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1 f zu{ g } 14 í } Çf Journal of Clinical Rehabilitative Tissue Engineering Research March 19, 2010 Vol.14, No.12 Îï ö ³¼ µ Š ÄŒ ³q *** d Ø e µ t Transmyocardial high-pressure injection revascularization combined with thermo-sensitive chitosan hydrogel effects on channels Xiong Lu, Huang Jing, Zhou Da-yan, Guo Rui Medical Xiong Lu, Studying for master s degree, Medical @qq.com Correspondence to: Huang Jing, Master, Doctoral supervisor, Medical huangjing_9901@ yahoo.com.cn Supported by: the National Natural Science Foundation of China (Key Program), No *, (General Program) No *; the Tackle Key Program in Science and Technology of City, No. CSTS2005AA * Received: Accepted: Abstract BACKGROUND: Many experiments have suggested that transmyocardial revascularization (TMR) is effective in refractory angina pectoris and end-stage coronary artery disease. The main problem for TMR, however, is occlusion of the transmural channels, which limits the application of the technology. OBJECTIVE: To explore the impact of transmyocardial high-pressure injection revascularization combined with thermo-sensitive chitosan hydrogel filled the channels on channel s patency and the effect of promoting angiogenesis and myocardial protection on acute myocardial infarction. METHODS: High-pressure injection system, Injex needle-free syringe was made by the appropriate transformation of post-production. Thermo-sensitive chitosan hydrogel was made of chitosan hydrochloride, β-glycerol phosphate and hydroxyethyl cellulose prepared in accordance with a certain concentration ratio. A total of 24 healthy hybrid dogs were randomly assigned to three groups. In the simple myocardial infarction group (SMI), acute myocardital infarction models were made by ligation of the left anterior descending coronary artery. No treatment was given in SMI group. In the transmyocardial high-pressure injection revascularization group (TMIR) with thermo-sensitive chitosan hydrogel group (TMIR+chitosan), transmyocardial high-pressure injection revascularization was performed on infarct myocardium and about 8 to 10 transmural channels were created in ischemic area, one channel per square centimeter. In the TMIR group, the same volume saline was used in the identical site. Hemodynamics, capillary density and myocardial infarct size were detected at 6 weeks after treatment. Hematoxylin and eosin staining and Sirius red staining were used to detect channel patency and collagenous fiber proliferation, and the ratio of type, collagen was calculated. RESULTS AND CONCLUSION: The channels in TMIR group had significantly narrowed; some segments had been completely occluded. However, channels in TMIR + chitosan group had not been occluded, the opening diameter was about μm; some segments had been endothelialization. Compared with the SMI group, TMIR group and TMIR + chitosan group promoted angiogenesis in the infarct area, and TMIR + chitosan group reduced the infarct size and improved left ventricular remodeling. These indicated that transmyocardial high-pressure injection revascularization combined with thermo-sensitive chitosan hydrogel filled the channels is helpful to maintain the channel patency and can promote angiogenesis around the channels, reduce infarct size and improve left ventricular remodeling. It may be a viable approach in the treatment of myocardial infarction. Xiong L, Huang J, Zhou DY, Guo R.Transmyocardial high-pressure injection revascularization combined with thermo-sensitive chitosan hydrogel effects on channels. Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu. 2010;14(12): [ u{ÿ ² ž~ Œ oä o ¾ o ž² ý² ³ Œ À Â³n Áü v ÂÍo q n rq: Îï Šü ³¼ µ Š ÄŒ ³q xö o gqž~ mö q n : Injex ¾ ² ³ýÍ Îï n Š r r βm w ¾ ˆ j d q Í Š ÄŒ Ÿ yg 24 ùã Ég 3 ê Í Øýr ºŒ + ÄŒ Š ÄŒp x Ð ŸÎï ² 8~10 f(1 /cm 2 ) n}ƒ zmkr prüµƒÿ 6 ýÿž Ù ~ ž~ Åz Ÿ ³³n À hh Œñ m À ~ Œñ ý 6 ³ µé ¹Á + ÄŒ ³v Á, r 100~300 μm,µé ¼qä ê ± + ÄŒ ²o çž~ m d + ÄŒ o Åz z o xîï Šü ³¼ Š Ä Œ µ Ùp ³q³n Œ ² ³ ž~ m Åz º q n o q yùÿq ºÀ Îï ³ Š ÄŒ ž~ m doi: /j.issn d Ø e µt.îï ö ³¼ µ Š ÄŒ ³q [J].f zu{ g (12): [

