1. INTRODUCTION Most complications after elective or urgent reconstructive operations on abdominal aorta are predictable and it is possible to prevent them. The development of the operating techniques, a good preoperative preparation of patients and post-operative nursing of patients enables to achieve good results of treatment when the post-operative death-rate is from 0 to 12 percent [Hallin A., 2001]. The better results depend on the prevention of especially dangerous complications, such as colon ischemia, apropos diagnostics and adequate treatment. The selection of patients of high risk becomes extra important. The proper evaluation of preoperative aortography while being aware of the fact that the reconstruction of IMA is needed, and following the specific requirements for the operating techniques strictly, enables to avoid ischemia of the gut completely or to reduce its frequency to a minimum [Belov I.V., 2002]. Post-operative GIC can be especially serious. Due to them the hospitalization period can prolong and the post-operative mortality generally increases [Chan K.H., 1989; Huddy S.P., 1991; Christenson J.T., 1994; Mercado P.D., 1994; Lubetkin E.I., 1996]. Less seldom but very difficult GIC occur to those patients for whom have been made none abdominal high coverage operations. The given frequency of the spread of GIC is about 2 percent after open heart operations [Huddy S.P., 1991; Christenson J.T., 1994; Mercado P.D., 1994], 7 percent after neurosurgical operations... [to full text]

Abstract During cardiac and aortic surgery, disturbance of the blood supply in the central nervous system occurs when the repair of aortic pathologies is performed or a bloodless operation field is needed in complex cardiac surgery. To enable the suitable operation environment, the technique named hypothermic circulatory arrest (HCA) has been utilized via heart-lung machine. In this method, the core temperature is lowered to the target temperature, after which blood circulation is halted for a certain period of time. A challenge is that the successful usage of HCA, however still involves the risks of postoperative neurological complications and mortality. In cardiac and aortic arch surgery, the brain is at the highest risk for deficits, whereas in the repair of thoracoabdominal aortic aneurysms (TAAAs), spinal cord injury remains the most severe adverse outcome. Adjunctive protective strategies are required to reduce ischemic injury in these settings. In this thesis, Studies I and II focused on the spinal cord and the Study III on the brain. The studies were performed using acute (II, III) or subacute (I) experimental porcine models, primarily aiming to assess the effectiveness of remote ischemic preconditioning (RIPC) in spinal cord protection along with the aim of studying the underlying mechanisms of RIPC in neuroprotection. Studies I and II demonstrated enhanced motor evoked potential (MEP) responses in both hind limbs, indicating spinal cord protection by RIPC. The faster recovery of brain damage marker S100B along with higher cardiac index and lower systemic lactate levels confirmed the cardio- and neuroprotective properties of RIPC in Study III. The protective mechanism of RIPC was associated with increased antioxidant response (II, III). / Tiivistelmä Sydän- ja aorttakirurgiassa, keskushermoston verenkiertoa joudutaan häiritsemään toteutettaessa aortan korjausleikkauksia tai vaikeissa sydänkirurgisissa toimenpiteissä verettömän leikkausalueen saavuttamiseksi. Sydän-keuhkokoneen avulla toteutettava täydellinen verenkierron pysäytys mahdollistaa vaaditut olosuhteet. Tässä menetelmässä ydinlämpötilaa lasketaan ja verenkierron pysäytys toteutaan tavoitellussa kohdelämpötilassa tietyssä aikaikkunassa. Kyseisen menetelmän onnistunut käyttö sisältää kuitenkin riskejä operaatioiden jälkeisiin neurologisiin komplikaatioihin ja kuolleisuuteen. Sydämen ja aortankaaren kirurgiassa aivot ovat suurimmassa vaarassa vaurioille. Rinta- ja vatsa-aortan aneurysmien eli pullistumien korjausleikkauksiin liittyvä selkäydinvaurio on puolestaan yksi vakavimmista ja vaikeimmista seurauksista. Lisäsuojausmenetelmiä tarvitaan vähentämään iskeemistä vauriota näissä asetelmissa. Väitöskirjan osatyöt I ja II keskittyivät selkäytimeen. Osatyö III käsitteli puolestaan aivojen suojausta. Osatyöt toteutettiin akuutteina (II, III) ja subakuutteina (I) kokeellisina porsasmalleina. Tutkimusten tavoitteina oli arvioida esialtistavan perifeerisen raajaiskemian vaikuttavuutta selkäytimen suojauksessa sekä tutkia raajaiskemian taustalla olevia mekanismeja hermokudoksen suojauksessa. Osatöissä I, II havaittiin motoristen herätepotentiaalien parantuneita vasteita molemmissa takajaloissa osoittaen esialtistavan raajaiskemian suojaavan selkäydintä simuloidussa rinta-aortan korjaustoimenpiteessä. Osatyö III keskittyi alhaisessa lämpötilassa toteutettavaan täydelliseen verenkierron pysäytykseen. Tässä tutkimuksessa todetut aivovauriomarkkeri S100B tason nopeampi lasku, korkeampi sydänindeksi ja alhaisemmat laktaattitasot varmistivat raajaiskemian sydän- ja hermokudossuojausvaikutusta. Esialtistavan perifeerisen raajaiskemian suojaava mekanismi voidaan liittää parantuneeseen solujen antioksidanttivasteeseen (II, III).

