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  • 1. Aneman, A.
    et al.
    Svensson, M.
    Broome, M.
    Karolinska Institutet.
    Biber, B.
    Petterson, A.
    Fandriks, L.
    Specific angiotensin II receptor blockage improves intestinal perfusion during graded hypovolemia in pigs2000Other (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes. INTERVENTIONS: Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10). MEASUREMENTS AND MAIN RESULTS: Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group. CONCLUSIONS: Specific AT1 blockade before acute hypovolemia significantly ameliorated mesenteric and, in particular, jejunal mucosal hypoperfusion. In addition, cardiovascular stability was improved, and mortality in conjunction with acute hypovolemia and retransfusion could be completely avoided. These findings support a fundamental role of the renin-angiotensin system in the mesenteric response to acute hypovolemia and indicate a substantial interventional potential for candesartan in conjunction with circulatory stress.

  • 2. Bertaccini, E. J.
    et al.
    Yoluk, Özge
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lindahl, Erik R.
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Trudell, James Robert
    Department of Anesthesia, Stanford University School of Medicine, United States .
    Assessment of homology templates and an anesthetic binding site within the ?-aminobutyric acid receptor2013In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 119, no 5, p. 1087-1095Article in journal (Refereed)
    Abstract [en]

    Background: Anesthetics mediate portions of their activity via modulation of the ?-aminobutyric acid receptor (GABAaR). Although its molecular structure remains unknown, significant progress has been made toward understanding its interactions with anesthetics via molecular modeling. Methods: The structure of the torpedo acetylcholine receptor (nAChR?), the structures of the ?4 and ?2 subunits of the human nAChR, the structures of the eukaryotic glutamate-gated chloride channel (GluCl), and the prokaryotic pH-sensing channels, from Gloeobacter violaceus and Erwinia chrysanthemi, were aligned with the SAlign and 3DMA algorithms. A multiple sequence alignment from these structures and those of the GABAaR was performed with ClustalW. The Modeler and Rosetta algorithms independently created three-dimensional constructs of the GABAaR from the GluCl template. The CDocker algorithm docked a congeneric series of propofol derivatives into the binding pocket and scored calculated binding affinities for correlation with known GABAaR potentiation EC50s. Results: Multiple structure alignments of templates revealed a clear consensus of residue locations relevant to anesthetic effects except for torpedo nAChR. Within the GABAaR models generated from GluCl, the residues notable for modulating anesthetic action within transmembrane segments 1, 2, and 3 converged on the intersubunit interface between ? and ? subunits. Docking scores of a propofol derivative series into this binding site showed strong linear correlation with GABAaR potentiation EC50. Conclusion: Consensus structural alignment based on homologous templates revealed an intersubunit anesthetic binding cavity within the transmembrane domain of the GABAaR, which showed a correlation of ligand docking scores with experimentally measured GABAaR potentiation.

  • 3.
    Broome, M.
    Umeå Universitet.
    Acute effects of Angiotensin II on myocardial performance2001Other (Refereed)
    Abstract [en]

    Background: Specific angiotensin II (Ang II) receptors exist in many organs including peripheral blood vessels, cardiac myocytes and the central nervous system. This suggests multiple sites of actions for Ang II throughout the cardiovascular system. Cardiac effects of Ang II are not completely understood, though its prominent vasoconstrictor actions are well described. This study was designed to assess left ventricular function during administration of Ang II using relatively load-independent methods in a whole-animal model. Methods: Ang II was infused in incremental doses (0-200 µg/h) in anaesthetised instrumented pigs (n=10). Cardiac systolic and diastolic function was evaluated by analysis of the left ventricular pressure-volume relationship. Results: Heart rate (HR), mean arterial pressure (MAP) and systemic vascular resistance (SVR) increased dose-dependently with Ang II, while cardiac output (CO) remained unchanged. Systolic function indices end-systolic elastance (Ees) and preload recruitable stroke work (PRSW) demonstrated dose-dependent increases. The diastolic function parameter tau (t) did not change with increasing Ang II dose. Conclusion: Ang II infusion caused increases in contractility indices in anaesthetised pigs in the doses used in this study. The mechanisms for these systolic function effects may be a direct myocardial effect or modulated through changes in autonomic nervous system activity.

  • 4.
    Broome, M.
    Karolinska Institutet.
    Exogenous Angiotensin II - An experimental study of integrated circulatory effects in heart, splanchnic organs and kidney2001Other (Refereed)
    Abstract [en]

