許利冬　綜述　李為民　審校

(哈爾濱醫(yī)科大學(xué)附屬第一醫(yī)院心內(nèi)科，黑龍江 哈爾濱150001)

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左主干解剖形態(tài)與左冠狀動(dòng)脈粥樣硬化研究新進(jìn)展

許利冬綜述李為民審校

(哈爾濱醫(yī)科大學(xué)附屬第一醫(yī)院心內(nèi)科，黑龍江 哈爾濱150001)

【摘要】左冠狀動(dòng)脈主干是指左冠狀動(dòng)脈發(fā)出后至分支前的節(jié)段，冠狀動(dòng)脈解剖形態(tài)是冠狀動(dòng)脈血流動(dòng)力學(xué)與冠狀動(dòng)脈粥樣硬化病變形成的一個(gè)關(guān)鍵性因素。以往的研究表明,因冠狀動(dòng)脈解剖形態(tài)造成的血流切應(yīng)力變化在冠狀動(dòng)脈粥樣硬化的發(fā)生和發(fā)展過程中起到重要作用，它的高低與血管壁厚度間存在負(fù)相關(guān)。在分叉處的外側(cè)壁，血流切應(yīng)力與粥樣硬化斑塊的形成密切相關(guān)。通過分析左冠狀動(dòng)脈主干的長(zhǎng)度、分叉角度、直徑等解剖因素，探討左冠狀動(dòng)脈主干-長(zhǎng)度、分叉角度、直徑等潛在的血流動(dòng)力學(xué)因素與左冠狀動(dòng)脈局部動(dòng)脈粥樣硬化斑塊形成及左冠狀動(dòng)脈急性心肌梗死的相關(guān)性，了解左冠狀動(dòng)脈主干的長(zhǎng)度、分叉角度、直徑作為危險(xiǎn)因素對(duì)左冠狀動(dòng)脈主干發(fā)生急性心肌梗死發(fā)生的價(jià)值，從而為冠心病患者預(yù)防急性心肌梗死的發(fā)生及相關(guān)高危人群的早期干預(yù)提供重要信息。

【關(guān)鍵詞】左主干解剖形態(tài)；動(dòng)脈粥樣硬化；心肌梗死；

目前冠狀動(dòng)脈粥樣硬化性心臟病(冠心病)是最主要的心血管疾病，急性心肌梗死是冠心病的一種嚴(yán)重表現(xiàn)類型，其具有發(fā)病急、并發(fā)癥多、病死率高的特點(diǎn)，其中尤以左主干急性心肌梗死的嚴(yán)重程度為顯著。急性心肌梗死是由冠狀動(dòng)脈血流急劇減少或中斷所致的心肌缺血壞死。既往的研究顯示其發(fā)生與遺傳基因、性別、年齡、吸煙、高血壓、高血脂、糖尿病以及新發(fā)現(xiàn)的致血栓致炎因子、高尿酸血癥等相關(guān)[1-4]。隨著研究的進(jìn)一步深入，發(fā)現(xiàn)因冠狀動(dòng)脈自身的解剖特性引起的血流動(dòng)力學(xué)改變，進(jìn)而可引起冠狀動(dòng)脈粥樣硬化及心肌梗死。目前，國(guó)外已有關(guān)于左主干解剖形態(tài)在左冠狀動(dòng)脈粥樣硬化病變分布間關(guān)系的研究[5]，但其相關(guān)性的研究仍未見報(bào)道。冠心病是多種因素共同作用的結(jié)果，但不同血管動(dòng)脈粥樣硬化的發(fā)生概率差別很大，動(dòng)脈粥樣硬化主要發(fā)生在大血管及血管分叉或發(fā)出分支處等血流變化明顯的部位，而上述因素都不能完全解釋動(dòng)脈粥樣硬化發(fā)生的局部性，因此推測(cè)，這種動(dòng)脈粥樣硬化斑塊形成在解剖學(xué)上有著明顯傾向，自然是與某種有選擇定位作用的致病因素聯(lián)系在一起。許多國(guó)內(nèi)外學(xué)者研究證實(shí)，異常血液流動(dòng)導(dǎo)致血流切應(yīng)力改變?cè)趧?dòng)脈硬化形成過程中起著重要作用[6]。血流切應(yīng)力的高低、血流動(dòng)力學(xué)形態(tài)的變化等亦對(duì)動(dòng)脈粥樣硬化的發(fā)生產(chǎn)生重要影響[7]。

