脊髓电刺激治疗房颤模型犬炎性因子水平的变化
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摘要
背景:有研究表明脊髓电刺激治疗可通过调节心脏自主神经的平衡起到抑制房颤的作用,但脊髓电刺激治疗对房颤引起的炎症反应的影响亦少见文献报道。目的:观察脊髓电刺激治疗对房颤模型犬炎性因子水平的影响。方法:选取昆明医科大学实验动物中心的成年比格犬9只作为实验犬,将其随机分为空白对照组3只,房颤模型组3只,接受脊髓电刺激的房颤模型组3只,后2组通过右心房快速起搏制作房颤犬模型,并植入心电追踪器监测房颤负荷,脊髓电刺激组实验犬造模成功后植入脊髓刺激器并对其进行长期慢性电刺激(12周),分别在房颤模型组建立房颤模型的前后(即植入起搏器前及第一次出现大于15 min的持续性房颤时),脊髓电刺激组行脊髓电刺激治疗前后(即脊髓电刺激治疗前及脊髓电刺激治疗12周结束时)抽取实验犬静脉血,同期抽取空白对照组犬静脉血(与房颤模型组植入起搏器前同时抽血),分离血清以ELISA法测定炎性因子C-反应蛋白、超敏C-反应蛋白、白细胞介素1,6及补体C3的浓度。结果与结论:(1)炎性因子质量浓度:房颤模型组各炎性因子质量浓度较空白对照组均升高(P <0.05);脊髓电刺激组较房颤模型组各炎性因子质量浓度均降低(P <0.05);房颤模型建模后的炎性因子均较建模前升高(P <0.05);脊髓电刺激组治疗后炎性因子均较治疗前降低(P <0.05);(2)房颤负荷:脊髓电刺激组较房颤模型组的房颤负荷明显降低(P <0.05);(3)结果证实,房颤可引起炎症反应,脊髓电刺激治疗对房颤有明显抑制作用,可抑制由房颤引起的炎症反应。
BACKGROUND: Some studies have shown that spinal cord stimulation can inhibit atrial fibrillation by regulating the balance of cardiac autonomic nerves. However, it is less reported on the effect of spinal cord stimulation on the inflammatory response to atrial fibrillation. OBJECTIVE: To investigate the effect of spinal cord stimulation on the serum levels of inflammatory factors in canine atrial fibrillation models. METHODS: Nine adult beagles from the Experimental Animal Center of Kunming Medical University were selected as laboratory canines and divided into control group(n=3), atrial fibrillation group(n=3) and atrial fibrillation+spinal cord stimulation group(n=3) at random. The canine atrial fibrillation models were made by rapid right atrial pacing in the latter two groups. The spinal cord stimulators were implanted into the canine atrial fibrillation models in the atrial fibrillation+spinal cord stimulation group and had released stimulation for 12 weeks. The miniaturized insertable cardiac monitors were implanted into the canine atrial fibrillation models for monitoring AT/AF burden. Venous blood samples of the experimental beagles were extracted, in which the serum levels of inflammatory factors(C-reactive protein, hypersensitive C-reactive protein, interleukin-1, interleukin-6 and complement-3) were tested by ELISA. In the atrial fibrillation group, the blood samples were taken before and after modeling(before pacemaker implantation and when atrial fibrillation had lasted for 15 minutes), while in the atrial fibrillation+spinal cord stimulation group, the blood samples were extracted before and after spinal cord stimulation therapy(before spinal cord stimulation therapy and when spinal cord stimulation had implemented for 12 weeks). Meanwhile, venous blood samples were taken from each beagle in the control group. RESULTS AND CONCLUSION: The serum levels of inflammatory factors in the atrial fibrillation group were significantly higher than those in the control group(P < 0.05), while the levels were significantly decreased in the atrial fibrillation+spinal cord stimulation group compared to the atrial fibrillation group(P < 0.05). For the canine models of atrial fibrillation, the serum concentration of inflammatory factors in the beagles which had received spinal cord stimulation therapy for 12 weeks were all lower than those without spinal cord stimulation(P < 0.05). The AT/AF burden of the atrial fibrillation+spinal cord stimulation group declined significantly compared with the atrial fibrillation(P < 0.05). To conclude, atrial fibrillation can induce inflammatory response, and spinal cord stimulation can suppress atrial fibrillation and further inhibit the inflammatory response caused by atrial fibrillation.