    Aim: Exogenous Angiotensin II (Ang II) is currently used for treatment of hypotensive vasodilated shock, despite limited context-specific information about regional circulatory or cardiac responses. We aimed to experimentally investigate sites of action and mechanisms for the cardiovascular acute effects of Ang II infusion with emphasis on regional circulatory control and myocardial systolic and diastolic function. Methods: In healthy anaesthetised pigs, perivascular ultrasound flowmetry, laser-doppler flowmetry and tissue micro-oximetry were employed regionally (kidney and splanchnic organs), while cardiac function was evaluated by left ventricular pressurevolume loop analysis as derived from continuous intracardiac conductance volumetry and tip-manometry. Ang II was administered either systemically (i.v.) or in the left coronary artery in a continuous, dose-variable regimen. Regional perfusion pressures were artificially controlled either by pharmacological (nitroprusside) modulation of systemic arterial pressure or by local arterial graded occlusion (perivascular clamp). Cardiac afterload was controlled by pharmacological (nitroprusside) vasodilation. Results: Ang II exerted similarly powerful vasoconstrictions in the splanchnic and renal circulations. However, the splanchnic vascular bed differed in its responsiveness to Ang II in the sense that concomitant artificial maintenance of systemic normotension fully inhibited the increase in splanchnic vascular tone. Further, splanchnic vasoconstriction by Ang II was potentiated by increases in local arterial pressure. Heart rate and systolic function indices increased dose-dependently by systemic administration of Ang II, regardless of prevailing afterload conditions. Diastolic function was impaired or unchanged. On the other hand, these cardiac effects could not be reproduced when Ang II was administered via the intracoronary route. Conclusions: In the splanchnic vascular bed, the vascular responses of Ang II are powerfully modulated by local vasomotor control. Thus, during concurrent increases in systemic arterial pressure, autoregulatory myogenic increases in vascular smooth muscle tone serves to potentiate the local vasoconstrictive actions of Ang II. This implies that blood pressure alterations have an important role for the prediction of changes in splanchnic vascular resistance during Ang II treatment. Cardiac effects of Ang II include increases in contractile function, but seem to be predominantly mediated via extracardiac structures and mechanisms. This implies that the integrity of remote mechanisms for control of myocardial function are important for the cardiac effects of Ang II treatment. Keywords: Renin-Angiotensin System, Angiotensin II, Angiotensin Amide, Nitroprusside, Swine, Conductance volumetry (non-MESH), Cardiac function, Systolic function, Diastolic function, Vasoconstriction, Splanchnic Circulation, Renal Circulation

  • 5.
    Broome, M.
    Karolinska Institutet.
    MEDIQ Anaesthesia Simulator2003Other (Other academic)
  • 6.
    Broome, M.
    Karolinska Institutet.
    MEDIQ Kinetics2003Other (Other academic)
  • 7.
    Broome, M.
    et al.
    Karolinska Institutet.
    Aneman, A.
    Haney, M.
    Haggmark, S.
    Johansson, G.
    Biber, B.
    Angiotensin II mesenteric and renal vasoregulation: dissimilar modulatory effects with nitroprusside2000Other (Refereed)
    Abstract [en]

    BACKGROUND: The role of systemic arterial pressure for the vascular effects of angiotensin II (Ang II) and the interactions between Ang II and perfusion pressure-dependent local vascular control mechanisms are not well understood. This study addresses these aspects of exogenous Ang II in the mesenteric and renal regional circulations. METHODS: Ang II was infused in incremental doses (0-200 microg/h) in anesthetized instrumented pigs (n=10). Renal and portal blood flows were measured by perivascular ultrasound. In the second part of the study, sodium nitroprusside (SNP) was infused at doses titrated to keep mean arterial pressure constant, in spite of concurrent Ang II administration. RESULTS: Powerful dose-dependent vasoconstrictions by Ang II were found in renal and mesenteric vascular beds (at highest Ang II doses vascular resistances increased by 109% and 88% respectively). Ang II-induced vasoconstriction was fully inhibited in the mesenteric, but not in the renal circulation, during conditions of constant mean arterial pressures achieved by SNP infusion. CONCLUSIONS: Mesenteric, but not renal, vasoconstriction by Ang II was inhibited by pharmacological maintenance of perfusion pressure. This could reflect differences between these vascular beds as regards the importance of co-acting myogenic pressure-dependent vasoconstriction. Alternatively, as the drug chosen for pressure control, sodium nitroprusside, serves as a nitric oxide donor, the relative balance between nitric oxide-mediated vasodilation and Ang II-induced vasoconstriction could have regional differences.

  • 8.
    Broome, M.
    et al.
    Umeå Universitet.
    Aneman, A.
    Lehtipalo, S.
    Arnerlov, C.
    Johansson, G.
    Winso, O.
    Biber, B.
    Splanchnic vasoconstriction by angiotensin II is arterial pressure dependent2002Other (Refereed)
    Abstract [en]

