Peripheral nerve graft architecture affects regeneration Vleggeert-Lankamp, Carmen Lia Anne-Marie
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(16) HSBGUXBTJNQMBOUFEDPVMEOPUCFSFDPHOJ[FEBTTVDI*OUIFHSPVQPGUIF. TMPXMZEFHSBEBCMF . HSBGUT UIFTJUFXIFSFUIFHSBGUTIBECFFOJNQMBOUFEXBTDMFBSMZEJTUJOHVJTIBCMFCFDBVTFUIF UVCFIBEEFGPSNFEUPBHFMMJLFTIFMMBSPVOEUIFUJTTVFDBCMFUIBUDPOOFDUFEUIFUXPOFSWF TUVNQT"UJTTVFCSJEHFXBTQSFTFOUJOBMMSBUTJOCPUITZOUIFUJDOFSWFHSBGUHSPVQT. .JEHSBGUNPSQIPMPHZ *ONJEHSBGUDSPTTTFDUJPOTPGCPUIUZQFTPGTZOUIFUJDOFSWFHSBGUTBDFOUSBMMZMPDBUFEOFSWFMJLF TUSVDUVSFXBTTVSSPVOEFECZBDFMMSJDIPVUFSMBZFS mH 5IFOFSWFMJLFTUSVDUVSFDPOUBJOFE NZFMJOBUFEOFSWFmCSFT DFMMOVDMFJ BUMFBTUTPNFPGUIFN4DIXBOODFMMOVDMFJTJODFNZFMJO XBTQSFTFOUBSPVOEUIFOFSWFmCSFT BOEBOBNPSQIPVTFYUSBDFMMVMBSNBUSJY5IFPVUFSMBZFS DPOUBJOFEDJSDVMBSMZPSJFOUFEGVTJGPSNDFMMT QSFTVNBCMZmCSPCMBTUT FNCFEEFEJOBOFYUSBDFM MVMBSNBUSJYSJDIJODPMMBHFO5IJOXBMMFECMPPEWFTTFMTBOEDBQJMMBSJFTXFSFPCTFSWFEUISPVHI PVUUIFDSPTTTFDUJPO UIPVHINPTUPGUIFMBSHFSWFTTFMTXFSFMPDBUFEJOUIFPVUFSMBZFS*O UIFTMPXMZEFHSBEBCMF HSBGUT UISPVHIPVUUIFDFMMSJDIMBZFSUSBCFDVMBSTUSVDUVSFTXFSFQSFTFOU UIBUXFSFNPTUMJLFMZUPCFUIFSFNBJOTPGUIFUVCBMXBMM5IFTFTUSVDUVSFTXFSFOPUQSFTFOUPS GSBHNFOUFEJOUIFDFMMSJDIMBZFSTPGUIF GBTUEFHSBEBCMF HSBGUT5IVT JOUIF TMPXMZEFHSBEBCMF OFSWFHSBGUT UIFSFNBJOTPGUIFUVCBMXBMMBQQFBSFEUPCFQSFTFOUAFOCMPRVF5ISPVHIPVUUIF DFMMSJDIMBZFSPGCPUI TMPXMZEFHSBEBCMF BOE GBTUEFHSBEBCMF HSBGUTQJFDFTPGTNPPUINBUFSJBM TVSSPVOEFECZSJOHTPGMBSHFSPVOEDFMMTDPVMECFEJTUJOHVJTIFE5IFTNPPUINBUFSJBMNBEF UIFJNQSFTTJPOPGUIFSFNBJOTPGCJPNBUFSJBM CSPLFOEPXOCZUIFSPVOEMBSHFDFMMT 'JHVSF-JHIUNJDSPTDPQJDNJEHSBGUDSPTTTFDUJPOTPGSFHFOFSBUJOHOFSWFT. A:Slowlydegradableguide. *. B:Fastdegradableguide. 0.5 mm. 50 mm. 50 mm. 5SBOTWFSTF ǃN DSPTTTFDUJPOTPGNJEHSBGUTDJBUJDOFSWFT JNNFSTJPOmYFEBGUFSFMFDUSPQIZTJPMPHJDBMFWBMVBUJPO BOETUBJOFE XJUIIBFNBUPYZMJOFPTJO BDDPSEJOHUPUIFNFUIPEPGMàWFS#BSSFSBUPDMFBSMZJEFOUJGZNZFMJOTIFBUIT<> BOEBDDPSEJOH UPUIFNFUIPEPG7FSIPFGWBO(JFTPOUPDMFBSMZJEFOUJGZDPMMBHFO<>BSFEFQJDUFE*OBMMmHVSFT UIFMFGUQBOFMSFQSFTFOUT UIF7FSIPFGWBO(JFTPOTUBJOFEOFSWFTFDUJPOBTBXIPMF&MBTUJDmCSFTBSFTUBJOFECMBDL OVDMFJCMVFBOEDZUPQMBTNZFMMPX CSPXO5IFNJEEMFQBOFMSFQSFTFOUTBOFOMBSHFETBNQMFPGUIFIBFNBUPYZMJOFPTJOOFSWFTFDUJPOBOEEFNPOTUSBUFTUIF NPSQIPMPHZPGUIFOFSWFJOEFUBJM5IFSJHIUQBOFMEFQJDUTBOFOMBSHFETBNQMFPGUIFOFSWFTFDUJPO TUBJOFEBDDPSEJOHUPUIF NFUIPEPG,MàWFS#BSSFSB JOXIJDIUIFNZFMJOTIFBUIJTEFFQCMVFBOEJTUIFSFGPSFNPSFQSPOPVODFE "$SPTTTFDUJPOPGBTMPXMZEFHSBEBCMFOFSWFHSBGU#$SPTTTFDUJPOPGBGBTUEFHSBEBCMFOFSWFHSBGU. .