BACKGROUND: Some studies have shown that spinal cord stimulation can inhibit atrial fibrillation by regulating the balance of cardiac autonomic nerves. However, it is less reported on the effect of spinal cord stimulation on the inflammatory response to atrial fibrillation. OBJECTIVE: To investigate the effect of spinal cord stimulation on the serum levels of inflammatory factors in canine atrial fibrillation models. METHODS: Nine adult beagles from the Experimental Animal Center of Kunming Medical University were selected as laboratory canines and divided into control group(n=3), atrial fibrillation group(n=3) and atrial fibrillation+spinal cord stimulation group(n=3) at random. The canine atrial fibrillation models were made by rapid right atrial pacing in the latter two groups. The spinal cord stimulators were implanted into the canine atrial fibrillation models in the atrial fibrillation+spinal cord stimulation group and had released stimulation for 12 weeks. The miniaturized insertable cardiac monitors were implanted into the canine atrial fibrillation models for monitoring AT/AF burden. Venous blood samples of the experimental beagles were extracted, in which the serum levels of inflammatory factors(C-reactive protein, hypersensitive C-reactive protein, interleukin-1, interleukin-6 and complement-3) were tested by ELISA. In the atrial fibrillation group, the blood samples were taken before and after modeling(before pacemaker implantation and when atrial fibrillation had lasted for 15 minutes), while in the atrial fibrillation+spinal cord stimulation group, the blood samples were extracted before and after spinal cord stimulation therapy(before spinal cord stimulation therapy and when spinal cord stimulation had implemented for 12 weeks). Meanwhile, venous blood samples were taken from each beagle in the control group. RESULTS AND CONCLUSION: The serum levels of inflammatory factors in the atrial fibrillation group were significantly higher than those in the control group(P < 0.05), while the levels were significantly decreased in the atrial fibrillation+spinal cord stimulation group compared to the atrial fibrillation group(P < 0.05). For the canine models of atrial fibrillation, the serum concentration of inflammatory factors in the beagles which had received spinal cord stimulation therapy for 12 weeks were all lower than those without spinal cord stimulation(P < 0.05). The AT/AF burden of the atrial fibrillation+spinal cord stimulation group declined significantly compared with the atrial fibrillation(P < 0.05). To conclude, atrial fibrillation can induce inflammatory response, and spinal cord stimulation can suppress atrial fibrillation and further inhibit the inflammatory response caused by atrial fibrillation.
引文
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[6]Falowski S,Celii A,Sharan A.Spinal cord stimulation:an update.Neurotherapeutics.2008;5(1):86-99.
[7]Grimaldi R,de Luca A,Kornet L,et al.Can spinal cord stimulation reduce ventricular arrhythmias.Heart Rhythm.2012;9(11):1884-1887.
[8]Liu Y,Yue WS,Liao SY,et al.Thoracic spinal cord stimulation improves cardiac contractile function and myocardial oxygen consumption in a porcine model of ischemic heart failure.J Cardiovasc Electrophysiol.2012;23(5):534-540.
[9]Jesus S,Alo KM,Torre-Amtone G,et al.Initial experiencer with spinal cord stimulation for the treatment of advanced heart failure.J Card Fail.2010;16(8):S67.
[10]侯月梅杨新春.心房颤动模型制作与评价[J].中国心脏起搏与心电生理杂志,2006,20(3):194-197.
[11]Tan AY,Zhou S,Song J,et al.Neural mechanisms of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia in ambulatory canines.Circulation.2008;118(9):916.
[12]Allessie M,Kirchhof C,Scheffer GJ,et al.Regional control of atrial fibrillation by rapid pacing in conscious dogs.Circulation.1991;84(4):1689-1697.
[13]Morillo CA,Klein GJ,Jones DL,et al.Chronic rapid atrial pacing:a structural,functional,and electrophysiological characteristics of a newmodel of sustained atrial fibrillation.Circulation.1995;91(5):1588-1595.
[14]Sanders P,Pürerfellner H,Pokushalov E,et al.Performance of a new atrial fibrillation detection algorithm in a miniaturized insertable cardiac monitor:results from the reveal LINQ usability study.Heart Rhythm.2016;13(7):1425-1430.
[15]Shen MJ,Zipes DP.Role of the autonomic nervous system in modulating cardiac arrhythmias.Circ Res.2014;114(6):1004.
[16]Patterson E,Lazzara R,Szabo B,et al.Sodium-calcium exchange initiated by the Ca2+transient:an arrhythmia trigger within pulmonary veins.J Am Coll Cardiol.2006;47:1196-1206.
[17]Coumel P,Attuel P,Lavallée J,et al.The atrial arrhythmia syndrome of vagal origin.Arch Mal Coeur Vais.1978;71(6):645-656.
