國(guó)產(chǎn)牛心包補(bǔ)片在羊肺動(dòng)脈和主動(dòng)脈補(bǔ)片實(shí)驗(yàn)中的安全性和有效性

米爾阿迪力江·阿布都帕塔爾 陸樹(shù)洋 陳金淼 何 晨 王春生 洪 濤

(復(fù)旦大學(xué)附屬中山醫(yī)院心外科 上海 200032)

國(guó)產(chǎn)牛心包補(bǔ)片在羊肺動(dòng)脈和主動(dòng)脈補(bǔ)片實(shí)驗(yàn)中的安全性和有效性

米爾阿迪力江·阿布都帕塔爾▲陸樹(shù)洋▲陳金淼 何 晨 王春生 洪 濤△

(復(fù)旦大學(xué)附屬中山醫(yī)院心外科 上海 200032)

目的 本研究對(duì)國(guó)產(chǎn)牛心包補(bǔ)片的安全性和有效性進(jìn)行評(píng)價(jià),為進(jìn)一步臨床應(yīng)用提供實(shí)驗(yàn)基礎(chǔ)。方法采用綿羊肺動(dòng)脈及降主動(dòng)脈補(bǔ)片植入模型,以4只羊作為實(shí)驗(yàn)組,在肺動(dòng)脈干和降主動(dòng)脈干兩處共植入8枚國(guó)產(chǎn)牛心包補(bǔ)片;以2只羊作為對(duì)照組,在肺動(dòng)脈干和降主動(dòng)脈干兩處共植入4枚進(jìn)口牛心包補(bǔ)片。術(shù)前對(duì)所有動(dòng)物進(jìn)行常規(guī)生化檢查,術(shù)后第1個(gè)月、第2個(gè)月隨訪超聲心動(dòng)圖,第3個(gè)月時(shí)進(jìn)行取材,比較兩組植入補(bǔ)片的內(nèi)皮化、炎癥和鈣化程度等。結(jié)果 (1) 所有動(dòng)物均存活,未發(fā)生手術(shù)相關(guān)并發(fā)癥;(2) 超聲心動(dòng)圖第1個(gè)月、第2個(gè)月的結(jié)果顯示肺動(dòng)脈和主動(dòng)脈補(bǔ)片內(nèi)無(wú)縫合處漏血、無(wú)鈣化、無(wú)血栓形成、無(wú)贅生物、無(wú)明顯動(dòng)脈瘤樣擴(kuò)張;(3) 肉眼觀察兩組補(bǔ)片均無(wú)內(nèi)膜增生,厚度和韌度較術(shù)前無(wú)明顯改變;兩組補(bǔ)片內(nèi)膜光滑,均無(wú)肉眼可見(jiàn)的鈣化和異物。(4) 微生物學(xué)檢測(cè)提示兩組補(bǔ)片均未出現(xiàn)微生物感染,均有良好的內(nèi)皮化,均有炎癥細(xì)胞浸潤(rùn),壞死、鈣化程度差異無(wú)顯著統(tǒng)計(jì)學(xué)意義。結(jié)論 國(guó)產(chǎn)牛心包補(bǔ)片在綿羊肺動(dòng)脈和主動(dòng)脈補(bǔ)片試驗(yàn)中具有良好的安全性和有效性。

牛心包補(bǔ)片; 國(guó)產(chǎn)補(bǔ)片; 肺動(dòng)脈/羊; 主動(dòng)脈/羊

牛心包是一種優(yōu)良的心血管修補(bǔ)重建材料,其具有良好的張力強(qiáng)度、適中的厚度及柔軟度、不易感染、不漏血、不必預(yù)凝、來(lái)源廣泛、價(jià)格便宜等優(yōu)點(diǎn),因而被廣泛應(yīng)用于各種先天性和后天性心臟大血管等疾病的手術(shù)治療[1]。中國(guó)患者心血管病手術(shù)應(yīng)用人工組織材料日益增加,但是國(guó)產(chǎn)的牛心包產(chǎn)品極少,大部分牛心包產(chǎn)品依賴從國(guó)外進(jìn)口,目前批準(zhǔn)進(jìn)入中國(guó)市場(chǎng)的牛心包產(chǎn)品種類有限,因而導(dǎo)致牛心包來(lái)源少,價(jià)格昂貴。為了解決牛心包材料的來(lái)源和購(gòu)買成本問(wèn)題,生產(chǎn)出中國(guó)自主品牌的牛心包材料符合中國(guó)的國(guó)情需要。目前,經(jīng)戊二醛處理的牛心包應(yīng)用最廣泛,然而鈣化及退行性變是當(dāng)今牛心包補(bǔ)片的最主要缺點(diǎn)[2]。本研究以新型國(guó)產(chǎn)牛心包作為補(bǔ)片,通過(guò)動(dòng)物實(shí)驗(yàn)對(duì)其安全性和有效性進(jìn)行評(píng)價(jià),為此產(chǎn)品進(jìn)入臨床應(yīng)用提供實(shí)驗(yàn)依據(jù)。