(17) 5IFTMPXMZEFHSBEBCMF HSBGUTXFSFFODBQTVMBUFECZBDPOUJOVPVTTUSVDUVSF XIJDIXBTSJDI JODPMMBHFO5IJTFODBQTVMBUJOHTUSVDUVSFBMTPDPOUBJOFEQJFDFTPGTNPPUINBUFSJBM XIJDI SFNBSLBCMZEFNPOTUSBUFEUPIBWFSPVOEMBSHFDFMMTJOUIFDFOUFS BTUIPVHICSFBLEPXOPG UIFCJPNBUFSJBMUPPLQMBDFGSPNUIFJOTJEFPGUIFQJFDFTPGCJPNBUFSJBM5IJTFODBQTVMBUJOH TUSVDUVSFXBTBCTFOUJOUIF GBTUEFHSBEBCMF HSBGUT 5IFDSPTTTFDUJPOBMTJ[FPGUIFTUSVDUVSFTUIBUSFHFOFSBUFEUISPVHIUIFEFHSBEBCMFQPSPVT HSBGUTXBTTNBMMFSDPNQBSFEUPUIFTUSVDUVSFTUIBUSFHFOFSBUFEUISPVHIUIF TMPXMZEFHSBEBCMF HSBGUT*UXBTOPUFWJEFOUXIFUIFSUIJTXBTDBVTFECZBTNBMMFSDFOUSBMBSFB BTNBMMFSDFMMSJDI BSFBPSUIFBCTFODFPGBOFODBQTVMBUJOHTUSVDUVSF*OBMMTZOUIFUJDOFSWFHSBGUT CVUNBJOMZ JOUIF TMPXMZEFHSBEBCMF HSBGUT UIFDSPTTTFDUJPOBMTIBQFPGSFHFOFSBUFETUSVDUVSFXBTPWBM BTUIPVHIUIFHSBGUTXFSFQBSUJBMMZTRVFF[FE JOWJWP DBVTJOHUIFSFHFOFSBUFEOFSWFDBCMFUP . BEPQUUIJTTIBQF. . .PSQIPMPHZPGUIFQFSPOFVT -JHIUNJDSPTDPQZPGTFDUJPOTEFNPOTUSBUFEUIBUUIFSFHFOFSBUFEQFSPOFBMOFSWFTXFSFWBTDV MBSJ[FEBOEFODMPTFEJOBDPOOFDUJWFUJTTVFTIFBUI5IFZDPOUBJOFENBOZNZFMJOBUFEBYPOT BCVOEBOUFOEPOFVSJBMDPOOFDUJWFUJTTVFBOECMPPEWFTTFMT mH MFGUDPMVNO 5IFNZFMJO TIFBUITPGUIFOFSWFmCSFTJOHSBGUFEOFSWFTXFSFUIJOJODPNQBSJTPOUPUIPTFJODPOUSPMT 5IFOFSWFmCSFTJOUIFBVUPHSBGUQFSPOFBMOFSWF BOEUPBMFTTFSFYUFOU JOUIF GBTUEFHSBEBCMF QFSPOFBMOFSWF XFSFGSFRVFOUMZGBTDJDVMBUFEXJUIJOBSFBTPGTJ[FDPNQBSBCMFUPUIFDSPTT TFDUJPOPGTJOHMFNZFMJOBUFEmCSFTJOUIFDPOUSPMOFSWF TVHHFTUJOHSFHFOFSBUJPOPGTFWFSBM OFSWFmCSFTUISPVHITJOHMF4DIXBOODFMMCBTBMMBNJOBSTDBõPMETUIBUQFSTJTUFEBGUFS8BMMFSJBO EFHFOFSBUJPOPGUIFPSJHJOBMNZFMJOBUFEOFSWFmCSFT<>5IFmCSFEJBNFUFSGSFRVFODZEJTUSJ CVUJPOT mH NJEEMFBOESJHIUDPMVNO EFNPOTUSBUFEUIBUJOSFHFOFSBUJOHQFSPOFBMOFSWFT mCSFEJBNFUFSTTIJGUFEUPTNBMMFSTJ[FT "MMOFSWFBSFBTXFSFPGDPNQBSBCMFTJ[F mH" BOEUIFmCSFEJBNFUFSTPGHSBGUFEOFSWFT XFSFIBMWFEDPNQBSFEUPDPOUSPMT mH# 5IFUPUBMOVNCFSBOEUIFEFOTJUZPGOFSWFmCSFT XFSFEPVCMFEBGUFSBVUPHSBGUJOH BOESFNBJOFEVODIBOHFEJOFYQFSJNFOUBMMZHSBGUFEOFSWFT mH$BOE% ,PMNPHPSPW4NJSOPXUFTUTSFWFBMFEBIPNPHFOFPVTmCSFTJ[FEJTUSJCVUJPOUISPVHIPVU DPOUSPMOFSWFT BOEBIPNPHFOFPVTmCSFTJ[FEJTUSJCVUJPOXJUIJOJOEJWJEVBMDPOUSPMOFSWFT *OUIFSFHFOFSBUJOHOFSWFT CPUIIFUFSPHFOFJUZBOEIPNPHFOFJUZJOmCSFTJ[FEJTUSJCVUJPOT CFUXFFOOFSWFT BOEXJUIJOJOEJWJEVBMOFSWFT XFSFFODPVOUFSFE 5IFTVNPGUXPMPHOPSNBMEJTUSJCVUJPOTDPVMETBUJTGBDUPSJMZCFmUUFEUPUIFmCSFEJBNFUFS EJTUSJCVUJPOTPGCPUIDPOUSPMBOEHSBGUQFSPOFBMOFSWFT mH SJHIUDPMVNO *OBMMFYBNJOFE OFSWFT UIF"*$XBTEFUFSNJOFEBOETIPXOUPCFTNBMMFS Q . . GPSUXPQPQVMBUJPOTDPN . QBSFEUPPOF JOEJDBUJOHUIBUUIFmCSFEJBNFUFSEJTUSJCVUJPODPVMECFNPSFBQUMZEFTDSJCFECZ UIFTVNPGUXPMPHOPSNBMEJTUSJCVUJPOTSBUIFSUIBOCZPOFMPHOPSNBMEJTUSJCVUJPO *ODPOUSPMQFSPOFBMOFSWFT UIFOVNCFSPG"ƹmCSFTXBTTPNFXIBUIJHIFSDPNQBSFEUPUIF OVNCFSPG"ƸmCSFT mH& *OSFHFOFSBUFEOFSWFTJUXBTUIFPUIFSXBZSPVOEUIFOVNCFSPG.
