velikost textu

Vyšetřovací metody mikrocirkulace kůže u syndromu diabetické nohy

Upozornění: Informace získané z popisných dat či souborů uložených v Repozitáři závěrečných prací nemohou být použity k výdělečným účelům nebo vydávány za studijní, vědeckou nebo jinou tvůrčí činnost jiné osoby než autora.
Název:
Vyšetřovací metody mikrocirkulace kůže u syndromu diabetické nohy
Název v angličtině:
Examination methods of skin microcirculation in diabetes foot syndrome
Typ:
Disertační práce
Autor:
MUDr. Michal Krčma
Školitel:
Prof.MUDr. Zdeněk Rušavý, Ph.D.
Oponenti:
Prof.MUDr. Jan Filipovský, CSc.
prof. MUDr. Karel Horký, DrSc.
doc. MUDr. Martin Prázný, CSc. Ph.D.
Id práce:
93987
Fakulta:
Lékařská fakulta v Plzni (LFP)
Pracoviště:
I.interní klinika (14-310)
Program studia:
Vnitřní nemoci (P5129)
Obor studia:
-
Přidělovaný titul:
Ph.D.
Datum obhajoby:
3. 5. 2010
Výsledek obhajoby:
Prospěl/a
Jazyk práce:
Čeština
Abstrakt:
Univerzita Karlova v Praze, /pNDVNiIDNXOWDY Plzni ,LQWHUQtNOLQLND)13O]H 08'U0LFKDO.UþPD V<â(729$&Ë0(72'<0,.52&,5.8/$&(.ä( U SYNDROMU DIABETICKÉ NOHY AXWRUHIHUiWGLVHUWDþQtSUiFH RERU 9QLWQtQHmoci 3O]H 'LVHUWDþQtSUiFHE\ODY\SUDFRYiQDY rámci kombinované formy doktorského studijního programu v RERUX9QLWQtQHPRFLQD,LQWHUQtNOLQLFH)1D/)8.Y Plzni. 8FKD]Hþ 08'U0LFKDO.UþPD ,LQWHUQtNOLQLND)13O]H/)8.3O]H Školitel: Prof. 08'U=GHQN5XãDYê3K' ,LQWHUQtNOLQLND)13O]H/)8.3O]H Oponenti: Prof. MUDr. Karel Horký, DrSc. II. interní klinika VFN Praha, 1. LF UK Praha Prof. MUDr. Jan Filipovský, CSc. ,,LQWHUQtNOLQLND)13O]H/)8.3O]H Doc. MUDr. Martin Prázný, CSc., Ph.D. III. interní klinika VFN Praha, 1. LF UK Praha S GLVHUWDþQtSUDFtMHPRåQRVHVH]QiPLWQD'NDQiWX/)8.3O]H+XVRYD Autoreferát byl rozeslán dne: 2EKDMREDGLVHUWDþQtSUiFHVHNRQiGQH/)8.3O]HâDIUiQNYSDYLORQ$OHM 6YRERG\3O]H 2 1. Úvod 4 0LNURFLUNXODFHNåHGLDEHWLFNpKRSDFLHQWD 4 3. Vliv inzulínu na parametry mikrocirkulace 6 9\ãHWRYDFtPHWRG\PLNURFLUNXODFHNåH 8 4.1. Transkutánní oxymetrie (tcpO2) .. 8 3tPiNDSLODURVNRSLH .. 8 4.3. Laser-doppler flowmetrie (LDF) .. 8 4.3.1. Iontoforéza.. 9 4.3.2. Laser Doppler Perfusion Imaging.. 10 4.3.3. Spektrální analýza vasomoce.. 10 4.3.4. Praktické aplikace LDF a transkutánní oxymetrie.. 10 5. Cíle výzkumu 11 6. Vliv fyziologické a suprafyziologické inzulinémie na reaktivitu kožní mikrocirkulace u zdravých GREURYROQtN 12 6.1. Metodika.. 12 6.2. Výsledky.. 13 6.3. Diskuse a limitace práce .. 14 6.=iYU.. 15 7. Vliv samotné fyzické aktivity na reaktivitu kožní mikrocirkulace u nemocných v riziku syndromu diabetické nohy. 15 7.1. Metodika.. 15 7.2. Výsledky.. 16 7.3. Diskuse a limitace práce .. 17 =iYU.. 17 NRUHODFHPH]LStWRPQRVWtNDUGLRYDVNXOiUQtDXWRQRPQtQHXURSDWLHDMHGQRWOLYêPLNRPSRQHQWDPL spektrální analýzy laser-doppler flowmetrie 17 8.1. Metodika.. 17 8.2. Výsledky.. 18 'LVNXVHD]iYU\.. 19 9\XåLWtY\ãHWHQtPLNURFLUNXODFHXVOHGRYiQtKRMHQtUány po aplikaci gelu z autologní plazmy 19 9.1. Platelet rich plasma.. 19 9.2. Metodika.. 20 9.3. Výsledky.. 20 'LVNXVHD]iYU\.. 20 8UþHQtUREXVWQtKRSDUDPHWUXSRSLVXMtFtKR325+NLYNXYHY]WDKXNY]HVWXSXSHUI~]HSR]DKiWt 21 10.1. Úvodní poznámky .. 21 10.2. Metodika.. 22 9êVOHGN\D]iYU .. 22 11. Literatura 22 12. PXEOLNDþQtþLQQRVWDXWRUD 27 3 1. ÚVOD 6DPRWQê SRMHP PLNURFLUNXODFH MH SHNYDSLY VWDUê -Lå Y VWROHWt QNROLN desetiletí po REMHYX NUHYQtKR REKX :LOOLDPHP +DUYH\HP SRSLVXMH 0DUFHOOR 0DOSLJKL ÄYOiVNRYLWi³ VSRMHQt PH]L WHSQDPL D åtODPL Y SOLFtFK åDE D QD]êYi MH YOiVHþQLFHPL FDSLOODULHV 9 URFH 1920 získává Nobelovu cenu August Krogh za objev regulace kapilárního SUWRNX X kosterního svalu. 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Porucha mikrocirkulace souvisí s neuropatickým postižením, což demonstruje i studie (73), NWHUi ]NRXPDOD PLNURFLUNXODFL X GLDEHWLN W\SX EH] ]QiPHN V\QGURPX GLDEHWLFNp QRK\, UR]GOHQêFK GR GYRX VNXSLQ SRGOH StWRPQRVWL SHULIHUQt QHXURSDWLH 0HQp SDUDPHWU\ NOLGRYi SHUI~]H RGSRY QD ]DKiWt SRVWRNOX]LYQt K\SHUpPLH Y\ND]RYDO\ VLJQLILNDQWQt ]PQ\ X SDFLHQW V QHXURSDWLt NGH E\OD SURGORXåHQi D QLåãt PD[LPiOQt SRVWRNOX]LYQí K\SHUpPLHDQLåãtUHDNWLYLWDQDORNiOQt]DKiWt 9H YêãH ]PtQQêFK VWXGLtFK E\OD NH VOHGRYiQt PLNURFLUNXODFH SRXåLWD SHGHYãtP ODVHURYi dopplerometrie, výhodná je kombinace s transkutánní oximetrií, jejíž výsledky korelují se ]PQDPLYQXWULWLYQtþiVWLHþLãW3UiFHSRURYQiYDODKRGQRW\WFS2YOHåHXSDFLHQWV 5 diabetem 2.typu s neuropatií, ale bez známek syndromu diabetické nohy (6,04 ± 0,52 kPa), s diabetiky bez neuropatie (7,14 ± 0,43 kPa) a zdravými kontrolami (8,10 ± 0,44 kPa). Bylo ]MLãWQR VLJQLILNDQWQt VQtåHQt SDUFLiOQtKR WODNX N\VOtNX X SDFLHQW V QHXURSDWLt QD UR]GtO RG SHGFKR]tFK GYRX VNXSLQ RGFK\ON\ E\O\ QHMYWãt Y OHåH 5R]GtO YêVOHGN YOHåHYVHG MH YêUD]QY\ããtXGLDEHWLNVQHXURSDWLt Využití LDF k predikci vzniku syndromu diabetLFNp QRK\E\OR SHGPWHP VWXGLH NGH E\O\YêVOHGNHPVLJQLILNDQWQQLåãtKRGQRW\/')XSDFLHQWGRVXGEH]GHIHNWDOHVFpYQtPL NRPSOLNDFHPLQHERQHXURSDWLt1HJDWLYQtYêVOHGN\SLQHVODSUiFH/DZDOHWDONGH E\OR SDFLHQW VH V\QGURPHP GLDEHWLFNp QRK\ Y\ãHWHQR YLGHRNDSLODURVNRSLFN\ E\O ]PHQ WUDQVNXWiQQt WODN L /') 3DFLHQWL E\OL UR]GOHQL GR VNXSLQ SRGOH HWLRORJLH – neuropatické, cévní a smíšené. Nebyly zaznamenány významné rozdíly ani v jedné z použitých metod. 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U SDFLHQW V QHXURSDWLt GRãOR N YêUD]Q QLåãtPX ]YêãHQt SHUI~]H SR ]DKiWt & PLQ QD SHGORNWt L QD QR]H YH VURYQiQt VH ]GUDYêPL NRQWURODPL L GLDEHWLN\ EH] QHXURSDWLH PH]L NWHUêPLQHE\O\VWDWLVWLFN\Yê]QDPQpUR]GtO\8]GUDYêFKGREURYROQtNE\ODUHDNFHQDSRGiQt acetylcholinu i nitroprusidu menší na noze než na SHGORNWt X SDFLHQW V QHXURSDWLt UR]GtO ]DFKRYiQ SL VQtåHQêFK RERX KRGQRWiFK 1HStPi YDVRGLODWDFH SL SRXåtWt DFHW\OFKROLQX PHQiQDUR]GtORGStPp/')VRQGRXYEOt]NRVWLLRQWRIRUHWLFNpNRPUN\– cca 5mm) byla YêUD]Q VQtåHQi X QHXURSDWLt þiVWHþQ VQtåHQi L X GLDEHWLN EH] QHXURSDWLH 3RGREQp YêVOHGN\XND]XMHLSUiFH0RUULVHDVSROXSUDFRYQtN 9OLYHPR[LGXGXVQpKRDSURVWDJODQGLQQDNUHYQtSUWRNVH]DEêYDODSUiFHNG\E\ODX ]GUDYêFKGREURYROQtNPHQD ODVHU-dopplerometricky perfúze SLLRQWRIRUp]HDFHW\OFKROLQX D QLWURSUXVLGX =iURYH E\OD SURYHGHQD IUHNYHQþQt DQDOê]D YêVOHGN 9êVOHGN\ XNi]DO\ åH NRåQt SHUI~]H ]D ED]iOQtFK SRGPtQHN MH þiVWHþQ RYOLYRYiQD SHV 12 QHSURNi]DOD RYOLYRYiQtFHVWRXHQGRJHQQtFKSURVWDJODQGLQ 2GSRYQD LRQWRIRUp]XDFHW\OFKROLQX E\ODVWDWLVWLFN\Yê]QDPQ Y\ããt QHå X QLWURSUXVLGX D GHLRQL]RYDQpYRG\SRXåLWpMDNRSODFHER8]GUDYêFKNRQWURODGLDEHWLNEH]QHXURSDWLH MHSRGtOYDVRGLODWDFHLQGXNRYDQpDFHW\OFKROLQHPFHVWRXQHXURD[RQiOQtRGSRYGL]KUXEa 1/3 z FHONRYp8GLDEHWLNVQHXURSDWLtMHYê]QDPQQLåãt 3. 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V<â(729$&Ë0(72'<0,.52&,5.8/$&(.ä( 4.1. Transkutánní oxymetrie (tcpO2) 3UYQt ]NXãHQRVWL V PHQtP REVDKX N\VOtNX Y WNiQL SRFKi]HMt ] OHW VWROHWt ] 86$ 1DUR]GtORG EåQ SRXåtYDQpKRPHQt VDWXUDFH22, které stanovuje fotometrickou metodou procento hemoglobinu s navázaným kyslíkem z celkového hemoglobinu v krvi, stanovuje tcpO2 StPRREVDKN\VOtNXGLIXQGXMtFtKRWNiQtGRSRYUFKRYêFKYUVWHYNåH3RXåtYiNWRPX SRODURJUDILFNê SULQFLS PHQt NG\ MH VRQGD WVQ SLORåHQD QD NåL D HOHNWURGD VH SHV NRQWDNWQt UR]WRN StPR GRWêNi SRYUFKX NåH 0D[LPiOQt YD]RGLODWDFH VH GRVDKXMH ]DKiWtP QDWHSORWXGR&Y\ããtWHSORWDQHPi]DQiVOHGHNYêUD]QMãtYD]RGLODWDFLDQDYtFPåHEêW QHStMHPQi SUR SDFLHQWD 7FS22 O]H SRXåtW V XUþLWêPL YêKUDGDPL MDNR PDUNHU SUWRNX QXWULWLYQtPL NDSLOiUDPL ]D SHGSRNODGX ]DFKRYiQt NRQVWDQWQtFK YQMãtFK SRGPtQHN experimentu). 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Shrneme-OLSURSUDNWLFNpY\XåLWtOLWHUiUQt~GDMHO]HtFLåHXYLDELOQtWNiQWUDQVNXWiQQtWODN N\VOtNXSHY\ãXMH PP+JPP+J StSDGQ SLYGHFKRYiQt þLVWpKR2 NOLGRYê WFS22 VWRXSQHDOHVSRQDGYRMQisobek. 