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13331号 / 論医博第2199号 / 新制||医||1044(附属図書館) / (主査)教授 湊谷 謙司, 教授 横出 正之, 教授 戸口田 淳也 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Minimal access approaches in cardiac surgery and for procedures on the aortic valve began to develop in the 1990s. Several variations were performed in search of the most appropriate technique before the median ministernotomy was established. Despite limited exposure, difficult deairing or cardioplegia application and longer surgical times were described in the literature, surgeons believed that this technique would reduce surgical trauma and bleeding, improve chest stability, reduce pain and respiratory failure and shorten hospitalization and costs, while keeping mortality and morbidity low. The aim of this retrospective study was to review the techniques of minimal invasive surgery on the thoracic aorta in use in Heart Center Leipzig from 1998 to 2011 as well as the preoperative circumstances, intraoperative setup and early and late postoperative outcome of these patients. The results were to be integrated in the current literature and commented on. All 199 patients who underwent a procedure on the proximal aorta through minimal access incision were selected and included in this study. The procedures were completed with a standard surgical setup. Perioperative and intraoperative data were collected from surgical and discharge reports. Elective surgery was performed in 95.5% of the patients. 8.5% were redo procedures. Indication for surgery was dilatation of the proximal aorta in 92.5%, accompanied by pathology of the aortic valve in 87.9%. Access to the surgical site was L-type partial sternotomy in 59.7%. Cannulation for cardiopulmonary bypass was performed mostly through the ascending aorta or aortic arch (arterial line) and right atrium (venous line). Intermittent antegrade cardioplegia was delivered in all patients. Brain protection strategies for patients undergoing aortic arch replacement included hypothermic circulatory arrest and selective cerebral perfusion. Following procedures were performed: isolated aortic arch replacement (n=1); supracoronary ascending aorta replacement (isolated n=15, combined to aortic arch replacement n=8, combined to aortic valve replacement n=37 or combined to both n=10), and aortic root surgery (isolated aortic root replacement or repair n=95, aortic root replacement or repair combined to aortic arch replacement n=33). Cardiopulmonary bypass time was 123 ± 44 minutes. Conversion to full sternotomy was performed in 5 patients due to low cardiac output syndrome or bleeding. Thirty-day mortality was 5.0% (n=10) and ischemic stroke rate was 2.5% (n=5). Reoperation due to bleeding was performed on 13.1% (n=26). The estimated 10-year survival was 76 ± 4%. Clinical research to this subject is limited, based in studies with small populations and heterogenous procedures. Our study confirms the feasibility of minimal access proximal aortic surgery because neither inadequate exposure nor problems with deairing or cardioplegia were reported. Surgical times were shorter than described in the literature. Mortality, stroke, cardiac and sternal complication rates were low and comparable to the results in the literature. We consider that our higher reexploration rate of because of bleeding was caused primarily due to pathological coagulation state. We present the first long term results for minimal access proximal aortic surgery at 10 years. We consider that our results reflect better the risk inherent to minimal access proximal aortic surgery than studies with smaller cohorts but recognize it is limited by its retrospective form and heterogeneity of the reported procedures. Randomized prospective studies should bring more information about the safety of this procedure, but we support ministernotomy as a promising access for selected patients.