(18) 'JHVSF-JHIUNJDSPTDPQJDDSPTTTFDUJPOTBOEGSFRVFODZEJTUSJCVUJPOTPGDPOUSPMBOEHSBGUQFSPOFBMOFSWFT. A:Contr ol 250 6. F[f] (%). n[f]. 200. 150. 4. 100 2. 50. 0. 0 1. 3. 5. 7. 9. 11 13. 0. 2. 4. 6. d[f] (mm). 8. 10. 12. 14. 16. 18. d[f] (mm). B: Autograft 250. 6. F[f] (%). 200. n[f]. 150. . 4. 100. 2 50. 0. 0 1. 3. 5. 7. 9. 11 13. 0. 2. 4. 6. d[f] (mm). 8. 10. 12. 14. 16. 18. 12. 14. 16. 18. 12. 14. 16. 18. d[f] (mm). C:Slowlydegradableguide 250. 6. F[f] (%). n[f]. 200. 150. 4. 100. 2 50. 0. 0. 1. 3. 5. 7. 9. 11 13. 0. 2. 4. 6. D:Fastdegradableguide. 8. 10. d[f] (mm). d[f] (mm) 20 mm 250. 6. F[f] (%). 200. n[f]. 150. 4. 100. 2 50. 0. 0 1. 3. 5. 7. 9. d[f] (mm). 11 13. 0. 2. 4. 6. 8. 10. d[f] (mm). 5SBOTWFSTFTFNJUIJO ǃN DSPTTTFDUJPOTPGQFSPOFBMOFSWFT JNNFSTJPOmYFEBGUFSFMFDUSPQIZTJPMPHJDBMFWBMVBUJPO BOE TUBJOFEXJUIBUPMVJEJOFCMVFCPSBYTPMVUJPO<>BSFEFQJDUFE*OBMMmHVSFT UIFMFGUQBOFMSFQSFTFOUTUIFOFSWF TFDUJPOBTBXIPMF XIFSFBTJOUIFNJEEMFQBOFMBOFOMBSHFETBNQMFPGUIJTOFSWFTFDUJPO TRVBSF EFNPOTUSBUFTUIF NPSQIPMPHZPGUIFOFSWFJOEFUBJM5IFSJHIUQBOFMEFQJDUTUZQJDBMFYBNQMFTPGUIFGSFRVFODZEJTUSJCVUJPOTPGmCSFEJBNFUFST PGDPOUSPM BVUPHSBGUFE TMPXMZEFHSBEBCMFBOE GBTUEFHSBEBCMFHSBGUFEQFSPOFBMOFSWFT*OFBDIHSBQI EJBNFUFSTPGUIF OFSWFmCSFTXFSFEJTUSJCVUFEJOUPDMBTTFTPGǃNFBDI BOEQMPUUFEBHBJOTUUIFmCSFEJBNFUFSDMBTTGSFRVFODZ5IFEPUT SFQSFTFOUUIFDBMDVMBUFEmCSFEJBNFUFSDMBTTGSFRVFODZQFSmCSFEJBNFUFSDMBTT UIFTUSBJHIUMJOFSFQSFTFOUTUIFmUPGUPUBM DVSWF UIFEPUUFEMJOFSFQSFTFOUTUIF"ƹmCSFQPQVMBUJPO BOEUIFEBTIFEMJOFSFQSFTFOUTUIF"ƸmCSFQPQVMBUJPO.