材 料 和 方 法

實(shí)驗(yàn)材料 欣吉特牛心包補(bǔ)片(Cingular patch,CP),由上海欣吉特生物科技有限公司提供。采用干片射線滅菌后用保存于0.625%的戊二醛溶液中,厚度為0.2～0.72 mm,補(bǔ)片大小為6 cm×8 cm。佰仁思牛心包補(bǔ)片(Balmedic patch,BP)購(gòu)自北京佰仁醫(yī)療科技有限公司。采用化學(xué)滅菌后保存于戊二醛溶液中,補(bǔ)片厚度為0.2～0.6 mm。

實(shí)驗(yàn)分組 2歲左右綿羊(上海匯智贏華醫(yī)療科技研發(fā)有限公司動(dòng)物部),雌雄不拘,體質(zhì)量40～45 kg ,共6只。其中實(shí)驗(yàn)組4只,欣吉特牛心包片組;對(duì)照組2只,佰仁思牛心包片組。

實(shí)驗(yàn)步驟 通過(guò)面罩吸入異氟烷誘導(dǎo)麻醉,氣管插管,在胃內(nèi)安置胃管,綿羊右側(cè)臥位,左第四肋間切口進(jìn)入左側(cè)胸腔,切開(kāi)心包,顯露心臟和大血管。使用側(cè)壁鉗,夾住需要切開(kāi)的肺動(dòng)脈壁,人工剪出大小為3 cm×3 cm的肺動(dòng)脈壁缺口,將牛心包補(bǔ)片裁剪成缺口大小,4-0聚丙烯縫線連續(xù)縫合,將牛心包補(bǔ)片縫合在肺動(dòng)脈壁上。暴露降主動(dòng)脈,使用側(cè)壁鉗夾住降主動(dòng)脈一側(cè),人工剪為大小為3 cm×3 cm的降主動(dòng)脈壁缺口,將牛心包補(bǔ)片裁剪成缺口大小,4-0聚丙烯縫線連續(xù)縫合,將牛心包補(bǔ)片縫合在降主動(dòng)脈壁上。仔細(xì)止血,置胸腔引流管1根,逐層縫合切口,布比卡因75 mg局部注射鎮(zhèn)痛。

術(shù)后護(hù)理 將動(dòng)物放回籠內(nèi)。術(shù)后5天內(nèi),肌肉注射呋塞米20 mg,2次/日,預(yù)防胸水形成;術(shù)后1周內(nèi),肌肉注射頭孢拉定2 g,2次/日,用于消炎及預(yù)防感染治療;口服華法林3 mg至植入后1個(gè)月為止,1次/日,用于抗凝治療。術(shù)后1周內(nèi)每天監(jiān)測(cè)綿羊的體溫、心率和呼吸頻率以及切口愈合情況。

檢測(cè)方法

生化檢查 術(shù)后第3個(gè)月,綿羊處死前采集外周血標(biāo)本,檢測(cè)白細(xì)胞、中性粒細(xì)胞計(jì)數(shù)等來(lái)評(píng)估術(shù)后感染。測(cè)量國(guó)際標(biāo)準(zhǔn)化比值(international normalized ratio,INR)、血清鈣離子反應(yīng)血液凝固和鈣含量。測(cè)磷酸肌酸酶、尿素、肌酐等反映術(shù)后并發(fā)癥等其他問(wèn)題。

超聲心動(dòng)圖 術(shù)后1個(gè)月、2個(gè)月在無(wú)麻醉狀態(tài)下進(jìn)行右側(cè)臥位體外經(jīng)胸超聲心動(dòng)圖檢查,以獲得心臟圖像來(lái)評(píng)估植入的牛心包補(bǔ)片。以是否有牛心包縫合處漏血、有無(wú)鈣化、有無(wú)血栓形成、有無(wú)贅生物等來(lái)進(jìn)行評(píng)價(jià)。