[18]Schauerte P,Scherlag B,Patterson E,er al.Focal atrial fibrillation:experimental evidence for a pathophysiologic role of the autonomic nervous system.J Cardiovasc Electrophysiol.2010;12(5):592-599.
[19]Shealy CN,Mortimer JT and Reswick JB.Electrical inhibition of pain by stimulation of the dorsal columns:preliminary clinical report.Anesth Analg.1967;46:489-491.
[20]Olgin JE,Takahashi T,Wilson E,et al.Effects of thoracic spinal cord stimulation on cardiac autonomic regulation of the sinus and atrioventricular nodes.J Cardiovasc Electrophysiol.2002;13(5):475-481.
[21]Friedrichs K,Klinke A,Baldus S.Inflammatory pathways underlying atrial fibrillation.Trends Mol Med.2011;17(10):556-563.
[22]Jalife J,Kaur K.Atrial remodeling,fibrosis,and atrial fibrillation.Trends Cardiovasc Med.2015;25(6):475-484.
[23]Bruins P,Velthuis H,Yazdanbakhsh AP,et al.Activation of the complement system during and after cardiopulmonary bypass surgery:postsurgery activation involves c-reactive protein and is associated with postoperative arrhythmia.Circulation.1997;96(10):3542-3548.
[24]Frustaci A,Chimenti C,Bellocci F,et al.Histological substrate of atrial biopsies in patients with lone atrial fibrillation.Circulation.1997;96(4):1180-1184.
[25]Aviles RJ,Martin DO,Apperson HC,et al.Inflammation as a risk factor for atrial fibrillation.Circulation.2003;108(24):3006-3010.
[26]Hu YF,Chen YJ,Lin YJ,et al.Inflammation and the pathogenesis of atrial fibrillation.Nat Rev Cardiol.2015;12(4):230-243.
[27]Patel P,Dokainish H,Tsai P,et al.Update on the association of inflammation and atrial fibrillation.JCardiovasc Electrophysiol.2010;21(9):1064-1070.
[28]Kornej J,Reinhardt C,Kosiuk J,et al.Response of high-sensitive C-reactive protein to catheter ablation of atrial fibrillation and its relation with rhythm outcome.PLoSOne.2012;7(8):e44165.
[29]Zheng LH,Yao Y,Wu LM,et al.Relationships of high-sensitive C-reactive protein and P-wave dispersion in lone atrial fibrillation.Chin Med J(Engl).2015;128(11):1450-1454.
[30]Smit MD,Maass AH,De Jong AM,et al.Role of inflammation in early atrial fibrillation recurrence.Europace.2012;14(6):810-817.
[31]Wu N,Xu B,Xiang Y,et al.Association of inflammatory factors with occurrence and recurrence of atrial fibrillation:a meta-analysis.Int J Cardiol.2013;169(1):62-72.
[32]Marcus GM,Smith LM,Ordovas K,et al.Intracardiac and extracardiac markers of inflammation during atrial fibrillation.Heart Rhythm.2010;7(2):149-154.
[2]Fuster V,Ryden LE,Cannom DS,et al.ACC/AHA/ESC2006 Guidelines for the management of patients with atrial fibrillation:full text:a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines(Writing Committee to Revise the 2001 guidelines for the management of patients with atrial fibrillation):developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.Europace.2006;8(9):651-745.
[3]Bernstein SA,Wong B,Vasquez C,et al.Spinal cord stimulation protects against atrial fibrillation induced by tachypacing.Heart Rhythm.2012;9(9):1426-1433.
[4]Lanza GA,Barone L,Di Monaco A.Effect of spinal cord stimulation in patients with refractory angina:evidence from observational studies.Neuromodulation.2012;15(6):542-549.
[5]Borjesson M,Andrell P,Mannheimer C,et al.Spinal cord stimulation for long-term treatment of severe angina pectoris:what does the evidence say?Future Cardiol.2011;7(6):825-833.
[6]Falowski S,Celii A,Sharan A.Spinal cord stimulation:an update.Neurotherapeutics.2008;5(1):86-99.
[7]Grimaldi R,de Luca A,Kornet L,et al.Can spinal cord stimulation reduce ventricular arrhythmias.Heart Rhythm.2012;9(11):1884-1887.
[8]Liu Y,Yue WS,Liao SY,et al.Thoracic spinal cord stimulation improves cardiac contractile function and myocardial oxygen consumption in a porcine model of ischemic heart failure.J Cardiovasc Electrophysiol.2012;23(5):534-540.
[9]Jesus S,Alo KM,Torre-Amtone G,et al.Initial experiencer with spinal cord stimulation for the treatment of advanced heart failure.J Card Fail.2010;16(8):S67.