3tPiNDSLODURVNRSLH 1HLQYD]tYQt PHQt SRPRFt RSWLFNp PLNURVNRSLH StSDGQ VSRMHQp V SRþtWDþRYêP Y\KRGQRFHQtP SRþWX D U\FKORVWL SRK\EX HU\WURF\W MH SRYDåRYiQR ]D ]ODWê VWDQGDUG Y KRGQRFHQt QXWULWLYQtKR ]iVREHQt WNiQ 9HONRX YêKRGRX MH VSRMení kapilaroskopie s RVYWOHQtPWNiQSRODUL]RYDQêP]HOHQêPVYWOHPSLþHPåSR]RUXMHPHSHVILOWUVSRVXQXWRX URYLQRX SRODUL]DFH R 7tP GRMGH N SRWODþHQt RGUD] RG WNiQ YH SURVSFK RGUD] RG SRK\EOLYêFKHOHPHQW1HYêKRGRXNDSLODURVNRSLHMHMHMtRPH]HQtYSUD[LKODYQQDNDSLOiU\ QHKWRYpKR OåND D UHODWLYQt SUDFQRVW Y\ãHWHQt .DSLODURVNRSLH WDNp QH]REUD]XMH VSROHKOLY KOXEãtSOHWHQ )RWRSOHW\VPRJUDILHPHWRGDNWHUiPtDEVRUSFLVYWODSURFKi]HMtFtKRWNiQtDQDMHMtP]iNODG relativní perfúzi, má v GQHãQtGRERPH]HQpY\XåLWt 4.3. Laser-doppler flowmetrie (LDF) Neinvazivní metoda na principu podobném klasickému ultrazvukovému doppleru. Optickým YOiNQHPMHGRVRQG\SLYHGHQODVHURYêSDSUVHNNWHUêMHþiVWHþQDEVRUERYiQWNiQt]þiVWLVH RGUiåt 3L RGUD]X RG SRK\EXMtFtFK VH þiVWLF NUHYQt EXN\ VH PQt MHKR YOQRYi GpOND QD ]iNODGIi]RYpKRSRVXQX- 'RSSOHUYSULQFLS9HOLNRVW]PQ\DMHMtIUHNYHQþQtUR]ORåHQtMH StPR~PUQpU\FKORVWLSRK\EXMtFtFKVHþiVWLFDMHMLFKSRþWX/DVHURYRXGRSSOHURPHWULt nelze SHVQ VWDQRYLW DEVROXWQt YHOLNRVW SUWRNX QDPHQê IUHNYHQþQt SRVXQ MH ]iYLVOê QD YODVWQRVWHFKWNiQNWHUpVHXNDåGpKRVXEMHNWXOLãt9êVWXSHPMHKRGQRWDSHUI~]HPHQiY PU (perfusion units) - EH]UR]PUQpþtVOR +ORXEND PHQt MH ]iYLVOi QD Y]GiOHQRVWL RSWLFNêFK YOiNHQ Y\VtODþH ODVHURYpKR VYWOD GiOH WUDQVPLWWHUX 7[ D SLMtPDþH UHFHLYHUX 5[ ýtP YWãt MH WDWR Y]GiOHQRVW Y DQJOLFNp OLWHUDWXH³ILEHUVHSDUDWLRQ´WtPYWãtMHGRVDKVRQG\+ORXENXPHQtGiOHRYOLYXMHYOQRYi 8 délka použitpKR VYWOD þtP YWãt YOQRYi GpOND WtP Y\ããt GRVDK D PHQãt SHVQRVW EåQ SRXåtYDQp StVWURMH VH SRK\EXMt Y RERUX þHUYHQpKR YLGLWHOQpKR VYWOD – cca 600-700 nm) a YODVWQRVWLWNiQDEVRUEFHVYWOD%åQpVRQG\PDMtRVRYRXY]GiOHQRVWYOiNHQFFDPP (SUPURSWLFNpKRYOiNQDPPVRFKUDQQêPREDOHPPPFRåRGSRYtGiKORXEFH PHQtSHUI~]HWNiQtGRFFD-PP/')O]HWHG\SRYDåRYDW]DPDUNHUORNiOQtKRSUWRNX YHãNHUêP FpYQtP HþLãWP DUWHULRO\ NDSLOiU\ YHQXO\ L DUWHULRYHQy]Qt VKXQW\ SLþHPå VH zkracující se osovou vzdáleností optických vláken a klesajícím objemem oblasti zájmu roste relativní podíl nutritivní perfúze. =YOiãWQtPW\SHPMVRXMHGQRYOiNQRYpVRQG\NGHMHNDQiOSURWUDQVPLWWHUDUHFHLYHUVSROHþQê 9êKRGRX MH ~]Nê SUPU YOiNna a jednoduchá manipulace (sterilizace apod.), nevýhodou QHPRåQRVWSHVQVWDQRYLWKORXENX]NRXPDQpWNiQSURQNWHUpSDSUVN\MHY]GiOHQRVW7[5[ URYQDSUPUXRSWLFNpKRYOiNQD– FFDPPSURQNWHUpVHOLPLWQEOtåt 9]KOHGHPNHVNXWHþQRVWLåHQHní možné hodnotit absolutní hodnotu perfúze, používá se celá DGD SURYRNDþQtFK WHVW NG\ VH Pt MLPL Y\YRODQp ]PQ\ Y SHUI~]L WNiQ 0H]L QHMSRXåtYDQMãtSDWt - ]DKiWtQD-44°C - okluze – W\SLFN\NRQþHWLQ\PDQåHWRXWRQRPHWUX - iontoforéza – použitíPIDUPDNRYOLYXMtFtFKSHUI~]LU]QêPLPHFKDQLVP\YL]GiOH - posturální – leg elevation test - chlad – SLPHQt5D\QDXGRYDIHQRPpQX - elektrická stimulace – stimulace C vláken nízkými proudy 0H]L QHMEåQMãt SURYRNDþQt WHVW\ SRXåtYDQp QD QDãHP SUDFRYLãWL SDWt SHGHYãtP ]DKiWt VRQG\ QD & NWHUp YHGH N GLODWDFL NRåQtFK NDSLOiU D WtP N QiUVWX SHUI~]H GiOH RNOX]H NRQþHWLQ\PDQåHWRXWRQRPHWUX9WRPWRStSDGMHQXWQpRNOX]tGRViKQRXWELRORJLFNpQXO\– W]Q]DVWDYHQtSUWRNXNDSLOiUDPL3RNUiWNpGREWUYiQtRNOX]HV– PLQXWVHPtþDV ]DMDNGORXKRGRViKQHSHUI~]HPD[LPDDKRGQRWDWRKRWRPD[LPDY]WDåHQiNKRGQRWSHUI~]H SHGSURYHGHQtPRNOX]H/DVHURYiGRSSOHURPHWULHMHUHODWLYQWHFKQLFN\QiURþQiY]KOHGHPN Y\VRNpYDULDELOLWPHQtDYHONp citlivosti (je nutné omezit rušivé vlivy – vibrace, konstantní WHSORWD Y PtVWQRVWL NOLGQp WLFKp SURVWHGt , KRGQRFHQt MH REWtåQMãt Y]KOHGHP N LQWHULQGLYLGXiOQtPUR]GtOP/')VH]HMPSURWRYNOLQLFNpSUD[L]DWtPSRXåtYiYêMLPHþQ– v plastické chiruUJLLNPRQLWRUDFLSHUI~]HãWSXDYVWRPDWRFKLUXUJLLNSRVRX]HQt~VSãQRVWL UHSODQWDFH ]XEX =PQX E\ PRKO\ SLQpVW QRYp GLPHQ]H KRGQRFHQt /') ]i]QDPX NWHUp SLQiãHMt]YOiãLQIRUPDFHRHQGRWHOLiOQtPSRGtOXSRUXFK\PLNURFLUNXODFHD]YOiãRSRVWLåHQt autoQRPQt LQHUYDFHFpYQtKR HþLãW – D Xå IUHNYHQþQt DQDOê]D ]i]QDPXQHER LRQWRIRUp]DV použitím acetylcholinu nebo nitroprusidu sodného. Ani pro jednu z uvedených modalit zatím nejsou k dispozici širší klinická data. 4.3.1. Iontoforéza Iontoforéza je metoda, NWHUiY\XåtYiHOHNWULFNpKRQiERMHLRQWNXU\FKOHQtMHMLFKSUQLNXGR WNiQ]DQRUPiOQtFKRNROQRVWtEH]YOLYXHOHNWULFNpKRSURXGXE\YVWHEiYiQtOiWHN]SRYUFKX NåH WUYDOR QNROLN GHVtWHN KRGLQ 9\XåtYi VH GYRX HOHNWURG – první, s nábojem stejného znaPpQNDMDNRPiSRXåLWêLRQWNWHUêMHWRXWRHOHNWURGRXRGSX]RYiQDSLWDKRYiQNHGUXKpV QiERMHP RSDþQpKR ]QDPpQND 'RFtOt VH WDN U\FKOHMãtKR D Y þDVH NRQVWDQWQtKR YVWHEiYiQt ]NRXPDQp OiWN\ 3UR GREURX SRURYQDWHOQRVW MHGQRWOLYêFK PHQt D SUR ]DMLãWQt VWabilních YODVWQRVWt WNiQ EKHP PHQt MH QXWQp LRQWRIRUp]X SURYiGW ]D NRQVWDQWQt WHSORW\ WNiQ QDS&3L]NRXPiQtPLNURFLUNXODFHVHSRXåtYDMtOiWN\SVREtFtQDFpYQtHþLãW - acetylcholin – MDNRQHXURWUDQVPLWWHUSVREtFHVWRX&YOiNHQ - pilokarpin – RYOLYXMHHQGRWHOFHVWRX12 - nitroprusid sodný – SVREtStPRQDHQGRWHO 9 Velikost proudu procházejícího tkání se pohybuje mezi 100 – PLNURDPSpU– vyšší proud E\ DNWLYRYDO StPR &-YOiNQD D WHQWR HIHNW E\ ]NUHVORYDO ]PQX SHUI~]H ]SVREHQRX ionWRIRUp]RX XUþLWp OiWN\ ,RQWRIRUp]D Pi L VYp NRQWUDLQGLNDFH – SHGHYãtP StWRPQRVW LPSODQWiW FLWOLYêFK QD HOHNWULFNp LPSXOV\ MDNR MH NDUGLRVWLPXOiWRU QHER NDUGLRYHUWHU GiOH SRãNR]HQtNåHYPtVWPHQtGHUPDWLWLGDXOFHUDFHDDOHUJLFNiUHDNFHQDSRXåitou látku v DQDPQp]H7HFKQLFNpSURYHGHQtMHQiURþQpQDStVWURMRYpLSHUVRQiOQtY\EDYHQtSURWRY\XåLWt LRQWRIRUp]\]VWiYiY\KUD]HQRSURYê]NXPQp~þHO\ 4.3.2. Laser Doppler Perfusion Imaging Laser Doppler Perfusion Imaging je technologie založená na zoEUD]HQtSHUI~]HYWãtKRRNUVNX WNiQREGREQêPSULQFLSHPMDNRNODVLFNiODVHUGRSSOHUIORZPHWULHDOH]DSRPRFLVNHQRYiQt Y]GiOHQêPODVHURYêPSDSUVNHP 9êKRGRXMHYWãt]REUD]HQêUHJLRQ QHYêKRGRXQHPRåQRVW NRQWLQXiOQtPRQLWRUDFH]PQSHUI~]HDOHMHQ]tVNiQí statického obrázku. 4.3.3. Spektrální analýza vasomoce Obr. 2. 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Praktické aplikace LDF a transkutánní oxymetrie 1DY]GRU\ VWRXSDMtFtPX SRþWX SXEOLNDFt V WpPDWHP PLNURFLUNXODFH D MHMtFK ]PQ X GLDEHWX QHQt ]DWtP Y\ãHWHQt YêãH MPHQRYDQêPL PHWRGDPL VRXþiVWt EåQp NOLQLFNp SUD[H 1DSURti WRPXPDNURFLUNXODFHMHY\ãHWRYiQDDLQWHUYHQRYiQDEåQ+ODYQtGYRGWRKRWRUR]SRUXWNYt Y WHFKQLFNp QiURþQRVWL Y\ãHWHQt PLNURFLUNXODFH D YH VORåLWRVWL LQWHUSUHWDFH YêVOHGN Y QHH[LVWHQFL MHGQR]QDþQêFK QRUHP D Y QHSRVOHGQt DG QHMVRX GRVWDWHþQ SRGložená GRSRUXþHQtMDNPLNURFLUNXODFLLQWHUYHQRYDW 6WDQRYHQt QRUHP /') SUR MHGQRWOLYp YNRYp VNXSLQ\ ]GUDYp SRSXODFH D SUR QHPRFQp V GLDEHWHP PHOOLWHP VL Y\åiGi VWXGLH QD YHONpP SRþWX SDFLHQW X WUDQVNXWiQQt R[\PHWULH MH situace v tomto ohledu jednodušší - za posledních 25 let jsou k dispozici data u více než 4500 10 SDFLHQWDVRXYLVORVWPH]LWUDQVNXWiQQtPWODNHPN\VOtNXDSUHGLNFtKRMHQtMHRYHQD~URYH GND]X % SHVWRåH QHH[LVWXMH ]DWtP MHGQR]QDþQi VKRGD QD FXW-RI KRGQRW PP+J 40mmHg). Slibné vêVOHGN\ SLQiãt Y\XåLWt ODVHU GRSSOHU IORZPHWULH SHGHYãtP SURYRNDþQtKR WHVWX ]DKiWtP N PHQt IXQNþQt UH]HUY\ PLNURFLUNXODFH D MHMt ]PQ\ SR LQWHUYHQFL QD makrocirkulaci. Zdá se, že zvýšení reaktivity mikrocirkulace také nastává velmi brzy po ~SUDY åLYRWQtKR VW\OX REp]QtFK QHPRFQêFK V GLDEHWHP GtYH QHå VH ]PQt RVWDWQt PHWDEROLFNpSDUDPHWU\ Y\XåLWt/')MDNRþDVQpKRPDUNHUXMHWDNpSHGPWHPYê]NXPX /pN\ NWHUp E\StPRRYOLYRYDO\PLNURFLUNXODFL QHMVRX]DWtPNOLQLFN\GRVWDWHþQRYHQp V malých sWXGLtFK VYM HIHNW SURNi]DOD QNWHUi DQWLWURPERWLND VXORGH[LG DQWLR[LGDQW\ S\FQRJHQRO D Qt]NRPROHNXOiUQt KHSDULQ\ 1RY MH SLNOiGiQD YHONi GOHåLWRVW polysacharidovému komplexu na endotelu cév, glykocalyxu, jehož poškození vlivem R[LGDþQtKR VWUHVX SHGFKi]t PRUIRORJLFNêP ]PQiP NDSLOiU ,QI~]H K\DOXURQLGi]\ Y H[SHULPHQWX QD ]YtHWL SRPiKi UHVWDXURYDW JO\FRFDO\[ SHGFKi]HW QHYUDWQêP ]PQiP PLNURFLUNXODFH D ]OHSãXMH MHMt UHDNWLYLWX (QGRWHOLiOQt D GHVWLþNRYp QDS EHFDSOHUPLQ UVWRYp IDNWRU\ SRYDåRYDQp ]D YHOPL QDGMQp SUR KRMHQt GLDEHWLFNêFK GHIHNW YWãtKR UR]ãtHQt QHGRViKO\ 9 SRVOHGQtFK OHWHFK VH YQXMH SR]RUQRVW DQWDJRQLVWP HQGRWHOLQRYêFK UHFHSWRU NWHUp VH SRGtOHMt QD YD]RNRQVWULNFL SL LQ]XOtQRYp UH]LVWHQFL NG\ VH DNWLYLWD UHFHSWRUSURWURPER[DQ$]Y\ãXMHGtN\R[LGDþQtPXVWUHVX /DVHU GRSSOHU IORZPHWULH QDOp]i Y\XåLWt L YH YêFKRGQt PHGLFtQ Y PtVWHFK WUDGLþQ R]QDþRYDQêFK]DDNXSXQNWXUQtERG\O]H]PLWVLJQLILNDQWQYWãtSUWRNPLNURFLUNXODFt]D bazálních podmínek (29). 