組織病理學(xué) 動(dòng)物通過(guò)面罩吸入異氟烷持續(xù)麻醉狀態(tài)下頸動(dòng)脈切割放血致死,無(wú)菌切取靠近植入端約2 cm處的一段組織,分離出牛心包補(bǔ)片。肉眼觀察牛心包補(bǔ)片有無(wú)贅生物、血腫、血栓形成、以及機(jī)械或生物的退化。取牛心包補(bǔ)片的代表性部分進(jìn)行石蠟切片,用蘇木精-伊紅(hematoxylin-eosin staining,HE)染色,Masson染色和茜素紅染色觀察炎癥、壞死、鈣化程度,內(nèi)皮化、細(xì)胞外結(jié)構(gòu),膠原纖維和彈性蛋白的聚集程度等。

結(jié) 果

實(shí)驗(yàn)結(jié)果 兩組羊均存活,圍手術(shù)期未出現(xiàn)發(fā)熱、體質(zhì)量下降等術(shù)后并發(fā)癥。整個(gè)實(shí)驗(yàn)中,動(dòng)物在行為學(xué)上無(wú)異常表現(xiàn),食欲、體征等未明顯改變。

生化檢查 兩組白細(xì)胞、中性粒細(xì)胞計(jì)數(shù),INR、鈣含量、肌酐和尿素等指標(biāo)比較,實(shí)驗(yàn)組均低于對(duì)照組,但差異無(wú)統(tǒng)計(jì)學(xué)意義(圖1)。血液微生物培養(yǎng)結(jié)果顯示,實(shí)驗(yàn)組及對(duì)照組均無(wú)細(xì)菌。

超聲心動(dòng)圖 術(shù)后1個(gè)月、2個(gè)月超聲心動(dòng)圖顯示兩組補(bǔ)片肺動(dòng)脈和主動(dòng)脈處牛心包縫合處未見(jiàn)漏血,無(wú)鈣化、血栓和贅生物形成等(圖2)。兩處補(bǔ)片均無(wú)明顯動(dòng)脈瘤樣擴(kuò)張,心臟收縮活動(dòng)和各瓣膜未見(jiàn)異常,無(wú)心包積液。

組織病理學(xué) 肉眼觀察補(bǔ)片可見(jiàn)內(nèi)面光滑,厚度未見(jiàn)變薄,無(wú)補(bǔ)片內(nèi)贅生物、血腫、血栓形成,無(wú)明顯的瘤樣膨出,未見(jiàn)補(bǔ)片撕裂、穿孔、鈣化、硬化,補(bǔ)片變形和回縮等(圖3)。

To evaluate the inflammation response of the animal,white blood cells and neutrophils in peripheral blood were tested.Meanwhile,creatinine,urea and calcium level were examined.CP:Cingular patch;BP:Balmadic patch.

After the pericardium was implanted into the artery ultrasonic cardiogram examination was taken after 2 months.A:Balmedic patch (BP) in aortic artery; B:Cingular patch (CP) in aortic artery;C:Balmedic patch (BP) in pulmonary artery;D:Cingular patch (CP) in pulmonary artery.

兩組全部標(biāo)本均有良好的新生內(nèi)膜覆蓋(圖4A),均有補(bǔ)片交界處炎性反應(yīng)(圖4B)。為了量化炎性反應(yīng)和壞死程度,按炎癥程度評(píng)分為0～3分:0分為無(wú)炎性反應(yīng);1分為小范圍炎性反應(yīng),炎癥范圍:0.1～0.3 mm (圖4D);2分為局部較大范圍的炎性反應(yīng),炎癥范圍:0.3～1.0 mm (圖4C);3分為有彌散性炎性反應(yīng)區(qū),炎癥區(qū)域大于1.0 mm (圖4B),兩組補(bǔ)片炎癥評(píng)分?jǐn)?shù)實(shí)驗(yàn)組略低于對(duì)照組(2.50±0.58vs.3.25±0.25),但差異無(wú)統(tǒng)計(jì)學(xué)意義(P=0.182,表1)。按壞死程度分評(píng)分為0～2分:0分為無(wú)壞死;1分為小范圍壞死,壞死區(qū)域小于補(bǔ)片的50%;2分為大范圍壞死,壞死區(qū)域大于補(bǔ)片的50% (圖4F),實(shí)驗(yàn)組補(bǔ)片壞死分?jǐn)?shù)等于對(duì)照組。按鈣化程度可評(píng)分為0～3分:0分為無(wú)鈣化;1分為點(diǎn)狀小鈣化,散在點(diǎn)狀微小鈣化;2分為小片狀鈣化壞死,鈣化區(qū)域小于補(bǔ)片的50%;3分為大范圍鈣化壞死,鈣化區(qū)域大于補(bǔ)片的50%,實(shí)驗(yàn)組鈣化分?jǐn)?shù)略低于對(duì)照組(1.25±0.50vs.1.50±0.50),但差異無(wú)統(tǒng)計(jì)學(xué)意義(P=0.63,表1)。上述積分規(guī)則進(jìn)行統(tǒng)計(jì),兩組補(bǔ)片總分?jǐn)?shù)實(shí)驗(yàn)組低于對(duì)照組(4.25±1.26vs.4.25±0.25),差異無(wú)統(tǒng)計(jì)學(xué)意義(P=0.35,表1)。Masson染色可以看出實(shí)驗(yàn)組膠原纖維含量比對(duì)照組多,但差異無(wú)統(tǒng)計(jì)學(xué)意義(圖5)。茜素紅染色看到兩組全部標(biāo)本均有鈣化,兩組補(bǔ)片鈣化程度差異無(wú)統(tǒng)計(jì)學(xué)意義(圖6)。

