張志鋼,李長永,譚洪文,儲國俊,朱玉峰,白元,許旭東,熊文峰,黃新苗,趙仙先,吳弘,秦永文
·實驗研究Experimental research·
一種建立實驗犬經(jīng)皮左心耳封堵途徑的方法
張志鋼,李長永,譚洪文,儲國俊,朱玉峰,白元,許旭東,熊文峰,黃新苗,趙仙先,吳弘,秦永文
目的驗證一種建立實驗犬經(jīng)皮左心耳封堵途徑方法的安全性及可行性。方法12只實驗犬房間隔穿刺后在不同體位左房造影后測量左心耳頸部直徑,沿導(dǎo)絲送入輸送封堵器的鞘管至左房中部,沿鞘管送入豬尾導(dǎo)管至左心耳內(nèi),沿豬尾導(dǎo)管推送輸送長鞘進入左心耳內(nèi),退出豬尾導(dǎo)管經(jīng)長鞘管造影觀察鞘管在左心耳內(nèi)的位置。術(shù)后1 h行心電圖及經(jīng)胸超聲檢查,即刻處死5只實驗犬,取心臟觀察房間隔穿刺位置、左房及左心耳內(nèi)損傷情況。其余犬術(shù)后1 h及2周經(jīng)胸超聲心動圖檢查,隨訪1個月。結(jié)果術(shù)中1只犬因心臟壓塞死亡。8只犬在RAO30°+CRA20°造影可以清楚顯示左心耳形態(tài),3只在RAO30°,1只在RAO30°+CAU20°清楚顯示左心耳形態(tài),測量左心耳頸部直徑為(13.6±5.2)mm,輸送長鞘管均成功送入左心耳遠端,無氣栓、血栓、心臟壓塞,2只穿刺點血腫,經(jīng)加壓包扎血腫吸收。術(shù)后即刻處死犬取心臟觀察心包腔內(nèi)未見血性液體,1只犬左房后壁輕度血腫,2只左心耳上緣內(nèi)膜輕度損傷可見血腫,手術(shù)操作時間(58±12)min,透視時間(10.1±2.5)min。其余犬術(shù)后及2周經(jīng)胸超聲隨訪無心包積液。隨訪1個月無猝死、卒中、感染。結(jié)論應(yīng)用本方法可安全有效的建立輸送左心耳封堵器至左心耳內(nèi)的途徑。
心房纖顫;左心耳;封堵器;犬
血栓栓塞是心房顫動(房顫)最嚴(yán)重的并發(fā)癥,導(dǎo)致非瓣膜性房顫患者腦卒中的栓子90%以上來源于左心耳[1]。外科瓣膜手術(shù)時結(jié)扎左心耳可以降低房顫患者腦卒中風(fēng)險[2],但是沒有外科指征的單純左心耳結(jié)扎會增加致殘率和病死率。隨著介入器械的發(fā)展,近年經(jīng)皮左心耳封堵術(shù)成為預(yù)防房顫患者腦卒中的新方法,目前大部分左心耳封堵器械的動物實驗都是使用實驗犬完成的[3-4],但是關(guān)于建立實驗犬左心耳封堵器械植入途徑方法的報道較少。本課題組探索了一種建立犬經(jīng)皮左心耳封堵器械途徑的方法。
1.1 材料
1.1.1 實驗動物健康成年雜種犬12只,體質(zhì)量12~15 kg,雌雄不限;由上海甲干生物科技有限公司提供。
1.1.2 實驗器械0.032英寸導(dǎo)引導(dǎo)絲及左房鋼絲,8 FSwartz房間隔穿刺鞘管,頭端彎曲角度塑形增大的Brockenbrough穿刺針,6 F防漏鞘管及豬尾導(dǎo)管,8~10 F塑形的室間隔輸送長鞘管及擴張管,V形實驗動物固定架。
1.1.3 實驗儀器X線放射成像系統(tǒng),心電圖機,心電壓力監(jiān)測儀及彩色超聲診斷儀。
1.1.4 實驗藥品2.5%戊巴比妥鈉,氯胺酮,對比劑(碘普羅胺注射液),青霉素鈉粉針。
1.2 方法
1.2.1 房間隔穿刺及左心耳造影實驗犬以氯胺酮5 mg/kg肌內(nèi)注射,麻醉后以特制固定架仰臥固定犬于手術(shù)臺上,心電監(jiān)護。常規(guī)消毒鋪無菌巾單,穿刺股靜脈后置入鞘管,以2.5%戊巴比妥鈉1m l/kg靜脈注射維持麻醉效果。沿鞘管送入0.032英寸導(dǎo)絲至上腔靜脈,退出鞘管沿導(dǎo)絲送入Swartz房間隔穿刺鞘管至上腔靜脈,按照王勝強等[5]報道的方法進行房間隔穿刺,穿刺時推送穿刺針卵圓窩上部滑動時,按照董建增等[6]報道的方法進行穿刺。穿刺成功后,固定穿刺針推送鞘管超出穿刺針1~2 mm,退出穿刺針,確認(rèn)無心臟壓塞后給予肝素(80~100 u/kg),沿擴張鞘置入0.032英寸左房兩圈半鋼絲至左房內(nèi)彎曲2~3圈,固定導(dǎo)絲及擴張鞘,推送Swartz鞘至左房中部,退出擴張鞘,沿導(dǎo)絲經(jīng)Swartz鞘送入豬尾導(dǎo)管至左心房后,退出導(dǎo)絲于后前位,右前斜30°+頭位20°(圖1),右前斜30°及右前斜30°+足位20°手推對比劑行左房造影,選擇心耳頸部清晰顯影的體位測量左心耳頸部直徑。
