Unterschiedliche zerebrale Protektionssysteme zur Verhinderung neurologischer Ereignisse während einer Karotis-Angioplastie sind derzeit im Einsatz. Dennoch zeigen Studien, dass diese Systeme die distale Mikroembolisation während der Intervention nicht vollständig verhindern können. Die vorliegende Arbeit vergleicht die Effektivität von zwei verschiedenen Protektionssystemen unter Anwendung der Methode der transkraniellen Dopplersonographie (TCD). Es wurden 42 Patienten mit einer hochgradigen Stenose der A. carotis interna während der Karotisangioplastie mit Stentimplantation untersucht. Zur Neuroprotektion wurde entweder ein Filtersystem (E.P.I. FilterWireTM, Boston Scientific, USA) oder ein proximales Ballonokklusionssystem (MO.MA-System Invatec, Italien) verwendet. Bei jedem Patienten erfolgte während der Intervention mittels TCD die Detektion der mikroembolischen Signale (MES). Die Anzahl der MES wurde während fünf verschiedener Prozedurphasen gezählt und miteinander verglichen. Die Ergebnisse der Arbeit zeigen, dass die Karotis-Angioplastie unter Schutz des MO.MA-Systems vor allem in den Phasen der Passage der Stenose, der Stentimplantation und der Nachdilatation mit signifikant niedrigeren MES assoziiert war, verglichen zur Angioplastie der A. carotis interna unter einem Filtersystem.

Abstract During surgery of the aortic arch and pediatric heart surgery, the blood flow to the brain has to be interrupted at times to allow a bloodless operation field and adequate conditions for surgical repair. During this no-flow period the brain is exposed to a high risk of ischaemic injury, as it will become irreversibly damaged after 5 minutes of circulatory arrest at 37°C. Additional time can be gained by cooling the patient with an extracorporeal heart-lung machine, as hypothermia reduces the cerebral metabolic rate and allows longer safe periods of circulatory standstill. This method of cerebral protection, called hypothermic circulatory arrest (HCA), is widely used in clinical practice. Thus the brain becomes susceptible to ischaemic injury after 30 minutes of HCA at 15°C. Lower temperatures than this are not practicable, however, as they require longer periods of cardiopulmonary bypass, which may further aggravate cerebral injury. To ensure a better outcome for patients undergoing these operations, additional ways of protecting the brain are required. The present work focuses on neuroprotective biochemical and fluid therapy methods for use during HCA, employing a surviving porcine model. Fructose-1,6-bisphosphate (FDP), a high-energy intermediate of glycolysis, was examined for potential neuroprotective properties in two cerebral injury settings associated with HCA. First, FDP was administered before and after a 75-minute period of HCA at a brain temperature of 18°C. This led to better survival, neurological recovery and brain histopathological findings and had supportive effects on brain metabolism (I). Second, a 25-minute period of HCA along with an iatrogenic embolic load produced by microsphere injection was used to generate a massive ischaemic injury to the brain. In this setting FDP did not affect the neurological outcome but had a clear supportive impact on cerebral metabolism (II). In addition, cerebral histopathological samples taken during the first study were analysed by electron microscopy, which revealed significant preservation of the ultrastructure in the FDP-treated animals (III). Hypertonic saline dextran (HSD) is a novel fluid therapy method which has been shown to enhance the outcome after hypovolaemic shock with or without head injury and is potentially very effective in reducing ischaemia-reperfusion injury. Its administration led to a decrease in intracranial pressure, improved brain metabolism, faster and better recovery and less histopathologically observable morphological damage (IV). The findings indicate that both FDP and HSD have significant neuroprotective properties and should be assessed in humans as well.