Gross look of the pericardium showedin the picture.A:Balmedic patch (BP) in pulmonary artery; B:Cingular patch (CP) in pulmonary artery;C:Balmedic patch (BP) in aortic artery;D:Cingular patch (CP) in aortic artery.

Microscopic views of extracted Cingular patches.Inflammation was restricted around the patch.A:Neointima was formed evenly with good endothelialization (A and E).B:Large amount of immune cells infiltrated in the tissue (1.0 mm < infiltration extent);C:Moderate immune response was seen in the patch (0.3 mm

表1 兩組綿羊炎癥、壞死、鈣化程度的量化Tab 1 Quantification of inflammation,necrosis and calcification in the two sheep groups

Inflammation score:0=absent;1=mild (0.1 mm

To evaluate the collagenases of the implanted patches,Masson staining of the patches were taken.A:Cingular patch (CP) at the pulmonary artery;B:Balmadic patch (BP) at the pulmonary artery;C:aortic artery of the Cingular patch (CP);D:Balmadic patch (BP) at the aortic artery.

討 論

在臨床實(shí)踐中,先天性心臟結(jié)構(gòu)缺損、先天性或后天性血管發(fā)育異常等疾病多數(shù)需要人工材料進(jìn)行手術(shù)修補(bǔ)和重建。這些修補(bǔ)材料有多種選擇,包括自體心包組織、動(dòng)物自然生物材料(牛心包、豬心包及馬心包等)、人工合成材料等,其中應(yīng)用最為廣泛的為牛心包片[3]。

A and B:spot calcification;;C:moderate calcification with necrosis of the patch;D:severe calcification and necrosis.Microcalcification grades:0=absent,1=spot calcification,2=mild calcification (<50% of the patch),3=marked calcification (≥50% of the patch).

牛心包片有很好的組織相容性。處理后的牛心包片為無(wú)細(xì)胞的膠原結(jié)構(gòu),這為宿主細(xì)胞遷移和增生、內(nèi)皮化和組織再生提供了天然的微環(huán)境。本研究中的兩組牛心包片肉眼觀察補(bǔ)片內(nèi)面光滑,厚度未見(jiàn)變薄,無(wú)補(bǔ)片撕裂、穿孔,未見(jiàn)血栓形成、贅生物等。另外,牛心包容易制造并加工成0.5 mm厚度均一的補(bǔ)片,提供可靠的縫線滯留,縫線部位不易漏血,順應(yīng)性與自體動(dòng)脈非常相似,這些特點(diǎn)使得牛心包片具有與自體組織高度的一致性[4]。本實(shí)驗(yàn)補(bǔ)片植入術(shù)后2個(gè)月心超可見(jiàn)兩組牛心包片縫合處均未漏血和瘤樣擴(kuò)張、無(wú)鈣化、硬化,補(bǔ)片變形和回縮等?？梢?jiàn)牛心包片作為人工生物材料具有安全性。

