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研究生:溫義嗣
研究生(外文):Yi-Szu Wen
論文名稱:逆行性頸靜脈低溫灌流術於熱中風處置的應用
論文名稱(外文):Application of Hypothermic Retrograde Jugular Vein Flush in the Management of Heatstroke
指導教授:林茂村林茂村引用關係李建賢李建賢引用關係
指導教授(外文):Mao-Tsun LinChen-Hsen Lee
學位類別:博士
校院名稱:國立陽明大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
中文關鍵詞:熱中風老鼠低溫逆行性腦灌流麩胺酸腦血流腦缺血
外文關鍵詞:HeatstrokeRatBrainHypothermiaRetrograde cerebral perfusionGlutamateCerebral blood flowCerebral ischemia
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熱中風為臨床醫學的一種合併全身各器官功能障礙的急症,其主要的臨床表現包括:超過40.5 ºC的高體溫和急性且多為不可回復性之神經傷害。熱中風的致死率為5 ~ 80 %;而熱中風的早期死亡可能是因為中樞神經的急性傷害造成。立即的全身性降溫是目前臨床上使用的治療方式;至今,仍沒有藥物可以有效的治療熱中風。若僥倖得以存活,仍有20 % 的病患會造成神經系統之永久傷害。
一般而言,急性神經傷害之形成為熱中風生成與否最重要之判別指標。在我們實驗室先前的研究中顯示:動物熱中風生成後,由於血壓下降及顱內壓升高,導致腦灌注壓(cerebral perfusion pressure)減少;而當腦灌注壓降低到無法由自主調控(autoregulation)來代償的程度時,會造成腦部缺血(ischemia)和腦神經細胞的傷害。這些發現表示:血壓下降及腦部缺血可能是造成熱中風的之主要原因。
先前的報告曾顯示出:在低體溫循環停止之後,逆行性腦部灌流(Retrograde Cerebral Perfusion)可以改善腦部的功能。因其實施簡便,這個方法被廣泛的使用在心臟血管外科和神經外科手術中;而 Imamaki等人更發現:使用較冰溫的血液來施行逆行性腦灌流時,會比傳統方式提供腦部更好的保護。這個發現意謂著頭或腦的低溫才是逆行性腦灌流有效保護功能的主要因素,而並不只是單純腦血流改善的結果。
為施行逆行性腦部灌流而做體外心肺循環,需要心臟外科醫師和額外的專業技術人員的幫助,在急診部門或緊急情況而言,這是非常費時和不切實際的。所以,臨床上需要簡易可行的方式來做逆行性腦灌流,以達到選擇性降低腦溫的目的;而經由內頸靜脈做中心靜脈插管,是一個較為簡易且經常在急診部門實施的步驟。此外,逆向的內頸靜脈穿刺常被使用在神經外科加護病房,以監測腦部的頸靜脈氧飽和度和耗氧量。因此,我們認為在緊急時,直接於頸靜脈逆行性灌注冰生理食鹽水來冷卻腦部,這個技術應該是可行性很高的。
本研究利用大鼠熱中風模式來測試頸靜脈逆向冰溫灌流術的治療之效果。於實驗中,監測頸靜脈逆向冰溫灌流術之給予對熱中風動物之存活時間、生理參數變化(包括體溫、動脈血壓、心跳速率、腦血流率、腦內麩胺酸之釋放)和腦損傷指數之影響。研究結果證明:這個技術可以有效降低腦溫,並減輕熱中風後的腦傷害;而其腦保護機轉主要是因為腦降溫造成腦血流的提升。因此,在大鼠熱中風生成後,其顯著降低的腦血流可以經由這個技術的治療,維持在正常範圍內,從而減輕因缺血所造成的腦傷害。
Heatstroke is a life-threatening illness characterized by hyperpyrexia, impaired consciousness, and occasionally multi-organ damage and dysfunction. Its mortality ranges from 5 to 80 percent, and early death probably occurs from central nervous system (CNS) injury. Cooling is the treatment of choice for heatstroke while no pharmacological agents are helpful. However, despite aggressive systemic cooling, residual brain damage occurs in about 20 percent of the patients.
Generally speaking, the presence of acute CNS injury is the most important indication for the diagnosis of heatstroke. Our previous studies have shown that increased intracranial pressure and decreased arterial pressure reduced cerebral perfusion pressure in hyperthermic animals after the onset of heatstroke. Reduction of cerebral perfusion pressure to below the auto-regulatory level would induce cerebral ischemia and neuronal damage in these animals. It appears that arterial hypotension and cerebral ischemic damage is the main reason for development of heatstroke syndrome.
Previous reports showed that retrograde cerebral perfusion (RCP) improved cerebral outcome after prolonged hypothermic circulatory arrest, and continuous RCP has become more widely used in cardiovascular surgery as an adjunct for cerebral protection because of its simplicity. Imamaki et al used deeply cooled blood during RCP to provide better protection of the brain. This finding suggests that enhanced cranial hypothermia, rather than brain perfusion, may be the major beneficial factor of retrograde cerebral perfusion.
Setting up cardiopulmonary bypass for RCP is time-consuming and impractical in the emergency department, because additional expertise by both the surgeon and the perfusionist are required. Methods that can be easily performed during resuscitation period is necessary in clinical practice to induce selected cranial hypothermia. On the other hand, central venous catheterization via internal jugular vein is a relatively simple procedure that is frequent performance in an emergency department. In addition, internal jugular veni- puncture in a cranial direction is used during neurosurgical intensive care to monitor jugular venous oxygen saturation and estimate oxygen consumption of the brain. Thus, we considered that this technique might be feasible for ice saline retrograde perfusion to cool the brain in an emergent situation.
The purpose of this research is to examine the effectiveness of treatment by hypothermic retrograde jugular vein flush in heatstroke rats. Survival time, changes of the physiological parameters, and neuron damage score were checked in the experiments. The results successfully demonstrated that this technique could effectively lower the brain temperature and reduce the brain damage after heat stroke. Further, increased cerebral blood flow (CBF) is the main reason for brain protection provided by this technique; In contrast to the significantly decreased CBF after onset of heatstroke, the CBF can be maintained within normal range by this technique in heatstroke rats. Cerebral ischemic damage after heatstroke is thus reduced.
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