5. CÍLE VÝZKUMU A. Posoudit vliv fyziologické a suprafyziologické inzulinémie na reaktivitu kožní PLNURFLUNXODFHX]GUDYêFKGREURYROQtN B. 8UþLWYOLYVDPRWQpI\]LFNpDNWLYLW\QDUHDNWLYLWXNRåQtPLNURFLUNXODFHXQHPRFQêFK v riziku syndromu diabetické nohy. C. Stanovit korHODFLPH]LStWRPQRVWtNDUGLRYDVNXOiUQtDXWRQRPQtQHXURSDWLHD jednotlivými komponentami spektrální analýzy laser-doppler flowmetrie (LDF). D. 9\XåtWY\ãHWHQtNRåQtPLNURFLUNXODFHSRPRFt/')N posouzení hojení syndromu diabetické nohy. E. =SWQRXDQDOê]RX]tVkaného souboru dat vytipovat robustní parametr popisující 325+NLYNXYHY]WDKXN Y]HVWXSXSHUI~]HSR]DKiWt 11 6. VLIV FYZIOLOGICKÉ A SUPRAFYZIOLOGICKÉ INZULINÉMIE NA REAKTIVITU KOŽNÍ MIKROCIRKULACE U ZDRAVÝCH DOBROVOLNË. 6.1. Metodika Mikrocirkulace bylDY\ãHWRYiQD]DNOLGRYêFKSRGPtQHNDSRVWLPXODFLI\]LRORJLFN\ P,8ODVXSUDI\]LRORJLFN\P,8O]YêãHQRXKODGLQRXLQ]XOtQX9\ãHWHQtE\OR provedeno u 12-WLQHREp]QtFK]GUDYêFKGREURYROQtNEH]DQDPQp]\GLDEHWXXURGLþD VRXUR]HQFEH]FKURQLFNêFKRQHPRFQQtEH]WUYDOpIDUPDNRWHUDSLHVYêMLPNRXNRQWUDFHSWLY XåHQVURYQDWHOQêFKYNRYLSRGOH]iNODGQtFKDQWURSRPHWULFNêFKLELRFKHPLFNêFK SDUDPHWUYL] níže WDEXONDþ3URWRNROVWXGLHE\OVFKYiOHQHWLFNRXNRPLVt/pNDVNpIDNXOW\ 8.3O]HYãLFKQLGREURYROQtFLE\OLGRSHGXSRGUREQVH]QiPHQLVSUEKHPH[SHULPHQWXD SRXåtYDQêPLPHWRGDPLFRåVWYUGLOLSRGSLVHPLQIRUPRYDQpKRVRXKODVX9GHQSHGFKi]HMtFt Y\ãHWHQt]DFKRYiYDOLGREURYROQtFLEåQêUHåLPVY\ORXþHQtPYWãtI\]LFNpQiPDK\D excesivní NRQ]XPDFHVDFKDULGWXNDDONRKROXDVSRVOHGQtPMtGOHPGRKRGLQ\%KHP GRSROHGQHQiVOHGXMtFtKRGQHE\OSURYHGHQGYRXVWXSRYêK\SHULQ]XOLQHPLFNêFODPSV cílovými inzulinémiemi 50 a 150 mIU/l dle zavedené metodiky (15), tedy s rychlostmi inzulínu 2,8PKRGD8PKRG8SRORYLQ\VXEMHNWE\OR]DPQQRSRDGt inzulinémií (tzn. nejprve 6,0 U/m2/hod a dále 2,4 U/m2/hod). Za bazálních podmínek a v RERXXVWiOHQêFKVWDYHFKE\OD]PHQDSHUI~]HSRPRFtODVHU-doppler flowmetrie a transkutánní oxymetrieUHVSLUDþQtNYRFLHQWDHQHUJHWLFNêYêGHMSRPRFtQHStPpNDORULPHWULH (V-max Sensormedics, Yorba Linda, CA, USA) podle standarní metodiky (65). Byla Y\SRþWHQD0KRGQRWDNDåGpKRFODPSXNSRVRX]HQt]PQ\LQ]XOLQRUH]LVWHQFH9êVOHGN\YH IRUPPHGLiQXDLQWHUNYDUWLORYpKRUR]SWtE\O\]KRGQRFHQ\:LOFR[RQRYêPWHVWHP. 7DEþ&KDUDNWHULVWLNDSUREDQG PHGLiQLQWHUNYDUWLORYpUR]SWtHYHQW1 SRþHWPXåLåHQ\ 12 (6/6) YN>URN\@ 24 (23 – 25) BMI [kg.m-2] 21,6 (20,7 – 23,7) obvod pasu [cm] 74,5 (66,3 – 80,0) lrevní tlak [mmHg] 113/75 (107/66 – 117/80) ODþQiJO\NpPLH>PPROO@ 4,7 (4,6 – 5,3) sérové triglyceridy [mmol/l] 0,8 (0,7 – 0,9) HDL cholesterol [mmol/l] 1,4 (1,1 – 1,6) LDL cholesterol [mmol/l] 2,5 (2,3 – 3,1) fibrinogen [mmol/l] 2,3 (2,2 – 2,5) Laser-doppler flowmetrie .RåQtSHUI~]H E\ODY\ãHWHQD]DED]iOQtFKSRGPtQHNSHGFODPSHPDYXVWiOHQpPVWDYXSL obou hladinách inzulínu. Byl použit systém Periflux 5000 (Perimed, Švédsko) se sondou PF HPLWXMtFt ODVHURYpVYWOR R IUHNYHQFL QP D YêNRQX P: 6RQGD E\OD SLORåHQD QD GRU]XP QHGRPLQDQWQt QRK\ D PHQt E\OR SURYHGHQR X YãHFK VXEMHNW SL VWDELOQt WHSORW & 1iVOHGQ E\O\ SRXåLW\ SURYRNDþQt WHVW\ – ]DKiWt ]DKiWt VRQG\ QD & PDMtFt ]D následek maximální vazodilataci) a okluzí (3 PLQXWRYiRNOX]HNRQþHWLQ\PDQåHWRXWRQRPHWUX QDIRXNQXWRX QD WODN R PP+J Y\ããt QHå V\VWROLFNê NUHYQt WODN NG\ E\O PHQ þDV GR GRVDåHQtPD[LPiOQtKRSURNUYHQtSRXYROQQtRNOX]H7\WRSURYRNDþQtWHVW\MVRXVWDQGDUGHP SL Y\ãHWRYiQt SHUI~]H WNiQt Y]KOHGHP N Y\VRNp þDVRYp D SURVWRURYp 12 YDULDELOLW SURVWpKR PHQt ED]iOQt SHUI~]H 9]RUNRYDFt NPLWRþHW E\O PV NH ]KRGQRFHQt YêVOHGNE\ORSRXåLWRILUHPQtKRVRIWZDUX3HULVRIW3HULPHGâYpGVNR Transkutánní oxymetrie Parciální tlak kyslíku byO PHQ SRPRFt WFS2 HOHNWURG\ 3) V\VWpPX 3HULIOX[ 3HULPHG âYpGVNR SUDFXMtFtP QD SRODURJUDILFNpP SULQFLSX =DKtYDQi &ODUNRYD HOHNWURGD & E\OD SLSHYQQD NH NåL GRU]D QRK\ YH VWDQGDUGQt ORNDOL]DFL PH]L D metatarzem) pomocí aGKH]LYQtKR NURXåNX SURVWRU PH]L HOHNWURGRX D Nåt E\O Y\SOQQ NRQWDNWQtPUR]WRNHP GRGDQêP YêUREFHP6RQGDE\OD DSOLNRYiQD PLQLPiOQ PLQXWSHG ]DþiWNHP PHQt 9]RUNRYDFt NPLWRþHW E\O PV NH ]KRGQRFHQt YêVOHGN E\OR SRXåLWR firemního softwaru Perisoft (Perimed, Švédsko). 6.2. Výsledky 3L I\]LRORJLFNp K\SHULQ]XOLQpPLL E\OR GRVDåHQR VWDWLVWLFN\ Yê]QDPQ Y\ããt SHUI~]H NRåQt mikrocirkulace v RERX WHVWHFK K\SHUpPLH SR ]DKiWt QD & – 1848% [984 – 2046] vs. 1599% [801 – @SSRORþDVGRVDåHQtPD[LPiOQtSHUI~]HSRXYROQQtRNOX]HV [0.9 – 2.6] vs. 4.9 s [1.8 – 11.4], p < 0,05. Došlo k statisticky významnému zvýšení R[\JHQDFHWNiQWFS2– 48.6 mmHg [45.5 – 49.7] vs. 38.9mmHg [35.5 – 40.8], p < 0,05. 3L VXSUDI\]LRORJLFNp K\SHULQ]XOLQpPLL E\OR GRVDåHQR MHãW Y\ããt SHUI~]H NRåQt mikrocirkulace v RERX WHVWHFK K\SHUpPLH SR ]DKiWt QD & – 1937% [1177 – 2488] vs. 1599% [801 – @SSRORþDVGRVDåHQtPD[LPiOQtSHUI~]HSRXYROQQtRNOX]HV [0.7 – 1.1] vs. 4.9 s [1.8 – 11.4], p < 0,005. Došlo k statisticky významnému zvýšení R[\JHQDFHWNiQWFS2– 57.4 mmHg [51.7 – 66.2] vs. 38.9mmHg [35.5 – 40.8], p < 0,005. Rozdíly v perfúzi a oxygenaci mezi fyziologickou a suprafyziologickou hyperinzulinémií nebyly statisticky významné. M-hodQRWDPHQiY clampu k posouzení inzulinorezistence se QHPQLOD Tab. 2. Výsledky PHGLiQLQWHUNYDUWLORYpUR]SWt basal 50 mIU/l 150 mIU/l PHQiLQ]XOLQpPLH [mIU/l] 3,5 * * 47,5 144,5 (1,8 – 4,1) (36,0 – 53,3) (115,9 – 170,5) LDF baseline [PU] 7,5 12,3NS 12,9NS (6,8 – 10,2) (9,2 – 21,8) (8,6 – 29,9) /')WHVW]DKiWtP [%] 1599 + * 1848 1937 (801 – 1836) (984 – 2046) (1177 – 2488) LDF post-okluzivní reaktivní 4,9 + * 1,2 1,0 hyperémie [s] (1,8 – 11,4) (0,9 – 2,6) (0,7 – 1,1) tcpO2 [mmHg] 38,9 + + 48,6 57,4 (35,5 – 40,8) (45,5 – 49,7) (51,7 – 66,2) + p < 0.05 * p < 0.005 NS nesignifikantní 13 6.3. Diskuse a limitace práce Alternativou k systémovému podání inzulínu je lokální kožní aplikace pomocí iontoforézy (13, 56), jehož výhodou je omezená lokální hyperinzulinémie, která nevyžaduje clampové Y\ãHWHQtVSRMHQpVLQI~]tWHNXWLQD]PQRXMDWHUQtSURGXNFHJOXNy]\DSDQNUHDWLFNp inzulínové sekrece. V naší práci jsme zvolili systémovou aplikaci, jejíž výhodou je fyziologická distribuce LQ]XOtQXDRGVWUDQQtYOLYXSUFKRGXHOHNWULFNpKRSURXGXNWHUêPåH FHVWRXQDSRY]iYLVOêFKQDWULRYêFKDNDOFLRYêFKNDQiOLQGXNRYDWYDVRNRQVWULNFL 9QNWHUêFKVWDUãtFKVWXGLtFKDXWRLSRSLVXMtQDUR]GtORGYêVOHGNXQDãtSUiFHåiGQp StSDGQVWDWLVWLFN\QHYê]QDPQp]YêãHQtSHUI~]HPLNURFLUNXODFHQiVOHGNHPLQI~]HLQ]XOtQX 1DSURWLWRPXQRYMãtSUiFHXND]XMtY]HVWXSSHUI~]HSLI\]LRORJLFNp K\SHULQ]XOLQpPLL9\VYWOHQtPPåHEêWSRXåLWtMLQpPHWRGLN\9HVWDUãtFKVWXGLtFKE\OD PHQDSHUI~]HVRQGRXSRX]H]DED]iOQtFKSRGPtQHNDQHE\OSRXåLWåiGQê]YêãH]PtQQêFK SURYRNDþQtFKWHVW'OHQDãLFK]MLãWQtKRGQRWDED]iOQt/')SHUI~]HY\ND]RYDODSRX]H nesignifikantní trend k QiUVWXFRåNRUHVSRQGXMHVGtYHQDPHQêPLGDW\ Oti]NRXMH]GDVDPRWQiQiORåWHNXWLQEKHPFODPSRYpKRY\ãHWHQtQHYHGHNDNWLYDFL V\PSDWLNXDN]YêãHQtUHDNWLYLW\PLNURFLUNXODFH9OLWHUDWXHO]HQDMtWL]PtQNXRPtUQpP QiUVWXUHDNWLYLW\PLNURFLUNXODFHSLU\FKOpLQI~]LI\]LRORJLFNpKRUR]WRNX9QDšem H[SHULPHQWXMVPHSRGiYDOL]GUDYêPGREURYROQtNPYåG\EKHP-hodinového clampu celkem 1 – 1,5 l glukózy, nedošlo k vzestupu tepové frekvence a lze se domnívat, že rychlost LQI~]HWHNXWLQ\QHE\ODGRVWDWHþQiNY\YROiQtRGSRYGLV\PSDWLNX0H]LREPDSRGVkupinami SDFLHQWVQLåãtDY\ããtSRþiWHþQtLQ]XOLQpPLtWDNpQHE\OSR]RURYiQVLJQLILNDQWQtUR]GtOY