熱中風大鼠低溫逆行性頸靜脈灌流食鹽水和過氟碳化物

Hypothermic Retrograde Jugular Vein Flush with Saline and Perfluorocarbons in Heatstroke of Rats

熱中風病理生成可能由於熱直接損傷腦中溫控中心導致體溫調節喪失和休克。降溫為治療熱中風的方式，目前並無特效藥物。但是，儘管侵入性的全身降溫處理，仍有20%的患者有腦損傷的情形。所以，針對腦部冷卻降溫被認為具有減低腦部缺血性腦病變傷害的較有效方法。因此，我們推論低溫逆行性頸靜脈灌流(RJVF)可有效降低腦溫，並達成腦保護的目標。先前研究指出，過氟碳化物(PFCs)，一種高攜帶氧與二氧化碳的惰性有機化合物，可用於治療小組織缺血損傷。根據文獻報告，給予實驗動物靜脈投注PFCs對中風和出血性休克具治療效果。現今實驗中，我們將在熱中風大鼠從股靜脈或右外頸靜脈分別灌流(RJVF)生理食鹽水(NS)、4℃冰NS、PFCs或4℃冰PFCs，來評估跟比較其治療效果。熱中風誘發主要是將麻醉後動物體置於43℃高溫的環境下觀察，直到動物體平均動脈壓(MAP)和局部腦血流(CBF)從至高點瞬間滑落時，將此點定義成熱中風生成點，常溫控制組大鼠則置於室溫下(24℃)觀察。結果發現熱中風處理組大鼠於熱中風生成點後，MAP和CBF值相對於熱中風控制組明顯低落，而腦缺血情況和神經損傷情形則顯著增加。而於熱中風生成後立即給予大鼠以RJVF處理4℃冰NS，非4℃冰PFCs，其存活時間（從熱中風生成點至動物死亡時間）相較於其他各組顯著延長。同時，熱中風所誘發高腦溫、動脈壓低落和高度神經損傷情形，亦可被立即給予大鼠以RJVF處理4℃冰NS所改善。然而，於熱中風生成後立即給予大鼠以RJVF處理4℃冰PFCs組別，其存活時間較熱中風控制組短。根據結果我們認為實驗熱中風所致之症狀可經由RJVF靜脈注射4℃冰生理食鹽水，來達到有效的改善而延長熱中風存活時間。而PFCs (FC-77)的給予，則需進一步更小心詳細的評估跟討論其用法及用量。

Pathogenesis of heatstroke may be due to direct thermal injury of the thermoregulatory centers in the brain that thermoregulatory failure and shock. Cooling is the treatment of choice for heatstroke, whereas no pharmacologic agents are helpful. However, despite aggressive systemic cooling, residual brain damage occurs in about 20% of patients. Since brain cooling has been considered an effective method for reducing ischemic injury of the brain, we speculated on the effectiveness of hypothermic retrograde jugular vein flush (RJVF) to cool the brain. In many investigations, perfluorocarbons (PFCs), inert organic compounds had a high affinity for oxygen and carbon dioxide, have been proposed as a replacement for donor blood as well as a therapy for minimizing ischemic tissue damage. According to reports, the intravenous infusion of PFCs has been shown to be beneficial in the treatment of stroke and hemorrhagic shock in animals. In present study, the intravenous treatment with normal saline (NS), ice NS at 4℃,PFCs, and PFCs at 4℃ via femoral vein or right external retrograde jugular vein flush (RJVF) would be evaluated and compared the therapeutic efficacy in rats of heatstroke. In experiment of heatstroke induction, animals under anesthesia were exposed to high ambient temperature (Ta) of 43℃ until mean arterial pressure (MAP) and local cerebral blood flow (CBF) in the striatum began to decrease from peak level, which was arbitrarily defined as the onset of heatstroke. Normothermic control rats were exposed to a temperature of 24℃. The values of MAP and CBF after heatstroke onset were all significantly lower than those in control rats. However, the situation of cerebral ischemia and neuronal damage in the striatum were greater. In rats intravenously infused with ice NS at 4℃ via RJVF immediately after the onset of heatstroke, the values of survival time ( interval between the onset of heatstroke and animal death) were apparently prolonged in contrast with another groups. Meanwhile, the heatstroke-induced hyperthermia of brain, arterial hypotension, and high degree of neuronal damage in heatstroke rats were all attenuated significantly by ice NS at 4℃ via RJVF administered immediately at the onset of heatstroke. Nevertheless, in PFCs-treated rats groups, the values of survival time were shorter than heatstroke control rats. Our results suggested that the experimental heatstroke syndromes can be effectively improved by ice NS at 4℃ via RJVF and led to prolong the survival time. However, the intravenous treatments with PFC (FC-77) in heatstroke rats need to assess further and discuss more closely.