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研究生： 吳一凡
Wu, Yi-Fan
論文名稱： 探討成人開心手術對血液流變特性的影響
Hemo-rheological changes in cardiac surgery patients
指導教授： 陳彥龍
Chen, Yeng-Long
口試委員: 蔡建松
Tsai, Chien-Sung
董奕鍾
Tung, Yi-Chung
王潔
Wang, Jane
許博順
Hsu, Po-Shun
學位類別： 博士
Doctor
系所名稱： 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年： 2018
畢業學年度： 107
語文別： 英文
論文頁數： 100
中文關鍵詞： 血液流變學 、黏彈性 、紅血球聚集 、開心手術 、體外循環 、心血管疾病
外文關鍵詞： Hemo-rheology, Viscoelasticity, RBC Aggregation, Cardiac Surgery, Cardiopulmonary Bypass, Cardiovascular disease
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    • 現今心血管疾病與相關併發症已成為十大死因常見的排行中，因此開心手術搭配體外循環機來維持生命被視為常見的治療手段之一，包含：心臟繞道手術、瓣膜置換…等。然而手術所造成的發炎反應將會造成紅血球的聚集與凝集，將容易導致靜脈栓塞、中風、記憶喪失…等術後併發症。
    血液流變學(Hemorheology)多年來在臨床上已被運用在血液循環效率與保健上，由於其紅血球的聚集程度將直接影響血液的物理特性。本研究中，我們認為術後併發症可能與血液黏滯度變化有關，在實驗設計中，我們量測開心手術病人術後的血液黏性、彈性模數、紅血球聚集影像、生化數值的變化影響，並與手術前狀態及健康正常人相比。血液流變學與紅血球聚集影響將分別於病人手術前(M0)，手術後與長期復原變化 (M1 ~ M3)，以及獨立招募的正常族群。實驗使用流變儀Anton-Paar MCR501量測黏度與彈性模數，此外，我們也以問卷與病歷來記錄病人日常習慣與生化數據作為參考，譬如：抽煙、喝酒、或低密度膽固醇…等。
    實驗結果顯示，術後一天(M1)和術後一星期(M2)的紅血球血比容(HCT)與術前(M0)相比有發現顯著的降低，這可能與體外循環所造成血液稀釋影響有關，但在調整於相同血比容下，實驗結果觀察到手術後的紅血球聚集變得較劇烈，形成較大聚集面積與較圓的聚集形狀，這與血漿內的纖維蛋白上升濃度有顯著正相關。同樣在這期間，當校正於相同濃度下的血液黏度在術後病人(M1, M2)於低剪切速率下也有顯著的升高，意味著手術後短期內病人的血液有具較高的降伏應力(yield stress)，表示具有較高的紅血球聚集結構與類膠體特性，但在手術後半年～一年(M3)，多數的參數皆回歸正常數值。
    本研究量測成果初步對於施加開心手術治療之心血管疾病患者流變學特性的臨床診斷與病程追蹤，提供新的思考與助力，希望能對患者做出貢獻。

    Cardiovascular diseases (CVD) and heart-related complications are the most common causes of death worldwide at this time. Coronary Artery Bypass Graft (CABG) and Mitral Valve Replacement (MVR) surgeries are widely accepted treatments for advanced atherosclerosis and coronary artery disease. However, elevated red blood cell (RBC) aggregation may be related to common side-effects such as microinfarction systemic inflammation, and deep vein thrombosis during rehabilitation.
    Hemorheology is an established tool for monitoring the blood perfusion efficacy and health care. The blood physical properties changes and the correlation between blood microstructure, viscoelastic response and biochemical changes following cardiac surgery with cardiopulmonary bypass (CPB) have been investigated. This study investigated blood physical properties changes and the correlation between blood microstructure, viscoelastic response and biochemical changes following cardiac surgery with cardiopulmonary bypass (CPB). The blood rheology and RBC aggregate size were measured in the pre-surgery disease state (M0), post-surgery state and long-term recovery state (from M1 to M3) of cardiac surgical patients and healthy subjects. The Physica Rheometer MCR 501(Anton-Paar, Graz, Austria) was used to measure viscosity and elastic moduli. The life questionnaire also recorded patients habits that may be indicators for CVD (smoking habit, blood pressure, and low-density lipoprotein cholesterol).
    One day (M1) and one week (M2), the patient RBC concentration was significantly lower due to CPB. At 1% HCT, the RBC aggregate shape became larger and more rounded, which is correlated to the elevated plasma fibrinogen concentration caused by the systemic inflammatory response. During the same period, the low shear rate viscosity adjusted by normalizing RBC concentration increased significantly, as did the yield stress, indicating more solid-like behavior for blood. Six months to one year later (M3), all the physical and biochemical properties measured returned to baseline.
    These rheological properties could serve as distinct indicators for monitoring post-surgical recovery as well as identifying patients requiring surgery.

    ABSTRACT--- 2 ACKNOWLEDGEMENTS ---7 FRONT MATTER: LIST OF ABBREVIATIONS, HEMORHEOLOGICAL PARAMETERS--- 8 1. GENERAL INTRODUCTION--- 14 1.1 RESEARCH MOTIVATION--- 14 1.2 RESEARCH BACKGROUND--- 17 1.3 LITERATURE REVIEW--- 20 1.4 AIM OF THE STUDY--- 24 2. MATERIALS AND METHODS--- 27 2.1 PATIENT ENROLLMENT--- 27 2.2 PHYSIOLOGICAL MEASUREMENTS--- 31 2.3 RBC AGGREGATION MEASUREMENTS--- 32 2.4 RHEOLOGICAL MEASUREMENTS--- 36 2.5 DATA ANALYSIS--- 41 3. RESULTS--- 43 3.1 BIOCHEMICAL CHANGES--- 43 3.2 RBC AGGREGATION CHARACTERIZATION--- 45 3.3 VISCOSITY AND ELASTIC MODULUS--- 49 3.4 CORRELATIONS BETWEEN BLOOD VISCOSITY, RBC AGGREGATE SIZE, AND FIBRINOGEN--- 59 4. DISCUSSION--- 61 4.1 DIFFERENTIATION BETWEEN HEART DISEASE PATIENTS AND CONTROL SUBJECTS--- 61 4.2 PROLONGED INFLAMMATORY RESPONSE FOLLOWING CARDIAC SURGERY--- 62 4.3 LONG-TERM RECOVERY STATE OF CARDIAC SURGICAL PATIENTS--- 64 5. OUTLOOK--- 65 5.1 MIXING RBCS WITH ALLOGENEIC PLASMA--- 65 5.2 REGULAR EXERCISE TRAINING--- 67 6. CONCLUSION--- 70 7. REFERENCES--- 72 8. APPENDIX –ORIGINAL IRB-APPROVED PROPOSAL--- 79

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