PHQêFKSDUDPHWUHFKSHVWRåHSRGDQpPQRåVWYtWHNXWLQSLSUYQtPDGUXKpPXVWiOHQpP VWDYXVHOLãLOR1HSURYHGHQtNRQWUROQtFKY\ãHWHQtEH]SRGiQtJOXNy]\DLQ]XOtQXSHVWRO]H SRYDåRYDW]DXUþLWRXOLPLWDFLSUiFH 1iPLSR]RURYDQêQiUVWWUDQVNXWiQQtKRWODNXN\VOtNXRGSRYtGiSHGFKR]tPOLWHUiUQtP ~GDMPNG\SLNRQWLQXiOQtSRGNRåQtLQI~]LLQ]XOtQXVWRXSODDUWHULRYHQy]QtGLIHUHQFH N\VOtNXFRåQDVYGþXMHUHGLVWULEXFLSUWRNXYHSURVSFKIXQNþQtKRHþLãW1DSURWLWRPXX SDFLHQWVGLDEHWHPPHOOLWHPW\SXNGHMHStWRPQDLQ]XOLQRUH]LVWHQFHDK\SHULQ]XOLQpPLH MHWUDQVNXWiQQtWODNN\VOtNXQHStPR~PUQêLQ]XOLQpPLL– s jejím zvýšením klesá (33). U obézních pacientek s metabolickým syndromem, ale bez diabetu, byla popsána (12) snížená 14 YDVRPRFHDUHGXNFHRGSRYGLQDORNiOQSRGDQêLQ]XOtQ7DWRGDWDQDVYGþXMtRGOLãQpPX FKRYiQtHþLãWPLNURFLUNXODFHXK\SHULQ]XOLQpPLFNêFKLQ]XOLQRUH]LVWHQWQtFKSDFLHQWNde je RGSRYPLNURFLUNXODFHQDH[RJHQQtSRGiQtLQ]XOtQXDOWHURYiQDDQHGRFKi]tNH]OHSãHQt QXWULWLYQtSHUI~]HPRåQiGRNRQFHNH]KRUãHQt]DWtPFRXSDFLHQWVHQ]LWLYQtFKQDLQ]XOtQ vede jeho podání k otvíráQtYWãtKRPQRåVWYtQXWULWLYQtFKNDSLOiU0HFKDQLVPXVSDWRJHQH]H ]PQUHDNWLYLW\VHGiYiGRVRXYLVORVWLVR[LGDþQtPVWUHVHPY\YRODQêPK\SHUOLSLGpPLtD inzulínovou rezistencí, který vede k vazokonstrikci cestou zvýšené aktivity endotelinových UHFHSWRUSURWURPER[DQ$YKODGNpVYDORYLQFpY=DMtPDYpYWpWRVRXYLVORVWLEXGH VOHGRYDWLQ]XOtQHP]SURVWHGNRYDQRXUHGLVWULEXFLPLNURFLUNXODFHXQHPRFQêFKVFKURQLFNêP VUGHþQtPVHOKiQtPOpþHQêFKQRYY\YtMHQêPLHQGRWHOLQRYêPLUHFHSWRURYêPLDQWDJRQLVW\ 6.4=iYU 8]GUDYêFKGREURYROQtNSLV\VWpPRYpPSRGiQtLQ]XOtQXYHGHK\SHULQ]XOLQpPLHN vzestupu reaktivity mikrocirkulace i vzestupu transkutánního tlaku kyslíku. Tento efekt se zvyšující se KODGLQRXLQ]XOtQXQHOLQHiUQVWRXSi5R]GtOQêYOLYLQ]XOtQXXREp]QtFKVXEMHNWDQHPRFQêFK s GLDEHWHPPHOOLWHPW\SXVLY\VYWOXMHPHStWRPQRVWtR[LGDþQtKRVWUHVXSLK\SHUOLSLGpPLL a inzulinorezistenci. 7. VLIV SAMOTNÉ FYZICKÉ AKTIVITY NA REAKTIVITU KOŽNÍ MIKROCIRKULACE U NEMOCNÝCH V RIZIKU SYNDROMU DIABETICKÉ NOHY. 7.1. Metodika 8 GREURYROQtN, nemocných s GLDEHWHPPHOOLWHPW\SXQHVSRUWXMtFtFKE\OR]DD]HQRGR VWXGLHSRSRGSLVXLQIRUPRYDQpKRVRXKODVX9\ORXþHQLE\OLQemocní s limitovanou mobilitou, LVFKHPLFNRXFKRURERXVUGHþQt!$3,VWYMDNpPNROLVWiGLXischemické choroby dolních NRQþHWLQþLV\QGURPHPGLDEHWLFNpQRK\QHERMLQêPRQHPRFQQtPNGHMHQXWQRVW ]DFKRYiYiQtNOLGRYpKRUHåLPX-DNRPtUQiI\]LFNiDNWLYLWDE\ODXåLWDFK]HSURWRåHãORR QHVSRUWXMtFtSUREDQG\,QWHQ]LWD]iWåHE\ODREMHNWLYL]RYiQDNURNRPUHP0LNURYDVNXOiUQt UHDNWLYLWDDNRåQtSHUI~]HQDGROQtNRQþHWLQE\ODPHQDODVHUGRSSOHUIORPZHWULtD transkutánní oxymetrií (Periflux 5000, Perimed, Švédsko). Tab. 3. Charakteristika SUREDQG. V2 V3 V4 SRþHWNURN 3439 (2915 – 4230) 4189 (3335 – 5550)* 3489 (2917 – 4316) YN 62 (54 – 69) trvání diabetu 12,0 (10,0 – 15,5) systolický TK 128 (121 – 130) 133 (115 – 135) 128 (125 – 130) diastolický TK 80 (73 – 84) 75 (70 – 80) 75 (71 – 79) ODþQiJO\NpPLH [mmol/l] 8,4 (7,3 – 9,8) 8,4 (4,4 – 11,8) 8,5 (6,4 – 12,3) NS HbA1c [% IFCC] 6,4 (6,1 – 7,6) 6,5 (4,7 – 8,5) 6,3 (5,5 – 6,7) NS triglyceridy [mmol/l] 2,4 (1,6 – 3,0) 2,4 (1,5 – 3,3) 2,2 (1,8 – 2,6) NS cholesterol [mmol/l] 4,8 (4,0 – 5,5) 4,4 (4,2 – 4,8) 4,7 (4,1 – 4,9) NS ]PQDYiK\ [kg] 0,1 (-0,4 – +0,8) 0,3 (-0,4 - +0,5) 0,5 (+0,1 - +0,5) NS * p <0.001 3LSUYQtQiYãWYE\OLSDFLHQWLHGXNRYiQLRSRXåtYiQtNURNRPUXDE\O\]KRGQRFHQ\ 15 DQWURSRPHWULFNpDPHWDEROLFNpSDUDPHWU\MHMLFK]GUDYRWQtKRVWDYXYNYêãNDYiKDREYRG pasu, laþQiJO\NpPLHJO\NRYDQêhemoglobin, triglyceridy, cholesterol, sérový kreatinin). V QiVOHGXMtFtFKWêGQHFKE\OLQHPRFQtLQVWUXRYiQLR]DFKRYiYiQtEåQpI\]LFNpDNWLYLW\D QRãHQtNURNRPUXDOHVSRNDåGêGUXKêGHQ3LGUXKpQiYãWYSRXSO\QXWtWêGQEyl VSRþtWiQMHMLFKGHQQtSUPUNURNDQHPRFQtE\OLSRåiGiQLR]YêãHQtVYpI\]LFNpDNWLYLW\R 10 – 15%. Po další 4-WêGHQQtSHULRGE\OLLQVWUXRYiQLRSWNHVQtåHQt]iWåHNH]Y\NOpPX UHåLPXSLWpWRQiYãWYSUREKORVWHMQpY\ãHWHQtPHWDEROLFNêFKDDQWUopometrických SDUDPHWUMDNRSLSUYQtNRQWUROH3RVOHGQtQiYãWYDSUREKODRSWVHVWHMQêPY\ãHWHQtPD SRWêGQHFK]Y\NOpI\]LFNpDNWLYLW\3LNDåGpNRQWUROHRGQiYãWY\E\OVSRþtWiQSRþHW NURND]PHQDUHDNWLYLWDPLNURFLUNXODFHSRPRFtODVHUGRSSOer flowmetrie a transkutánní oxymetrie. Výsledky byly zhodnoceny Friedmanovým a párovým Wilcoxonovým testem. 7.2. Výsledky 3RWêGQHFKOHKFH]YêãHQpDHUREQtDNWLYLW\FK]HFFD>– @PHWUGHQQ odpovídající 20% navýšení), došlo ke zvýšení reaktivity mikrocirkulace v obou testech, a to VWDWLVWLFN\Yê]QDPQS UHVSS9\ããtUR]GtOE\OStWRPHQY WHVWX]DKiWtP =YêãHQiSHUI~]HSHWUYiYDODY PHQãtPtHLSRQiVOHGXMtFtFKWêGQHFKEåQpI\]LFNpDNWLYLW\ ale rozdíl nebyl proti vstupním hodnotám statisticky významný (p = 0,30). Metabolické a DQWURSRPHWULFNpSDUDPHWU\DQLWUDQVNXWiQQtWODNN\VOtNXVHQH]PQLO\ Tab 4. Výsledky V1-V2 V2-V3 V3-V4 (zvyklá (zvýšená (zvyklá aktivita) aktivita) aktivita) /')WHVW]DKiWtP>@ 490 (440 – 540) 610 (570 – 680) 520 (480 – 610) p <0,01 LDF postokluzivní 4,1 (2,7 – 5,4) 3,1 (2,4 – 4,0) 3,8 (2,7 – 5,0) p <0,05 reaktivní hyperémie [s] 2EU]PQDUHDNWLYLW\PLNURFLUNXODFHSL]YêãHQtDRSWRYQpPVQtåHQtI\]LFNpDNWLYLW\ 7 6 5,5 6,5 5 6 time-to-half-max [s] heating test [n] 4,5 5,5 4 3,5 5 3 4,5 2,5 4 2 habitual activity increased activity habitual activity habitual activity increased activity habitual activity 16 7.3. Diskuse a limitace práce 1DUR]GtORGREGREQpSUiFHE\O\]DD]HQLSRX]HREp]QtDQHVSRUWXMtFtSDFLHQWLSURWL QiKRGQY\EUDQêPSDFLHQWPW\SLFNpKRGLDEHWRORJLFNpKRFHQWUD&K]HE\ODSUR~þDVWQtN\ studie jedinou relevantní fyzickou aktiYLWRX'YRGSURþVHQDãHYêVOHGN\OLãtO]HQDMtWYH GYRXURYLQiFK-HGQDNMHRWD]Qp]GDSOKRGLQRYpFYLþHQt[WêGQMHGRVWDWHþQpWUYiQt aktivity – v QDãtVWXGLLE\OL]DD]HQLSDFLHQWLV nízkou úrovní fyzické aktivity, jak již bylo ]PtQQRDOHSRGHOãtþDV– RGKDGHPPLQXWGHQQDOHV RKOHGHPQDGHVLJQQHO]HSHVQRX GREXXUþLW'UXKêGYRGMH]DD]HQtSRX]HSDFLHQWVHVHGDYêP]SVREHPåLYRWDNGHMH QHMYWãtUH]HUYDSUR]OHSãHQtPLNURYDVNXOiUQtFKIXQNFtVNU]HFYLþHQt Diskrepance mezi zvýšenou reDNWLYLWRXPLNURFLUNXODFHPHQRX/')DQH]PQQêPWFS22 SHGVWDYXMH]DMtPDYp]MLãWQt+RGQRW\WFS22 byly v normálním rozmezí pro zdravou populaci EDVDOWFS2!PP+JSDFLHQWLE\OLEH]LVFKHPLFNpFKRURE\GROQtFKNRQþHWQLQ 3HGSRNOiGiPHåH]GHQHQtSHrferní deficit kyslíku a proto není rezerva pro zvýšení následkem fyzické aktivity. =iYU Malá, metabolicky a antropometricky nevýznamná fyzická aktivita má potenciál zvýšit perfúzi mikrocirkulace u obézních a nesportující nemocných s diabetem mellitem 2. typu. 8. .25(/$&(0(=,3Ë720NOSTÍ KARDIOVASKULÁRNÍ AUTONOMNÍ NEUROPATIE A JEDNOTLIVÝMI KOMPONENTAMI SPEKTRÁLNÍ ANALÝZY LASER-DOPPLER FLOWMETRIE 8.1. Metodika $XWRQRPQtQHXURSDWLHMHEåQRXNRPSOLNDFtGpOHWUYDMtFtKRGLDEHWXPHOOLWXW\SXDSRGtOtVe QDY\ããtPRUELGLWLPRUWDOLW RKURåXMHSDFLHQW\QiKORXDU\WPLFNRXVUGHþQtVPUWt%åQ Y\ãHWXMHPHMHMtNDUGLiOQtVORåNX.$1SRPRFtþDVRYpDQDOê]\YDULDELOLW\VUGHþQtIUHNYHQFH (VSF) spolu s reakcí krevního tlaku na vertikalizaci (Ewingova baterie teVWQHERVSHNWUiOQt DQDOê]RX96)8SDFLHQWVGLDEHWHPPHOOLWHPE\ODSRSRGSLVXLQIRUPRYDQpKRVRXKODVX Y\ãHWHQD]DNOLGRYêFKSRGPtQHN.$1SRPRFt(ZLQJRYDWHVWXDVSHNWUiOQtDQDOê]D 9DULD&DUGLR3&6LPD0HGLD2ORPRXFý5=iURYHE\OD]PHQDNRåQt mikrocirkulace pomocí laser doppler flowmetrie (Periflux 5000, Perimed, Švédsko) jednak za bazálních SRGPtQHNSLNRåQtWHSORW&MHGQDNSR]DKiWtQD& 3DFLHQWLE\OLUR]GOHQLGRGYRXVNXSLQQHOLãtFtFKVHYNHPSRKODYtPGRERXWUYiQtGLDEHWX OLSpPLtYêãtNUHYQtKRWODNXDQL%0,DOHOLãtFtFKVHStWRPQRVWtPDQLIHVWQtQHER]iYDåQp VNXSLQDDQHStWRPQRVWtVNXSLQD.