2 d }. Îï ö ³¼ µ Š ÄŒ ³q 0 q¾gùœv ¾gÙŒ g q ž² o ž ofö o q n ¾ ž~o ²ey o Ío ÂÍ [1-3] u{ÿ ž² (transmyocardial laser revascularization, TMLR) g È oè oq y ù oä o ¾ o [4-10] np ³ rmq nxö ³¼Œñ m ˆ ³ u Â¼ pá Â Ío q n [11] Í nqîï y ºÌ nî³ qñk ž r 1.2 mmq² ³ ³ n qü Œý ³¼ ù Â qmg ³²mg ³q n º u Â¼ mq Œñ µ Á d qmg ù Â¼ ¹Â v ˆ ³ È qð Ùg Í ~Ž º ùÿ Í ² q o n Ã dùg Í Âö Íp200902/10 çy ÍÙgf ç zu{ Ÿ yg24ù ÄÄ Â ƒ«9~12 kg çy Ùgf ( ù úscxk( ) ) Í²zf Ùg ˆ}ü2006 y µö qºp ÍÙgq [12] g Ï Ï Š r r mgä Â¹ú βm w ¾ Sigma¹ú ˆ j m mg z Â¹ú Ã t VWF Dako ¹ú SP o ä äsf mg Ïr Â¹ú Í ¾ q Í Injex ¾ ( Rösch AG Medizintechnik¹ú) ² ³ ýí Îï 1 a: DOA collagenous fiber staining b: SDS collagenous fiber staining A B1 B2 B3 B4 C A: ampoule; B1B4: different dynamic spring; C: ejector Figure 1 High-pressure injection system 1 Îï npñ Injex ¾ q Ù r ± (0.172 mm), ŸÎï ƒùx{²gyƒ Œ Ð ² ý ¼ d q ³r ± ( 0.6 mm) Ø oûœ± q g Ù ü o r ²Ÿgyƒö ƒ Œ Í öj r g 0.5 mm ³ g58 m/s(b3 ) Œ 80 μl Š ÄŒÉ8~10 Ð ¼ r 1.2 mmq² ³ Š ÄŒqÍ õd Hoemann} [13] Í Š ÄŒq g n3y ƒ É A g 400 mg Š r r(œj 83% äg ÿ 18.61%) p8 ml Ë Í 5% q,îï20 min B g230 mg βm w ¾ p2 ml Ë Í 11.5%q C g62.5 mgˆ j p2.5 ml Ë Í 2.5%q B C ² Ã 8 ml A 2 ml B 2.5 mlc À fµé â,n ³ýq m 80 μl ü ºˆp37 ~ f 30 min Ø ŒÁg ÄŒ ÍÉ 24ù ÍgÃ Ég3 ê Îï ( ) Îï + Š ÄŒ µ ( + ÄŒ ) 8ù Í Ã ² g z«30 g/l ¾ Ø (1 ml/kg) Ùg ì Œ ~ ~ ±Ù p Ð Œ}4 ÂÉ q ² È Éy Ó }5 Î ŸÓ â Å Œ p} x 1 cm Þ{ œ Þ ù 1984 t Þ{ Þ x ¾ ñ Ôd @ qq.com ¹ Ò Þ{ œ Þ cn f É ú:r318 h u:b ú: (2010) º ( /W Q) 2133

ÐÂ ý Ð È ÙÃ n xst Î gí Ø Îï ² ê Í Øýr ºŒ + ÄŒ 80 μl Ø ŒÁgq Š ÄŒp x Ð ŸÎ ï ² 8~10f(1 /cm 2 ) n m }ƒzmkr prüµƒÿîï ² 8~10f(1 /cm 2 ) ý ü â ² ºŒ ÍÙg jz ý Ç ~ ~ Ê»6 ý5 d² ÅÄ 200 U/d ž Ù 6 ý Ø ÉyúÈ ÙŒ ²

0 cm) 40 g/l Šn Œ uœâ ³ Ÿ ýí Éf Ÿ hh vwf o ä ù µé ³Ÿ nà vwf o ä ž~ ž~¼q Œ vwf o ä ý 400 À Ã ² 5f f ¼ p p20 μmq ž~éì ígüžq g 6 ýÿž Ù, ~ ž ~ Åz Ÿ n À ³³n À hh Œñ m À ~ Œñ g} g}p ² ˆnr É nspss 10.

05) Ÿ1 Ÿ 1 ý 6 ü ž Ù ± Table 1 Comparison of hemodynamics at 6 weeks after surgery Group SMI (n = 5) TMIR (n = 6) TMIR+ chitosan (n=7) Heart rate (beat/min) 152.50±21.67 151.40±17.99 149.75±18.