圖1 左心房造影(右前斜30°+頭位20°)
1.2.2 建立植入經(jīng)皮左心耳封堵器械途徑左心房造影后,沿豬尾導(dǎo)管送入左房鋼絲至左房,退出豬尾導(dǎo)管及Swartz鞘管,沿左房鋼絲送入經(jīng)改裝的室間隔輸送長鞘及擴張鞘至左房中部,固定擴張鞘及導(dǎo)絲推送輸送鞘至左房中部,保留左房鋼絲退出擴張管。沿左房導(dǎo)絲送入豬尾導(dǎo)管至左房中部,退出導(dǎo)絲。調(diào)整豬尾導(dǎo)管進入左心耳內(nèi),推注對比劑證實在左心耳內(nèi)后,固定豬尾導(dǎo)管沿豬尾導(dǎo)管推送輸送長鞘管進入左心耳內(nèi)(圖2),輕微調(diào)整豬尾導(dǎo)管及輸送長鞘的位置使鞘管安全位于左心耳內(nèi)并且具有良好同軸性,位置理想后回抽豬尾導(dǎo)管內(nèi)血液,邊緩慢退出豬尾導(dǎo)管邊向豬尾導(dǎo)管內(nèi)注射肝素鹽水,排除輸送鞘管內(nèi)空氣,經(jīng)鞘管造影觀察鞘管在左心耳內(nèi)的位置(圖3)。
圖2 沿豬尾導(dǎo)管推送輸送鞘管至左心耳內(nèi)(右前斜30°+頭位20°)
圖3 經(jīng)輸送鞘管造影觀察鞘管位置(右前斜30°+頭位20°)
1.2.3 術(shù)后處理及隨訪術(shù)后心電監(jiān)護1 h后行心電圖和心臟超聲檢查,處死5只實驗犬,取心臟標(biāo)本觀察房間隔穿刺位置及左房內(nèi)損傷情況。其余犬術(shù)后經(jīng)胸超聲心動圖觀察有無心包積液后給予青霉素10萬u/kg靜脈推注后拔除鞘管,穿刺點”8”字縫合[7]。隨訪犬術(shù)后3 d青霉素肌內(nèi)注射預(yù)防感染,2 d后拆線,2周時行經(jīng)胸超聲心動圖檢查,隨訪1個月觀察卒中、感染等手術(shù)并發(fā)癥。
12只實驗犬中9只1次穿刺房間隔成功,1只第2次穿刺房間隔成功,無1只犬房間隔穿刺術(shù)中發(fā)生心臟壓塞,房室傳導(dǎo)阻滯。12只犬中8只在RAO30°+CRA20°(圖1)、3只在RAO30°,1只在RAO30°+CAU20°投照體位造影可以清楚顯示左心耳形態(tài),測量左心耳開口直徑為(13.6±5.2)mm,輸送鞘管均成功送入左心耳遠端,術(shù)中無氣栓、血栓、心臟壓塞。術(shù)后處死犬取心臟觀察見心包腔內(nèi)未見血性液體,房間隔穿刺點位于卵圓孔近似中央,周圍輕度血腫,邊緣整齊無撕裂,距離上腔、下腔靜脈,冠狀竇及左右房室瓣口距離均>5 mm,1只犬左房后壁輕度血腫,2只左心耳上緣內(nèi)膜輕度損傷可見血腫,手術(shù)操作時間(58±12)min,透視時間(10.1±2.5)min。未處死6只犬2只穿刺點血腫,經(jīng)加壓包扎血腫吸收。術(shù)后及2周均無心包積液。隨訪1個月無猝死、卒中、感染等并發(fā)癥。
經(jīng)皮左心耳封堵術(shù)是近年發(fā)展起來的一種替代華法令預(yù)防房顫腦卒中事件的治療措施,尤其適用于有抗凝禁忌證的高危腦卒中房顫患者[8]。由于犬心耳的解剖形態(tài)與人體相似目前經(jīng)皮左心耳封堵的動物實驗均是使用犬完成的[9]。術(shù)中房間隔穿刺成功后置入左房0.032英寸導(dǎo)絲,沿導(dǎo)絲置入豬尾導(dǎo)管后進行左心耳造影,左房0.032英寸兩圈半鋼絲不僅能夠提供有效的支撐,其頭端彎曲能防止穿刺鞘及導(dǎo)絲從左房滑出以及器械損傷左房及左心耳,是建立經(jīng)皮左心耳封堵途徑的理想工作導(dǎo)絲。左心耳造影是評估左心耳大小及形狀的重要方法之一。造影時在房間隔穿刺鞘送入6 F豬尾導(dǎo)管一方面可以避免交換導(dǎo)管時導(dǎo)絲脫出左心房,另一方面,使豬尾導(dǎo)管后端側(cè)孔位于穿刺鞘內(nèi),造影時不會造成左右心房同時顯影影響觀察。左心耳造影時的投照體位文獻報道不盡相同[9-10],我們通過觀察對比不同體位的影像發(fā)現(xiàn),大多數(shù)犬在右前斜30°加頭位20°造影可清晰顯示左心耳的開口、頸部直徑及形態(tài),當(dāng)該體位造影心耳影像重疊時可在右前斜30°或者右前斜30°加足位20°造影顯示左心耳形態(tài)。
