Introduction The neuropsychological deterioration after cardiac surgery involving cardiopulmonary bypass (CPB), is ascribed to brain ischaemia caused by, amongst others, hypotension, cerebral hyperthermia, cerebral embolism, interaction between pharmacological methods and hypothermia during ischaemia, and the directly neurotoxic of anaesthetic drugs. AimTo investigate the effect of the anaesthetic techniques midazolam plus ketamine (MK) or sufentanil (S) on the quantitative EEG (QEEG), reaction time (RT), serum neuron specific enolase (NSE), and serum S-100<font face="symbol">b</font> protein after cardiac surgery involving CPB in humans. Patients and methodsThe sample consisted of a total of 42 patients scheduled for elective coronary artery bypass (CABG) or valve replacement (VR). All patients were not available for all the postoperative tests. Patients were allocated randomly to group MK or S. Anaesthetic technique: S or MK. Isoflurane was administered when necessary. CPB technique: 30°C, membrane oxygenation, a 40 <font face="symbol">m</font>m filter in the arterial cannula and <font face="symbol">a</font>-stat-blood gas management, blood pressure of 50 to 70 mm Hg and a haematocrit <font face="symbol">></font> 22%. Patients were weaned from CPB when nasopharyngeal temperature reached a maximum of 37,5°C. QEEG and RT was performed 1 to 2 days preoperatively and 5 to 6 days postoperatively.Serum-NSE and -S-100<font face="symbol">b</font> protein were measured preoperatively, 2 minutes after going on CPB, after rewarming to 37°C, just before the end of CPB and 2, 4, 10, 20, 30, and 48 hours after CPB. ResultsQEEG: The most noticable finding was an increase in slow wave activity (relative <font face="symbol">q</font> and <font face="symbol">s</font>). The QEEG outcome was better after CABG than after VR (p < 0,001), but not different between MK and S (p = 0,5000). <font face="symbol">Dq</font>% was better with MK than S (p = 0,0120). <font face="symbol">Dq</font>% (p = 0,0010), <font face="symbol">Da/q</font>% (p = 0,0090) and <font face="symbol">D</font>PS% (p = 0,0025) was better after CABG than VR. Reaction time: There was a significant deterioration in 5/18 (27,78%) of MK and 12/18 (66,67%) of S (p = 0,0220). The change in accuracy in sequential reation time 1 (p = 0,0100), and sequential reation time 2 (p = 0,0970) and the cumulative accuracy was better with MK than S(p = 0,0020). Chemical markers: Over groups 14,8% of patients had a poor NSE and 61,9% a poor S-100<font face="symbol">b</font> outcome. Within groups a poor NSE outcome was found in 14,8% of MK and 14,8% of S (p = 1,0000), and 4,8% of CABG but 23,8% of VR (p = 0,1840). Within groups as adverse S-100<font face="symbol">b</font> outcome was found in 42,9% of MK but 81,0% van S (p = 0,0250; Fisher's exact test), and 66,7% of CABG and 57,1% of KV (p = 0,7510. According to area under the curve of corrected NSE, CABG had a better outcome than VR (p = 0,0040). According to both maximum S-100<font face="symbol">b</font> level and the area under the curve of S-100<font face="symbol">b</font>, an interaction occurred between the anaesthetic technique and the procedure, with VR doing better with MK while CABG did significantly better with S (p = 0,0180 en 0,0040 respectively). Conclusion, shortcomings, significance and contribution This study has shown that, in as far as brain damage is concerned, the outcome was probably better with MK than with S, and CABG better than VR. An interaction was found between the anaesthetic technique and the type of operation. / Thesis (MD)--University of Pretoria, 2003. / Anaesthesiology / unrestricted

Stroke is one of the major causes of death and disability worldwide. The area that surrounds the infarcted core is the location of the continuing damage that takes place hours and days following an insult, and is referred to as the penumbra. By creating an oxygen deprived environment in the neuronal-like PC12 and NT2 cells and an in vivo photothrombotic model of stroke (PTS) in mice, two different strategies were created to replicate the conditions of an ischaemic brain. In differentiated PC12 and NT2 cells, following hypoxia, preferential activation of HIF-2α transcription and protein expression was detected. Increased expression of the neural progenitor stem cell-like markers, thought to be transcriptionally regulated by HIF-2α, were also observed. Furthermore, hypoxia caused loss of neuronal characteristics in differentiated cells. This is highly significant as it shows neuronal cells possess molecular mechanisms which could trigger recovery following ischaemic insult. The expression of the chloride co-transporters, NKCC1 and KCC2, mediators of the GABAergic response, was assessed following hypoxia in differentiated PC12 and NT2 cells and PTS. In PC12 and NT2 cells exposed to hypoxia, the expression of KCC2 was significantly decreased at both the transcript and protein level whereas NKCC1 expression remained unmodified. In the in vivo model, the development of the penumbra in the days following injury was assessed with specific markers allowing the identification of the penumbra up to 200 ❍m from the ischaemic core and a progressive neuronal loss was observed within. Our results show an increase in the number of neurons expressing NKCC1 in the penumbra up to 5 days following the insult when compared to the contralateral hemisphere. On the contrary, KCC2 positive cells were dramatically decreased in this area. In mice treated with bumetanide, an NKCC1 antagonist, a significant reduction in neuronal loss was observed. Our results show a reversal on the chloride co-transporters expression in vitro and in vivo and how treatments targeting these channels might represent a novel strategy to reduce the damage associated with stroke.

