surgery and up to their return as outpatients was studied and correlated with protein and metabolomic markers.

Methods

Patients undergoing elective aortic valve surgery were recruited. Muscle mass (RFcsa), strength (handgrip, knee extension and spirometry), body composition (by bioimpedance) and health-related quality of life (generic questionnaire EQ-5D-5L) were determined pre-operatively, 7 days after surgery and at outpatient follow-up. Blood samples were taken on Days 0, 1, 3, 7 and follow-up. The plasma metabolome was determined in 20 patients at Days 0, 3, 7 and follow-up.

Results

Of 31 participants, 20 were male: mean age 68.8 years with a range between 48 and 85 years. Proportionate mean loss of RFcsa between pre-op and Day 7 values was 6.44% [95% CI 4.21 to 8.68, n = 31]; between pre-op and follow-up 9.69% [95% CI 4.92 to 14.96, n = 22]; and between Day 7 and follow-up 3.60% [95% CI −1.30 to 8.48, n = 22]. By contrast to measures of muscle bulk, the strength and functionality assessments (knee extension, handgrip, spirometry and short physical performance battery) decreased in the first week after surgery (pre-op to Day 7) followed by a return to baseline (Day 7 to follow-up). Health-related quality of life (cross-walk index) changed little over the course of the study but correlated positively at follow-up with muscle bulk (RFcsa: r = 0.58 [95% CI 0.19 to 0.81] p = 0.005) and strength of knee extension (r = 0.54 [95% CI 0.14 to 0.79] p = 0.010) and handgrip (r = 0.63 [95% CI 0.27 to 0.83] p = 0.002: n = 22). Both pre-operative and peak (Day 3) plasma levels of short-chain acyl-carnitine markers of mitochondrial dysfunction correlated with proportional muscle loss at follow-up and with strength at all timepoints.

Conclusions

Prolonged follow-up after aortic surgery demonstrated a divergence between the consistent recovery of strength and a significant proportion of patients continuing to lose muscle bulk. Markers of baseline and acute mitochondrial dysfunction predicted poor muscle outcomes up to outpatient follow-up.

Abstract Image

线粒体功能障碍有助于心脏手术后持续肌肉损失:一项前瞻性观察研究
背景:作为一种主要的全身损伤,心脏手术可导致显著的肌肉损失,这增加了恢复时间,并与死亡率相关。术后一周内肌肉质量(0%-40%股直肌横截面积[RFcsa])和力量的高度变化性损失有助于理解急性疾病后肌肉减少症的机制。为了包括肌肉恢复,研究了手术后第一周之后患者的肌肉表型,直到他们作为门诊患者返回,并与蛋白质和代谢组学标志物相关。方法选取择期主动脉瓣手术患者。术前、术后7天及门诊随访时测定肌肉质量(RFcsa)、力量(握力、膝关节伸展和肺活量测定)、身体成分(生物阻抗测定)和健康相关生活质量(EQ-5D-5L)。在第0、1、3、7天及随访时采集血样。20例患者在第0、3、7天及随访时测定血浆代谢组。结果31名参与者中,20名男性,平均年龄68.8岁,年龄范围在48 - 85岁之间。术前至第7天RFcsa的比例平均损失为6.44% [95% CI 4.21至8.68,n = 31];术前与随访9.69% [95% CI 4.92 ~ 14.96, n = 22];第7天至随访期间为3.60% [95% CI - 1.30至8.48,n = 22]。与肌肉量测量相比,在手术后第一周(术前至第7天),力量和功能评估(膝关节伸展、握力、肺活量测定和短时间物理性能电池)下降,随后返回基线(第7天至随访)。与健康相关的生活质量(交叉行走指数)在研究过程中变化不大,但在随访中与肌肉量(RFcsa: r = 0.58 [95% CI 0.19至0.81]p = 0.005)、膝关节伸展强度(r = 0.54 [95% CI 0.14至0.79]p = 0.010)和握力(r = 0.63 [95% CI 0.27至0.83]p = 0.002: n = 22)呈正相关。术前和峰值(第3天)血浆短链酰基肉碱线粒体功能障碍标志物水平与随访时的比例肌肉损失和所有时间点的力量相关。结论:主动脉手术后的长期随访表明,力量的持续恢复与相当比例的患者继续失去肌肉量之间存在差异。基线和急性线粒体功能障碍的标志物预测到门诊随访的不良肌肉预后。
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来源期刊
Journal of Cachexia Sarcopenia and Muscle
Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-
CiteScore
13.30
自引率
12.40%
发文量
234
审稿时长
16 weeks
期刊介绍: The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.
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