左心耳封堵術(shù)中心臟壓塞、氣栓等并發(fā)癥限制了該技術(shù)的推廣[11],并發(fā)癥主要發(fā)生于房間隔穿刺、操作鞘管、釋放及回收封堵器時[12],隨著術(shù)者經(jīng)驗積累手術(shù)并發(fā)癥可明顯降低[13]。Watchman植入過程中將鞘管經(jīng)導(dǎo)絲經(jīng)房間隔送入左房后,送入豬尾導(dǎo)管,然后先將豬尾導(dǎo)管送入左上肺靜脈再逆時針旋轉(zhuǎn)導(dǎo)管使其進入左心耳內(nèi),沿左心耳內(nèi)豬尾導(dǎo)管送入輸送長鞘減少心臟壓塞并發(fā)癥[14],而動物實驗通常將輸送鞘管直接置入左心耳內(nèi)[3,15]。我們在動物實驗中發(fā)現(xiàn),也可以直接應(yīng)用左房鋼絲將豬尾導(dǎo)管送入左心耳遠端,然后沿豬尾導(dǎo)管將輸送長鞘送入左心耳遠端,利用豬尾導(dǎo)管頭端彎曲替代擴張鞘管的尖形頭端可減少心耳損傷,并且豬尾導(dǎo)管直徑較導(dǎo)絲粗可防止鞘管頭端頂在心耳內(nèi)壁上,有利于安全將鞘管送入左心耳遠端。實驗中通過術(shù)后即刻解剖實驗犬發(fā)現(xiàn)無心包血性積液,大體觀察心臟標(biāo)本,其中2只動物左心耳上緣輕度血腫,心耳內(nèi)無穿孔、血栓,其余犬均無心包填塞表現(xiàn)。左心耳壁薄,內(nèi)有小梁及梳狀肌,在調(diào)整輸送鞘的位置時需要小心操作,尤其是推送鞘管時防止鞘管損傷左心耳上緣導(dǎo)致穿孔。
空氣栓塞及血栓是左心耳封堵術(shù)中的并發(fā)癥,操作中經(jīng)?;爻榍使懿⒁愿嗡佧}水沖洗可以減少此類并發(fā)癥[12]。輸送長鞘進入左心耳后,由于導(dǎo)管頭端與心耳壁接觸可造成回抽液體不通暢,無法進行有效排氣,在退出其內(nèi)的豬尾導(dǎo)管時邊緩慢回撤導(dǎo)管邊向豬尾導(dǎo)管內(nèi)注射肝素鹽水是避免氣栓及血栓的方法之一,也可以略微回撤長鞘、回抽液體后常規(guī)沖洗排氣但是這樣可能使鞘管移位。本實驗中存活犬隨訪1個月均無與手術(shù)操作相關(guān)的并發(fā)癥。
經(jīng)皮左心耳封堵術(shù)是一項創(chuàng)傷較小,操作相對簡單的介入治療,隨著介入器械的發(fā)展及手術(shù)醫(yī)師經(jīng)驗的積累,以及更多臨床相關(guān)研究的進行,該技術(shù)將更加完善,其適應(yīng)證會進一步拓展。目前歐洲指南中將左心耳封堵作為有抗凝禁忌的房顫腦卒中高?;颊叩囊豁椫委煷胧?6]。本研究中探索的方法可以有效的建立輸送左心耳封堵器至預(yù)定封堵部位的途徑,動物實驗證實該方法安全、可行由于樣本量少,使用經(jīng)驗有限,本法尚需進一步進行驗證。
[1]Blackshear JL,Odell JA.Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation[J]. Ann Thorac Surg,1996,61:755-759.
[2]García-Fernández M,Pérez-David E,Quiles J,et al.Role of left atrial appendage obliteration in stroke reduction in patients withmitral valve prosthesis:a transesophageal echocardiographic study[J].JAm Coll Cardiol,2003,42:1253-1258.
