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研究生:許立民
研究生(外文):Li-MIin Hsu
論文名稱:清醒鼠模式下Propofol對於敗血症存活時間及敗血症誘發自主神經失能之影響
論文名稱(外文):Propofol improves autonomic dysfunction and survival time in conscious septic rat model
指導教授:楊瑞成楊瑞成引用關係
指導教授(外文):RC Yang
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱: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:2009
畢業學年度:97
語文別:中文
論文頁數:57
中文關鍵詞:敗血症心律變異自主神經
外文關鍵詞:sepsispropofolHRV
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近年來敗血症的死亡率仍然沒有顯著的改善。敗血性休克的發生是造成敗血症死亡率高的主要原因,佔加護病房死亡原因的10%。加護病房常使用Propofol來鎮靜病人,但 Propofol除了麻醉鎮靜效果外,於細胞實驗中也發現有抗發炎以及清除自由基的角色。本研究以清醒大鼠闌尾結紮穿刺術誘發敗血症模式,觀察Propofol是否對於敗血症具有保護效果。實驗內容包括紀錄敗血症存活時間、敗血性休克血壓變化情形,以非侵入性的心率變異性分析(HRV- LF/HF ratio)作為交感神經調控功能的指標,並以敗血症大鼠腦幹誘發型一氧化氮合成酶(i-NOS)的偵測探討作用機轉。實驗結果發現敗血性休克後血壓在5小時內迅速下降,發生循環功能突然失能(cardiovascular sudden collapse),病程中後期交感神經調控功能會減低,Propofol可經由減緩循環功能突然失能發生的時間,延長存活時間。這效應似乎與腦幹內減低誘發型一氧化氮合成酶合成有關,進而透過保護交感神經調控功能,避免循環功能突然失能,達到延長敗血症存活時間。
本研究提供了Propofol在大鼠體內保護交感神經調控系統的基礎證據,可提供臨床上對於敗血症治療策略另一有效的選擇。
Although several clinical trails have been performed, there is not much improvement in septic mortality in recent years. The major cause of septic mortality is septic shock, which also accounts for 10% of mortality in intensive care unit (ICU). In ICU, propofol is often used for sedation. In addition to the effects of anesthesia and sedation, propofol also has anti-inflammation and free radicles scavenger effects in vitro study. The present study aimed to understand whether propofol has any benefit in treatment of sepsis. This is an in vivo study. We adapted awake CLP-induced sepsis rat model without any anesthesia agent. In the study, there were records of sepsis survival time and the change status of blood pressure. In addition, HRV LF/HF ratio (heart ate variability, low frequency/high frequency), a method of non-invasive recording of ANS (autonomic nervous system) was also used. The rat brain stem i-NOS was detected by western blot to explain the mechanism. The results show that cardiovascular sudden collapse happened after the onset of septic shock, and the modulation function of ANS decreased after the late stage of sepsis. Propofol would protect the dysfunction of ANS modulation by reducing the i-NOS production in rat brain stem during sepsis. With above mechanisms, propofol would improve the condition of cardiovascular sudden collapse after septic shock and prolong the survival time of sepsis.
The study showed the basic evidence, that propofol would protect the function of ANS modulation in septic rat model. The results would provide another choice in treating sepsis patients.
Key words: sepsis, septic shock, HRV, propofol
摘要 4
第一章 序論 7
第二章 研究動機與目的 14
第三章 實驗材料與方法 16
第四章 結果 24
第五章 討論 38
參考文獻 50
1.Parrillo JE: Pathogenetic mechanisms of septic shock. N Engl J Med 1993, 328(20):1471-1477.
2.Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R et al: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008, 34(1):17-60.
3.Bridges EJ, Dukes S: Cardiovascular aspects of septic shock: pathophysiology, monitoring, and treatment. Crit Care Nurse 2005, 25(2):14-16, 18-20, 22-14 passim; quiz 41-12.
4.Sessler CN, Shepherd W: New concepts in sepsis. Curr Opin Crit Care 2002, 8(5):465-472.
5.Landry DW, Oliver JA: The pathogenesis of vasodilatory shock. N Engl J Med 2001, 345(8):588-595.
6.Hinshaw LB: Sepsis/septic shock: participation of the microcirculation: an abbreviated review. Crit Care Med 1996, 24(6):1072-1078.