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Unterschiedliche zerebrale Protektionssysteme zur Verhinderung neurologischer Ereignisse während einer Karotis-Angioplastie sind derzeit im Einsatz. Dennoch zeigen Studien, dass diese Systeme die distale Mikroembolisation während der Intervention nicht vollständig verhindern können. Die vorliegende Arbeit vergleicht die Effektivität von zwei verschiedenen Protektionssystemen unter Anwendung der Methode der transkraniellen Dopplersonographie (TCD). Es wurden 42 Patienten mit einer hochgradigen Stenose der A. carotis interna während der Karotisangioplastie mit Stentimplantation untersucht. Zur Neuroprotektion wurde entweder ein Filtersystem (E.P.I. FilterWireTM, Boston Scientific, USA) oder ein proximales Ballonokklusionssystem (MO.MA-System Invatec, Italien) verwendet. Bei jedem Patienten erfolgte während der Intervention mittels TCD die Detektion der mikroembolischen Signale (MES). Die Anzahl der MES wurde während fünf verschiedener Prozedurphasen gezählt und miteinander verglichen. Die Ergebnisse der Arbeit zeigen, dass die Karotis-Angioplastie unter Schutz des MO.MA-Systems vor allem in den Phasen der Passage der Stenose, der Stentimplantation und der Nachdilatation mit signifikant niedrigeren MES assoziiert war, verglichen zur Angioplastie der A. carotis interna unter einem Filtersystem.

Background: Despite the successful development in cardiac surgery, cerebrovascular accidents (CVA) remain a devastating complication. Aortic atherosclerosis has been identified as a major risk factor for CVA. The present thesis addresses this question in relation to aortic manipulation during cardiac surgery, being divided into a clinical (I-II) and an experimental part (III-V). Material and methods: Consecutive cardiac surgery cases (n=2641) were analyzed. Patients with CVA were extracted from a database designed to monitor clinical symptoms. Patient records were used to confirm clinical data and diagnosis. Subdivision was made into three groups: control subjects, immediate, and delayed CVA, being analyzed for neurological symptoms (I). Patients with CVA who also had been investigated with computer tomography (CT) (n=77) were further evaluated in terms of hemispheric and vascular distribution of lesions. The CT-findings were compared with CVA symptoms (II). An aortic perfusion model was developed using cadaver aorta onto which multiple cross-clamp manipulations were applied (III). Washout samples of perfusate were analyzed by computerized image processing and with subdivision into different particle spectra. The model was further developed with the introduction of intraluminal manipulation from cannula and intra-aortic filter (IV). A technique for macro-anatomic mapping of plaque distribution of cadaver thoracic aorta was developed (V). Variation in plaque density was analyzed in different anatomical segments, monitored by digital image analysis. Hazards associated with surgical manipulation were studied by superimposing cannulation and cross-clamp sites onto the aortic maps in a blinded fashion. Results: The incidence of immediate and delayed CVA was 3.0% and 0.9%, respectively. Aortic quality was a strongly associated with immediate but not delayed CVA. Left-sided symptoms of immediate CVA were significantly more frequent than of the contra-lateral side. Positive signs on CT were seen in 66% of the CVA patients. Right-hemispheric lesions were more frequent compared with the contra-lateral side and the middle-cerebral artery territory dominated. Aortic cross-clamping produced a substantial output of particulate matter. Manipulation by intra-aortic filter produced a significant washout of embolic particles that escaped the filter, although some particles were captured. Cannulation was an additional source of embolic material. In terms of plaque distribution was the anterior wall of the ascending part and arch of the aorta more affected than its posterior side. However, observing a plaque in the anterior wall of this aortic segment predicted to 83% a concomitant plaque in the posterior wall. Increased age correlated positively with plaque density. The theoretical chance of interfering with a plaque during cannulation and/or clamp positioning was 45.8%. Conclusions: Both CT scans and clinical symptoms confirmed that CVA after cardiac surgery had a right-hemispheric predominance. The perfusion model resulted in a profound output of material during cross-clamp maneuvers. The intra-aortic filter successfully collected particles but also generated embolic debris on its own. Aortic cannulation was an additional source of embolic debris. Plaques were frequently found in the cadaveric aorta, and there was a high risk of plaque interference during surgical manipulation. As expected, plaque density was age-dependent.