[3]Nakai T,Lesh MD,Gerstenfeld EP,et al.Percutaneous left atrial appendage occlusion(PLAATO)for preventing cardioembolism:first experience in caninemodel[J].Circulation,2002,105:2217-2222.
[4]Lam Y-Y,Yan BP,Doshi SK,et al.Preclinical evaluation of a new left atrial appendage occluder(Lifetech LAmbreTMdevice)in a caninemodel[J].Int JCardiol,2013,168:3996-4001.
[5]王勝強,秦永文,胡建強,等.經(jīng)靜脈房間隔穿刺法建立房間隔缺損動物模型[J].介入放射學(xué)雜志,2004,13:159-160.
[6]董建增,曹林生,馬長生,等.下腔靜脈造影指導(dǎo)犬房間隔穿刺術(shù)[J].中國介入心臟病學(xué)雜志,2005,13:111-113.
[7]Cilingiroglu M,Salinger M,Zhao D,et al.Technique of temporary subcutaneous“Figure-of-Eight”sutures to achieve hemostasis after removal of large-caliber femoral venous sheaths[J].Catheter Cardiovasc Interv,2011,78:155-160.
[8]Horstmann S,Zugck C,Krumsdorf U,et al.Left atrial appendage occlusion in atrial fibrillation after intracranial hemorrhage[J].Neurology,2014,82:135-138.
[9]Bass JL.Transcatheter occlusion of the left atrial appendage—experimental testing of a new Amplatzer device[J].Catheter Cardiovasc Interv,2010,76:181-185.
[10]楊志宏,吳弘,胡建強,等.左心耳造影方法的建立及最佳投照體位的研究[J].介入放射學(xué)雜志,2006,15:494-496.
[11]Holmes DR,Reddy VY,Turi ZG,etal.Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation:a randomised noninferiority trial[J].Lancet,2009,374:534-542.
[12]Price MJ.Prevention and Management of Complications of Left Atrial Appendage Closure Devices[J].Intervent Cardiol Clin,2014,3:301-311.
[13]Reddy VY,Holmes D,Doshi SK,et al.Safety of percutaneous left atrial appendage closure:results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF(PROTECT AF)clinical trial and the Continued Access Registry[J].Circulation,2011,123:417-424.
[14]Nakamura M,Kar S.Transcatheter Occlusion of the Left Atrial Appendage[J].Intervent Cardiol Clin,2013,2:225-234.