7.Rivers EP, McIntyre L, Morro DC, Rivers KK: Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. Cmaj 2005, 173(9):1054-1065.
8.Vincent JL, Gris P, Coffernils M, Leon M, Pinsky M, Reuse C, Kahn RJ: Myocardial depression characterizes the fatal course of septic shock. Surgery 1992, 111(6):660-667.
9.Kumar A, Schupp E, Bunnell E, Ali A, Milcarek B, Parrillo JE: Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock. Crit Care 2008, 12(2):R35.
10.Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345(19):1368-1377.
11.Huang DT, Clermont G, Dremsizov TT, Angus DC: Implementation of early goal-directed therapy for severe sepsis and septic shock: A decision analysis. Crit Care Med 2007, 35(9):2090-2100.
12.Vincent JL, Marshall JC: Surviving sepsis: a guide to the guidelines. Crit Care 2008, 12(3):162.
13.Shi KY, Shen FM, Liu AJ, Chu ZX, Cao YL, Su DF: The survival time post-cecal ligation and puncture in sinoaortic denervated rats. J Cardiovasc Pharmacol 2007, 50(2):162-167.
14.Julien C: Baroreflex control of sympathetic nerve activity and blood pressure variability. Clin Exp Pharmacol Physiol 2008, 35(4):512-515.
15.Ventura HO: "Read Guyton". Am J Cardiol 2004, 93(4):516-517.
16.Guyton ACaJEH: Textbook of Medical Physiology. Philadelphia: W. B. Saunder Company; 2000.
17.Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ: Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 1981, 213(4504):220-222.
18.Balanescu S, Corlan AD, Dorobantu M, Gherasim L: Prognostic value of heart rate variability after acute myocardial infarction. Med Sci Monit 2004, 10(7):CR307-315.
19.Electrophysiology ESoCatNASoPa: Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 1996, 17(3):354-381.
20.Gang Y, Malik M: Heart rate variability analysis in general medicine. Indian Pacing Electrophysiol J 2003, 3(1):34-40.
21.Basu S, Mutschler DK, Larsson AO, Kiiski R, Nordgren A, Eriksson MB: Propofol (Diprivan-EDTA) counteracts oxidative injury and deterioration of the arterial oxygen tension during experimental septic shock. Resuscitation 2001, 50(3):341-348.
22.Fowler CJ: Possible involvement of the endocannabinoid system in the actions of three clinically used drugs. Trends Pharmacol Sci 2004, 25(2):59-61.
23.Trapani G, Altomare C, Liso G, Sanna E, Biggio G: Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem 2000, 7(2):249-271.
24.Marik PE: Propofol: an immunomodulating agent. Pharmacotherapy 2005, 25(5 Pt 2):28S-33S.
25.Wang YH, Shen YC, Liao JF, Lee CH, Chou CY, Liou KT, Chou YC: Anti-inflammatory effects of dimemorfan on inflammatory cells and LPS-induced endotoxin shock in mice. Br J Pharmacol 2008, 154(6):1327-1338.
26.Liu MC, Tsai PS, Yang CH, Liu CH, Chen CC, Huang CJ: Propofol significantly attenuates iNOS, CAT-2, and CAT-2B transcription in lipopolysaccharide-stimulated murine macrophages. Acta Anaesthesiol Taiwan 2006, 44(2):73-81.
27.Chen RM, Wu GJ, Tai YT, Sun WZ, Lin YL, Jean WC, Chen TL: Propofol reduces nitric oxide biosynthesis in lipopolysaccharide-activated macrophages by downregulating the expression of inducible nitric oxide synthase. Arch Toxicol 2003, 77(7):418-423.
28.Kwak SH, Choi JI, Park JT: Effects of propofol on endotoxin-induced acute lung injury in rabbit. J Korean Med Sci 2004, 19(1):55-61.
29.Taniguchi T, Yamamoto K, Ohmoto N, Ohta K, Kobayashi T: Effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats. Crit Care Med 2000, 28(4):1101-1106.
30.Dellinger RP: Cardiovascular management of septic shock. Crit Care Med 2003, 31(3):946-955.
