慢性心衰竭患者內皮功能、下肢肌肉表現與代謝能力和生活功能之探討

Abstract

背景與目的：呼吸困難、疲勞及運動耐力不足為慢性心衰竭之典型症狀，目前研究認為運動受限原因和周邊系統功能受損有關，機制可能來自於神經內分泌和血管內在之異常，使血管阻力增加、周邊肌肉血流降低，進一步影響肌肉適能和生活功能。本研究目的在探討慢性心衰竭患者與對照之健康人和冠狀動脈疾患在膝直肌不同速度之最大等速肌力、肌耐力、下肢股內外側肌的灌流代謝、內皮功能和生活狀態的差異與其相關性。 方法：徵召21位平均年齡為62.0 ± 7.5歲男性慢性心臟衰竭患者（左心室射出率小於40%，診斷至少6個月且病情穩定3個月以上），另徵求29位平均年齡為59.9 ± 8.0歲無心衰竭之冠狀動脈疾病患者作為病人對照組，以及20位平均年齡57.0 ± 7.5歲且無心臟疾病診斷者作為健康對照組。排除條件為有骨骼肌肉系統疾病的臨床診斷，其他系統性的疾病可能會影響或不適合運動測試者。由病歷紀錄取得受試者病史、基本資訊、左心室射出率、紐約心臟學會分級及用藥情形，採集受試者血液分析內皮素-1與高敏感度C-反應蛋白。受試者接受身高、體重、身體組成和雷射都普勒血流測量儀合併離子電泳之測量，再用等速肌力儀讓受試者做三種不同角速度【慢速（60°s-1）、中速（180°s-1）和快速（240°s-1）】之最大膝伸直運動，以快速等速運動（膝蓋伸直30次）之總功評估受試者的肌耐力狀況。測試過程中同時利用近紅外線光譜偵測，計算肌肉中去氧血紅素（HHb）和組織氧飽合度（saturation）之改變量，近紅外線光譜的探頭位置為右股內、外側肌的下1/3處。受試者並接受一分鐘坐到站測試、六分鐘行走測驗，以及七日活動問卷、日常生活活動執行能力、明尼蘇達心衰竭生活狀態之問卷調查。以SPSS 13.0（SPSS Inc., Chicago, USA）進行統計分析，採用單因子變異數分析（one-way ANOVA）、無母數分析中克─瓦單因子等級變異數分析（Kruskal-Wallis one-way ANOVA by ranks）、或卡方檢定比較三組各參數之差異。並分析Ach和SNP相對改變量、肌肉灌流代謝基礎值、%改變量和半衰期時間、與肌力、肌耐力及生活功能之間的相關性，所有相關性分析皆使用淨相關分析（partial correlation），以年齡與身體活動量作為共變數。 結果：三組之基本資料相似。心衰竭患者之C-反應蛋白顯著高於冠狀動脈疾患，七日活動問卷活動量、60°s-1和180°s-1最大力矩和60°s-1和240°s-1最大力矩除以體重和生活品質均較冠狀動脈疾患差（明尼蘇打心臟衰竭問卷）。心衰竭患者之SNP血管擴張反應、在三種角速度下之最大力矩、最大力矩除以體重和肌耐力，以及五次坐到站的時間、一分鐘坐到站的次數、六分鐘行走距離亦顯著差於健康受試者；其日常生活活動執行能力的限制（PMADL-8總分），較健康受試者與冠狀動脈疾患高。骨骼肌氧合度方面，在60°s-1角速度時，心衰竭患者股內側肌組織氧飽合度回復到1/2改變量所需之時間顯著長於健康受試者；在180°s-1角速度時，心衰竭患者股外側肌與股內側肌的組織氧飽合度之%改變量/總功顯著大於健康受試者，股外側肌與股內側肌組織氧飽合度回復到1/2改變量所需之時間皆顯著長於健康受試者；在240°s-1角速度時，並無參數達顯著差異。 Ach之相對改變量與180°s-1和240°s-1之最大力矩、240°s-1總功、六分鐘行走距離呈現顯著正相關，SNP之相對改變量和240°s-1總功呈現顯著正相關。三種角速度下股外側肌之去氧血紅素基礎值皆與日常生活活動能力執行能力問卷呈顯著正相關。三種角速度下股外側和股內側肌組織氧飽合度之基礎值，除了於股外側和股內側肌60°s-1和股內側肌180°s-1與一分鐘坐到站次數無顯著差異外，其它與該速度之最大力矩、240°s-1總功、一分鐘坐到站次數、六分鐘行走測試距離呈顯著正相關，與五次坐到站時間和日常生活活動能力執行能力問卷呈顯著負相關。三種角速度之股外側肌去氧血紅素%改變量與該速度之最大力矩、240°s-1總功、五次坐到站時間、一分鐘坐到站次數呈顯著相關；股內側肌去氧血紅素%改變量則與該速度之最大力矩與日常生活活動執行能力問卷呈顯著相關。Ach與SNP之相對改變量和肌肉灌流代謝之間無顯著相關性。 結論：心衰竭患者之肌力、肌耐力、生活功能較健康受試者有下降的情況，肌力、生活功能和品質較冠狀動脈疾患差；在膝伸肌運動時氧氣傳遞能力下降，回復時間較長，代表骨骼肌代謝異常的情況，但在不同肌肉和收縮速度的表現並不一致。內皮功能、運動時肌肉去氧血紅素和休息時氧飽合度與肌肉表現和功能有相關性。