$1'iOHVHREVNXSLQ\OLãLO\NOLGRYRXWHSRYRX IUHNYHQFtNWHUiE\ODY\ããtXSDFLHQWV KAN a výskytem periferní diabetické polyneuropatie DK (testované Weinsteinovými mikrofilamenty a biothesiometrem). %\ODSURYHGHQDVSHNWUiOQtDQDOê]DRERX]i]QDPVY\SRþWHQtPVSHNWUiOQtVtO\YUR]PH]tFK RGSRYtGDMtFtHQGRWHOLiOQtDNWLYLW – +]DNWLYLWV\PSDWLNX– 0,06 Hz), YODVWQtP\RJHQQtDNWLYLW– 0,20 Hz), respiraci (0,2 – +]DNDUGLiOQtDNWLYLW– 1,6 Hz). Výsledky byly zhodnoceny neparametrickými testy (Mann-Whitney U test, 6SHDUPDQYWHVW 17 SRþHW>0ä@ 13/16 14/18 NS YN>URN\@ 32,4 ± 11,5 37,6 ± 10,4 NS HbA1C [% IFCC] 7,5 ± 2,6 7,8 ± 2,6 NS cholesterol [mmol/l] 5,1 ± 1,0 5,4 ± 2,3 NS triglyceridy [mmol/l] 1,3 ± 0,7 1,6 ± 1,8 NS TF [min-1] 68 ± 8 80 ± 9 p<0,01 STK [mmHg] 116 ± 13 120 ± 12 NS DTK [mmHg] 71 ± 10 72 ± 11 NS retinopatie 8 / 16 7 / 18 NS nefropatie 3 / 16 5 / 18 NS polyneuropatie DK 4 / 16 10 / 18 p < 0,05 makroangiopatie 2 3 NS 8.2. Výsledky 6NXSLQ\VHQDY]iMHPQHOLãLO\ED]iOQtPSUWRNHPPLNURFLUNXODFtNåHDQLY]HVWXSHPSR ]DKiWt[YV[8SDFLHQWVStWRPQRX.$1E\ODVWDWLVWLFN\Yê]QDPQQLåãt VSHNWUiOQtVtODYREODVWLRGSRYtGDMtFtHQGRWHOLiOQtDNWLYLWSDNWLYLWV\PSDWLNX SDKUDQLþQQLåãtYREODVWLRGSRYtGDMtFtYODVWQtP\RJHQQtDNWLYLWS SL PHQtED]iOQtKRSUWRNX3LPHQt]Dmaximální vasodilatace došlo ke snížení rozdílu, SHGHYãtPHQGRWHOLiOQtDNWLYLW\NWHUêVHSRK\ERYDOQDKUDQLFLVWDWLVWLFNpYê]QDPQRVWL Obr. 5. KAN a variabilita perfúze (spektrální síla v jednotlivých oblastech) – Y\ãHWHQtSL NRåQtWHSORW& 3 2,5 2 1,5 Obr. 6. KAN a variabilita perfúze (spektrální síla v jednotlivých oblastech) – Y\ãHWHQtSL NRåQtWHSORW& 1 0,5 0 bez KAN - KAN - bez KAN - KAN - bez KAN - KAN - endoteliální endoteliální sympatická sympatická myogenní myogenní 18 12 10 8 6 4 2 0 bez KAN - KAN - bez KAN - KAN - bez KAN - KAN - endoteliální endoteliální sympatická sympatická myogenní myogenní 'LVNXVHD]iYU\ 1NROLNSUDFtVH]DEêYDORVRXYLVORVWt96)DSUWRNXNRåQtPLNURFLUNXODFtQHE\ODSURNi]iQD Yê]QDPQMãtVRXYLVORVW3LWRPVHSHGSRNOiGiåHSUiYSRNOHVDNWLYLW\V\PSDWLNXYHGHN UHGLVWULEXFLSHUI~]HYHSURVSFK$9VKXQWDQD~NRUQXWULWLYQtFKNDSLOiUDWtPY]QLNXWHSOp ischémie mikrocirkulace. 0HQtXND]XMHåH]PQ\SR]RURYDWHOQpXGLDEHWLFNêFKSDFLHQWVNDUGLRYDVNXOiUQt DXWRQRPQtQHXURSDWLtMVRXGHWHNRYDWHOQpLYSHULIHUQtPFpYQtPHþLãWLPLNURFLUNXODFHE\ MHMLFKYêãHQHVWDþtNRYOLYQQtSUWRNXPHQpKR/')1DEt]tVHWDNDOWHUQDWLYQtPHWRGD Y\ãHWHQtDXWRQRPQtQHXURSDWLHStPRYSHULIpULLNGHMHMtSRVWLåHQtSVREtQHMYWãt]PQ\ /pSHY\FKi]HMt]PQ\PHQpSLNRåQtWHSORW&EHUHPH-li hranici spektrální síly v pásmu sympatiku pro predikci KAN 0,5, pak je senzitivita 79%, specificita 84%, PPV 85%, NPV 78%-HWHEDPtWQDYGRPt PDOêSRþHWSDFLHQWWXGtåVWDWLVWLFNiVtODWFKWRYêVOHGN QHQtGRVWDWHþQYHONiSURIRUPXORYiQtQRUP\ 9. V<8ä,7Ë9<â(7(1Ë0,.ROCIRKULACE U SLEDOVÁNÍ HOJENÍ RÁNY PO APLIKACI GELU Z AUTOLOGNÍ PLAZMY 9.1. Platelet rich plasma 5HODWLYQQRYRXPHWRGRX]DWtPSRXåtYDQRXUXWLQQYNDUGLRFKLUXUJLLDGHQWiOQtFKLUXUJLLMH ORNiOQtRãHWRYiQtUDQQêFKSORFKSRPRFtDXWRORJQtWURPERF\W\RERKDFHQpSOD]P\353 NWHUiSVREtQDKRMHQtSHGHYãtPSURVWHGQLFWYtP]GHVWLþHNRGYR]HQpKRUVWRYpKRIDNWRUX (PDGF). Trombocyty jsou získávány z vlastní krve pacienta, ze které se speciálním VHSDUiWRUHP]tVNiRERKDFHQiSOD]PDýiVWHþQêPVSXãWQtPNRDJXODþQtNDVNiG\MHGRVDåHQR JHORYLWpNRQ]LVWHQFHStSUDYNXNWHUiMHYêKRGQiSURDSOLNDFLQDUDQQpSORFK\353REVDKXMH 10x více tromERF\WQHåMHY NUHYQtSOD]P1HMGOHåLWMãtIDNWRU\]tVNDQp] GHVWLþHNSODWHOHW derived growth factor (PDGF) a transforming growth factor E (TGF-E), byly zkoumány v 19 SRVOHGQtFKGHVHWLOHWtFKDMHMLFKHIHNWLQYLWURQDDQJLRJHQH]XDSUROLIHUDFLEXQNE\OGREH doložen. 9.2. Metodika 'RSLORWQtVWXGLHE\ORSRSRGSLVXLQIRUPRYDQpKRVRXKODVX]DD]HQRFHONHPSDFLHQWVH V\QGURPHPGLDEHWLFNpQRK\LVFKHPLFNpQHERSHYiåQLVFKHPLFNpStþLQ\V nehojícími se GHIHNW\YtFHQHåPVtFHVWDELOQtPLUR]PURYY SRVOHGQtPPVtFLEH]]iQWXþL DQWLELRWLFNpOpþE\9\OXþXMtFtNULWpULD]DKUQRYDODSDFLHQW\V SURYHGHQêPLQWHUYHQþQtP výkonem na tepnách DK v SRVOHGQtFKPVtFtFKSDFLHQW\WåNRXLVFKHPLFNRXFKRURERX VUGHþQt1<+$,,,-IV), pacienty s jiným autoimunním oQHPRFQQtPQHERSDFLHQW\OpþHQp kortikosteroidy. Pacientovi bylo odebráno 50 ml krve a v separátoru (Magellan, Medtronic, USA) získáno 5 ml plazmy obohacené trombocyty. Po dobrém lokálním debridementu byl gel nanesen na defekt a pod okluzivním obvazem ponHFKiQGQ\1iVOHGQE\OSURYHGHQVWUQDPLNURELRORJLFNRXNXOWLYDFLDSURYHGHQDGDOãt DSOLNDFH353JHOX.DåGêSDFLHQWSRGVWRXSLOFHONHPDSOLNDFH353JHOX(IHNWOpþE\E\O SRVRX]HQSRPRFtSORFK\GHIHNWX]MLãWQpGLJLWiOQtIRWRJUDILtQD]DþiWNXOpþE\QDNRQFLOpþE\ a po 4-WêGQHFKSROpþESHGDSRDSOLNDFL353E\OD]PHQDSHUI~]HPLNURFLUNXODFH pomocí laser-doppler flowmetrie. 9.3. Výsledky %KHP-WêGQVWXGLHVHSORFKDGHIHNW]PHQãLODY SUPUXRY porovnání s 5% v SHGFKR]tFKWêGQHFKSHGDSOLNDFt3531HE\OSR]RURYiQORNiOQt]iQWDQLQHE\O]MLãWQ pozitivní mikrobiologický nález. Kožní perfúze, hodnocená laser-doppler-flowmetrií, byla lehce zvýšena (jak bazální perfúze, tak reaktivita v WHVWX]DKiWtPQD 44°C). Detailní statistická analýza nebyla s RKOHGHPQDQt]NêSRþHWSDFLHQWSURYHGHQD 'LVNXVHD]iYU\ /LPLWDFtVWXGLHMHSHGHYãtPQt]NêSRþHWSDFLHQW6WXGLHVH~þDVWQLORSDFLHQWXWtE\OR StWRPQROHKþtSRVWLåHQt– st. 1-2 dle Wagnerovy klasifikace syndromu diabetické nohy a dva SDFLHQWLE\OLVDGXPVtFQHKRMtFtPVHSDKêOHPSRWUDQVPHWDWDU]iOQtDPSXWDFLNGHE\OD zvažována vyšší amputace. Nebyli tedy zahrnuti pacienti s Wagner 3 a 4. 6WXGLHQHPODNRQWUROQtVNXSLQXNDåGêSDFLHQWE\ONRQWURORXViPVRE6URYQiYDOVHHIHNW- týdenní standardní terapie versus 4-WêGQSR353DSOLNDFL=SRKOHGXPHGLFtQ\]DORåHQpQD GND]HFKMHWRWRQHMYWãtOLPLWDFtSUiFH 20 9ãLFKQLSDFLHQWLE\OLSUR353OpþEX GQSLMDWLNKRVSLWDOL]DFL9OLYLPRELOL]DFHNRQþHWLQ\ QHQtWDNYHONêMDNRXQHXURSDWLFNpGLDEHWLFNpQRK\DOHQHO]HMHMWDNHSRGFHRYDW 3LORWQtVWXGLHXNi]DODVOLEQêHIHNWJHOX353QDY]UVWPLNURYDVNXOiUQtSHUI~]HDXU\FKOHQt KRMHQtLVFKpPLFNpKRMLQDNQHHãLWHOQpKRGHIHNWX3HVQMLRGSRYtDårandomizovaná studie. 10. U5ý(1Ë52%8671Ë+23$5AMETRU POPISUJÍCÍHO PORH .,9.89(9=7$+8. VZESTUPU PERFÚZE PO =$+È7Ë. 10.1. Úvodní poznámky Laser-doppler-IORZPHWULHSRVN\WXMHUHODWLYQNRPSOH[QtGDWDDMHQNG\REWtåQpY\EUDW adekvátní metodu vyhodnocení3RþtQDMHPHQtPED]iOQtKRSUWRNXSHVSURYRNDþQtWHVW\ ]PtQQpY ~YRGXDåVSHNWUiOQtDQDOê]X1DãtPFtOHPE\ORQDMtWQRYêU\FKOHPLWHOQêD UREXVWQtSDUDPHWUGREHNRUHOXMtFtV Y]HVWXSHPSHUI~]HSR]DKiWtWHQWRSURYRNDþQtWHVWMH OLWHUiUQQHMUR]ãtHQMãtDLGOHQDãLFK]NXãHQRVWtSRVN\WXMHGREUpDRSDNRYDWHQpYêVOHGN\ 1HYêKRGRXWHVWX]DKiWtPMHGORXKiGREDPHQtSHY\ãXMtFtYþHWQStSUDY\SDFLHQWD PLQXW1HMPpQ-15 minut trvá stabilizace maximální vasodilatace a jsou i takové pacienti, kde se doba pohybuje nad 20 minut. Naproti tomu test postokluzivní hyperémie je rychlý, u ]GUDYêFKVXEMHNWGREHKRGQRWLWHOQêDOHQDUiåtQDSUREOpPXGLDEHWLFNêFKQHPRFQêFK zejména s QHXURSDWLtNGHWYDUW\SLFNpSHI~]QtNLYN\MHVLOQDOWHURYiQ ObrÄ,GHiOQt³325+NLYNDV QiVOHGXMtFtP]DKiWtP 21 2EU =OHYDStNODG\SDFLHQW– diabetes mellitus bez neuropatie, s neuropatií a s neuropatií DWåNRXLVFKHPLFNRXFKRURERXGROQtFKNRQþHWLQ =HMPiREWtåQRVWKRGQRFHQtXSDFLHQWV QHXURSDWLtD,&+'.QiVSLYHGODN testování RVWDWQtFKPRåQêFKSDUDPHWUNLYN\ 10.2. Metodika =HVRXERUXYãHFKSDFLHQWXQLFKåE\OGREHKRGQRWLWHOQê]i]QDPY\ãHWHQtPLNURFLUNXODFH v WHVWXK\SHUpPLtSR]DKiWtDNWHtPOL]PHQê325+ WHVWE\ORY\EUiQRQiKRGQ PHQtXSDFLHQW%\OL]DVWRXSHQLQHPRFQtV REPDW\S\GLDEHWXPHOOLWXLEH]GLDEHWX s LEH]SHULIHUQtLDXWRQRPQtQHXURSDWLHU]QpKRYNXSRKODYtDWUYiQtGLDEHWX9ãHFKQD PHQtE\ODSURYHGHQDQDStVWURML3HULIOX[3HULPHGâYpGVNRYåG\E\ODPHQt provedena na nártu nedominantní nohy. Ke statistické analýze bylo použito Spearmanova NRUHODþQtKRNRHILFLHQWX pacienti s DM / bez DM 94 / 11 YN [roky] 58 ± 19 BMI [kgm-2] 29 ± 6 trvání diabetu DM [yr] 14 ± 11 HbA1C [% IFCC] 6,2 ± 1,8 cholesterol [mmol/l] 4,8 ± 1,2 9êVOHGN\D]iYU 3RPUãSLþNRYpKRSUWRNX3)SHDNIORZN ED]iOQtPXEDVHOLQHWVQNRUHORYDOV výsledky WHVWX]DKiWtPU S'UXKêQHMOHSãtSDUDPHWUMHED]iOQtSUWRNEaseline) samotný – s KRUãtPLYêVOHGN\U S 3RORþDVGRVDåHQtPD[LPDWLPHWRKDOI PD[7+QHPOVWDWLVWLFN\Yê]QDPQRXNRUHODFLV WHVWHP]DKiWtP parametr baseline biological peak flow time to time to PF / BZ / zero (BZ) (PF) max half max baseline baseline correlation 0,72 -0,56 0,55 -0,32 -0,15 0,95 0,29 p = 0,05 p = 0,1 p = 0,06 p = 0,3 p = 0,5 p < 0,01 p = 0,3 6WDQRYHQtSRPUXãSLþNRYpKRNXED]iOQtPXSUWRNX3)EDVHOLQHPåHSHGVWDYRYDWGREUê SDUDPHWUY\ãHWRYiQtPLNURFLUNXOace zejména tam, kde je test postokluzivní hyperémie ]NUHVOHQDUWHIDNW\MDNWRPXEêYiXWåNpLVFKHPLFNpFKRURE\GROQtFKNRQþHWLQ 11. LITERATURA 1. 