當(dāng)補(bǔ)片植入后,與原組織發(fā)生免疫反應(yīng),炎性細(xì)胞侵入,各種細(xì)胞如免疫細(xì)胞、成纖維細(xì)胞、內(nèi)皮細(xì)胞等移行至植入補(bǔ)片內(nèi),使補(bǔ)片細(xì)胞化,促進(jìn)補(bǔ)片新生內(nèi)皮的形成。內(nèi)皮細(xì)胞在維護(hù)組織正常結(jié)構(gòu)和生理功能方面起著重要作用。正常自體組織表面覆蓋一層完整的內(nèi)皮細(xì)胞,阻止血漿蛋白的滲入和血栓形成,使血中游離的鈣離子不能在膠原組織中沉積,并且有營(yíng)養(yǎng)和自身修復(fù)作用[5]。通常,補(bǔ)片植入后第30天左右開(kāi)始內(nèi)皮化,3個(gè)月左右完全內(nèi)皮化。因此本實(shí)驗(yàn)隨訪至術(shù)后第90天。實(shí)驗(yàn)結(jié)果顯示兩組補(bǔ)片均有完整的內(nèi)皮化、新生內(nèi)膜生成。當(dāng)補(bǔ)片內(nèi)皮化完成、新生內(nèi)膜出現(xiàn)后,血栓形成、內(nèi)膜感染及瘤樣擴(kuò)張的機(jī)率明顯減少,從而延長(zhǎng)補(bǔ)片壽命,減少并發(fā)癥[6-7]。欣吉特牛心包采用內(nèi)皮化處理技術(shù),補(bǔ)片內(nèi)皮化處理后可促進(jìn)其完全內(nèi)皮化,防止血栓和贅生物的形成。缺乏內(nèi)皮細(xì)胞的襯被與覆蓋,這是導(dǎo)致補(bǔ)片鈣化和退變、耐久性差的主要原因之一。Guldner等[8]報(bào)道,內(nèi)皮化處理能明顯改善補(bǔ)片鈣化,促進(jìn)新生內(nèi)膜的形成,增強(qiáng)其組織相容性和使用壽命。因此內(nèi)皮化對(duì)生物補(bǔ)片有重要意義。

修補(bǔ)材料作為外源性的異體植入物,存在潛在的免疫反應(yīng)和潛在的感染風(fēng)險(xiǎn)。牛心包有其自身的特點(diǎn),主要由膠原纖維、彈性纖維和多種結(jié)締組織成分組成,含量最多的是膠原,其中又以Ⅰ型膠原為主[9]。膠原作為醫(yī)療器械產(chǎn)品最重要的特點(diǎn)在于與其他具有免疫原性的蛋白質(zhì)相比,它是大分子物質(zhì),但結(jié)構(gòu)重復(fù)性大,免疫原性較低[10-11]。因此,牛心包片植入體內(nèi)后不會(huì)發(fā)生嚴(yán)重的免疫反應(yīng)。本研究的生化結(jié)果顯示,兩組外周血與炎癥免疫有關(guān)的白細(xì)胞、中性粒細(xì)胞計(jì)數(shù),INR、肌酐和尿素等指標(biāo)都無(wú)明顯增高,欣吉特補(bǔ)片組略小于對(duì)照組,差異無(wú)統(tǒng)計(jì)學(xué)意義。除了牛心包有其自身較低的抗原性的特點(diǎn),商業(yè)化的牛心包都予以戊二醛處理,降低了其抗原性。牛心包戊二醛處理后封鎖了其抗原性基團(tuán)抑制免疫排斥反應(yīng),減少了血栓形成,降低了感染風(fēng)險(xiǎn)。0.625%戊二醛交聯(lián)處理不僅可以殺菌,而且可增加生物組織膠原蛋白分子間的交聯(lián),掩蓋生物組織的抗原部位和中和生物組織表面的正電荷,從而增加生物組織的穩(wěn)定牢固性,使牛心包機(jī)械強(qiáng)度明顯提高;同時(shí)也去除了大量的可溶性蛋白、黏多糖和糖蛋白、膠原纖維的交聯(lián),掩蓋和封鎖了抗原性基團(tuán),抑制免疫排斥反應(yīng),減少了血栓形成[12-13]。本實(shí)驗(yàn)補(bǔ)片亦用0.625%戊二醛交聯(lián)處理,可見(jiàn)補(bǔ)片與原組織交界處均有免疫炎性反應(yīng),可見(jiàn)到免疫細(xì)胞浸潤(rùn)、少量的組織壞死鈣化形成。欣吉特牛心包片相對(duì)于對(duì)照組炎癥、壞死程度小,差異無(wú)統(tǒng)計(jì)學(xué)意義。降低生物材料的抗原性,可降低免疫排斥反應(yīng)、促進(jìn)補(bǔ)片的內(nèi)皮化,并減少補(bǔ)片內(nèi)壞死、鈣化的形成,增強(qiáng)補(bǔ)片組織相容性和使用壽命。