1左冠狀動(dòng)脈主干解剖形態(tài)與左冠狀動(dòng)脈局部動(dòng)脈粥樣硬化

左冠狀動(dòng)脈主干起源于主動(dòng)脈，然后分叉形成左前降支動(dòng)脈和左回旋動(dòng)脈。從組織學(xué)角度看，左冠狀動(dòng)脈主干是一個(gè)相當(dāng)奇特的肌性動(dòng)脈，因?yàn)樗苯悠鹪从谥鲃?dòng)脈壁缺乏外膜的缺口。左冠狀動(dòng)脈主干的中膜有著極其豐富的平滑肌細(xì)胞和彈性組織。左冠狀動(dòng)脈主干彈性組織比任何其他冠狀動(dòng)脈分支更為豐富，并且越向左冠狀動(dòng)脈主干遠(yuǎn)端發(fā)展，彈性組織越少，因此左冠狀動(dòng)脈主干的特定解剖特征，能夠緩沖來自主動(dòng)脈的冠狀動(dòng)脈血流量和減輕長(zhǎng)期血流動(dòng)力引起的下游分支血管損傷[8]。根據(jù)Gatopoulos報(bào)道，左冠狀動(dòng)脈主干的長(zhǎng)度可能與動(dòng)脈粥樣硬化發(fā)病率和嚴(yán)重程度相關(guān)，而且羅德里格斯格拉尼洛還表明左冠狀動(dòng)脈主干的分叉角度及血流動(dòng)力學(xué)變化可能是動(dòng)脈粥樣硬化的誘因[9]。根據(jù)以上相關(guān)潛在關(guān)系，左冠狀動(dòng)脈主干的解剖特點(diǎn)可能與左冠狀動(dòng)脈粥樣硬化或急性心肌梗死的發(fā)生有關(guān)。

1.1左冠狀動(dòng)脈主干長(zhǎng)度、直徑與左冠狀動(dòng)脈局部動(dòng)脈粥樣硬化

左主干分支動(dòng)脈粥樣硬化病變的發(fā)展速度受左冠狀動(dòng)脈主干自身長(zhǎng)度的影響[10]。Gazetopoulos等[11]認(rèn)為短左冠狀動(dòng)脈主干是左冠狀動(dòng)脈粥樣硬化斑塊形成及發(fā)展過程中的先天性危險(xiǎn)因素。Lewis和 Gotsman證明了短左冠狀動(dòng)脈主干與左冠狀動(dòng)脈粥樣硬化斑塊的關(guān)系 。Gazetopoulos等[11]的另一項(xiàng)研究表明短左冠狀動(dòng)脈主干比長(zhǎng)左冠狀動(dòng)脈主干更容易出現(xiàn)下游分支動(dòng)脈粥樣硬化，且粥樣硬化斑塊出現(xiàn)較早，進(jìn)展較快，同時(shí)也更加容易出現(xiàn)斑塊破裂造成急性心肌梗死，血流量和血流速度與血管直徑成正比，而與血管長(zhǎng)度成反比。冠狀動(dòng)脈造影中校正的TIMI血流幀數(shù)(CTFC)能夠反映下游分支血管的血流量及血流速度。在冠狀動(dòng)脈造影中，左冠狀動(dòng)脈主干長(zhǎng)度與CTFC正相關(guān)。CTFC作為一種簡(jiǎn)單、直觀的連續(xù)血流指數(shù)已經(jīng)被證實(shí)與血流量及遠(yuǎn)端血流峰值平均速度負(fù)相關(guān)[12]。較短的左主干長(zhǎng)度會(huì)增加其分支血管的血流速度與血流量，因此短左冠狀動(dòng)脈主干會(huì)減低左冠狀動(dòng)脈主干分支血流的切應(yīng)力，低切應(yīng)力則會(huì)誘導(dǎo)冠狀動(dòng)脈斑塊形成[13]。值得注意的是，最近Cademartiri等[14]用冠狀動(dòng)脈64排CT評(píng)估左主干尺寸與斑塊之間的關(guān)系，指出左冠狀動(dòng)脈主干長(zhǎng)度和直徑與斑塊相關(guān)，特別是開口處的直徑和角度與動(dòng)脈粥樣硬化斑塊之間相關(guān)性更高，這些研究結(jié)果表明，左冠狀動(dòng)脈主干解剖特性在左冠狀動(dòng)脈粥樣硬化的形成中扮演重要角色。