(19) 'JHVSF.PSQIPNFUSJDBOBMZTJT. A. B. D. C. 2. 3. #. Fast degr. 2. #. Slowly degr. 3. # #. 10. Control. Autograft. Fast degr. Slowly degr. Autograft. 0. Control. Slowly degr. Fast degr. Control. 20. F *. 4. 8. 2. #. #. 0. 4. *. * *. *. *. *. Fast degr. Slowly degr. Autograft. Fast degr. Slowly degr. Autograft. Control. 0. Control. 3. 4. 0. Autograft. Slowly degr. Fast degr. Control. Autograft. E Number of nerve fibres (x 10 ). . *. *. 0. 0. . Number of fibres (x10 ). Nerve diameter (mm). 100. *. 4. Nerve diameter (mm). Nerve area (x103 mm2). 8 200. Fibre density (x10 /mm ). *. *. .PSQIPNFUSJDEBUBPGUIFDPOUSPM BVUPHSBGUFEBOETZOUIFUJDHSBGUFEOFSWFTBSFEFQJDUFE1FSPOFBMOFSWFTGSPNUIFDPOUSPM HSPVQXFSFBTFMFDUMZDIPTFOGPSFWBMVBUJPO O 'SPNUIFBVUPHSBGUFE O BOETZOUIFUJDHSBGUFE O QFSHSPVQ HSPVQT BMMQFSPOFBMOFSWFTXFSFFWBMVBUFE"5IFUPUBMTVSGBDFPGUIFOFSWFDSPTTTFDUJPO OFSWFBSFB #UIFOFSWFmCSF EJBNFUFS $UIFOVNCFSPGOFSWFmCSFT %UIFOFSWFmCSFEFOTJUZ &UIFOVNCFSPGOFSWFmCSFTGPSUIF"ƸBOE"ƹmCSF QPQVMBUJPOTFQBSBUFMZ BOE'UIFOFSWFmCSFEJBNFUFSGPSUIF"ƸBOE"ƹmCSFQPQVMBUJPOTFQBSBUFMZ%BUBBSFSFQSFTFOUFE BTNFBO TE %JõFSFOUDPNQBSFEUPDPOUSPMOFSWFT %JõFSFOUDPNQBSFEUPBVUPHSBGUOFSWFT. "ƸmCSFTXBTIJHIFSUIBOUIFOVNCFSPG"ƹmCSFT*OBVUPHSBGUQFSPOFBMOFSWFT UIFOVNCFS PG"ƸmCSFTJODSFBTFEmWFGPME XIJMFJOUIFTZOUIFUJDHSBGUFEOFSWFTUIFOVNCFSPG"ƸmCSFT SFNBJOFEFRVBM*OBMMSFHFOFSBUFEOFSWFT UIFOVNCFSPG"ƹmCSFTSFNBJOFEVODIBOHFE 5IFEJBNFUFSPG"ƸmCSFTEFDSFBTFEUISFFUJNFTBOEUIFEJBNFUFSPG"ƹmCSFTIBMWFEJOBMM FYQFSJNFOUBMOFSWFmCSFT mH' . .PSQIPMPHZPGUIFNVTDMFT $POUSPMUJCJBMBOEHBTUSPDOFNJDNVTDMFTDPOUBJOFEQSFEPNJOBOUMZUZQF**mCSFT*OUIFUJCJBM NVTDMF POMZPGUIFNVTDMFmCSFTXFSFUZQF*mCSFT BOEUIFTFXFSFEJTQFSTFEUISPVHIPVU UIFNVTDMF*OUIFHBTUSPDOFNJDNVTDMF PGUIFNVTDMFmCSFTXFSFUZQF*mCSFT UIFTFXFSF QSFEPNJOBOUMZMPDBMJ[FEJOUIFMBUFSBMCFMMZ UIPVHITPNFXFSFSBOEPNMZEJTQFSTFEUISPVHI UIFSFTUPGUIFNVTDMF*OOFSWFHSBGUNVTDMFT UZQF**NVTDMFmCSFTXFSFTUJMMQSFEPNJOBOUJO UIFUJCJBM UP BOEHBTUSPDOFNJD UP NVTDMFT CVUUIFHSPVQFEQSFTFODFPG UZQF*mCSFTJOUIFMBUFSBMCFMMZPGUIFHBTUSPDOFNJDNVTDMFTIBEEJTBQQFBSFE.
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(21) 'JHVSF3FDPSEJOHTPGDPNQPVOEOFSWFBDUJPODVSSFOUT. A:Stimulusr ecruitmentcurves 400. 300 200. 400. 300 200. 100. 100. 0. 0. 0. 1. 2. 3. 4. Amplitude (nA). Amplitude (nA). Amplitude (nA). 500. 500. 500. 200. 0 1. 2. 3. 4. 5. 6. 7. 0. 8. 1. 2. 4. 5. 7. 6. 8. Fast degradable. Slowly degradable. Autograft. 3. Time (ms). Time (ms). Time (ms). B:Responserate. 300. 100. 0. 5. 400. C:Q max,StR. C:Q max,IpR. 1200. 1200. D:MCV. Charge (pC). * #. * #. *. *. Fast degr. Autograft. Slowly degr. 0. Control. Fast degr. Autograft. Slowly degr. 0. Control. Fast degr. Autograft. Slowly degr. 0. * #. *. Slowly degr. * # 0. 20. 400. Fast degr. 400. *. Control. *. Autograft. Charge (pC). 