[15]Cheng Y,Conditt G,Yi G,et al.First in-vivo evaluation of a flexible self-apposing left atrial appendage closure device in the canine model[J].Catheter Cardiovasc Interv,2013,[Epub ahead of print].
[16]Camm AJ,Lip GY,De Caterina R,et al.2012 focused update of the ESC Guidelines for the management of atrial fibrillation:an update of the 2010 ESC Guidelines for the management of atrial fibrillation.Developed with the special contribution of the European Heart Rhythm Association[J].Eur Heart J,2012,33:2719-2747.
Percutaneous occlusion of left atrial appendage in experimental canine models:the establishment of
the delivery pathway ZHANG Zhi-gang,LIChang-yong,TAN Hong-wen,CHU Guo-jun,ZHU Yu-
QINYong-wen,E-mail:qyw2011@126.com
ObjectiveTo evaluate the feasibility and safety of a delivery pathway for the performance of percutaneous left atrial appendage(LAA)occlusion in experimental caninemodels.MethodsTransseptal puncture was performed via femoral vein approach under fluoroscopic and angiographic guidance in 12 experimental dogs.A pigtail catheter was advanced into the left atrium(LA),which was followed by LA angiography.The diameters of the neck of LAA were measured on LAA angiogram obtained in appropriate projection.A fter the delivery sheath was advanced along the wire into LA,a pigtail catheter was inserted into the ostium of the LAA and the sheath was then advanced over the pigtail into the LAA.LAA angiography was then performed through the delivery sheath to confirm the position of the delivery sheath.One hour after the procedure both electrocardiography(ECG)and transthoracic echocardiography(TTE)were carried out in five dogs to check the results,immediately afterwhich the five dogswere sacrificed tomacroscopically observe the damages of the puncture site of inter-atrial septum as well as inside the LA and LAA.One hour and 2 weeks after the procedure TTE was conducted in the remaining 7 dogs and these dogs were followed up for one month.ResultsOne dog died of pericardial tamponade during the operation.In 8 dogs the LAA was clearly displayed in the projection position of right anterior oblique(RAO)30°/cranial(CRA)20°,while in 3 dogs the LAA was well visualized in the projection position of RAO 30°,and in one dog in the projection position of RAO 30°/caudal(CAU)20°.The diameter of LAA neck was(13.6±5.2)mm.The delivery sheath was safely advanced into the LAA along the pigtail catheter in all dogs,and no air embolism,thrombus or pericardial tamponade occurred.Hematoma at puncture point of groin occurred in 2 dogs,which was absorbed through pressure dressing.Macroscopic examination of the heart performed immediately after the operation showed that no bloody pericardial effusion was found,and mild hematoma at posterior wall of LA was seen in one dog and mild damage of the upper-margin intima of LAA was noted in 2 dogs.Themean fluoroscopy timewas(10.1±2.5)minutes and themean operation timewas(58±12)minutes.TEE showed no pericardial effusion 2 weeks after the procedure.During the follow-up period of one month no sudden death,stroke or infection occurred.Conclusion Thismethod of placing the delivery sheath into the LAA is clinically safe and effective,and it can reliably establish a pathway to advance the LAA occluder into LAA.(J Intervent Radiol,2014,23:897-900)
atrial fibrillation;leftatrial appendage;occluder;dog
R541.7
B
1008-794X(2014)-10-0897-04feng,BAIYuan,XU Xu-dong,XIONGWen-feng,HUANG Xin-miao,ZHAO Xian-xian,WU Hong,QIN Yong-wen.Department of Cardiology,Changhai Hospital,Second Military Medical University,Shanghai 200433,China
2014-04-07)
(本文編輯:李欣)
10.3969/j.issn.1008-794X.2014.10.015
上海市自然科學(xué)基金B(yǎng)ZR1409500;上海市衛(wèi)生局級科研課題重點課題
200433上海第二軍醫(yī)大學(xué)長海醫(yī)院心內(nèi)科[張志鋼(現(xiàn)在南京軍區(qū)福州總醫(yī)院心內(nèi)科)、李長永、譚洪文、儲國俊、朱玉峰、白元、許旭東、黃新苗、趙仙先、吳弘、秦永文],超聲科(熊文峰)
秦永文E-mail:qyw2011@126.com