    BACKGROUND: Our hypothesis was that splanchnic vasoconstriction by exogenous angiotensin II (Ang II) is significantly potentiated by local mechanisms increasing vasomotor tone and that splanchnic tissue oxygenation during administration of Ang II is perfusion pressure dependent. The aim was to study local splanchnic circulatory effects and tissue oxygenation during intravenous infusion of Ang II at different levels of regional arterial driving pressure in a whole-body large animal model. METHODS: Ang II was infused in incremental doses (0-200 microg x h-1) in anaesthetised instrumented pigs (n=8). Mean superior mesenteric arterial pressure (PSMA) was adjusted by a local variable perivascular occluder. Perivascular ultrasound and laser-Doppler flowmetry were used for measurements of mesenteric venous blood flow and superficial intestinal blood flow, respectively. Intestinal oxygenation was evaluated by oxygen tissue tension (PtiO2) and lactate fluxes. RESULTS: Ang II produced prominent and dose-dependent increases in mesenteric vascular resistance (RSMA) when the intestine was exposed to systemic arterial pressure, but Ang II increased RSMA only minimally when PSMA was artificially kept constant at a lower level (50 mmHg) by the occluder. Although Ang II decreased PtiO2 at a PSMA of 50 mmHg, splanchnic lactate production was not observed. CONCLUSION: We demonstrate that splanchnic vasoconstriction by exogenous Ang II is dependent on arterial driving pressure, suggesting significant potentiation through autoregulatory increases in vasomotor tone. Intestinal hypoxaemia does not seem to occur during short-term infusion of Ang II in doses that significantly increases systemic arterial pressure.

  • 9.
    Broome, M.
    et al.
    Umeå Universitet.
    Haney, M.
    Haggmark, S.
    Johansson, G.
    Aneman, A.
    Biber, B.
    Acute effects of angiotensin II on myocardial performance2001Other (Refereed)
    Abstract [en]

    BACKGROUND: Specific angiotensin II (Ang II) receptors exist in many organs including peripheral blood vessels, cardiac myocytes and the central nervous system. This suggests multiple sites of actions for Ang II throughout the cardiovascular system. Cardiac effects of Ang II are not completely understood, though its prominent vasoconstrictor actions are well described. This study was designed to assess left ventricular function during administration of Ang II using relatively load-independent methods in a whole-animal model. METHODS: Ang II was infused in incremental doses (0-200 microg x h(-1)) in anaesthetised instrumented pigs (n=10). Cardiac systolic and diastolic function were evaluated by analysis of the left ventricular pressure-volume relationship. RESULTS: Heart rate (HR), mean arterial pressure (MAP) and systemic vascular resistance (SVR) increased dose-dependently with Ang II, while cardiac output (CO) remained unchanged. Systolic function indices, end-systolic elastance (Ees) and preload recruitable stroke work (PRSW), demonstrated dose-dependent increases. The diastolic function parameter tau (tau) did not change with increasing Ang II dose. CONCLUSION: Ang II infusion caused increases in contractility indices in anaesthetised pigs in the doses used in this study. The mechanisms for these systolic function effects may be a direct myocardial effect or modulated through changes in autonomic nervous system activity.

  • 10.
    Broome, M.
    et al.
    Umeå Universitet.
    Haney, M.
    Osterlund, B.
    Haggmark, S.
    Johansson, G.
    Biber, B.
    The cardiac effects of intracoronary angiotensin II infusion2002Other (Refereed)
    Abstract [en]

    Angiotensin II (Ang II) is a potent vasoconstrictor, which recently has been shown to also have significant inotropic effects. Previous results regarding the mechanisms of the acute inotropic effects of Ang II are not conclusive. We designed this study to investigate the local cardiac effects of intracoronary Ang II infusion in doses not affecting systemic circulation. Ang II (2.5-40 microg/h) was infused in the left coronary artery of Yorkshire pigs (n = 9) reaching calculated intracoronary Ang II concentrations of 842 +/- 310, 3342 +/- 1238, and 12448 +/- 4393 pg/mL, respectively. Cardiac systolic and diastolic function was evaluated by analysis of the left ventricular pressure-volume relationship. Coronary flow was measured by using a coronary sinus catheter and the retrograde thermodilution technique. No significant changes were seen in the systolic and diastolic function variables of heart rate, end-systolic elastance, preload recruitable stroke work, the time constant for isovolumetric relaxation, or in coronary vascular resistance and flow. The positive inotropic and chronotropic effects of Ang II seen in previous studies seem thus to be mediated via extracardiac actions of Ang II. Coronary vascular tone is not affected by local Ang II infusion in anesthetized pigs. IMPLICATIONS: The positive inotropic and chronotropic effects of angiotension II (Ang II) seen in previous studies seem to be mediated via extracardiac actions of Ang II. Coronary vascular tone is not affected by local Ang II infusion in anesthetized pigs.

  • 11.
    Broome, Michael
    Karolinska Institutet.
    MEDIQ CorVascSim2011Other (Other academic)
  • 12.
    Broome, Michael
    Karolinska Institutet.
    Simulation of cardiovascular physiology and pathology with CorVascSim: A PC software for advanced education and research2004Other (Other academic)
    Abstract [en]

    Background and Goal: The rapid development of computer technology makes simulation of cardiovascular physiology and pathology possible. The current work presents a scientifically based cardiovascular model, with a self-explanatory interface. Material and Methods: An electrical analogue of the cardiovascular system including resistances, capacitances and inductances was constructed. The contractile function of the cardiac atria and ventricles are represented by time-varying elastances. Valvular function, pericardial volume, ventricular interaction and intrathoracic pressure are represented by constants and functions, which can interact. Pressures, flows and volumes are recalculated every millisecond and presented on-line as numerical and high-resolution graphics. Results and Discussion: The validity of the simulation models is based on the references (1-4). The software makes it possible to illustrate a great diversity of circulatory pathological findings including systolic and diastolic heart failure, valve diseases, pericardial effusion, arteriosclerosis and effects of changes in intrathoracic pressure. The model is being used to educate doctors and nurses in cardiac surgery, cardiac anaesthesia, and cardiology, but its pedagogical value remains to be validated. Conclusion: Simulation of cardiac physiology and pathology provides a new way to study the heart. Results from simulations can be used in education as well as in interpretation of clinical invasive monitoring, echocardiography and experimental research.