INTRODUÇÃO: A angioplastia carotídea com stent (ACS) sob proteção cerebral é opção terapêutica em pacientes com estenose carotídea. Existe o risco de embolia apesar da utilização do filtro e as modificações na perfusão cerebral após tratamento da estenose carotídea não são claras. O propósito deste estudo é avaliar, após ACS sob proteção cerebral por filtros, modificações nas seqüências de RM de difusão (DWI) e perfusão (PWI), correlacionando-as com os aspectos técnicos da ACS, com as características da estenose e com dados demográficos dos pacientes. MÉTODO: Trinta e seis pacientes portadores de estenose carotídea com idade média de 72,08 anos foram submetidos a exame de RM um dia antes e até 72 horas após a ACS com filtro de proteção. Todos os pacientes eram assintomáticos após a ACS. Áreas de restrição na DWI após a ACS foram correlacionadas com aspectos demográficos, com aspectos da técnica de angioplastia e com a presença de infartos prévios por RM. Os parâmetros CBV volume sanguíneo cerebral, MTT tempo de trânsito médio e TTP tempo para o pico são empregados para análise por PWI. RESULTADOS: Na DWI, 18 de 36 (50,00%) pacientes apresentaram novos focos (NF) de restrição na DWI após ACS. Todos os NF foram clinicamente silenciosos (100%). Estes NF eram localizados em território cerebral nutrido pela artéria carótida submetida à ACS em 77,19% e menores que 10 mm em 91,53%. Os NF em território cerebral não irrigado pela artéria carótida submetida à angioplastia correspondiam a 22,81% destes. A presença de infartos cerebrais prévios na RM foi o único fator com influência no aparecimento de NF (p=0,037). Fatores demográficos e aspectos relacionados com a técnica de angioplastia não tiveram importância na gênese dos NF. Na PWI foi observada melhora nos parâmetros temporais TTP (p<0,001) e MTT (p=0,019) quando comparados de forma normalizada em relação ao território contralateral. CONCLUSÃO: Os novos focos de restrição na DWI após ACS (NF) foram mais comuns no território ipsilateral (77,19%), no entanto houve NF no território contralateral à ACS (22,81%), possivelmente, associados ao cateterismo diagnóstico. Os NF, na sua maioria, são de pequeno diâmetro (<10 mm em 91,53%). Melhora precoce na PWI, observada nos dados normalizados, foi demonstrada nos parâmetros temporais (TTP e MTT). / INTRODUCTION: Carotid angioplasty with stent (CAS) under cerebral protection is a therapeutic option in patients with carotid stenosis. There is a risk of embolism even with a filter, and changes in cerebral perfusion after treatment are not clearly understood. The purpose of this study was to evaluate changes in diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging (MRI) sequences correlating them with the technical aspects of CAS, stenosis characteristics and patient demographic data. METHODS: Thirty-six carotid stenosis patients with an mean age of 72.08 years were submitted to MRI exam one day before and up to 72 hours after CAS with filter protection. All patients were asymptomatic after CAS. Areas of restriction on DWI were correlated to demographic aspects, technique of angioplasty as well the presence of previous stroke by MRI. The parameters, CBV - cerebral blood volume; MTT - mean transit time, and TTP- time to peak, are used for PWI analysis. RESULTS: Eighteen of the 36 patients (50.00%) presented new focus (NF) of restriction by DWI after CAS. All new focus were clinically silent. The NF were located in the cerebral area fed by the carotid artery submitted to CAS in 77.19% and smaller than 10mm in 91.53%. NF in cerebral area not irrigated by carotid artery submitted by angioplasty correspond to 22,81 %. The presence of previous ischemic lesion on MRI was the only factor which influenced the appearance of NF (p=0.037). Demographic factors and aspects related to angioplasty technique had no importance on NF genesis. Improvement in PWI timing parameters - TTP (p<0.001) and MTT (p=0.019) were observed in relation to the contralateral territory (normalized data). CONCLUSION: The restriction NF in the DWI after CAS are more common in the ipsilateral territory (77.19%), however there were some NF in the contralateral territory to the CAS (22.81%), possibly associated with diagnostic catheterization. Most of the NF were small in diameter (<10mm in 91.53%). Short-term improvement in PWI were demonstrated by normalized timing parameters (TTP and MTT).

