尼可地爾改善心臟停搏液對(duì)心臟的保護(hù)作用

1、尼可地爾改善心臟停搏液對(duì)心臟的保護(hù)作用         07-11-16 15:33:00     編輯：studa20                     作者：史紅宇，朱曉峰，戰(zhàn)鵬，溫福興，龍村 【關(guān)鍵詞】  心肌保護(hù)    摘要：

2、目的 觀察在HTK液和UW液中加入尼可地爾（Nicorandil）對(duì)心肌保存液保存效果的影響。方法  實(shí)驗(yàn)分為4組：UW液（U）組 ；HTK液（H）組；UW液組+Nicorandil（U+N） 組；HTK液+Nicorandil（H+N） 組；每組8只大白鼠。麻醉和抗凝后，快速取下鼠心并懸掛在Langendorff灌注模型上灌注，測(cè)定血流動(dòng)力學(xué)基礎(chǔ)值。分別用四組保存液灌停離體鼠心并低溫（4）浸泡保存6h。復(fù)溫、復(fù)灌后再次測(cè)定血流動(dòng)力學(xué)值，留取標(biāo)本分別測(cè)定心肌水含量、心肌酶漏出量、心肌細(xì)胞ATP和CP含量和心肌細(xì)胞超微結(jié)構(gòu)變化。結(jié)果  心肌血流動(dòng)力學(xué)恢復(fù)率： H+N組U+N組

3、H組U組。心肌水含量：4組間差異無顯著意義。灌脈流出液中心肌酶漏出量：H+N組H組U+N組U組。心肌中ATP和CP含量：H+N組U+N組H組U組。心肌細(xì)胞超微結(jié)構(gòu)變化：H+N組心肌損害最輕，H組輕于U+N組，U組心肌損害最嚴(yán)重。結(jié)論 HTK液和UW液都是比較合適的心肌保存液，HTK液對(duì)心肌的保護(hù)作用優(yōu)于UW液，鉀離子通道開放劑Nicorandil 能夠善器官保存液HTK液和UW液對(duì)心肌的保存效果。關(guān)鍵詞：HTK液；UW液；尼可地爾；心肌保護(hù)The Myocardial Preservation Effect of Nicorandil in HTK Solution and UW Soluti

4、onAbstract: OBJECTIVE  We investigated the efficacy of HTK solution and UW solution with Nicorandil（NCR） in the isolated rat heart models. METHODS   The hearts were divided into four groups:  UW solution （U ） group;  HTK solution （H ） group; UW solution with Nicorandil （U+N

5、）group; HTK solution with Nicorandil （ H+N） group. The hearts isolated from Wistar rats were mounted on a Langendorff apparatus to estimate baseline hemodynamic values. They were arrested and stored at 4 in each preservation solution for 6 hours. The recovery of myocardial function were measured. My

6、ocardial tissue water content was evaluated. Myocardial tissue Adenosine Triphosphate (ATP) and Creatine Phosphate(CP) content in each group were also measured. The leakage of myocardial enzymes were measured as well. Finally, myocardial ultrastructure was observed. RESULTS  The recovery rate o

7、f myocardial function: the group of H+N > the group of U+N > the group of H > the group of U. The myocardial tissue water content: there was no significant changes in four groups; The leakage of myocardial enzymes: the group of H+N < the group of H < the group of U+N < the group of

8、 U. The level of ATP and CP in myocardial tissue: the group of H+N > the group of U+N > the group of H > the group of U. The myocardial ultrastructure: The histological changes of myocardial cell and the damage of vascular endothelial cell were more significant in U+N group compared with th

9、at in H+N group. The histological changes were severer in U group than that in U+N  group.CONCLUSION  These results suggest that HTK solution is more effective than UW solution for myocardial preservation, and that NCR provides still better protection in the heart transplantation.Key words