1.2左冠狀動(dòng)脈主干分叉角度與左冠狀動(dòng)脈局部動(dòng)脈硬化

局部血流動(dòng)力學(xué)在冠狀動(dòng)脈粥樣硬化斑塊的形成中起主要作用。冠狀動(dòng)脈分叉角度會(huì)影響冠狀動(dòng)脈血流的類型、流量和流速，從而影響斑塊的形成[15]。早期的研究報(bào)告表明，動(dòng)脈粥樣硬化斑塊傾向于出現(xiàn)在冠狀動(dòng)脈的特定位置，如近分叉、分叉等低血流切應(yīng)力和流體分離的區(qū)域。之后的進(jìn)一步研究證實(shí)了早期的研究，并進(jìn)一步發(fā)現(xiàn)低血流切應(yīng)力出現(xiàn)在血管分叉部位[16]。隨著冠狀動(dòng)脈分叉角度的變化，冠狀動(dòng)脈血流的速度、角度及對(duì)內(nèi)皮細(xì)胞沖擊力發(fā)生變化，進(jìn)而會(huì)引起內(nèi)皮細(xì)胞受損，誘導(dǎo)動(dòng)脈粥樣硬化斑塊形成。分叉角度增大，血流多呈現(xiàn)湍流狀態(tài)，血流切應(yīng)力較低，分叉角度較小，血流多呈現(xiàn)層流狀態(tài)，穩(wěn)定性較高。斑塊多形成于左前降支和左冠狀動(dòng)脈主干分叉處的外側(cè)管壁，呈偏心分布。隨著冠狀動(dòng)脈分叉角度增大，其遠(yuǎn)端發(fā)生冠狀動(dòng)脈斑塊的概率增加，冠狀動(dòng)脈分叉角度與冠狀動(dòng)脈分叉處斑塊的發(fā)生率及分布相關(guān)[17]。血管內(nèi)超聲的相關(guān)研究同樣也證明了動(dòng)脈粥樣硬化好發(fā)于低血流切應(yīng)力的區(qū)域，例如血管的內(nèi)部彎曲處和分叉口的外側(cè)壁[18]，原因是低血流切應(yīng)力使流量導(dǎo)向的內(nèi)皮細(xì)胞受損，從而造成黏附分子的增強(qiáng)表達(dá)和細(xì)胞連接的削弱，最終導(dǎo)致脂質(zhì)和巨噬細(xì)胞的滲透增加和血管壁的增厚。同時(shí)通過血管內(nèi)超聲發(fā)現(xiàn)低切應(yīng)力區(qū)域較震蕩切應(yīng)力區(qū)域易形成較大斑塊，并且斑塊所含脂質(zhì)、平滑肌成分較多，膠原成分較少[19]。Ajayi 等[20]通過對(duì)170多例冠狀動(dòng)脈造影的圖像分析后認(rèn)為，斑塊位于接近分叉處較分支遠(yuǎn)端存在斑塊者左冠狀動(dòng)脈主干長(zhǎng)度更長(zhǎng)且分叉角度更大 。

2左冠狀動(dòng)脈主干解剖形態(tài)與急性心肌梗死

Dong等[21]連續(xù)性回顧分析1 825例患者的臨床資料及冠狀動(dòng)脈造影圖像，分組對(duì)比后表明左冠狀動(dòng)脈主干長(zhǎng)度以及左冠狀動(dòng)脈主干與前降支分叉角度，對(duì)于預(yù)測(cè)冠心病患者發(fā)生急性心肌梗死是兩個(gè)強(qiáng)有力并且獨(dú)立的預(yù)測(cè)因素。短左冠狀動(dòng)脈主干和更大的左冠狀動(dòng)脈主干與前降支分叉角度的患者，其發(fā)生急性心肌梗死的危險(xiǎn)性更大(敏感性為72%，特異性為86%)。目前，大多數(shù)研究多是通過多層計(jì)算機(jī)斷層掃描，血管內(nèi)超聲等評(píng)價(jià)斑塊易損性主要集中在斑塊的分布、斑塊負(fù)荷及形態(tài)以及血管重塑。然而血管自身的解剖特性是否會(huì)影響動(dòng)脈粥樣硬化斑塊破裂的報(bào)道則相對(duì)較少。血流動(dòng)力學(xué)是在血管解剖特性中最常被提到的因素，血流動(dòng)力學(xué)是引起斑塊破裂的重要危險(xiǎn)因素，其中血流切應(yīng)力起關(guān)鍵作用。動(dòng)脈粥樣硬化斑塊破裂中血流切應(yīng)力主要發(fā)揮兩種作用：低切應(yīng)力誘導(dǎo)穩(wěn)定斑塊向薄纖維帽過渡并促進(jìn)易損斑塊的形成；高切應(yīng)力促進(jìn)粥樣硬化斑塊的裂縫形成及斑塊破裂[22]。Kawasaki等研究稱左冠狀動(dòng)脈主干與左前降支角度增加，其分支血管的側(cè)壁切應(yīng)力相應(yīng)增加可能會(huì)誘導(dǎo)斑塊破裂。Gijsen 等冠狀動(dòng)脈分叉口是動(dòng)脈粥樣硬化和血管正性重構(gòu)的好部位，兩者均與血流切應(yīng)力的降低有關(guān)，由于向心性斑塊造成的管腔狹窄又導(dǎo)致了其遠(yuǎn)側(cè)血流切應(yīng)力的升高。他們的后續(xù)研究指出，對(duì)于已經(jīng)形成的斑塊，高血流切應(yīng)力可能會(huì)動(dòng)搖斑塊，導(dǎo)致斑塊破裂[23]。通常，血管狹窄的程度作為冠狀動(dòng)脈粥樣硬化病變嚴(yán)重程度的指標(biāo)，但與斑塊的脆性相關(guān)性較差[24-25]。因?yàn)檠芮粌?nèi)的粥樣硬化斑塊總是處于血壓和流量產(chǎn)生的確定機(jī)械負(fù)荷之下，當(dāng)額外負(fù)荷增加超過纖維化斑塊的強(qiáng)度時(shí)，斑塊很容易發(fā)生破裂[26-28]。因此，應(yīng)該在評(píng)估病變斑塊的脆性和高危患者中考慮血管的形態(tài)和病變局部的機(jī)械特性對(duì)斑塊的影響。