INTRODUÇÃO: A angioplastia carotídea com stent (ACS) sob proteção cerebral é opção terapêutica em pacientes com estenose carotídea. Existe o risco de embolia apesar da utilização do filtro e as modificações na perfusão cerebral após tratamento da estenose carotídea não são claras. O propósito deste estudo é avaliar, após ACS sob proteção cerebral por filtros, modificações nas seqüências de RM de difusão (DWI) e perfusão (PWI), correlacionando-as com os aspectos técnicos da ACS, com as características da estenose e com dados demográficos dos pacientes. MÉTODO: Trinta e seis pacientes portadores de estenose carotídea com idade média de 72,08 anos foram submetidos a exame de RM um dia antes e até 72 horas após a ACS com filtro de proteção. Todos os pacientes eram assintomáticos após a ACS. Áreas de restrição na DWI após a ACS foram correlacionadas com aspectos demográficos, com aspectos da técnica de angioplastia e com a presença de infartos prévios por RM. Os parâmetros CBV volume sanguíneo cerebral, MTT tempo de trânsito médio e TTP tempo para o pico são empregados para análise por PWI. RESULTADOS: Na DWI, 18 de 36 (50,00%) pacientes apresentaram novos focos (NF) de restrição na DWI após ACS. Todos os NF foram clinicamente silenciosos (100%). Estes NF eram localizados em território cerebral nutrido pela artéria carótida submetida à ACS em 77,19% e menores que 10 mm em 91,53%. Os NF em território cerebral não irrigado pela artéria carótida submetida à angioplastia correspondiam a 22,81% destes. A presença de infartos cerebrais prévios na RM foi o único fator com influência no aparecimento de NF (p=0,037). Fatores demográficos e aspectos relacionados com a técnica de angioplastia não tiveram importância na gênese dos NF. Na PWI foi observada melhora nos parâmetros temporais TTP (p<0,001) e MTT (p=0,019) quando comparados de forma normalizada em relação ao território contralateral. CONCLUSÃO: Os novos focos de restrição na DWI após ACS (NF) foram mais comuns no território ipsilateral (77,19%), no entanto houve NF no território contralateral à ACS (22,81%), possivelmente, associados ao cateterismo diagnóstico. Os NF, na sua maioria, são de pequeno diâmetro (<10 mm em 91,53%). Melhora precoce na PWI, observada nos dados normalizados, foi demonstrada nos parâmetros temporais (TTP e MTT). / INTRODUCTION: Carotid angioplasty with stent (CAS) under cerebral protection is a therapeutic option in patients with carotid stenosis. There is a risk of embolism even with a filter, and changes in cerebral perfusion after treatment are not clearly understood. The purpose of this study was to evaluate changes in diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging (MRI) sequences correlating them with the technical aspects of CAS, stenosis characteristics and patient demographic data. METHODS: Thirty-six carotid stenosis patients with an mean age of 72.08 years were submitted to MRI exam one day before and up to 72 hours after CAS with filter protection. All patients were asymptomatic after CAS. Areas of restriction on DWI were correlated to demographic aspects, technique of angioplasty as well the presence of previous stroke by MRI. The parameters, CBV - cerebral blood volume; MTT - mean transit time, and TTP- time to peak, are used for PWI analysis. RESULTS: Eighteen of the 36 patients (50.00%) presented new focus (NF) of restriction by DWI after CAS. All new focus were clinically silent. The NF were located in the cerebral area fed by the carotid artery submitted to CAS in 77.19% and smaller than 10mm in 91.53%. NF in cerebral area not irrigated by carotid artery submitted by angioplasty correspond to 22,81 %. The presence of previous ischemic lesion on MRI was the only factor which influenced the appearance of NF (p=0.037). Demographic factors and aspects related to angioplasty technique had no importance on NF genesis. Improvement in PWI timing parameters - TTP (p<0.001) and MTT (p=0.019) were observed in relation to the contralateral territory (normalized data). CONCLUSION: The restriction NF in the DWI after CAS are more common in the ipsilateral territory (77.19%), however there were some NF in the contralateral territory to the CAS (22.81%), possibly associated with diagnostic catheterization. Most of the NF were small in diameter (<10mm in 91.53%). Short-term improvement in PWI were demonstrated by normalized timing parameters (TTP and MTT).