<p>Otkrivanje embolusa u cerebralnoj cirkulaciji na egzaktan način moguće je samo upotrebom transkranijalnog doplera. Istraživanje je obuhvatilo 150 ispitanika, obolelih od akutnog ishemijskog cerebrovaskularnog događaja (ishemijskog moždanog udara i tranzitornog ishemijskog ataka) u zoni vaskularizacije a. cerebri medie (ACM), a lečenih na Klinici za neurologiju, Kliničkog centra Vojvodine. Ciljevi istraživanja su obuhvatili određivanje prevalence i frekvence MES kod bolesnika sa akutnim ishemijskim cerebrovaskularnim događajem (TIA, IMU) tokom serijskog monitoringa, utvrđivanje povezanost pojave MES u odnosu na etiologiju ishemijske epizode, procenjivanje efekata terapije (antiagregacione i antikoagulantne) na pojavu MES tokom serijskog monitoringa, i utvrđivanje prediktivnog značaja MES na dalji tok bolesti tj, rani povratni embolizam unutra tri meseca. Utvrdili smo da se mikroembolusi kao markeri aktivne embolizacije mogu registrovati primenom transkranijalnog doplera u akutnoj fazi moždanog udara u određenoj meri. U ispitivanom uzorku metodom transkranijalne detekcije kod 52 (34,7%) bolesnika je registrovana pojava cerebralnih mikroembolusa. Ovi ispitanici su činili MES (+) grupu pacijenata. Kod 98 (65,3%) bolesnika nisu registrovani ES, oni su činili MES (-) grupu pacijenata. Detekcija je vr&scaron;ena u prvih 72h od vremena nastanka IMU ili TIA. Zaključili smo da se serijskim monitoringom registruje smanjenje prevalence i frekvence embolijskih signala. Utvrdili smo da su starija životna dob, hipertenzija i dijabetes statistički značajno povezani sa pojavom mikroembolusnih signala. Najveća zastupljenost mikroembolusa registrovana je u aterotrombotičnom podtipu ishemijskog moždanog udara. Utvrđen je prediktivni značaj aterosklerotske bolesti velikih krvnih sudova na pojavu MES. Registrovana je statistički značajno če&scaron;ća pojava MES kod simptomatske karotidne stenoze, visokog stepena (70-90%), neravne i ulcerisane povr&scaron;ine plaka. Nije utvrđena statistički značajna povezanost pojave MES, kliničkih manifestacija bolesti i neuroradiolo&scaron;kog nalaza. Nije registrovan uticaj antitrombotičke terapije na pojavu mikroembolusnih signala. Zabeležena je veća stopa recidiva IMU i TIA kod bolesnika sa registrovanim cerebralnim mikroembolusima. Utvrđen je prediktivni značaj MES na pojavu recidiva IMU ali ne i prediktivni značaj na pojavu letalnog ishoda.</p> / <p>Detection of emboli in the cerebral circulation to the exact way it is possible only by using transcranial doppler. The study included 150 patients of acute ischemic cerebrovascular events (ischemic stroke and TIA) in a zone of vascularization a. cerebri media (ACM), and treated at the Clinic of Neurology, Clinical Center of Vojvodina Research objectives included the determination of the prevalence and frequency of MES in patients with acute ischemic cerebrovascular accident (TIA, IMU) during serial monitoring, establishing the link between the appearance MES in relation to the etiology of ischemic episodes, assessing the effects of therapy<br />(antiplatelet and anticoagulant) on the occurrence of MES during serial monitoring and determine the predictive value MES in the further course of the disease, ie. return early embolism within three months. We have found that microemboli as markers of active embolization can register by using transcranial Doppler in the acute phase of stroke in certain extent. In the examined sample using transcranial detection with 52 (34.7%) patients the occurrence of cerebral microemboli is registered. These respondents are accounted for MES (+) group of patients. With 98 patients (65.3%) is not registered EC, they account for MES (-) group of patients. Detection was performed during 72 hours from the time of occurrence of ischemic stroke or TIA. We concluded that serial monitoring registers decrease in prevalence and frequency of embolic signals. We found that older age, hypertension, and diabetes are significantly associated with the appearance of microembolic signals. The highest incidence of microemboli was registered in atherothrombotic ischemic stroke subtype. It is determined the predictive significance of atherosclerotic disease of large blood vessels on the occurrence of MES. More common MES is significantly registered with symptomatic carotid stenosis, greater degree (70-90%), uneven surfaces and ulcerated plaque. There was no statistically significant correlation between the occurrence of MES, clinical manifestations and neuroradiological findings. It is not registered impact of antithrombotic therapy on the incidence of microembolic signals. We are noticed thet the higher rate of recurrence of ischemic stroke and TIA patients with cerebral microemboli is registered. The predictive significance of MES in recurrence of ischemic stroke is determined, but not predictive significance of the occurrence of a lethal outcome.</p>