  • 13.
    Broome, Michael
    et al.
    Karolinska Institutet.
    Palmer, K.
    Schersten, H.
    Frenckner, B.
    Nilsson, F.
    Prolonged extracorporeal membrane oxygenation and circulatory support as bridge to lung transplant2008In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 86, no 4, p. 1357-1360Article in journal (Refereed)
    Abstract [en]

    A 38-year-old man with progressive alveolitis secondary to polymyositis was treated for 52 days with venovenous and venoarterial extracorporeal membrane oxygenation as a bridge to bilateral lung transplantation. The patient survived, despite multiple complications, and is now back home with good pulmonary function. He is working part-time nearly 3 years post-transplant. This case shows that long-term extracorporeal lung assist is a viable but demanding alternative for bridging patients to pulmonary transplantation. This case also shows that right ventricular failure necessating conversion to veno-arterial assist does not necessarily predict right ventricular failure post-transplant.

  • 14.
    Broomé, Michael
    et al.
    Umeå Universitet.
    Haney, M.
    Häggmark, S.
    Johansson, G.
    Åneman, A.
    Biber, B.
    Pressure-independent cardiac effects of angiotensin II in pigs2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 182, no 2, p. 111-119Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor with an important role in the development of cardiovascular disease. Earlier results have shown a positive acute inotropic effect of Ang II in anaesthetized pigs together with significant vasoconstriction. This investigation was designed to study cardiac effects of Ang II, when blood pressure was maintained constant by experimental means. METHODS: Ang II (200 microg h(-1)) was infused in anaesthetized pigs (n = 10) at two different arterial blood pressures, the first determined by the effects of Ang II alone, and the second maintained at baseline blood pressure with nitroprusside. Cardiac systolic and diastolic function was evaluated by analysis of left ventricular pressure-volume relationships. RESULTS: Heart rate, end-systolic elastance (Ees) and pre-load adjusted maximal power (PWRmax EDV(-2)) increased at both blood pressure levels, although less when blood pressure was kept constant with nitroprusside. The time constant for isovolumetric relaxation (tau(1/2)) was prolonged with Ang II alone and shortened with Ang II infused together with nitroprusside. CONCLUSION: Ang II infusion in the pig has inotropic and chronotropic properties independent of arterial blood pressure levels, although the effects seem to be blunted by pharmacological actions of the nitric oxide donor nitroprusside.

  • 15.
    Callerström, Emma
    KTH, School of Technology and Health (STH).
    Clinicians' demands on monitoring support in an Intensive Care Unit: A pilot study, at Capio S:t Görans Hospital2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Patients treated at intensive care units (ICUs) are failing in one or several organs and requireappropriate monitoring and treatment in order to maintain a meaningful life. Today clinicians inintensive care units (ICUs) manage a large amount of data generated from monitoring devices.The monitoring parameters can either be noted down manually on a monitoring sheet or, for some parameters, transferred automatically to storage. In both cases the information is stored withthe aim to support clinicians throughout the intensive care and be easily accessible. Patient datamanagement systems (PDMSs) facilitate ICUs to retrieve and integrate data. Before managinga new configuration of patient data system, it is required that the ICU makes careful analysis ofwhat data desired to be registered. This pilot study provides knowledge of how the monitoringis performed in an Intensive Care Unit in an emergency hospital in Stockholm.The aim of this thesis project was to collect data about what the clinicians require and whatequipment they use today for monitoring. Requirement elicitation is a technique to collectrequirements. Methods used to collect data were active observations and qualitative interviews.Patterns have been found about what the assistant nurses, nurses and physicians’ require of systems supporting the clinician’s with monitoring parameters. Assistant nurses would like tobe released from tasks of taking notes manually. They also question the need for atomized datacollection since they are present observing the patient bed-side. Nurses describe a demanding burden of care and no more activities increasing that burden of care is required. Physicians require support in order to see how an intervention leads to a certain result for individual patients.The results also show that there is information about decision support but no easy way to applythem, better than the ones used today. Clinicians state that there is a need to be able to evaluatethe clinical work with the help of monitoring parameters. The results provide knowledge about which areas the clinicians needs are not supported enough by the exciting tools.To conclude results show that depending on what profession and experience the clinicians have the demands on monitoring support di↵ers. Monitoring at the ICU is performed while observing individual patients, parameters from medical devices, results from medical tests and physical examinations. Information from all these sources is considered by the clinicians and is desired to be supported accordingly before clinicians commit to action resulting in certain treatment,diagnosis and/or care.