50. Control. . 40. Response rate (%). . Conduction velocity (m/s). 100. "&YBNQMFTPGUIFUJNFDPVSTFTPGDPNQPVOEBDUJPODVSSFOUTBTBGVODUJPOPGTUJNVMVTWPMUBHFPGTZOUIFUJDHSBGUFETDJBUJD OFSWFT*OFBDIHSBQI UIFDVSWFTGSPNCPUUPNUPUPQSFQSFTFOUDPNQPVOEBDUJPODVSSFOUT FWPLFECZJODSFBTJOHTUJNVMVT WPMUBHFT4UJNVMVTBSUJGBDUTXFSFFSBTFE%VFUPUIFWJSUVBMDBUIPEFFõFDU<>UIFPOTFUPGUIFDVSSFOUNPWFTDMPTFSUP UIFTUJNVMVTBSUJGBDUVQPOJODSFBTJOHUIFTUJNVMJ3VOEPXOPGUIFDPNQPVOEBDUJPODVSSFOUEVFUP JOWJUSPEFUFSJPSBUJPO PGUIFOFSWFmCSFTXBTDBMDVMBUFEGSPNUIFTQPOUBOFPVTEFDSFBTFPG2 NBYEVSJOHNFBTVSFNFOUT BOEBNPVOUFEUPIS JODPOUSPMBOEISJOBVUPHSBGUFEOFSWFT*OBQJMPUFYQFSJNFOUXJUITZOUIFUJDOFSWFHSBGUT XFOPUFEUIBUSVOEPXO XBTNPSFQSPOPVODFEDPNQBSFEUPDPOUSPMBOEBVUPHSBGUFEOFSWFT DBVTJOHUIFSFTQPOTFUPEFUFSJPSBUFTJHOJmDBOUMZBGUFS BQQSPYJNBUFMZmWFUPUFONJOVUFTPGNFBTVSJOH*OUIFDVSSFOUFYQFSJNFOUUIFNFBTVSFNFOUTOFWFSMBTUFEMPOHFSUIBOmWF NJOVUFT #&MFDUSPQIZTJPMPHJDBMSFTQPOTFSBUF $2NBYEFSJWFEGSPNTUJNVMVTSFDSVJUNFOUEBUB %2NBYEFSJWFEGSPNJOUFSQVMTFUJNFSFDSVJUNFOUEBUB &.$7 %BUBBSFSFQSFTFOUFEBTNFBOTE %JõFSFOUDPNQBSFEUPDPOUSPMOFSWFT %JõFSFOUDPNQBSFEUPBVUPHSBGUOFSWFT. 5IFTUJNVMVTSFDSVJUNFOUDVSWFT mH" DPSSFTQPOEJOHUPUIFmHVSFTSFQSFTFOUJOHUIF NPOPQIBTJDBDUJPODVSSFOUT mH" EFNPOTUSBUFEUIBUUIFDPOUSJCVUJPOPGUIF"ƸmCSFTUP 2NBYXBTMBSHFSUIBOUIFDPOUSJCVUJPOPGUIF"ƹmCSFT BTJODPOUSPMBOEBVUPHSBGUFEOFSWFT mH# 5IFNFBOWPMUBHFUISFTIPME 7. . XBTIJHIFSJOHSBGUFEOFSWFTJODPNQBSJTPOUPDPOUSPM. OFSWFT mH$ BOEUIFWBMVFTPGCPUI7. Ƹ. BOE7 ƹEPVCMFEJOBMMSFHFOFSBUJOHOFSWFT mH. % *OBMMSFHFOFSBUJOHOFSWFT UIFNFBOUISFTIPMEWPMUBHFPGUIF"ƸmCSFT 7. Ƹ. XBTBQ . QSPYJNBUFMZIBMGUIFWBMVFPG7 ƹ JOBHSFFNFOUXJUIUIFWBMVFTJOUIFDPOUSPMOFSWFT 5IFJOUFSQVMTFUJNFSFDSVJUNFOUDVSWFT DPSSFTQPOEJOHUPUIPTFOFSWFTPGXIJDIUIFTUJNV MVTSFDSVJUNFOUDVSWFTXFSFEFQJDUFEJOmHVSF" EFNPOTUSBUFEBHBJOUIBUUIFDPOUSJCVUJPO.
(22) 'JHVSF4UJNVMVTSFDSVJUNFOUDVSWFT. A:Q/V graphs 120. 120. Aa 100. 100. Aa 80. Q (pC). Q (pC). 80. 60. 60. 40. 40. Ab. 20. Ab. 20. 0. 0. 0. 1. 2. 3. 4. 5. 7. 6. 9. 8. 0. 1. 2. 3. 4. 5. 7. 6. 9. 8. Voltage (V). Voltage (V). Fast degradable. Slowly degradable. . D: V50,a/b. C: V50. *. 5. 5. *. 800. * V50 (V). 1. 0. 0. ^. ^ ^. *. Slowly degr. Fast degr. Slowly degr. Autograft. Control. 0. 1. Autograft. * # * #. Control. * # * #. * 2. Slowly degr. ^. *. ^ 3. 2. Fast degr. ^. 3. Control. *. 4. *. Autograft. V50 (V). Charge (pC). 4. 