[10]侯月梅杨新春.心房颤动模型制作与评价[J].中国心脏起搏与心电生理杂志,2006,20(3):194-197.
[11]Tan AY,Zhou S,Song J,et al.Neural mechanisms of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia in ambulatory canines.Circulation.2008;118(9):916.
[12]Allessie M,Kirchhof C,Scheffer GJ,et al.Regional control of atrial fibrillation by rapid pacing in conscious dogs.Circulation.1991;84(4):1689-1697.
[13]Morillo CA,Klein GJ,Jones DL,et al.Chronic rapid atrial pacing:a structural,functional,and electrophysiological characteristics of a newmodel of sustained atrial fibrillation.Circulation.1995;91(5):1588-1595.
[14]Sanders P,Pürerfellner H,Pokushalov E,et al.Performance of a new atrial fibrillation detection algorithm in a miniaturized insertable cardiac monitor:results from the reveal LINQ usability study.Heart Rhythm.2016;13(7):1425-1430.
[15]Shen MJ,Zipes DP.Role of the autonomic nervous system in modulating cardiac arrhythmias.Circ Res.2014;114(6):1004.
[16]Patterson E,Lazzara R,Szabo B,et al.Sodium-calcium exchange initiated by the Ca2+transient:an arrhythmia trigger within pulmonary veins.J Am Coll Cardiol.2006;47:1196-1206.
[17]Coumel P,Attuel P,Lavallée J,et al.The atrial arrhythmia syndrome of vagal origin.Arch Mal Coeur Vais.1978;71(6):645-656.
[18]Schauerte P,Scherlag B,Patterson E,er al.Focal atrial fibrillation:experimental evidence for a pathophysiologic role of the autonomic nervous system.J Cardiovasc Electrophysiol.2010;12(5):592-599.
[19]Shealy CN,Mortimer JT and Reswick JB.Electrical inhibition of pain by stimulation of the dorsal columns:preliminary clinical report.Anesth Analg.1967;46:489-491.
[20]Olgin JE,Takahashi T,Wilson E,et al.Effects of thoracic spinal cord stimulation on cardiac autonomic regulation of the sinus and atrioventricular nodes.J Cardiovasc Electrophysiol.2002;13(5):475-481.
[21]Friedrichs K,Klinke A,Baldus S.Inflammatory pathways underlying atrial fibrillation.Trends Mol Med.2011;17(10):556-563.
[22]Jalife J,Kaur K.Atrial remodeling,fibrosis,and atrial fibrillation.Trends Cardiovasc Med.2015;25(6):475-484.
[23]Bruins P,Velthuis H,Yazdanbakhsh AP,et al.Activation of the complement system during and after cardiopulmonary bypass surgery:postsurgery activation involves c-reactive protein and is associated with postoperative arrhythmia.Circulation.1997;96(10):3542-3548.
[24]Frustaci A,Chimenti C,Bellocci F,et al.Histological substrate of atrial biopsies in patients with lone atrial fibrillation.Circulation.1997;96(4):1180-1184.
[25]Aviles RJ,Martin DO,Apperson HC,et al.Inflammation as a risk factor for atrial fibrillation.Circulation.2003;108(24):3006-3010.
[26]Hu YF,Chen YJ,Lin YJ,et al.Inflammation and the pathogenesis of atrial fibrillation.Nat Rev Cardiol.2015;12(4):230-243.
[27]Patel P,Dokainish H,Tsai P,et al.Update on the association of inflammation and atrial fibrillation.JCardiovasc Electrophysiol.2010;21(9):1064-1070.
[28]Kornej J,Reinhardt C,Kosiuk J,et al.Response of high-sensitive C-reactive protein to catheter ablation of atrial fibrillation and its relation with rhythm outcome.PLoSOne.2012;7(8):e44165.
[29]Zheng LH,Yao Y,Wu LM,et al.Relationships of high-sensitive C-reactive protein and P-wave dispersion in lone atrial fibrillation.Chin Med J(Engl).2015;128(11):1450-1454.
[30]Smit MD,Maass AH,De Jong AM,et al.Role of inflammation in early atrial fibrillation recurrence.Europace.2012;14(6):810-817.
[31]Wu N,Xu B,Xiang Y,et al.Association of inflammatory factors with occurrence and recurrence of atrial fibrillation:a meta-analysis.Int J Cardiol.2013;169(1):62-72.
[32]Marcus GM,Smith LM,Ordovas K,et al.Intracardiac and extracardiac markers of inflammation during atrial fibrillation.Heart Rhythm.2010;7(2):149-154.