Post-conditionnement induit par la D-Ala-D-Leu-Enképhaline (DADLE) dans le myocarde humain in vitro et sur un modèle d'arrêt cardiaque in vivo

Le but de l étude a été d examiner, in vitro : si Morphine et D-Ala-2-Leu5 enképhaline (DADLE), administrés au début de la réoxygénation sur le myocarde humain, induisent Postcondionnement via la modulation d ouverture du pore de transition de perméabilité mitochondriale (mPTP); in vivo si l administration intraveineuse des DADLE après arrêt cardiaque (AC) peut réduire la mortalité et la mort neuronale retardée (MNR). In vitro: trabécules humaines ont été soumis à hypoxie-réoxygénation. DADLE10nM, 50nM, 100nM ou DADLE100nM+actractyloside50 M ont été administrées au début de reoxygenation. La force de contraction (FoC60), à la fin de la réoxygénation, a été comparée. In vivo : mâles Sprague-Daweley rats ont été soumis à un modèle AC hypoxique. Hypothermie, DADLE et DADLE hypothermie ont été administrées au début de la reperfusion. La mortalité et MNR ont été comparées. In vitro, l administration des DADLE50nM (76+-11%) et DADLE100nM (81+-4%) en début de réoxygénation a significativement augmenté la FoC60 (P<0,001vs groupe contrôle). En présence d atractyloside, l effet des DADLE100nM est supprimé (P<0,001vsDADLE 100nM). In vivo, la mortalité est plus basse dans les groupes arrêt traités (P<0.001vsgroupe arrêt). La MNR est plus élevée dans les groupes arrêt et arrêt DADLE, mais cette différence n est pas statistiquement significative.Conclusion : in vitro, l administration des Morphine et DADLE, en début de reperfusion, protègent le myocarde humain de l hypoxie-réoxygénation, via la prévention de l ouverture du mPTP. In vivo, l administration intraveineuse DADLE après AC réduit la mortalité avec un effet comparable à l hypothermie modérée, mais ne peut pas réduire la MNR.In vitro, the aim of the study was: morphine and DADLE induced postconditioning in isolated human myocardium model exposed to hypoxia-reoxygenation, by the inhibition of mitochondrial permeability transition pore (mPTP). Human atrial trabeculae were exposed to 30-min hypoxia and 60-min reoxygenation. In treatment groups, morphine 0.5 M, DADLE (10nM, 50nM and 100nM) were administered during the first 15-min of reoxygenation. In 2 additional groups, morphine and DADLE 100nM were administered in the presence of atractyloside (50 M). The force of contraction at the end of reoxygenation was compared between the groups. Morphine, DADLE 50nM and 100nM increased significantly (P<0.001 vs control group). DADLE 10nM did not modify the FoC60. The enhanced recovery of FoC60 induced by morphine and DADLE were abolished in the presence of atractyloside (P<0.001). In conclusion, morphine and DADLE administration, in early reoxygenation, protected human myocardium, in vitro, against reoxygenation injury, at least in part, by the inhibition of mPTP opening. In vivo, the aim of the study was: DADLE intravenous (i.v) administration, at the onset of reperfusion, reduced mortality and induced cerebral protection. Hypoxic cardiac arrest (3 min) was induced in 47 male Sprague-Daweley rats. In treated control and arrest groups, DADLE, hypothermia and DADLE-hypothermia were administered. Mortality and delayed neuronal death (DND) were compared between groups. Mortality was lower in the treated arrest groups (P <0.001), but no treatment showed a better survival. Otherwise, DND did not reduce after DADLE i.v. In conclusion, DADLE i.v. reduced mortality, but it failed to induce cerebral protection.CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

The use of indomethacin in the treatment of plateau waves : effects on cerebral perfusion and oxygenation

OBJECT: Plateau waves are sudden and steep increases in intracranial pressure (ICP) that can develop in patients with cerebral injuries, reduced pressure-volume compensatory reserve, and preserved autoregulation. They are caused by cerebral vasodilation in response to a reduction in cerebral perfusion and are associated with increased cerebral blood volume and reduced cerebral blood flow. The authors evaluated the hypothesis that administration of indomethacin, a potent cerebral arteriolar vasoconstrictor, could interrupt the vicious cycle that occurs during plateau waves, extinguishing these waves and, ultimately, restoring cerebral perfusion and oxygenation. METHODS: Plateau waves developed in nine patients, seven with severe traumatic brain injury and two with intraparenchymal hemorrhage. One to four episodes of plateau waves per patient were treated with indomethacin (15-20 mg), which was delivered by an intravenous bolus injection. Each patient's mean arterial blood flow (MABP), ICP, cerebral perfusion pressure (CPP), and cerebral tissue PO2 were continuously monitored and the data obtained were stored in a personal computer. Each patient's jugular venous O2 saturation (SjvO2) and venoarterial difference in PCO2 were evaluated by intermittent blood sampling. During five episodes of plateau waves, middle cerebral artery flow velocities were evaluated by transcranial Doppler ultrasonography. Indomethacin extinguished all plateau waves. On average, the ICP decreased from an initial value of 58.9 +/- 11.6 mm Hg to 21.2 +/- 8.6 and 25.8 +/- 13.7 mm Hg after 5 and 10 minutes, respectively (p < 0.01). The MABP did not change significantly. As a consequence the CPP increased by 98 and 81% after 5 and 10 minutes, respectively (p < 0.01). Five and 10 minutes after indomethacin was administered, SjvO2 increased from an initial value of 50 +/- 10.5% to 62 +/- 7.6 and 59.9 +/- 9.3%, respectively (p < 0.01); the cerebral tissue PO2 increased from an initial value of 13.4 +/- 10.6 mm Hg to 23.6 +/- 9.58 and 21.9 +/- 9.2 mm Hg, respectively (p < 0.05); and the venous-arterial PCO2 decreased significantly. The mean and diastolic flow velocities increased significantly, whereas the pulsatility index decreased from 1.39 +/- 0.56 to 1.09 +/- 0.4 at 5 minutes and 1.06 +/- 0.36 at 10 minutes (p < 0.05). CONCLUSIONS: The findings confirm that plateau waves are caused by vasodilation and show that indomethacin, by constricting the cerebral arteries, is effective in extinguishing plateau waves, ultimately restoring cerebral perfusion and oxygenation

The surgical patient with Brugada syndrome: a four-case clinical experience.