400. *. *. Fast degr. B:Q max,StR. 4PMJEDJSDMFTSFQSFTFOUEBUBQPJOUT$POUJOVPVTMJOFTSFQSFTFOUUIFmUUFEDVSWFT*ODBTFUIFWBMVFTGPSUIF"ƸBOE"ƹmCSFT XFSFWFSZNVDIBMJLF JUXBTOPUJOBMMFMFDUSPQIZTJPMPHJDBMMZSFTQPOEJOHOFSWFTQPTTJCMFUPmUUIFTVNPGUXPFSGGVODUJPOT UPUIFEBUB5PTUJMMPCUBJOBOFYUSBQPMBUFEWBMVFGPS2 NBY ƸBOE2 NBY ƹGPSUIPTFOFSWFT UIFNFBOQFSDFOUVBMDPOUSJCVUJPOT PGUIF"ƸBOE"ƹmCSFTUP2 NBYPCUBJOFEJOUIBUHSPVQXFSFBQQMJFEUPUIFJNQMJDBUFE2NBY*GJUDPODFSOFE2 NBY ƸBOE2NBY ƹ PCUBJOFEGSPNUIFTUJNVMVTSFDSVJUNFOUDVSWF WBMVFTGPS7 ƸBOE7 ƹXFSFOPUPCUBJOFEJOUIPTFOFSWFT5IF"*$QSPWFEUP CFTNBMMFS Q GPSUXPQPQVMBUJPOTDPNQBSFEUPPOF#5IF2 CMBDL BOE2NBY ƹ XIJUF PGDPOUSPM BVUPHSBGUFE TMPXMZ NBY Ƹ EFHSBEBCMFBOE GBTUEFHSBEBCMFHSBGUFEOFSWFTEFSJWFEGSPNUIFTUJNVMVTSFDSVJUNFOUEBUB5IFQSFEJDUFEWBMVFTPG2 NBY Ƹ BOE2 NBY ƹBSFSFQSFTFOUFECZVOmMMFECBST$.FBOWPMUBHFUISFTIPME 7 PGDPOUSPM BVUPHSBGUFE BOETZOUIFUJDHSBGUFE TDJBUJDOFSWFT%.FBOmSJOHUISFTIPMEGPSUIF"ƸBOE"ƹmCSFTTFQBSBUFMZ 7 ƸBOE7 ƹ PGDPOUSPM BVUPHSBGUFE BOE TZOUIFUJDHSBGUFETDJBUJDOFSWFT5IFQSFEJDUFEWBMVFTPG7 ƸBOE7 ƹBSFSFQSFTFOUFECZVOmMMFECBST%BUBBSFSFQSFTFOUFE BTNFBO TE %JõFSFOUDPNQBSFEUPDPOUSPMHSPVQ %JõFSFOUDPNQBSFEUPBVUPHSBGUHSPVQ ~ %JõFSFOUDPNQBSFE UPQSFEJDUFEWBMVFT Q ~~ %JõFSFOUDPNQBSFEUPQSFEJDUFEWBMVFT Q . PGUIF"ƸmCSFTUP2 NBYXBTMBSHFSUIBOUIFDPOUSJCVUJPOPGUIF"ƹmCSFT mH" BTJODPOUSPM BOEBVUPHSBGUFEOFSWFT mH# 5IFSFTQPOTFJOUIFBVUPBOETMPXMZEFHSBEBCMFHSBGUFEOFSWFTXBTDIBSBDUFSJ[FECZBMPOHFS NFBOSFGSBDUPSZQFSJPE U DPNQBSFEUPDPOUSPMOFSWFT mH$ *OUIFGBTUEFHSBEBCMFHSBGUFE OFSWFT U XBTDPNQBSBCMFUPDPOUSPMOFSWFT5IFNFBOSFGSBDUPSZQFSJPEPGUIF"ƸmCSFT U Ƹ XBTBQQSPYJNBUFMZPOFUIJSEPGU ƹ CPUIJODPOUSPMBOEJOHSBGUFEOFSWFT mH% 5IFWBMVFPG U ƸEPVCMFEJO TMPXMZEFHSBEBCMF HSBGUFEOFSWFT CVUSFNBJOFEFRVBMJOBVUPHSBGUFEBOE GBTU.
(23) 'JHVSF*OUFSQVMTFUJNFSFDSVJUNFOUDVSWFT A:Q/tgraphs 120. 120. 100. 100. 80. Q (pC). Q (pC). 80. Aa 60. Aa 60. Ab 40. 40. 20. 20. Ab. 0. 0. 0. 5. 10. 15. 20. 25. 35. 30. 0. 5. 10. Time (ms). 20. 25. 35. 30. Time (ms). Fast degradable. Slowly degradable. B:Q max,IpR. D:t 50,a/b. C:t 50. . 16. 16. 12. 12. Fast degr. 0. Slowly degr. 0. Autograft. 4. Control. t50 (ms). 8. 4. Slowly degr. Fast degr. Slowly degr. Autograft. Control. 0. 8. Fast degr. 400. Control. t50 (ms). Charge (pC). 800. Autograft. . 15. "*OUFSQVMTFUJNFSFDSVJUNFOUHSBQITDPSSFTQPOEJOHUPUIFFYBNQMFTEFQJDUFEJOmHVSF"4PMJEDJSDMFTSFQSFTFOUEBUB QPJOUT$POUJOVPVTMJOFTSFQSFTFOUUIFmUUFEDVSWFT5IFUIFPSFUJDBMEBUBTFU ɂU 2 XBTBEEFEUPUIFEBUB5IF EVSBUJPOPGUIFBDUJPODVSSFOUXBTTPNFUJNFTTPMPOHUIBUJU BMNPTU FRVBMMFEUIFJOUFSQVMTFUJNFJOUFSWBM*OUIBUDBTF OPSFMFWBOUDVSWFDPVMECFPCUBJOFE BOEUIVTOPWBMVFGPS2 NBYDPVMECFPCUBJOFEGSPNUIFJOUFSQVMTFUJNFSFDSVJUNFOU DVSWF*ODBTFUIFWBMVFTGPSUIF"ƸBOE"ƹmCSFTXFSFWFSZNVDIBMJLF JUXBTOPUJOBMMFMFDUSPQIZTJPMPHJDBMMZSFTQPOEJOH OFSWFTQPTTJCMFUPmUUIFTVNPGUXP FSGGVODUJPOTUPUIFEBUB5PTUJMMPCUBJOBOFYUSBQPMBUFEWBMVFGPS2 NBY ƸBOE2 NBY ƹGPS UIPTFOFSWFT UIFNFBOQFSDFOUVBMDPOUSJCVUJPOTPGUIF"ƸBOE"ƹmCSFTUP2 NBYPCUBJOFEJOUIBUHSPVQXFSFBQQMJFEUP UIFJNQMJDBUFE2NBY*GJUDPODFSOFE2NBY ƸBOE2NBY ƹPCUBJOFEGSPNUIFJOUFSQVMTFUJNFSFDSVJUNFOUDVSWF WBMVFTGPSU ƸBOE U ƹXFSFOPUPCUBJOFEJOUIPTFOFSWFT5IF"*$QSPWFEUPCFTNBMMFS Q GPSUXPQPQVMBUJPOTDPNQBSFEUPPOF#5IF 2NBY Ƹ CMBDL BOE2 NBY ƹ XIJUF PGDPOUSPM BVUPHSBGUFE TMPXMZEFHSBEBCMFBOE GBTUEFHSBEBCMFHSBGUFEOFSWFTEFSJWFEGSPN UIFJOUFSQVMTFUJNFSFDSVJUNFOUEBUB5IFQSFEJDUFEWBMVFTPG2 NBY ƸBOE2 NBY ƹBSFSFQSFTFOUFECZVOmMMFECBST$.FBO SFGSBDUPSZQFSJPE U PGDPOUSPM BVUPHSBGUFE BOETZOUIFUJDHSBGUFETDJBUJDOFSWFT%.FBOSFGSBDUPSZQFSJPEGPSUIF"ƸBOE "ƹmCSFTTFQBSBUFMZ U ƸBOEU ƹ PGDPOUSPM BVUPHSBGUFE BOETZOUIFUJDHSBGUFETDJBUJDOFSWFT5IFQSFEJDUFEWBMVFTPGU Ƹ BOEU ƹBSFSFQSFTFOUFECZVOmMMFECBST%BUBBSFSFQSFTFOUFEBTNFBO TE %JõFSFOUDPNQBSFEUPDPOUSPMHSPVQ %JõFSFOUDPNQBSFEUPBVUPHSBGUHSPVQ %JõFSFOUDPNQBSFEUPGBTUEFHSBEBCMFBOETMPXMZEFHSBEBCMFHSPVQ ~ %JõFSFOU DPNQBSFEUPQSFEJDUFEWBMVFT Q ~~ %JõFSFOUDPNQBSFEUPQSFEJDUFEWBMVFT Q . EFHSBEBCMFHSBGUFEOFSWFT5IFWBMVFPGU ƹJODSFBTFEJOUIFBVUPHSBGUFEBOETMPXMZEFHSBEBCMF HSBGUHSPVQ CVUSFNBJOFEVODIBOHFEJOUIF GBTUEFHSBEBCMF HSBGUHSPVQ. 3FMBUJPOPGNPSQIPNFUSJDBOEFMFDUSPQIZTJPMPHJDBMEBUB 5IFNFBTVSFE7 JOUIF"ƸmCSFTXBTMPXFSUIBOQSFEJDUFE CPUIJOUIF TMPXBOEGBTUEFHSBE BCMFHSBGUHSPVQT mH" *OUIF TMPXMZEFHSBEBCMF OFSWFHSBGUHSPVQ UIFNFBTVSFEU. . JOUIF.
(24) 'JHVSF0CTFSWFEBOEQSFEJDUFEWBMVFT. A: meanthresholdvoltageandpredictedvalues. B: meanrefractoryperiodandpredictedvalues 16. 6 5. 12. 3 #. *#. 2. T50 (ms). V50 (V). 4 8 #. 4. 1 0. 0 Slowly degradable. Slowly degradable. Fast degradable. C: Chargestimulusrecruitmentandpredictedvalues. Fast degradable. D: Chargeinterpulsetimerecruitmentandpredictedvalues 200. 150. . 150 Charge (pC). Charge (pC). 200. 100 *#. 100. 50. # 50. 0 Slowly degradable. 0. Fast degradable. Slowly degradable. Fast degradable. 5IFNFBTVSFEWBMVFTPG7 PGUIF"ƸmCSFT EBSLHSFZ BOEUIF"ƹmCSFT MJHIUHSFZ BSFDPNQBSFEXJUIUIFJSQSFEJDUFE WBMVFT XIJUF %BUBBSFSFQSFTFOUFEBTNFBO TE %JõFSFOUDPNQBSFEUPQSFEJDUFEWBMVFT Q %JõFSFOU DPNQBSFEUPQSFEJDUFEWBMVFT Q . "ƸmCSFTXBTBMTPMPXFSUIBOQSFEJDUFE mH# *OUIF GBTUEFHSBEBCMF OFSWFHSBGUHSPVQIPX FWFS UIFNFBTVSFEU JOUIF"ƸBOEJOUIF"ƹmCSFTDPVMEOPUTUBUJTUJDBMMZCFEJTDFSOFEGSPN QSFEJDUFEWBMVFT*OUIF"ƹmCSFT UIFNFBTVSFE7. . BOEU XFSFBDDPSEJOHUPQSFEJDUJPOT. *OTMPXMZEFHSBEBCMF OFSWFHSBGUFEOFSWFT UIFNFBTVSFEDIBSHFJOUIF"ƸmCSFTXBTMPXFS UIBOQSFEJDUFE XIJMFJO GBTUEFHSBEBCMF OFSWFHSBGUFEOFSWFTUIFNFBTVSFEDIBSHFXBTBD. . DPSEJOHUPQSFEJDUJPOT#PUIJO TMPXBOEGBTUEFHSBEBCMF OFSWFHSBGUFEOFSWFT UIFNFBTVSFE DIBSHFJOUIF"ƹmCSFTXBTKVTUBTXBTFYQFDUFECBTFEPONPSQIPMPHJDBMDIBOHFT. %JTDVTTJPO 5IFJOnVFODFPGCJPEFHSBEBUJPOPGBTZOUIFUJDOFSWFHSBGUPOQFSJQIFSBMOFSWFSFHFOFSBUJPO XBTJOWFTUJHBUFEBOEJUXBTEFNPOTUSBUFEUIBUUIF. GBTUEFHSBEBCMF HSBGUBDUVBMMZEFTJOUF . HSBUFEXJUIJOUXFMWFXFFLTXIJMFUIF TMPXMZEFHSBEBCMF HSBGUSFNBJOFEQBSUJBMMZJOUBDU8F PCTFSWFETVCUMFEJõFSFODFTJOFMFDUSPQIZTJPMPHJDBMQSPQFSUJFTCFUXFFOUIFUXPLJOETPG TZOUIFUJDHSBGUFEOFSWFT BOEEFNPOTUSBUFEUIBUOFSWFmCSFTXFSFQPTJUJWFMZJOnVFODFECZ GBTUFSEFHSBEBUJPOPGUIFTZOUIFUJDOFSWFHSBGU.