  • 16.
    Donker, Dirk W.
    et al.
    Univ Utrecht, Dept Intens Care Med, Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Brodie, Daniel
    Columbia Univ, Coll Phys & Surg, New York Presbyterian Hosp, Div Pulm Allergy & Crit Care Med, New York, NY USA..
    Henriques, Jose P. S.
    Univ Amsterdam, Dept Cardiol, Acad Med Ctr, Amsterdam UMC, Amsterdam, Netherlands..
    Broomé, Michael
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Left ventricular unloading during veno-arterial ECMO: a review of percutaneous and surgical unloading interventions2019In: Perfusion, ISSN 0267-6591, E-ISSN 1477-111X, Vol. 34, no 2, p. 98-105Article, review/survey (Refereed)
    Abstract [en]

    Short-term mechanical support by veno-arterial extracorporeal membrane oxygenation (VA ECMO) is more and more applied in patients with severe cardiogenic shock. A major shortcoming of VA ECMO is its variable, but inherent increase of left ventricular (LV) mechanical load, which may aggravate pulmonary edema and hamper cardiac recovery. In order to mitigate these negative sequelae of VA ECMO, different adjunct LV unloading interventions have gained a broad interest in recent years. Here, we review the whole spectrum of percutaneous and surgical techniques combined with VA ECMO reported to date.

  • 17. Frenckner, B.
    et al.
    Broomé, Michael
    Karolinska Institutet.
    Lindström, M.
    Radell, P.
    Platelet-derived growth factor inhibition: a new treatment of pulmonary hypertension in congenital diaphragmatic hernia?2008In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 43, no 10, p. 1928-1931Article in journal (Refereed)
    Abstract [en]

    Increased pulmonary vascular resistance causing pulmonary artery hypertension is a major problem in the treatment of congenital diaphragmatic hernia with a strong association to mortality. We here report a patient with intractable pulmonary hypertension at 4 weeks of age unresponsive to conventional treatment. After administration of the platelet-derived growth factor (PDGF) receptor antagonist imatinib, pulmonary artery pressure gradually decreased to acceptable levels and the patient's clinical condition gradually improved.

  • 18.
    Fuchs, Gabriel
    et al.
    Sundsvall Reg Hosp, Sundsvall, Sweden..
    Berg, Niclas
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW.
    Broman, Mikael
    Karolinska Hosp, ECMO Ctr, Stockholm, Sweden..
    Prahl Wittberg, Lisa
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW.
    Blood clots in the ECMO-system - a theoretical platelet activation study2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 964-965Article in journal (Other academic)
  • 19.
    Fuchs, Gabriel
    et al.
    Sundsvall Reg Hosp, Sundsvall, Sweden..
    Broman, Mikael
    Karolinska Univ Hosp, ECMO Ctr, Stockholm, Sweden..
    Wittberg, Lisa Prahl
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW.
    Non-invasive detection of pump-associated blood clots in the ECMO-system2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 964-964Article in journal (Other academic)
  • 20. Gunes, I.
    et al.
    Kucuk, A.
    Comu, F. M.
    Sivgin, V.
    Alkan, M.
    Arslan, M.
    Unal, Y.
    I kappa B Kinase 2 impairs Platelet Activation2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 221, p. 248-250Article in journal (Other academic)
  • 21. Gunther, A. C.
    et al.
    Schandl, A. R.
    Berhardsson, J.
    Bjärtå, A.
    Wållgren, M.
    Sundin, O.
    Alvarsson, Jesper
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Marcus Wallenberg Laboratory MWL.
    Bottai, M.
    Martling, C. -R
    Sackey, P. V.
    Pain rather than induced emotions and ICU sound increases skin conductance variability in healthy volunteers2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 8, p. 1111-1120Article in journal (Refereed)
    Abstract [en]

    BackgroundAssessing pain in critically ill patients is difficult. Skin conductance variability (SCV), induced by the sympathetic response to pain, has been suggested as a method to identify pain in poorly communicating patients. However, SCV, a derivate of conventional skin conductance, could potentially also be sensitive to emotional stress. The purpose of the study was to investigate if pain and emotional stress can be distinguished with SCV. MethodsIn a series of twelve 1-min sessions with SCV recording, 18 healthy volunteers were exposed to standardized electric pain stimulation during blocks of positive, negative, or neutral emotion, induced with pictures from the International Affective PictureSystem (IAPS). Additionally, authentic intensive care unit (ICU) sound was included in half of the sessions. All possible combinations of pain and sound occurred in each block of emotion, and blocks were presented in randomized order. ResultsPain stimulation resulted in increases in the number of skin conductance fluctuations (NSCF) in all but one participant. During pain-free baseline sessions, the median NSCF was 0.068 (interquartile range 0.013-0.089) and during pain stimulation median NSCF increased to 0.225 (interquartile range 0.146-0.3175). Only small increases in NSCF were found during negative emotions. Pain, assessed with the numeric rating scale, during the sessions with pain stimulation was not altered significantly by other ongoing sensory input. ConclusionIn healthy volunteers, NSCF appears to reflect ongoing autonomous reactions mainly to pain and to a lesser extent, reactions to emotion induced with IAPS pictures or ICU sound.