Brugada syndrome is characterized by a distinctive electrocardiographic pattern (right bundle branch block and ST segment elevation in precordial leads) and a high risk of cardiac arrest for malignant dysrhythmia. The genetic basis is a molecular defect of the cardiac sodium channel and the pattern of inheritance is autosomal dominant. Many factors during general anesthesia (medications, bradycardia, temperature changes) could precipitate malignant dysrhythmia in these patients. Because criteria to identify the surgical patient at high risk for developing malignant dysrhythmia are lacking, we can only speculate about the available studies on nonsurgical patients. We describe four patients during general anesthesia and propose intraoperative and postoperative monitoring (the first 36 h). ©2005 by the International Anesthesia Research Society

Right ventricular failure after left ventricular assist device insertion: preoperative risk factors.

Right ventricular failure after left ventricular assist device placement is the major concern on weaning from cardiopulmonary bypass and it is one of the most serious complications in the postoperative period. This complication has a poor prognosis and is generally unpredictable. The identification of pre-operative risk factor for this serious complication is incomplete yet. In order to determine pre-operative risk for severe right ventricular failure after left ventricular assist device support we analyzed preoperative hemodynamics, laboratory data and characteristics of 48 patients who received Novacor (World Heart Corp., Ottawa, ON, Canada). We compared the data from the patients who developed right ventricular failure and the patients who did not. Right ventricular failure occurred in 16\% of the patients. There was no significant difference between the groups in demographic characteristics. We identified as preoperative risk factors the pre-operative low mean pulmonary artery and the impairment of hepatic and renal function on laboratory data. Our results confirm in part the findings of the few previous studies. This information may be useful for the patient selection for isolated left ventricular assist device implantation, but other studies are necessary before establishing criteria for patient selection for univentricular support universally accepted

Antiphospholipid antibodies and neurological complications after pulmonary endarterectomy

Pružatelji mrežnih usluga uglavnom nemaju uvid u iskustvenu kvalitetu krajnjih korisnika usluge YouTube zbog toga što je sav promet šifriran. Obzirom na te uvjete, pružatelji mrežnih usluga obično ne mogu otkriti KPI-jeve kao što su početno kašnjenje, zaustavljanje videa ili promjene kvalitete iz prometa koji prolazi kroz njihove mreže. Na Fakultetu elektrotehnike i računarstva izrađeno je mnogo eksperimenata kako bi se razvila rješenja za procjenu iskustvene kvalitete i ključnih indikatora performansi za strujanje videa iz šifriranog prometa. Ti su pokusi napravljeni u kontroliranom ili stvarnom okruženju. Tijekom analize skupa podataka, gdje je skup podataka niz eksperimenata, bilo je mnogo ponavljajućeg rada. Drugi je problem bio u organiziranom pohranjivanju podataka i nedostatku alata za učinkovit pristup, spajanje i filtriranje podataka. Cilj ovog diplomskog rada bio je razviti web aplikaciju koja će riješiti navedene probleme. Vrijeme za analizu skupova podataka bit će značajno smanjeno s razvijenom aplikacijom Auto-A Storage jer će se sva obrada podataka obavljati automatski. Ova aplikacija će pružiti prilagođeno rješenje za pohranu svih mjernih podataka. Neke od glavnih značajki Auto-A Storage-a su spremanje, uređivanje, preuzimanje i filtriranje skupova podataka, kao i preuzimanje generiranih podataka spremnih za strojno učenje. Implementirana je provjera autentikacije i autorizacije tako da nitko ne može pristupiti Auto-A Storage-u bez dozvole administratora aplikacije. Korisnično sučelje Auto-A Storage-a implementirano je u JavaScript biblioteci React, dok je back-end implementiran u Spring Boot-u, u programskom jeziku Java.Network providers for the most part lack insight into YouTube end-users' QoE because of traffic encryption. Given these conditions, network providers usually cannot detect KPIs like initial delay, stalling events or quality switches from the traffic passing through their networks. At the Faculty of Electrical Engineering and Computing, University of Zagreb, a lot of experiments were performed to collect both application and network data, and develop machine learning-based solutions for estimating video streaming QoE/KPIs from encrypted traffic. Those experiments were performed in a controlled or a real environment. During dataset analysis, where a dataset is a collection of experiments, there was a lot of repetitive work. Another problem was related to storing data in an organized way, and lack of tools for efficient access, merging, and filtering of the data. As a result, the aim of this thesis was to develop a web application that could solve listed problems. The time to analyze datasets will be significantly reduced with developed application Auto-A Storage since all processing of the data will be done automatically.the This application will provide a customized solution for storage for all measurement data. Some of the main features of Auto-A Storage are storing, editing, downloading, and filtering of datasets, as well as downloading generated ML-ready data. It has implemented authentication and authorization so nobody can access to Auto-A Storage without application administrators' permission. The front-end of Auto-A Storage was implemented in React, a JavaScript library, while the back-end was implemented in Spring Boot, a Java framework