46 ab LVSP: left ventricular systolic pressure; LVEDP: left ventricular end diastolic pressure; +dp/dt max and dp/dt max : maximum rate of intraventricular pressure rise; TMIR: transmyocardial

3 ÐÂ ý Ð È ÙÃ n xst Î gí Ø Îï ² ê Í Øýr ºŒ + ÄŒ 80 μl Ø ŒÁgq Š ÄŒp x Ð ŸÎ ï ² 8~10f(1 /cm 2 ) n m }ƒzmkr prüµƒÿîï ² 8~10f(1 /cm 2 ) ý ü â ² ºŒ ÍÙg jz ý Ç ~ ~ Ê»6 ý5 d² ÅÄ 200 U/d ž Ù 6 ý Ø ÉyúÈ ÙŒ ² ~Ž,² m k y i(hr) ï(lvedp) ï(lvsp) ¼ï é³i(+dp/dt max ) ¼ï Â³i(-dp/dt max ) Åz ~ õdfreyman} [14] ~ Åz q ² KCl ÈÙŒ Ùg Ç Œ ŸÑ Œ Éy qç ²Ó ÉÌz«x «/ «100% g ÅzqÉ ÉfÍ É ÿ ³q¹ (x ³g f r 0.5~1.0 cm) 40 g/l Šn Œ uœâ ³ Ÿ ýí Éf Ÿ hh vwf o ä ù µé ³Ÿ nà vwf o ä ž~ ž~¼q Œ vwf o ä ý 400 À Ã ² 5f f ¼ p p20 μmq ž~éì ígüžq g 6 ýÿž Ù, ~ ž ~ Åz Ÿ n À ³³n À hh Œñ m À ~ Œñ g} g}p ² ˆnr É nspss 10.0 ±zé «Í xx _ ±sÿx ü iâ ± nê É q f ee ± ee ± nq Í P < 0.05g i 2.1 ð 24ùg Í ²z fê r3ù r2ù + ÄŒ r1ù º18ùÙg² É 2.2 ö î ÆgÎ«ê üž Ù i(p > 0.05) 2134 d }. Îï ö ³¼ µ Š ÄŒ ³q ê ± + Ä Œ ï Â ¼ï Â³iéÎ i(p < 0.05) Ÿ1 Ÿ 1 ý 6 ü ž Ù ± Table 1 Comparison of hemodynamics at 6 weeks after surgery Group SMI (n = 5) TMIR (n = 6) TMIR+ chitosan (n=7) Heart rate (beat/min) ± ± ±18.46 LVSP(kPa) 18.39± ± ±1.02 LVEDP(kPa) 1.96± ± ±0.20 ab +dp/dt max (kpa/s) ± ± ±3.56 dp/dt max (kpa/s) ± ± ±2.46 ab LVSP: left ventricular systolic pressure; LVEDP: left ventricular end diastolic pressure; +dp/dt max and dp/dt max : maximum rate of intraventricular pressure rise; TMIR: transmyocardial high-pressure injection revascularization; SMI: simple myocardial infarction; a P < 0.05, vs. SMI group; b P < 0.05, vs. TMIR group 2.3 à k ã ý6 ³ µé ¹Á + ÄŒ ³ Á r 100~300 μm dµé ¼qä 2 a: Haematoxylin-eosin staining ( 400) c: Endothelial cells along the channel (Imunostaining for factor vwf, 400) b: Scanning electron microscope image of channel surface ( 250) Endo d: Channel openings in the endocardium (Haematoxylineosin staining, 100) The inner diameter (*) still reached about 250 μm; TMIR: transmyocardial high-pressure injection revascularization Figure 2 Channel patency in TMIR+chitosan group 2 Îï + Š ÄŒ µ ³³n À 2.4 ¾ Â ê Åz i(p > 0.05) ê ± + ÄŒ Åz (P < 0.05) p20 μmq ž~ ü Â i(p > 0.05) ê ± + ÄŒ p20 μmq ž~ Ø dý Ø g ü Â P.O. Box 1200, Shenyang cn.zglckf.com * Epi

Capillary Capillary percentage (%) (< 20 μm) (> 20 μm) SMI 5 29.34±2.39 94.80±10.35 6.20±1.04 TMIR 6 28.89±2.08 98.83±9.20 9.

05, b P < 0.01, vs. SMI group; c P < 0.05, d P < 0.01 vs.

infarct border zone( 100) 4 rnç hh ( 100) 2.

in infarct myocardial tissues (Immunostaining for factor vwf, 400) 3 fq mž~ (vwf o ä 400) 2.

01 Ÿ3 4 Ÿ 3 ü Œñ ± Table 3 Comparison of and collagen in each group Group n collagen (%) collagen (%) / SMI 5 10.28±2.50 1.99±0.

4 d }. Îï ö ³¼ µ Š ÄŒ ³q i(p < 0.05) Ÿ2 3 Ÿ 2 ü Åz ëqé ž~ Table 2 Percentage of infarction size and capillary counting in each group Group n Infarcttion size Capillary Capillary percentage (%) (< 20 μm) (> 20 μm) SMI ± ± ±1.04 TMIR ± ± ±1.22 b TMIR+chitosan ±2.17 ac ± ±1.57 bd a: SMI group b: TMIR group simple myocardial infarction; a P < 0.05, b P < 0.01, vs. SMI group; c P < 0.05, d P < 0.01 vs. TMIR group c: TMIR +chitosan group simple myocardial infarction a: SMI group b: TMIR group Figure 4 Sirius red staining of the infarct border zone( 100) 4 rnç hh ( 100) 2.6 Þ Ê ¾ h + ÄŒ g Í²z r1ù Ò 7ù Š ÄŒýÇj ö 4~6 ýž ² Â ºw ö c: TMIR +chitosan group simple myocardial infarction Figure 3 Neovessels in infarct myocardial tissues (Immunostaining for factor vwf, 400) 3 fq mž~ (vwf o ä 400) 2.5 Ê À c Ê À ù ŒñŸ ŒñŸ ê ± + ÄŒ Œñ m Ã (P < 0.05) Œñ Â ƒ(p < 0.01 Ÿ3 4 Ÿ 3 ü Œñ ± Table 3 Comparison of and collagen in each group Group n collagen (%) collagen (%) / SMI ± ± ±1.18 TMIR ± ± ±1.02 TMIR+chitosan ±2.19 a 2.35± ±0.58 bc simple myocardial infarction; a P < 0.05, b P < 0.01, vs. SMI group; c P < 0.05, vs. TMIR group ³²ÎØi ä rm ³ ²zfrmqÎ ˆ~ ä o öä v ŽmÀ ŒŸÅ ƒ z ýož q ö¼ q Œý q²z ²z f rm, q ~³ ² ý mà q ² ú~ Œ²z Å± º~Û [15] np ²zr v Í rð p Íu {Â ² q ³µŸ ÁÈ [16-22] y g q x j ³q ÍŸ g yù Š Ä Œº q Ù ù mg r r Ð npq Î ±Î Œ x xöž~ } zè [23-26] Í³²Îï ² Š ÄŒ Í ³¼, öj ý6 Š ÄŒ ¹µ Â ³ ³n µé ³ r³ r 100~300 μm dµé ³ ¼qä ² 2135