  • 22. Holzgraefe, B.
    et al.
    Broome, Michael
    Karolinska Institutet.
    Kalzen, H.
    Konrad, D.
    Palmer, K.
    Frenckner, B.
    Extracorporeal membrane oxygenation for pandemic H1N1 2009 respiratory failure2010In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Severe respiratory failure related to infection with the pandemic influenza A/H1N1 2009 virus is uncommon but possibly life-threatening. If, in spite of maximal conventional critical care, the patient's condition deteriorates, extracorporeal membrane oxygenation (ECMO) may be a life-saving procedure. METHODS: An observational study approved by the local ethics committee was carried out. Data from all patients treated with ECMO at the ECMO Center Karolinska for influenza A/H1N1 2009-related severe respiratory failure were analyzed. The main outcome measure was survival three months after discharge from our department. RESULTS: Between July 2009 and January 2010, 13 patients with H1N1 2009 respiratory failure were treated with ECMO. Twelve patients were cannulated for veno-venous ECMO at the referring hospital and transported to Stockholm. One patient was cannulated in our hospital for veno-arterial support. The median ratio of the arterial partial oxygen pressure to the fraction of inspired oxygen (P/F ratio: PaO2 /FiO2) before cannulation was 52.5 (interquartile range 38-60). Four patients were converted from veno-venous to veno-arterial ECMO because of right heart failure (three) or life-threatening cardiac arrhythmias (one). The median maximum oxygen consumption via ECMO was 251 ml/min (187-281 ml/min). Twelve patients were still alive three months after discharge; one patient died four days after discharge due to intracranial hemorrhage. CONCLUSION: Patients treated with veno-venous or veno-arterial ECMO for H1N1 2009-related respiratory failure may have a favorable outcome. Contributing factors may include the possibility of transport on ECMO, conversion from veno-venous (v-v) or veno-arterial (v-a) ECMO if necessary, high-flow ECMO to meet oxygen requirements and active surgery when needed.

  • 23. Larsson, M.
    et al.
    Talving, P.
    Palmér, K.
    Frenckner, B.
    Riddez, L.
    Broomé, Michael
    Karolinska Institutet.
    Experimental extracorporeal membrane oxygenation reduces central venous pressure: an adjunct to control of venous hemorrhage?2010In: Perfusion, ISSN 0267-6591, E-ISSN 1477-111X, Vol. 25, no 4, p. 217-223Article in journal (Refereed)
    Abstract [en]

    Background: Venoarterial ECMO has been utilized in trauma patients to improve oxygenation, particularly in the setting of pulmonary contusions and ARDS. We hypothesized that venoarterial ECMO could reduce the central venous pressure in the trauma scenario, thus, alleviating major venous hemorrhage. Methods: Ten swine were cannulated for venoarterial ECMO. Central venous pressure, mean arterial pressure, portal vein pressure and portal vein flow were recorded at three different flow rates in both a hemodynamic normal state and a setting of increased central venous pressure and right ventricular load, mimicking acute lung injury. Results: Venoarterial ECMO reduced the central venous pressure (CVP(sup)) from 9.4 +/- 0.8 to 7.3 +/- 0.7 mmHg (p < 0.01) and increased the mean arterial pressure from 103 +/- 8 to 119 +/- 10 mmHg (p < 0.01) in the normal hemodynamic state. In the state of increased right ventricular load, the CVP(sup) declined from 14.3 +/- 0.4 to 11.0 +/- 0.7mmHg (p < 0.01) and the mean arterial pressure (MAP) increased from 66 +/- 6 to 113 +/- 5 mmHg (p < 0.01). Conclusion: Venoarterial ECMO reduces systemic venous pressure while maintaining or improving systemic perfusion in both a normal circulatory state and in the setting of increased right ventricular load associated with acute lung injury. ECMO may be a useful tool in reducing blood loss during major venous hemorrhage in both trauma and selected elective surgery.