3展望

左冠狀動(dòng)脈主干自身的解剖特性對(duì)左冠狀動(dòng)脈、動(dòng)脈粥樣硬化斑塊形成及分布產(chǎn)生重要影響，并在動(dòng)脈粥樣硬化性斑塊破裂中起一定的作用。應(yīng)在今后的臨床工作中高度重視左冠狀動(dòng)脈主干自身的解剖特點(diǎn)。通過分析在冠心病患者的特殊左冠狀動(dòng)脈主干造影形態(tài)特征或者冠狀動(dòng)脈CT造影來預(yù)測(cè)左冠狀動(dòng)脈急性冠狀動(dòng)脈事件?；颊叩奶厥饨馄试煊疤攸c(diǎn)應(yīng)該得到更積極和深入的關(guān)注。壁切應(yīng)力及生物力學(xué)的風(fēng)險(xiǎn)因素的分析，為臨床醫(yī)生估計(jì)斑塊易損性并確定適當(dāng)?shù)闹委熀透深A(yù)提供了附加的診斷依據(jù)。

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New Progress Between Left Main Coronary Anatomy and Left Coronary Atherosclerosis

XU Lidong,LI Weimin

(DepartmentofCardiology,TheFirstAffiliatedHospitalofHarbinMedicalUniversity,Harbin150001,Heilongjiang,China)

【Abstract】Left main coronary artery refers to the left coronary artery segments before branching.Coronary anatomy is a key factor in coronary hemodynamics and coronary atherosclerotic lesion formation.Previous studies showed that shear stress changes caused from coronary anatomy plays an important role in the occurrence and development of coronary artery atherosclerosis in blood vessels between its high and low wall thickness and the presence of a negative correlation.In the outer wall of the bifurcation, shear stress is closely related to the formation of atherosclerotic plaque.The length of the left main, bifurcation angle, diameter and other anatomical factors is analyzed and the left main length, bifurcation angle, diameter and other potential hemodynamic factors and the left coronary artery partial formation of atherosclerotic plaques and the left coronary artery relevance are explored.Additionally, it is important to know the length of the left main, bifurcation angle and diameter as a risk factor for the left main coronary artery in and when acute myocardial infarction value occurs, so as to prevent coronary heart disease in patients with acute myocardial infarction and to provide important information and early intervention to patients and population with related risk.

【Key words】Left main anatomical form; Atherosclerosis; Myocardial infarction

收稿日期：2015-09-06修回日期：2015-11-27

【中圖分類號(hào)】R543.3

【文獻(xiàn)標(biāo)志碼】A【DOI】10.16806/j.cnki.issn.1004-3934.2016.02.000

作者簡(jiǎn)介：許利冬(1988—)，住院醫(yī)師，在讀碩士，主要從事冠心病研究。Email：632076347@qq.com通信作者：李為民(1949—)，主任醫(yī)師，教授，主要從事冠心病、高血壓病、心律失常等研究。Email:Liweimin_2009@163.com