10、：HTK solution; UW solution; Nicorandil; Myocardial preservation                                       

11、60;               1967年人類首例心臟移植成功以來，心臟移植作為治療終末期心臟疾病的唯一有效手段，其生存率逐年提高，但臨床上觀察，心臟移植術(shù)后30天內(nèi)死亡的病例數(shù)與供體心臟保存不佳有著明顯的相關(guān)性。目前，在深低溫（04）的條件下，以UW液(Uinversity of Wisconsin Solution)和HTK液(Histidine-Trytophane-Ketoglutarate Solution)對(duì)心臟的保存效果為佳，但臨床離體心

12、臟保存安全時(shí)限只能達(dá)到46h1，且移植后心臟功能都有不同程度的下降。如何進(jìn)一步提高心臟保存液的保存效果和盡可能的延長心臟保存的安全時(shí)限是我們要解決的重要課題。尼可地爾（Nicorandil）是一種ATP-K離子通道開放劑，具有選擇性的開放ATP敏感鉀離子通道的功能，在心臟保存液中加入尼可地爾有可能提高心臟保存液的保存效果。本實(shí)驗(yàn)的目的是在離體鼠心Langendorff灌注模型上，檢驗(yàn)在器官保存液HTK液和UW液中加入鉀離子通道開放劑尼可地爾對(duì)心臟保存效果的影響。1  材料與方法  1.1 實(shí)驗(yàn)動(dòng)物和分組      

13、                       選用Wistar大白鼠32只，雌雄各半，體重300400g，由北京阜外心血管病醫(yī)院實(shí)驗(yàn)動(dòng)物科提供。隨機(jī)分為四組：UW液（U）組、HTK液（H）組、UW液+Nicorandil 組（U+N）、HTK液+Nicorandil（H+N） 組，每組8只。1.2 實(shí)驗(yàn)方法      

14、                       實(shí)驗(yàn)?zāi)Ｐ偷慕?、離體鼠心的切取、灌注和低溫保存：大白鼠稱體重后，腹腔注射戊巴比妥鈉（65mg/kg）麻醉，仰臥固定于實(shí)驗(yàn)臺(tái)上，游離出股靜脈，經(jīng)股靜脈內(nèi)注射肝素（3mg/kg）抗凝。迅速開胸，在主動(dòng)脈和右鎖骨下動(dòng)脈交界處切斷肺動(dòng)、靜脈，取出心臟，立即放入04 K-H緩沖液中，沖洗掉殘留在主動(dòng)脈內(nèi)的血液。主動(dòng)脈插管后，迅速移至Lange

15、ndorff灌注模型灌注針上，用K-H緩沖液持續(xù)灌注，灌注壓為75cmH2O，整個(gè)灌注期間用95O2和5%CO2混合氣體平衡，溫度維持在37。肺動(dòng)脈根部切開，使冠狀動(dòng)脈回流液引流充分。從開胸取心至灌注開始要在5070s內(nèi)完成，超過70s應(yīng)放棄實(shí)驗(yàn)。灌注3min后，切開左心耳，經(jīng)左心房、二尖瓣內(nèi)，將連接有測(cè)壓導(dǎo)管的心室球囊送入左心室，導(dǎo)管用生理鹽水充滿，勿存留氣體，另一端連接多導(dǎo)生理記錄儀。往心室球囊內(nèi)緩慢注射適量生理鹽水（4060l），使左心室舒張末壓為10mmHg。15min后，心臟搏動(dòng)可達(dá)到穩(wěn)定狀態(tài)，測(cè)定血流動(dòng)力學(xué)基礎(chǔ)值，包括左室收縮末壓(LVESP)、左室舒張末壓(LVEDP)、左室發(fā)展壓(LVDP)、左室壓力微分(±dp/dt)和冠脈流量。降低灌注溫度至30以下后，經(jīng)主動(dòng)脈根部分別灌注4的四組心臟保存液，根據(jù)冠脈流量調(diào)節(jié)灌注速度，灌注壓為75cmH2O。心臟停跳后，每只心臟在四種心臟保存液中分別低溫（04）浸泡保存6h。6h后，復(fù)溫至37，重新開始心臟灌注。1520min以后，心臟搏動(dòng)達(dá)到穩(wěn)定狀態(tài)，每隔10min測(cè)定