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Epub 2008 Dec 3. x 0LFKDO.UþPD 'DQLHODýHFKXURYi-LWND *UXEHURYi=GHQN-DQNRYHF6LOYLH/DFLJRYi 0LFKDOäRXUHN=GHQN5XãDYê,QIOXHQFHRISK\VLRORJLFDODQGVXSUDSK\VLRORJLFDO hyperinsulinemia on skin microcirculation in healthy volunteers. Odesláno k publikaci do Wiener Klinische Wochenschript, 2010. Publikace v þDVRSLVHFKV IF, spoluautor x Cechurová D, Lacigová S, Jankovec Z, Haladová I, Zourek M, Krcma M, Rusavý Z, Turek J., The insulin analog glargine during an unplanned pregnancy, Wien Klin Wochenschr. 2006 Oct;118(19-20):619-20. x Jankovec Z, Cechurova D, Krcma M, Lacigova S, Zourek M, Rusavy Z., The influence of insulin pump treatment on metabolic syndrome parameters in type 2 diabetes mellitus., Wien Klin Wochenschr. 2009;121(13-14):459-63. x Jankovec Z, Hahn M, Grunder S, Lacigova S, Cechurova D, Krcma M, Zourek M, Haladova I, Rusavy Z., Analysis of continuous patient data from the Czech National Register of patients with type 1 and type 2 diabetes using insulin pump therapy, Diabetes Res Clin Pract. 2010 Feb;87(2):219-23. Epub 2009 Oct 23. x Lacigova S, Bartunek L, Cechurova D, Visek J, Gruberova J, Krcma M, Jankovec Z, Rusavy Z, Zourek M., Influence of cardiovascular autonomic neuropathy on atherogenesis and heart function in patients with type 1 diabetes., Diabetes Res Clin Pract. 2009 Jan;83(1):26-31. Epub 2008 Nov 14. x Lacigová S, Safránek P, Cechurová D, Krcma M, Vísek J, Jankovec Z, Zourek M, Haladová I, Rusavý Z., Could we predict asymptomatic cardiovascular autonomic neuropathy in type 1 diabetic patients attending out-patients clinics? Wien Klin Wochenschr. 2007;119(9-10):303-8. x Zourek M, Kyselová P, Mudra J, Krcma M, Jankovec Z, Lacigová S, Vísek J, Rusavý Z., The relationship between glycemia, insulin and oxidative stress in hereditary hypertriglyceridemic rat., Physiol Res. 2008;57(4):531-8. Epub 2007 Jul 26. 27 Publikace v UHFHQ]RYDQêFKþDVRSLVHFKEH],), první autor x .UþPD0 5XãDYê=3tQRVY\ãHWHQtPLNURFLUNXODFHNåHXV\QGURPXGLDEHWLFNpQRK\ 3O]HVNêOpNDVNêVERUQtN x 0.UþPD Z. Rušavý, The effect of platelet rich plasma in local treatment of diabetic foot syndrome, New frontiers in the research of PhD students x 0.UþPD 8. workshop na téma Technologie v diabetologii Žinkovy 30.9. – 2.10. 2004 (zpráva ze sjezdu), Journal of Diabetes and its Complications – CZ x .UþPD0 Autoimunní polyglandulární syndrom 2. typu. Kazuistiky v diabetologii 2009, þ- Endokrinologie: 47-48 x .UþPD0 9êVN\WL]RORYDQpK\SRW\UR[LQpPLHXSDFLHQWHNVJHVWDþQtPGLDEHWHVPHOOLWXV- koincidence nebo kauzalita? Kazuistiky v diabetologii 2009, 7þ- Endokrinologie: 30- 32 $EVWUDNWDSHGQiãHNDSRVWHU, první autor x Krcma M, Jankovec Z, Rusavy Z: The Effect of Platelet Rich Plasma in Local Treatment of Diabetic Foot Syndrome, 6th Diabetes Technology Meeting 2006, Atlanta (sborník konference) x Krcma M, Rusavy Z, How insulinemia influences skin microcirculation of lower limbs in healthy subjects, 23rd European Conference on Microcirculation (2004) x Krcma M., Jankovec J., Mudra J, Rusavy Z: How Insulinemia Influences Skin Microcirculation of Lower Limbs in Healthy Subjects, 65th Annual Scientific Sessions ADA (sborník konference) x Krcma M., Jankovec Z., Lacigova S., Zourek M., Mudra J., Rusavy Z., How Insulinemia Influences Skin Microrcirculation of lower limbs in healthy subjects, J Vasc Res 2004;41(Suppl.2) x Krcma M., Rusavy Z.: Effect of Mild Increase of Physical Activity on Microvasculary reactivity in Obese Subjects with Diabetes Mellitus Type 2, European Conference on Microcirculation, 2006 (sborník konference) x .UþPD0-DQNRYHF=0XGUD-5XãDYê= +ow Insulinemia Influences Skin Microcirculation of Lower Limbs in Healthy Subjects. 65th Annual Scientific Sessions ADA, 2005 in Diabetes 2005, 54, Suppl 1: A619. x .UþPD0-DQNRYHF=/DFLJRYi6äRXUHN05XãDYê=9\XåLWtDXWRORJQtSOD]P\ bohaté na trRPERF\W\SLKRMHQtGLDEHWLFNêFKQHXURLVFKHPLFNêFKXOFHUDFt.RQIHUHQFH PODGêFKOpND%UQRþHUYHQ x .UþPD05XãDYê=6URYQiQtSHVQRVWLWtI\]LNiOQ-chemických metod bed-VLGHPHQt JO\NpPLHYLQWHQ]LYQtSpþL.RQIHUHQFHPODGêFKOpND%UQRþHUYen 2004 28 x .UþPD 0 5XãDYê = 9\XåLWt DXWRORJQt WURPERF\W\ RERKDFHQp NUHYQt SOD]P\ SL OpþE GLDEHWLFNêFK QHXURLVFKHPLFNêFK XOFHUDFt 6WXGHQWVNi YGHFNi NRQIHUHQFH /pNDVNp fakulty University Karlovy v 3O]QLNYWHQ6ERUQtNUHIHUiW6 -21. x .UþPD0 Z. Rušavý, The effect of platelet rich plasma in local treatment of diabetic foot syndrome, Medical Postgraduate Conference 2nd meeting, Hradec Králové, New frontiers in the research of PhD students, sborník konference x .UþPD00XGUD--DQNRYHF=/DFigová S., Rušavý Z: Vliv inzulínu na PLNURFLUNXODFLNåHQRK\X]GUDYêFKGREURYROQtN;/'LDEHWRORJLFNpGQ\/XKDþRYLFH 22.-24.4.2004, Diabetologie, Metabolismus, Endokrinologie, Výživa 7. 2004; Suppl 1: s.30. x .UþPD00XGUD-9OLYLQ]XOtQXQDPLNURFLUNXODFLNåH6WXGHQWVNiYGHFNi NRQIHUHQFH/)8.3O]HPtVWR x .UþPD05XãDYê=-DQNRYHF=âDIUiQHN3+iMNRYi/3RURYQiQtSHVQRVWLU]QêFK PHWRGPHQtJO\NpPLHXSDFLHQWYLQWHQ]LYQtSpþLNRQJUHV6.9,03+UDGHF.UiORYp x .UþPD05XãDYê=0HQtJO\NpPLHY LQWHQ]LYQtSpþLSRPRFtVXFKpFKHPLH1RYLQN\ OpþHEQpYêåLY\XNULWLFN\QHPRFQêFKNYWHQ3UDKD x .UþPD05XãDYê=6URYQiQtSHVQRVWLWtI\]LNiOQFKHPLFNêFKPHWRGPHQt glykémie v SRGPtQNiFKLQWHQ]LYQtSpþH;,GQ\LQWHQ]LYQtPHGLFtQ\þHUYHQ .URPtå x .UþPD05XãDYê=9OLYLQ]XOLQpPLHQDPLNURFLUNXODFLNåHQRK\69.3O]H x M Krcma, S Lacigova, Z Rusavy, Skin microvascular flow spectral analysis in diabetes and its connection to cardiovascular neuropathy, 25th European Conference on Microcirculation (2008) x M. Krcma, D. Cechurova, J. Gruberova, S. Lacigova, J. Meinlova, Z. Rusavy, SKIN MICROVASCULAR FLOW SPECTRAL ANALYSIS AND ITS CORRELATION TO CARDIOVASCULAR NEUROPATHY IN DIABETIC PATIENTS TYPE 1, ATTD 2009, 25.2.-28.2., Athény x M. Krcma, Z. Jankovec, J. Mudra, Z. Rusavy, How Insulinemia Influences Skin Microcirculation of Lower Limbs in Healthy Subjects, 65th Annual Scientific Sessions ADA x M. Krcma, Z. Jankovec, Z. Rusavy, The Effect of Platelet Rich Plasma in Local Treatment of Diabetic Foot Syndrome, 6th Diabetes Technology Meeting x M. Krcma, Z. Rusavy, Effect of Mild Increase of Physical Activity on Microvasculary Reactivity in Obese Subjects with Diabetes Mellitus Type 2, 24th European Conference on Microcirculation, (2006) x 0 .UþPD ' ýHFKXURYi ( 'YRiNRYi = 5XãDYê Izolovaná hypotyroxinémie u SDFLHQWHN V JHVWDþQtP GLDEHWHP PHOOLWHP - 4. rok sledování, XXXII Endokrinologické GQ\ýHVNê.UXPORY -26.9.2009 x 0.UþPD+:LQNHOKRIHURYi 1RYiPHWRGDORNiOQtOpþE\V\QGURPXGLDEHWLFNpQRK\– kasuistiky, Workshop Technologie v diabetologii, Žinkovy 2004 x 0.UþPDKasuistika - $GGLVRQVNiNUL]H;;;,,(QGRNULQRORJLFNpGQ\ýHVNê.UXPORY 24.9.-26.9.2009 29 x 0 .UþPD / 9RNXUNRYi ' ýHFKXURYi ( 'YRáková, L. Vokurková, Z. Rušavý, Izolovaná hypotyroxinémie u žen s JHVWDþQtP GLDEHWHP PHOOLWHP D MHMt YOLY QD SRWHEX LQ]XOtQXGLDEHWRORJLFNpGQ\/XKDþRYLFH-25.5.2009 x 0.UþPD ,QWHUQHWDWHFKQRORJLH:RUNVKRS7HFKQRORJLHY diabetologii, Žinkovy 2004 30
Abstract v angličtině:
