以多訊息脈波分析評估出血性休克大鼠之預後;Outcome Assessment in Hemorrhagic Shock Rats by Multi-information Pulse Analysis

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Title:	以多訊息脈波分析評估出血性休克大鼠之預後;Outcome Assessment in Hemorrhagic Shock Rats by Multi-information Pulse Analysis
Authors:	張鈺鑫;Yu-Hsin Chang
Contributors:	中國醫藥大學：中國醫學研究所博士班
Keywords:	出血性休克;脈搏;諧波頻譜分析;血壓變異性分析;心率變異性分析;預後;hemorrhagic shock;pulse;harmonic spectrum analysis;arterial pressure variability;heart rate variability;prognosis
Date:	2006-07-06
Issue Date:	2009-08-10 16:00:56 (UTC+8)
Abstract:	脈診是中醫臨床診斷方法中最具特色的一環，從歷代典籍文獻裡可知中醫早已大量運用脈搏跳動之特性來測知內在臟腑氣血變化，是臨床診療與決斷死生的重要依據。當維持生命所必需的氣血不循常道而大量脫失於脈管之外時，機體將會透過各個臟腑的代償反應，企圖重新建立一個新的生理平衡以維持生命。中醫理論認為當機體面臨氣血脫失時所引起的內在臟腑氣血變化，將反應於脈象的變動，同時此生物性律動的改變可由客觀量化的方法來表達，並可藉此預測機體的預後吉凶。為驗證此理論的可行性，本研究選擇以大鼠出血性休克模型進行動態血壓量測，並建構結合心率、脈形與脈勢的多訊息脈波分析平台以探討在急性重度失血的情況下，其脈波特徵的變化趨勢及其對預後判斷的相關性。首先為了解生物體在急性失血過程中如何透過臟腑生理動態地調節身體的氣血以維持機體之存活且是否存在相似的特徵趨勢，我們採用清醒大鼠40%估算血量（EBV）的急性重度失血模型，記錄放血前與放血後的動脈血壓波，並進行結合時域生理參數、脈搏諧波頻譜、脈搏血壓變異性與心率變異性的多訊息脈波分析。各脈波參數以放血後每五分鐘之均值進行單因子變異數分析，並以 Duncan’s multiple range test 進行事後檢定。研究結果顯示大鼠急性出血後30分鐘內，平均動脈壓自放血前的穩定狀態（約110 mmHg）迅速降低至35 mmHg，隨後逐漸平穩地上升至另一低態平衡（約80 mmHg），在這過程中各諧波隨著時間均朝向建立新的平衡而變動，其中與腎、脾藏象相關的C2與C3的變化百分比於放血後皆呈現顯著性上升，此變化可能與生物體在面臨氣血快速流失時，為達成身體氣血的重分配以維持生命的存活所引發之臟氣反應有關。進一步由麻醉大鼠進行三次不同程度（5%，10%和20%的EBV）的漸進性重度失血造型實驗，每次失血造型的間隔為30分鐘，第三次放血後持續觀察2小時（其中能存活至2小時者為存活組，存活時間小於2小時者則歸為死亡組），以比較在特定生理病理狀態下之多訊息脈波參數的變化規律與死生預後判斷的相關性。存活組與死亡組之兩組間比較採用兩獨立樣本t-test，以檢驗兩組之各項脈波參數於放血後各期間是否達顯著差異。各項指標對預測漸進性放血後二小時內存活的準確性評估，乃先將各連續性變項參數以Cox proportional harzards進行分析與篩選，並以ROC曲線決定最佳切分點後，再使用Log Rank test 來進行檢定。研究結果顯示麻醉大鼠在漸進性失血過程中，與腎藏象相關的C2及與脾藏象相關的C3皆呈現顯著性上升，但存活組與死亡組間之C2並無顯著差異，然而存活組之C3於第三次放血後顯著高於死亡組。存活分析結果顯示，心率、脈搏諧波頻譜分析參數中的直流值、C3、第三諧波變異係數，或脈搏血壓變異性之極低頻及低頻功率頻譜密度，或心率變異性之極低頻及低頻功率頻譜密度皆呈現較佳的預後評估能力。由本研究結果可知，藉由結合心率、脈形與脈勢的多訊息脈波分析可提供整體系統性的生物訊息，將有助於預後診斷與臨床治療之應用，且利用此平台分析所得的大鼠漸進性出血性休克過程之脈波反應特徵，我們推論生物體面臨氣血脫失時可能以脾藏象為中心的水穀氣反應狀態作為預後吉凶的判斷關鍵。 Traditional Chinese Medicine holds that Blood and Qi are fundamental substances in the human body for sustaining normal vital activity. The theory of Qi, Blood and Zang-Fu contribute the most important theoretical basis of human physiology in TCM. An animal model using conscious rats was employed in this study to further comprehend how organisms survive during acute hemorrhage by maintaining the functionalities of Qi and Blood through dynamically regulating visceral physiological conditions. Pulse waves of arterial blood pressure before and after 40% estimated blood volume（EBV） hemorrhage were taken in parallel to Multi-information Pulse Analysis. Mean arterial blood pressure and percentage differences of harmonics were analyzed in subsequent 5-minute intervals following the hemorrhage. Data were analyzed using a one-way analysis of variance with Duncan’s test for pairwise comparisons. Results showed that, within 30 minutes following the onset of acute hemorrhage, the reduction of mean arterial blood pressure was improved from 35 mmHg to 80 mmHg. Throughout the process, changes to the pulse spectrum appeared to result in a new balance over time. The percentage differences of the second (C2) and third harmonics (C3), which were related to Kidney and Spleen, both increased significantly than baseline and towards another steady state. The observed change could be attributed to the induction of functional Qi, and is a result of Qi-Blood balancing activity that organisms hold to survive against acute bleeding. Previous work has demonstrated the C2 and C3 related to Kidney and Spleen were both increased in rats after acute hemorrhage.In the following study, the difference of the pulse spectra patterns between survivors and non-survivors after progressive hemorrhage (by 5, 10 or 20% EBV) in anesthetized rats is determined. Nine rats died within 2 hours after 20% EBV hemorrhage（non-survivors）, and the other twelve rats were survived more than 2 hours（survivors）. Pulse waves of arterial blood pressure before and after the hemorrhage were measured in parallel to the Multi-information Pulse Analysis. Differences between survivor and non-survivor groups at each phase were analyzed using Student’s t-test. Cox proportional hazards analysis was used as appropriate. To assess the predictive value of continuous variables for dichotomous outcome, areas under the curve (AUCs) for sensitivity and specificity were constructed. The best prognostic cutoff for survival status at a given time point was defined as that which gave the highest product of sensitivity and specificity. Kaplan-Meier curves were constructed to characterize cumulative survival for a specific cut point. The study results showed that C2 increased significantly during progressive hemorrhage, the result failed to show any significant difference between survivors and non-survivors. After the third blood withdrawal process, the C3 raised more significantly in the survivors. Our results also showed that the HR, C0, C3, HCV3, SAP_lnVLF, SAP_lnLF, HR_lnVLF and HR_lnLF all have prognostic implications. We concluded that combination harmonic spectrum analysis、arterial pressure variability analysis and heart rate variability analysis can offer muti-information of organism and be used as a tool to measure the severity and outcome of hemorrhagic shock in rats. Our results suggest that the third harmonic might play an important role in physiology regarding surviving capability after progressive hemorrhage.
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