  • 24.
    Lund, M.
    et al.
    Karolinska Inst, Dept Anaesthesiol & Intens Care, CLINTEC, Div Anaesthesia, Huddinge, Sweden..
    von Dobeln, Alexandersson G.
    Karolinska Inst, Karolinska Univ Hosp, Dept Oncol Pathol, Oncol, Stockholm, Sweden..
    Lundell, L.
    Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Surg, Div Surg,CLINTEC, Stockholm, Sweden..
    Winter, R
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems. Royal Inst Technol, Sch Technol & Hlth, Cardiol Sect, Med, Stockholm, Sweden..
    Tsai, J. A.
    Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Surg, Div Surg,CLINTEC, Stockholm, Sweden..
    Kalman, S.
    Karolinska Inst, Dept Anaesthesiol & Intens Care, CLINTEC, Div Anaesthesia, Huddinge, Sweden..
    Neoadjuvant chemoradiotherapy but not chemotherapy impairs cardiac function in patients with cancer in the esophagus or gastroesophageal junction - a prospective randomized study2014In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 31, p. 55-55Article in journal (Other academic)
  • 25. Lund, Mikael
    et al.
    Tsai, Jon A.
    Nilsson, Magnus
    Winter, Reidar
    KTH, School of Technology and Health (STH). Karolinska Inst, Sweden.
    Lundell, Lars
    Kalman, Sigridur
    Effects of neoadjuvant chemo or chemoradiotherapy for oesophageal cancer on perioperative haemodynamics A prospective cohort study within a randomised clinical trial2016In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 33, no 9, p. 653-661Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Neoadjuvant chemoradiotherapy might improve oncological outcome compared with chemotherapy after surgery for oesophagus or gastrooesophageal junction cancer. However, radiotherapy may induce cardiovascular side-effects that could increase the risk of perioperative adverse effects and postoperative morbidity. OBJECTIVES The aim of this study was to compare the perioperative haemodynamics in patients undergoing oesophagectomy following neoadjuvant chemotherapy or chemoradiotherapy for cancer. DESIGN A prospective single-centre cohort study within a randomised multi-centre trial. SETTING A Swedish University Hospital from January 2009 to March 2013. PATIENTS A total of 31 patients (chemotherapy 17, chemoradiotherapy 14) included in a multi-centre trial randomising chemotherapy vs. chemoradiotherapy and operated at Karolinska University Hospital, Huddinge. INTERVENTIONS Cisplatin and 5-fluorouracil, either with or without concurrent radiotherapy (40 Gy), were given prior to surgery. Cardiac function was assessed with LiDCOplus (LiDCO Ltd, London, United Kingdom), echocardiography, troponin T and N-terminal pro-B-type natriuretic peptide, before, during and after surgery. MAIN OUTCOME MEASURES The primary outcome was the interaction effect of the neoadjuvant treatment on stroke volume index during the perioperative period. Secondary outcomes were the interaction effects of oxygen delivery index, cardiac index, echocardiography and biochemical markers. RESULTS The groups were matched regarding comorbidities, but patients in the chemoradiotherapy group were older (66 vs. 60 years P = 0.03). Haemodynamic values changed in a similar way in both groups during the study period. The chemoradiotherapy group had a lower cardiac index before surgery (2.9 vs. 3.4 l min(-1) m(-2), P = 0.03). On the third postoperative day, both groups displayed a hyperdynamic state compared with baseline, with no increase in troponin T, and a similar increase in N-terminal pro-B-type natriuretic peptide. CONCLUSION Neoadjuvant chemoradiotherapy for oesophageal or gastrooesophageal junction cancer seems to induce only a marginal negative effect on cardiac function compared with neoadjuvant chemotherapy. This difference did not remain when patients' haemodynamics were challenged by surgery.

  • 26.
    Micski, Erik
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    CO2 Flow Estimation using Sidestream Capnography and Patient Flow in Anaesthesia Delivery Systems2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Volumetric CO2 data from patients in anaesthesia delivery systems are sought after by physicians. The CO2 data obtained with the commonly used sidestream sampling technique are not considered adequate for volumetric CO2 estimation due to distortion and desynchrony with patient flow. The purpose of this thesis was to explore the possibility of using signal enhancing methods to the sidestream data to accurately estimate CO2 flow using a Flow-i anaesthesia delivery system.

    To evaluate sidestream performance, experimental data was acquired using a mainstream and a sidestream capnograph connected in series to a FRC test lung with known CO2 content, ventilated by a Flow-i anaesthesia machine. The data was then enhanced and analysed using signal processing methods including sigmoid modelling and neural networks.

    A Feed Forward Neural Network achieved results closest resembling the mainstream capnogram of the evaluated signal processing methods. The mainstream capnogram, considered the benchmark, produced large internal scattering and approximately 25 % offset from actual CO2 flow while using the inherent patient flow data produced by the Flow-i anaesthesia system. When using patient flow data from a Servo-i ventilator, the resulting CO2 flow estimates were drastically improved, producing estimates within 10 % error.

    This thesis concludes that there are several potential processing methods of the sidestream data to approximate the mainstream signal, however the patient flow of the Flow-i system are a suspected source of error in the CO2 flow estimation.

  • 27. Osterlund, B.
    et al.
    Jern, C.
    Seeman-Lodding, H.
    Johansson, G.
    Haggmark, S.
    Broome, M.
    Umeå Universitet.
    Biber, B.
    Intracoronary beta2 receptor activation induces dynamic local t-PA release in the pig2003Other (Refereed)
    Abstract [en]

    To investigate beta2 -adrenergic agonist-mediated effects on coronary fluxes of local fibrinolytic factors, healthy anaesthetised and instrumented pigs (n=10) were studied during infusion of isoprenaline (IPR) into the left main coronary artery. Coronary net fluxes of total t-PA antigen, active t-PA and total PAI-1 antigen were determined at baseline and at 3, 5, 7 and 10 minutes of IPR infusion. During IPR, net release of total t-PA increased in a biphasic pattern with transiently high levels at 3 (+440 %) and 7 minutes (+620%) and returned towards baseline at 10 minutes. Net coronary release of active t-PA increased with maximum levels at 3 minutes (+50%). Baseline coronary net flux of total PAI -1 showed a decrease which was most pronounced at 10 minutes. To conclude, a fast beta2 agonist-mediated local release of t-PA into the coronary vasculature was demonstrated. For total t-PA, this response was characterised by a biphasic release profile.