Introduction: Since the mid 1980s, a lot of attention has been dedicated to the importance of microcirculation; a part of arterial bed including arterioles, precapillary sphincters, capillaries, venules and arteriovenous shunts. It is a structure of decisive importance for an organism; in its domain an exchange of blood gases and metabolic products takes place and it contributes to thermoregulation. Mediation of vasomotor reaction and vasoarterial reflex maintaining a stable hydrostatic pressure is also an important function. Microcirculation is for its dimensions (capillary diameter approx. 5 x 10-5 mm2, blood flow velocity around 0.4 mm.s-1) relatively difficult to access for more detailed examination, yet its impairments are very severe and dominate in many metabolic disorders. Microcirculation impairment is crucial in diabetes mellitus, where arteriovenous shunts open at the expense of nutritive bed due to a loss of sympathetic tone in peripheral circulation in diabetic neuropathy (Netten, Houben). Blood flow is therefore seemingly sufficient, but the affected tissue undergoes ischemia (warm ischemia). To what extent hyperinsulinemia contributes to this effect is not yet clearly known, one of the possible explanations may be a stimulation of sympathetic activity. Not a few studies are dealing with insulin's vasodilatory effect, however, with inconsistent findings regarding the extent of microcirculatory response at various insulin levels upon acute and chronic insulin administration. Experimental work in rats showed an improvement in blood perfusion of sciatic nerve perineurium after a one-month insulin treatment, concurrently, amelioration in nerve conduction was proven electromyographically (Biessels). A short-term continuous subcutaneous insulin infusion (insulin pump treatment) led to an increase in capillary perfusion (Tymms) and to a decrease in venous oxygen tension in diabetic patients already after 9 days of treatment. This result suggests an existence of redistribution of skin perfusion favoring nutritive capillary bed. Acute hemodynamic effects of insulin were tested in an experiment, where healthy young men were treated with a short insulin, locally administered into brachial artery with a rate of 1 and 5 mU/min for a period of 90 minutes in a double blinded study design. Blood flow was measured using body plethysmography. Higher insulin dose led to a statistically significant vasodilatation (20%) compared to placebo. Administration of insulin + L-glucose (metabolically inactive stereoisomer) did not produce further increase in vasodilatation in comparison with pure insulin administration. Administration of insulin + D-glucose led to an increase in perfusion in comparison with pure insulin administration (47% compared to placebo). Glucose infusion itself did not cause any significant changes in blood flow (Ueda). In diabetes type 1 patients when using different insulin infusion rates (1.5 IU/hr, 15 IU/hr) there occurred an increase in blood flow measured by laser Doppler flowmetry (LDF) at the low dose of insulin, while a decrease occurred at the higher dose (Tooke). These measurements, however, were not performed in steady state conditions during clamp examination. Conversely, no statistically significant changes in perfusion of skin microcirculation were found in an experiment in healthy volunteers, where skin perfusion was monitored during a three-step insulin clamp with gradually increasing insulinemia levels 60 – 500 IU/ml. Arteriovenous difference of glucose attained maximum value already at the lowest insulinemia, subsequently it remained constant (Utriainen). An increase in perfusion measured using LDF was noted at supraphysiological hyperinsulinemia in anesthetized rats under clamp conditions concurrently associated with an increase in femoral artery flow (Vincent). Some studies dealing with physiologic hyperinsulinemia (approx. to 50 mIU/l) proved an increased blood flow through muscle and skin microvascular beds and increased density of opened capillaries under this condition (DeJongh, Serne). They used LDF and video capillary microscopy for measurements. In addition, local skin administration of insulin using iontophoresis has a vasodilatory effect in healthy volunteers, which diminishes with age (Rossi), was not proven in diabetes type 2 patients and is decreased in obese non-diabetic women (deJongh). An improvement in glycemic control leads to an increase in microvascular reactivity in diabetes type 2 patients (Forst). To summarize the abovementioned findings; it is relatively well proven that physiological and even supraphysiological hyperinsulinemia leads to an increase in total limb blood perfusion. Study results regarding insulin influence on microcirculation vary; some authors (Utriainen) suggest an insignificant role of physiological as well as supraphysiological insulinemia, others (Tooke, Serne) observed an increase in perfusion only in physiological hyperinsulinemia. Furthermore, it is not completely clear, what part of the vascular bed contributes to the increase in perfusion; whether it is an increase in blood flow through nutritive capillaries or arteriovenous shunts. Aim To examine vasodilatory effect of insulin on perfusion of skin microcirculation in healthy volunteers and assess, whether this effect follows a linear trend with insulinemia. Methods Microcirculation was examined at rest and after stimulation by physiologically (50 mIU/l) and supraphysiologically (150 mIU/l) increased level of insulin. The examination was performed in 12 non-obese healthy volunteers with no history of diabetes in parents and siblings, with no chronic disease, with no chronic medication except hormonal contraception in women, matched in age as well as in basic anthropometric and biochemical parameters (see Table 1). Study protocol was approved by ethical committee of Medical Faculty in Pilsen, Charles University in Prague. All volunteers were fully acquainted in advance with the experiment and methods used, which they confirmed by signing an informed consent. The day before study commencement, the volunteers maintained an ordinary daily routine with the exception of heavy physical exercise, excessive consumption of saccharides, fats and alcohol, and last meal until 9 pm. The following morning, a two-step hyperinsulinemic clamp with target insulinemia 50 and 150 mIU/l was performed according to a well-established method (DeFronzo), i.e. rate of insulin infusion 2.4 IU/m2/hr and 6.0 IU/m2/hr. The order of insulinemias was inverted in one half of the sujects (i.e. first 6.0 IU/m2/hr then 2.4 IU/m2/hr). We measured skin perfusion using LDF and transcutaneous oxymetry, and respiratory quotient and energy expenditure by indirect calorimetry (V-max Sensormedics, Yorba Linda, CA, USA) according to a standard method (Weir et al.) at basal conditions and in both steady states. M-value of each clamp was calculated to assess the change in insulin resistance. Results in form of median and interquartile range were evaluated by Wilcoxon test. Laser-doppler flowmetry Skin perfusion was examined at basal conditions before the clamp and in steady state at both insulin levels. System Periflux 5000 (Perimed, Sweden) with PF 5010 probe emitting laser with a wavelength of 780nm and power output 1mW was used for the measurement. The probe was placed to a dorsum of non-dominant foot and measurement was performed in all subjects at stable temperature of 33°C. Subsequently, stimulation tests (Muller et al.) were employed – heating (probe heating to 44°C inducing maximal vasodilatation) and occlusion (3-minute occlusion of a limb using a sphygmomannometer cuff inflated to a pressure of 30mmHg higher than systolic blood pressure), where time necessary for attaining maximal perfusion after cuff release was measured. These stimulation tests are a standard in examination of tissue perfusion (Leahy, Walmsley, Albrecht, Wohlrab et al.) owing to a considerable time and spatial