5 g² jtmrý ³ o u u{ÿ TMR ³ r³q ³ [27-28] ³ ²Åg oö ž mà qÿ² ²ž~¼m ž qž d mž~ oö z Érº ¾Î² rº [22] Í nîï k Ío q ž~ m n o ä ž~ öj ê ± + ÄŒ ç20 μmx q ž~ Ø º i d + ÄŒ Ø g Ÿ Š ÄŒº q ž~ m n Åz Œñ ž Ù x + ÄŒ o Åz d z o Îï ²zf Ùg r k i öm u tâ ö Ÿ ŒqË ¹ ²u{ Ÿ Îï Šü ³¼ Š ÄŒ µ Ùp ³q³n ² ³ ž~ m Åz z o o q yùÿq Ík q Â np nq Œö g q žq À Œ Ë dîï Š ÄŒ ~ˆ µéäœ² Žž qéã È r Ð u{ Îï ² ² ~ ä x j ¼ ü ² Ÿ ³ ³¼ö ³ ž À 4 õ h [1] Allen KB,Kelly J,Borkon AM,et al.transmyocardial laser revascularization: from randomized trials to clinical practice. A review of techniques, evidence-based outcomes, and future directions. Anesthesiol Clin (3): [2] Bahcivan M,Keceligil HT,Kolbakir F.Transmyocardial laser revascularization.anadolu Kardiyol Derg (1): [3] Wang LQ,Hu CS,Chang X,et al.shiyong Linchuang Yiyao Zazhi. 2008;12(2):1-5. i,œr,,}. ¼ž~ä Íq Íu{[J]. ng ç,2008,12(2):1-5. [4] Ak K,Isbir S,Gursu O,et al.the effect of transmyocardial laser revascularization on anginal symptoms and clinical results in patients with incomplete surgical revascularization.turk Kardiyol Dern Ars (4): [5] Briones E,Lacalle JR,Marin I,et al.transmyocardial laser revascularization versus medical therapy for refractory angina.cochrane Database Syst Rev.2009;21(1):CD [6] Horvath KA.Transmyocardial laser revascularization.j Card Surg (3): [7] Qu Z,Zheng JB,Zhang ZG.Single-center report of 5-year follow-up on 94 patients underwent transmyocardial laser revascularization.chin Med J (22): [8] Tasse J,Arora R.Transmyocardial revascularization: peril and potential.j Cardiovasc Pharmacol Ther (3) [9] Yang SS,Li WM,Yin LL,et al.chronic effects of percutaneous transmyocardial laser revascularization in patients with refractory angina.zhonghua Xin Xue Guan Bing Za Zhi (1): [10] Horvath KA.Mechanisms and results of transmyocardial laser revascularization.cardiology (1-3): [11] Wang Y,Liu XC,Zhang GW,et al.a new transmyocardial degradable stent combined with growth factor, heparin, and stem cells in acute myocardial infarction.cardiovasc Res (3): d }. Îï ö ³¼ µ Š ÄŒ ³q [12] The Ministry of Science and Technology of the People s Republic of China. Guidance Suggestions for the Care and Use of Laboratory Animals fét º y µ. ºp ÍÙgq [13] Hoemann CD,Chenite A,Sun J,et al.cytocompatible gel formation of chitosan-glycerol phosphate solutions supplemented with hydroxyl ethyl cellulose is due to the presence of glyoxal.j Biomed Mater Res A (2): [14] Freyman T,Polin G,Osman H,et al.a quantitative,randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction.eur Heart J (9): [15] Zhao J,Wang Y,Liu XC.Xinxueguanbingxue Jinzhan. 2007;28(6): Ÿ,iÈ,Ê z. ž² Íq ö ±[J]. ž~o ²,2007,28(6): [16] Kohmoto T,Fisher PE,Gu A,et al.does blood flow through holmium:yag transmyocardial laser channels?ann Thorac Surg. 1996;61: [17] Fischer PE,Khomoto T,Derosa CM,et al.histologic analysis of transmyocardial channels:comparison of co2 and Holmium:YAG lasers.ann Thorac Surg.1997;64: [18] Malekan R,Angiogenesis in transmyocardial laser revascularization. A nonspecific response to injury.circulation.1998;98: [19] Whittaker CP.Transmyocardial revascularization:the fate of myocardial channels.ann Thorac Surg.1999;68: [20] Gassler N,Wintzer HO,Stubbe HM,et al.transmyocardial laster revascularization histological features in human nonresponder myocardium.circulation.1997;95: [21] Mack CA,Channel patency and neovascularization after transmyocardial revascularization using an excimer laster.results and comparisons to nonlased channels.circulation.1997;96: [22] Chu VF,Giaid A,Kuang JQ,et al.angiogenesis in transmyocardial revascularization:comparis-on of laster versus mechanical punctures.ann Thorac Surg.1999;68(8): [23] Kim IY,Seo SJ,Moon HS,et al.chitosan and its derivatives for tissue engineering applications.biotechnol Adv.2008;26(1):1-21. [24] Lu WN,Lu SH,Wang HB,et al.functional improvement of infarcted heart by co-injection of embryonic stem cells with temperatureresponsive chitosan hydrogel.tissue Eng.2009; 15(6): [25] Thein-Han WW,Misra RD.Biomimetic chitosan-nanohydroxyapatite composite scaffolds for bone tissue engineering.acta Biomater. 2009;5(4): [26] Jiang T,Kumbar SG,Nair LS,et al.biologically active chitosan systems for tissue engineering and regenerative medicine.curr Top Med Chem.2008;8(4): [27] Fuchs S,Baffour R,Vodovotz Y,et al.laser myocardial revascularization modulates expression of angiogenic,neuronal,and inflammatory cytokines in a porcine model of chronic myocardial ischemia.j Card Surg.2002;17(5): [28] Malekan R.Angiogenesis in transmyocardial laser revascularization. A nonspecific response to injury.circulation.1998; 98: Ž Èq «Ù ß ½ «Ã Þ ¾Ð ƒ À ) ÞÁ ƒ (CSTS2005AA5008-5) d Ž Þ{ ck Ô c c c ì c Ó é od ÌrÀ{ í q d ÈqË ß Â u ¾ ¾{à Ä w d È q Â ß Î«å à öcû c À Â c œ ãd s Ä Ð Ú ì À ß Ä Ð k È ß d ò h ö î Ä d Èq ß Â ÂðÐ Ô r{à Ã d 2136 P.O. Box 1200, Shenyang cn.zglckf.com

Microsoft Word - 会行党_2014_7号-OK.doc

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