Background and Purpose: Shortness of breath, fatigue, and exercise intolerance are clinical symptoms of chronic heart failure (CHF). Recent studies suggested that peripheral impairment in neuroendocrine and vascular smooth muscle function was also related to their clinical symptoms. The increased peripheral resistance may influence limb blood flow, muscle fitness and activities of daily. The purposes of this study were to compare muscular strength, endurance, perfusion of quadriceps, endothelial function, and living status between CHF and coronary arterial disease (CAD) patients, as well as the healthy persons (HP), and the relations among the measured outcomes. Methods: Twenty-one male patients with stable CHF aged 62.0 ± 7.5 years were recruited from out-patient clinics at National Taiwan University Hospital. Patients were excluded if they have any other primary diseases that may affect the testing or the results. This study also recruited 29 subjects with CAD without heart failure (mean age: 59.9 ± 8.0 years) and 20 HP (mean age: 57.0 ± 7.5 years). Medical data, including medical history, left ventricular ejection fraction, NYHA functional classification, and medication, were retrieved from the chart review. Blood sample was collected to analyze endothelin-1 and high sensitivity C-reactive protein. All subjects took an isokinetic knee extension test at 60°s-1 (5 maximal contractions), 180°s-1 (5 maximal contractions), and 240°s-1 (30 maximal contractions) by Biodex isokinetic dynamometer, and the total work of 240°s-1 was used as indice of muscule endurance. Probes of NIRS were placed at the lowest 1/3 of right vastus lateralis (VL) and vastus medialis (VM) before and during the isokinetic testing. Subjects undertook the assessment of body composition, laser Doppler flowmetry combined iontophoresis, one minute sit-to-stand test, 6-minute walking test (6MWT), and filled in the questionnaire of 7-day recall physical activity questionnaire, Performance Measure for Activities of Daily Living-8 (PMADL-8), and Minnesota Living with Heart Failure Questionnaire (LHFQ). Group comparsions were made using one-way ANOVA or Kruskal-Wallis one-way ANOVA or chi-square test. The relationship among the relative change of Ach and SNP, resting and % change of HHb and saturation, muscle strength, endurance, one minute sit-to-stand test, 6MWT, and PDML-8 were analyzed by partial correlation coefficient, while age and physical activity were used as covariates. Results: The basic characteristics were similar among the three groups. Subjects in CHF group had higher CRP and lower physical activity, peak torque at 60°s-1 and 180°s-1, and also lower peak torque divided by body weight at 60°s-1 and 240°s-1 than CAD. Significantly lower SNP response, muscle strength and endurance, and sit-to-stand and 6MWT were noted in CHF than HP. CHF subjects had higher scores in PMADL-8 than HP and CAD and higher LHFQ scores than CAD, the lower values in PMADL-8 and LHFQ indicated better performance or quality. CHF had significantly longer recovery time in saturation (only VM) at 60°s-1, higher % change/work and longer recovery time of saturation (VL and VM) at 180°s-1 than HP. There was no significant difference in HHb or saturation at 240°s-1 for any between group comparsions. Relative change of Ach was positively correlated with peak torque at 180°s-1 and 240°s-1, total work of 240°s-1, and 6MWT. Relative change of SNP was significantly correlated with total work of 240°s-1. The baseline values of HHb in VL and VM were significantly correlated with PMADL-8. The baseline values of saturation in VL and VM were significantly correlated with peak torque, total work of 240°s-1, duration of 5 times sit-to-stand test, times of one minute sit-to-stand test, 6MWT, and PMADL-8, except 60°s-1 (VL and VM) and 180°s-1 (only VM) showed no significantly correlated with one minute sit-to-stand test. The % change of HHb in VL was only significantly correlated with peak torque, total work of 240°s-1, sit-to-stand test. The % change of HHb in VM was also significantly correlated with peak torque and PMADL-8. The relative change of Ach and SNP were not correlated significantly with HHb or saturation. Conclusion: Muscle strength, functional performance and quality of life were decreased in CHF compared with CAD. Oxygen saturation of quadriceps was decreased, and recovery time was prolonged in CHF. It suggested skeletal muscle metabolism was impaired in CHF; however, it was not consistent in different muscles or speed of contraction. Endothelial function indicated by Ach response, muscle HHb and O2 saturation had some correlations with their muscle and functional performance.