31.Lee RP, Wang D, Lin NT, Chen HI: Physiological and chemical indicators for early and late stages of sepsis in conscious rats. J Biomed Sci 2002, 9(6 Pt 2):613-621.
32.Takemoto Y: Dose effects of propofol on hemodynamic and cytokine responses to endotoxemia in rats. J Anesth 2005, 19(1):40-44.
33.Paxions G, and Watson, C.: The Rat Brain: In Stereotaxic Coordinates. New York: Academic Press; 1986.
34.Bigger JT, Fleiss JL, Rolnitzky LM, Steinman RC: The ability of several short-term measures of RR variability to predict mortality after myocardial infarction, vol. 88; 1993.
35.Yang CH, SHYR MH, KUO TBJ: Effects of propofol on nociceptive response and power spectra of electroencephalographic and systemic arterial pressure signals in the rat. J Pharmacol Exp Ther 1995, 275:1568.
36.Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue LW, 3rd, Bland KI, Chaudry IH: Cecal ligation and puncture. Shock 2005, 24 Suppl 1:52-57.
37.Freise H, Bruckner UB, Spiegel HU: Animal models of sepsis. J Invest Surg 2001, 14(4):195-212.
38.Pancoto JA, Correa PB, Oliveira-Pelegrin GR, Rocha MJ: Autonomic dysfunction in experimental sepsis induced by cecal ligation and puncture. Auton Neurosci 2008, 138(1-2):57-63.
39.Sharshar T, Gray F, Lorin de la Grandmaison G, Hopkinson NS, Ross E, Dorandeu A, Orlikowski D, Raphael JC, Gajdos P, Annane D: Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet 2003, 362(9398):1799-1805.
40.Zanotti Cavazzoni SL, Dellinger RP: Hemodynamic optimization of sepsis-induced tissue hypoperfusion. Crit Care 2006, 10 Suppl 3:S2.
41.Annane D, Trabold F, Sharshar T, Jarrin I, Blanc AS, Raphael JC, Gajdos P: Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach. Am J Respir Crit Care Med 1999, 160(2):458-465.
42.Koyama S, Santiesteban HL, Ammons WS, Manning JW: Centrally mediated hypotensive effect of E coli endotoxin in the anesthetized cat. Circ Shock 1982, 9(6):557-570.
43.Koyama S, Manning JW: Role of sympathetic nerve activity in endotoxin induced hypotension in cats. Cardiovasc Res 1985, 19(1):32-37.
44.Sayk F, Vietheer A, Schaaf B, Wellhoener P, Weitz G, Lehnert H, Dodt C: Endotoxemia causes central downregultaion of sympathetic vasomotor tone in healthy humans. Am J Physiol Regul Integr Comp Physiol 2008.
45.Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 1996, 17(3):354-381.
46.Winchell RJ, Hoyt DB: Spectral analysis of heart rate variability in the ICU: a measure of autonomic function. J Surg Res 1996, 63(1):11-16.
47.Marik PE, Zaloga GP: Therapeutic sedation: has its time come? Crit Care Med 2002, 30(4):949-952.
48.Taniguchi T, Kanakura H, Yamamoto K: Effects of posttreatment with propofol on mortality and cytokine responses to endotoxin-induced shock in rats. Crit Care Med 2002, 30(4):904-907.
49.Chan SH, Wang LL, Ou CC, Chan JY: Contribution of peroxynitrite to fatal cardiovascular depression induced by overproduction of nitric oxide in rostral ventrolateral medulla of the rat. Neuropharmacology 2002, 43(5):889-898.
50.Roman-Marchant O, Orellana-Jimenez CE, De Backer D, Melot C, Vincent JL: Septic shock of early or late onset: does it matter? Chest 2004, 126(1):173-178.
51.Chan SH, Wang LL, Wang SH, Chan JY: Differential cardiovascular responses to blockade of nNOS or iNOS in rostral ventrolateral medulla of the rat. Br J Pharmacol 2001, 133(4):606-614.
52.Gao J, Zhao WX, Zhou LJ, Zeng BX, Yao SL, Liu D, Chen ZQ: Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction. Inflamm Res 2006, 55(9):385-392.
53.Krassioukov AV, Gelb AW, Weaver LC: Action of propofol on central sympathetic mechanisms controlling blood pressure. Can J Anaesth 1993, 40(8):761-769.
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