京都大学 / 新制・課程博士 / 博士(社会健康医学) / 甲第23819号 / 社医博第119号 / 新制||社医||12(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 湊谷 謙司, 教授 永井 純正, 教授 波多野 悦朗 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Abstract The repair of thoracoabdominal aortic aneurysms carries a substantial risk of ischaemic perioperative spinal cord injury. Although several protective methods have been developed, the risk of paraplegia has not been eliminated. Moreover, aortic aneurysms, including arch aneurysms, are complex clinical challenges requiring cerebral protection with hypothermic circulatory arrest (HCA). Hypothermia lowers the rate of cerebral metabolism and allows a temporary halt of the systemic circulation. However, there is still a risk for cerebral damage and a need for additional neuroprotective methods. During the last 15 years, our research group has used a porcine model to investigate a variety of neuroprotective tools. In this thesis, an animal model was utilized to study the efficacy of remote ischaemic preconditioning (RIPC) to ameliorate ischaemic damage to the central nervous system, and to shed light on the potential mechanism. Moreover, diazoxide, the pharmacological mimetic of RIPC, was tested in the HCA animal model. In the first Study (I), RIPC showed beneficial effect on the spinal cord against ischaemic insult as recorded with motor-evoked potentials. Strikingly, the beneficial effect of RIPC was observed even before the ischaemia. In the second Study (II), some beneficial effect of RIPC was seen in the immunohistochemical analysis of the spinal cord ischemia but the result remains inconclusive. Similarly, the diazoxide-treated animals had better hemodynamic status postoperatively and mildy better antioxidant activity of the brain in the third Study (III). The fourth study (IV) was a review of the current knowledge of RIPC from the cardiovascular point of view. Our studies indicate that RIPC might be a potential adjunct for preventing neuronal ischaemic injury in the setting of thoracoabdominal aortic surgery. Our result indicates that further preclinical studies with diazoxide are required before studies can be conducted in humans. / Tiivistelmä Torakoabdominaalisen aortan aneurysman kirurginen korjaaminen sisältää riskin iskeemiselle selkäytimen vauriolle. Vaikka useita suojaavia tekniikoita on kehitetty, paraplegian riskiä ei ole saatu poistettua kokonaan. Kirurgisen korjaamisen haasteellisuus moninkertaistuu, jos aneurysma on laajentunut myös aortan kaareen. Tällöin vaaditaan hypotermista verenkierron pysäytystä (HCA). Hypotermia alentaa aivojen metabolista aktiivisuutta merkittävästi ja siten verenkierron väliaikainen pysäytys on mahdollista. Tästä huolimatta hypotermiseen verenkierron pysäytykseen liittyy riski aivokudoksen vauriolle. Meidän tutkimusryhmämme on tutkinut useita keskushermostoa suojaavia tekniikoita ja lääkeaineita viimeisen 15 vuoden aikana. Käytämme sikaa koe-eläin mallina, jota on tämänkin väitöskirjan osajulkaisuissa käytetty. Tämän väitöskirjatyön tarkoituksena on ollut tutkia sekä esialtistavan raajaiskemian (RIPC) että farmakologisen mimeetin, diazoxiden, keskushermostoa suojaavia vaikutuksia sekä niiden mahdollista vaikutusmekanismia. Ensimmäisessä osajulkaisussa esialtistava raajaiskemia paransi selkäytimen iskemian sietokykyä, mikä näkyi alaraajojen motorisissa herätepotentiaaleissa. Merkittävintä tutkimuksessa oli, että esialtistavan raajaiskemian edulliset vaikutuksen selkäytimeen oli nähtävissä jo ennen iskemiaa. Toisessa osajulkaisussa esialtistava raajaiskemialla oli nähtävissä edullisia, mutta ei varauksettomia, vaikutuksia selkäytimen iskemian immunohistokemiallisessa analyysissä. Kolmannessa osatyössä diazoxidin vaikutukset iskemiaa vastaan nähtiin parempana hemodynaamisena tilana ja antioksidatiivisen aktiivisuuden lisääntymisenä aivoissa, mutta tulos on myös tulkinnanvarainen. Neljäs osajulkaisu kokosi tämän hetken tietämyksen esialtistavasta raajaiskemiasta. Tutkimuksissamme osoitimme, että esialtistava raajaiskemiassa on potentiaalia tulla yhdeksi välineeksi keskushermoston iskemiaa vastaan torakoabdominaalisen aortan kirurgiassa. Lisäksi diazoxidin mahdolliset neuroprotektiiviset vaikutukset vaativat lisää koe-eläintutkimuksia ennen ihmiskokeisiin siirtymistä.