(25) 5XFMWFXFFLTBGUFSTVSHFSZ UIFNPSQIPNFUSJDBMQBSBNFUFSTPGUIFQFSPOFBMOFSWFTBOE UIFHBTUSPDOFNJDBOEUJCJBMNVTDMFTXFSFTJNJMBSJGOPUFRVBMJOCPUIFYQFSJNFOUBMHSPVQT &MFDUSPQIZTJPMPHJDBMMZ IPXFWFS UIFSFXBTBEJõFSFODF5IFSFGSBDUPSZQFSJPETPGUIF"ƸBOE "ƹmCSFTJOUIF GBTUEFHSBEBCMF OFSWFHSBGUTXFSFDPNQBSBCMFUPVOPQFSBUFEOFSWFT JODPO USBTUUPUIFSFGSBDUPSZQFSJPETJO TMPXMZEFHSBEBCMF OFSWFHSBGUT UIBUXFSFMPOHFS#BTFEPO UIJTPVUDPNF GBTUEFHSBEBCMF OFSWFHSBGUTBSFQSFGFSSFEPWFS TMPXMZEFHSBEBCMF OFSWFHSBGUT CFDBVTFBTIPSUFSSFGSBDUPSZQFSJPEFOBCMFTUIFBYPOUPGPMMPXUIFmSJOHGSFRVFODZPGUIF OFVSPONPSFFõFDUJWFMZ5IJTBMMPXTBNPSFBEFRVBUFUBSHFUPSHBOTUJNVMBUJPO 5PJOUFSQSFUUIFPCTFSWFEDIBOHFTJOFMFDUSPQIZTJPMPHJDBMQBSBNFUFSTPGCPUI. GBTUBOE. TMPXMZEFHSBEBCMF OFSWFHSBGUT XFDPNQBSFEUIFNFBTVSFEWBMVFTUPQSFEJDUFEWBMVFT TFF .BUFSJBMTBOE.FUIPET &RVBMJUZPGUIFNFBTVSFEBOEQSFEJDUFEWBMVFTXPVMEJOEJDBUFUIBU OPPUIFSDIBOHFTCVUDIBOHFTPGEJBNFUFS BOEOVNCFS IBEPDDVSSFE*OFRVBMJUZXPVME JOEJDBUFUIBUDIBOHFTPGPUIFSGBDUPSTUIBUJOnVFODFUIFTFQBSBNFUFSTNVTUIBWFQMBZFEB SPMFBTXFMM MJLFGPSJOTUBODFTIPSUFSJOUFSOPEBMEJTUBODFT NFNCSBOFDPNQPTJUJPO DIBOHFT JOUSBOTQPSUNFDIBOJTNT BOEBEKVTUNFOUTJOUIFJPODIBOOFMDPNQPTJUJPO5IFNPTUPCWJPVT BOECFTUEPDVNFOUFEPGTVDIGBDUPSTBSFDIBOHFTJOUIFFYQSFTTJPOPGJPODIBOOFMTBUPS OFBSUIF3BOWJFSOPEFT<>"QBSUGSPNUIFDPODMVTJPOUIBUUIFFYQSFTTJPOPGJPODIBOOFMT IBTQSPCBCMZDIBOHFE UIFEJSFDUJPOPGUIFDIBOHFDBOBMTPCFRVBMJmFEBTDPNQFOTBUJPO PWFSDPNQFOTBUJPOPSEFDPNQFOTBUJPO mH 4IPVMEUIFPCTFSWFEWBMVFPGBOFMFDUSPQIZTJ PMPHJDBMQBSBNFUFSGBMMCFUXFFODPOUSPMBOEQSFEJDUFEWBMVFT UIJTDPVMECFJOUFSQSFUFEBT NFBOJOHUIBUUIFOFSWFmCSFTCFIBWFNPSFMJLFOPSNBMUIBOFYQFDUFE JFUIBUTPNFLJOEPG DPNQFOTBUJPOIBTPDDVSSFEUPPõTFUDIBOHFTPGOFSWFmCSFEJBNFUFS BOEOVNCFS JOEJDBUFE BT DPNQFOTBUJPO "MPOHTJNJMBSMJOFTPGSFBTPOJOHPCTFSWFEWBMVFTCFZPOEUIFQSFEJDUFE 'JHVSF*OUFSQSFUBUJPO. 15 10 5. Decompensation. 20. Compensation. Compensationfor V50andt50 25. Overcompensation. 0 Control. Measuredvalu e. Measuredvalu e. Measuredvalu e. Predictedvalu e. 1500 1200 900 600 300. Decompensation. Compensationfor Qmax Compensation. . Overcompensation. . 0 Control. Measuredvalue. Measuredvalue. Measuredvalue. Predictedvalue. 4IPVMEUIFPCTFSWFEWBMVFPGBOFMFDUSPQIZTJPMPHJDBMQBSBNFUFSGBMMCFUXFFODPOUSPMBOEFYQFDUFEWBMVFT UIJTDPVMECF JOUFSQSFUFEBTNFBOJOHUIBUUIFOFSWFmCSFTCFIBWFNPSFMJLFOPSNBMUIBOFYQFDUFE JFUIBUTPNFLJOEPGDPNQFOTBUJPO IBTPDDVSSFEUPPõTFUDIBOHFTPGOFSWFmCSFEJBNFUFS BOEOVNCFS JOEJDBUFEBT DPNQFOTBUJPO"MPOHTJNJMBSMJOFTPG SFBTPOJOHPCTFSWFEWBMVFTCFZPOEUIFFYQFDUFEWBMVFTXPVMETJHOJGZEFDPNQFOTBUJPO BOEPCTFSWFEWBMVFTCFZPOEUIF OPSNBMWBMVFPWFSDPNQFOTBUJPO.
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