然而,人工修補(bǔ)材料缺乏組織重塑、再生和生長(zhǎng),這對(duì)于年輕或幼兒患者來(lái)說(shuō),隨著時(shí)間的延長(zhǎng)將增加再次手術(shù)的風(fēng)險(xiǎn)[14]。動(dòng)物生物材料牛心包、豬心包等,尤其是戊二醛處理過(guò)的心包組織在年輕病人中有出現(xiàn)補(bǔ)片的硬化、鈣化等改變[15-16]。本研究中的兩組牛心包片均有鈣化的改變,欣吉特牛心包片相對(duì)于對(duì)照組鈣化程度小,但差異無(wú)統(tǒng)計(jì)學(xué)意義。許多研究報(bào)告顯示,牛心包補(bǔ)片均出現(xiàn)鈣化,采用脫細(xì)胞措施或特殊的抗鈣化處理后的牛心包組織鈣化程度變小,但仍未徹底防止補(bǔ)片鈣化[17],因此生物材料鈣化機(jī)制研究以及抗鈣化的處理措施是有待需要解決和改進(jìn)的重點(diǎn)所在。因此本研究中,實(shí)驗(yàn)組欣吉特牛心包補(bǔ)片在其準(zhǔn)備過(guò)程中,使用射線干性滅菌法減少化學(xué)滅菌過(guò)程中對(duì)組織結(jié)構(gòu)的損害以及化學(xué)試劑的毒性作用,從而減少滅菌處理過(guò)程可能引起的補(bǔ)片鈣化。雖然牛心包作為人工生物材料有其有效性和安全性,但補(bǔ)片鈣化、退變問(wèn)題尚未完全解決,補(bǔ)片內(nèi)皮化、抗補(bǔ)片鈣化和退變是以后人工生物材料使用壽命關(guān)鍵所在。

欣吉特心包補(bǔ)片作為新型國(guó)產(chǎn)牛心包補(bǔ)片,在綿羊肺動(dòng)脈和主動(dòng)脈補(bǔ)片試驗(yàn)中具有良好的安全性和有效性,不亞于進(jìn)口的佰仁思牛心包補(bǔ)片,有望解決補(bǔ)片來(lái)源問(wèn)題。

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Safety and effectiveness of domestic bovine pericardium as ovine pulmonary artery and descending aorta patch

MIERADILIJIANG Abudupataer▲, LU Shu-yang▲, CHEN Jin-miao, HE Chen, WANG Chun-sheng, HONG Tao△

(DepartmentofCardiacSurgery,ZhongshanHospital,FudanUniversity,Shanghai200032,China)

Objective To evaluate the safety and effectiveness of a newly domestic bovine pericardium using a juvenile sheep model and to provide proof for clinical use. Methods Under the off-pump condition,8 domestic bovine pericardiums were implanted into the pulmonary artery and the descending aorta of 4 juvenile sheep as the trial group.As the control group,four imported bovine pericardiums were implanted into two juvenile sheep．Before the surgery,the juvenile sheep were given a physical examination and some laboratory tests.Ultrasonic cardiographs were taken after 1 month and 2 months of implantation.Sheep were sacrificed after 90 days and compared with the extent of endothelialization,inflammation and calcification of the two groups. Results (1) All the juvenile sheep survived without any complications.(2) Ultrasonic cardiograph showed the absence of leakage,thrombus,calcification,neoplasm or any structural deterioration.(3) Gross examination showed there was no intimal hyperplasia.The thickness and tenacity of all patches had no change compared with the pre-operation condition．All the patches showed smooth and pliable faces without degeneration,as well as absence of macroscopically calcification.(4) There was not any positive result in microbiological tests in both groups.The degree of inflammation,necrosis and calcification had no significant differencs between the two groups. Conclusions The data shows that the domestic bovine pericardium,a newly developed Chinese domestic-design and manufactured bovine pericardium,can exhibit long-term satisfactory safety and efficacy in the implantation of the pulmonary artery and the descending aorta of juvenile sheep.

bovine pericardium; domestic patch; pulmonary artery/sheep; aorta/sheep

國(guó)家自然科學(xué)基金(81501595)

R654.2

A

10.3969/j.issn.1672-8467.2017.02.014

2016-08-15;編輯:沈玲)

▲MIERADILIJIANG Abudupataer and LU Shu-yang contributed equally to this work

△Corresponding author E-mail:hong.tao@zs-hospital.sh.cn

*This work was supported by the National Natural Science Foundation of China (81501595).