variability of plain basal perfusion measurement. Sampling rate was 31ms, firmware Perisoft (Perimed, Sweden) was used for data evaluation. Transcutaneous oxygen monitoring Partial pressure of oxygen was measured using tcpO2 probe PF 5040 of Periflux 5000 system (Perimed, Sweden), based on principle of polarography (Lawall et al.). Heated Clark electrode (45°C) was attached to skin of foot dorsum at a standard location (between the 1st and 2nd metatarsus) using an adhesive ring, the space between the electrode and skin was filled with contact solution supplied by the producer. The probe was applied at least 10 minutes prior measurement commencement. Sampling rate was 31ms, firmware Perisoft (Perimed, Sweden) was used for data evaluation. Results: Data are clearly summarized in Table 2 and Graph 2, 3, and 4. The group, where the clamp with lower target insulinemia was performed first did not statistically differ from the group with initial higher insulinemic clamp. Statistically significant higher perfusion in skin microcirculation was achieved at physiological hyperinsulinemia in both tests (hyperemia after heating to 44°C – 1848% [984 – 2046] vs. 1599% [801 – 1836], p < 0.05, half time of reaching peak perfusion after occlusion release 1.2 s [0.9 – 2.6] vs. 4.9 s [1.8 – 11.4], p < 0.05.There occurred a statistically significant increase in tissue oxygenation (tcpO2 – 48.6 mmHg [45.5 – 49.7] vs. 38.9mmHg [35.5 – 40.8], p < 0.05). The perfusion of skin microcirculation was even higher at supraphysilogical hyperinsulinemia in both tests (hyperemia after heating to 44°C – 1937% [1177 – 2488] vs. 1599% [801 – 1836], p < 0.005, half time to reach peak perfusion after occlusion release 1.0 s [0.7 – 1.1] vs. 4.9 s [1.8 – 11.4], p < 0.005. There occurred a statistically significant increase in tissue oxygenation (tcpO2 – 57.4 mmHg [51.7 – 66.2] vs. 38.9 mmHg [35.5 – 40.8], p < 0.005). The difference in perfusion and oxygenation between physiological and supraphysiological hyperinsulinemia were not statistically significant. M-value measured during the clamp for insulin resistance evaluation did not change. Discussion: Studies that monitored an influence of insulin on microcirculation used either local skin administration using iontophoresis (DeJongh, Serne et al.) or systemic delivery (Utriainene, Tooke, Ueda et al.). The advantage of local administration is limited local hyperinsulinemia, which does not require a clamp examination associated with fluid infusion and change in hepatic production of glucose and pancreatic production of insulin. In our study we chose the systemic administration, advantage of which is physiological insulin distribution and elimination of influence of passage of electrical current, which can induce vasoconstriction via voltage-dependent sodium and calcium channels (Figueroa et al.). Simultaneous use of LDF and transcutaneous oxymetry methods was performed to distinguish perfusion of nutritive bed (assessed through O2 release) from total blood flow through microcirculation (including arteriovenous shunts) in the region of interest of LDF probe, to which corresponds microvascular reactivity. However, measuring transcutaneous partial oxygen pressure can only be considered a rough indicator of nutritive bed perfusion. The exchange of oxygen between the vascular bed and tissues takes place also on other levels (larger vessels, via interstitial fluid) and there was found a discrepancy between capillary density assessed through video capillary microscopy and transcutaneous oxymetry values (Ubbink et al.). In some older studies, (Utrainen, Tooke et al.) the authors describe no, or statistically insignificant, increase in microcirculation perfusion as a result of insulin infusion. On the other hand, more recent studies (Serne, deJongh et al.) demonstrate an increase in perfusion at physiological hyperinsulinemia. The explanation may lie in a different methodology used. In older studies the perfusion was measured by a probe only at basal conditions and no abovementioned stimulation test was employed. According to our findings the value of basal LDF perfusion showed only insignificant incremental trend (see Table 2.), which corresponds to data measured earlier (Utriainen, Tooke et al.). Transcutaneous oxygen pressure monitoring is important for estimation of amputation wound healing in diabetic foot syndrome (Faglia et al.) as well as for angioplasty effect monitoring in patients with critical limb ischemia (Caselli et al.), tcpO2 values at rest below 30 mmHg are an independent predictor of ischemia (Cechurova et al.). The increase in transcutaneous oxygen pressure observed in our study in consistent with previous study data (Tymms et al.), where arteriovenous difference of oxygen increased with continuous subcutaneous insulin infusion, which suggests a flow redistribution favoring functional vascular bed. On the contrary, in patients with diabetes mellitus type 2, where insulin resistance and hyperinsulinemia are present, transcutaneous oxygen pressure is inversely proportional to insulinemia – it falls with its increase (Kizu et al.). In obese patients with metabolic syndrome, but without diabetes, decreased vasomotion and reduced response to locally administered insulin was described (DeJongh et al.). These findings suggest a different behavior of microcirculatory vascular bed in hyperinsulinemic insulin-resistant patients, where the response of microcirculation to exogenous insulin administration is altered and there is no improvement of nutritive perfusion (possibly even deterioration), while in insulinsensitive patients, insulin administration causes more nutritive capillaries to open. Pathogenesis mechanism of reactivity changes is put in connection with oxidative stress induced by hyperlipidemia and insulin resistance, which causes vasoconstriction through augmentation of endothelin receptor activity (for thromboxane A2) in smooth muscle tissue (Xiang et al.). In this regard it will be interesting to observe insulin mediated microcirculation redistribution in patients with chronic heart failure treated with newly developed endothelin receptor antagonists, such study has not yet been done according to available literary data. The question is, whether the fluid load itself associated with clamp examination does not lead to sympathetic activation and microcirculation reactivity increase. In literature, we can find a mention about slight microcirculatory reactivity increase associated with fast infusion of saline (Frost et al.). In our experiment, healthy volunteers were administered always a total of 1 – 1.5 l of glucose during the 2-hour clamp, there was no increase in heart rate observed. This rate of fluid infusion cannot be considered sufficient to trigger a sympathetic response. In addition, no significant difference in measured parameters was observed between the two subgroups (initially lower and higher insulinemia) despite the fact that the administered fluid volume at the first and the second steady state varied. Nevertheless, the failure to perform control examinations without glucose and insulin administration can be considered a certain limitation of the study. Conclusion Hyperinsulinemia causes an increase in reactivity of microcirculation as well as an increase in transcutaneous oxygen pressure in healthy volunteers upon systemic administration of insulin. This effect rises non-linearly with increasing insulinemia. 
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