  • 28.
    Panzer, Matthew B.
    et al.
    Univ Virginia, Ctr Appl Biomech, Charlottesville, VA USA..
    Giudice, J. Sebastian
    Univ Virginia, Ctr Appl Biomech, Charlottesville, VA USA..
    Caudillo, Adrian
    Univ Virginia, Ctr Appl Biomech, Charlottesville, VA USA..
    Mukherjee, Sayak
    Univ Virginia, Ctr Appl Biomech, Charlottesville, VA USA..
    Kong, Kevin
    Univ Virginia, Ctr Appl Biomech, Charlottesville, VA USA..
    Cronin, Duane S.
    Univ Waterloo, Waterloo, ON, Canada..
    Barker, Jeffrey
    Univ Waterloo, Waterloo, ON, Canada..
    Gierczycka, Donata
    Univ Waterloo, Waterloo, ON, Canada..
    Bustamante, Michael
    Univ Waterloo, Waterloo, ON, Canada..
    Bruneau, David
    Univ Waterloo, Waterloo, ON, Canada..
    Corrales, Miguel
    Univ Waterloo, Waterloo, ON, Canada..
    Halldin, Peter
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Neuronic Engineering.
    Fahlstedt, Madelen
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Neuronic Engineering.
    Arnesen, Marcus
    Jungstedt, Erik
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Biocomposites. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Wallenberg Wood Science Center.
    Gayzik, F. Scott
    Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA..
    Stitzel, Joel D.
    Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA..
    Decker, William
    Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA..
    Baker, Alex M.
    Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA..
    Ye, Xin
    Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA..
    Brown, Philip
    Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA..
    NUMERICAL CROWDSOURCING OF NFL FOOTBALL HELMETS2018In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, no 16, p. A148-A148Article in journal (Other academic)
  • 29. Sundeman, H.
    et al.
    Aneman, A.
    Broome, M.
    Umeå Universitet.
    Haney, M.
    Johansson, G.
    Haggmark, S.
    Biber, B.
    Winso, O.
    Effects of desflurane on the pig intestinal circulation during hypotension1999Other (Refereed)
    Abstract [en]

    BACKGROUND: The aim of the present study was to analyze the perfusion pressure dependency for the splanchnic vascular effects of desflurane (DES). METHODS: We measured portal blood flow (QPORT, perivascular ultrasound) and jejunal mucosal perfusion (JMP; laser Doppler) in pentobarbital-anesthetized pigs (n=10). Experimentally, decreases in mean arterial pressure (MAP) were produced by pericardial infusions of dextran. The protocol included sets of measurements at incremental doses of DES (1, 2, 4 and 6%) prior to and during pericardial infusions. RESULTS: Although QPORT and JMP decreased significantly during pericardial infusions, DES, irrespective of dose, did not reduce QPORT until MAP had decreased below 65-70 mm Hg. In higher MAP ranges, vasodilation in pre-portal tissues was powerful enough to maintain QPORT in spite of concurrent decreases in driving arterial pressure, as produced by either DES or pericardial infusion, or by a combination of both. We found no effects of DES on JMP even at very low MAP (about 40 mm Hg during pericardial infusion), indicating that the normal physiological response of the small intestine to redistribute blood flow from deeper to more superficial layers during hypotension was unimpaired by DES. CONCLUSIONS: Our data suggest a wide dose-tolerability of DES as regards the splanchnic circulation during hypotensive states.

  • 30. Sundeman, H.
    et al.
    Haney, M.
    Broome, M.
    Umeå Universitet.
    Haggmark, S.
    Johansson, G.
    Winso, O.
    Biber, B.
    The effects of desflurane on cardiac function as measured by conductance volumetry in swine1998Other (Refereed)
    Abstract [en]

    The purpose of the investigation was to assess the effects of desflurane (DES) on left ventricular heart function during basal barbiturate anesthesia in a closed-pericardium, closed-chest acute swine model. The study was performed in 11 normoventilated adult pigs. Hemodynamic measurements were obtained using arterial, central venous, and pulmonary artery catheters, as well as a conductance volumetry and tip manometry catheter placed in the left ventricle. Hemodynamic measurements were recorded during basal pentobarbital anesthesia and with the addition of 1%, 2%, 4%, and 6% DES. DES dose-dependently decreased mean arterial pressure, systemic vascular resistance, left ventricular end-systolic pressure, dP/dtMAX and dP/dtMIN. At doses >1%, decreases in CO, stroke volume, ejection fraction, end-systolic elastance, preload recruitable stroke work, preload adjusted maximal power, and peak filling rate were observed. Heart rate decreased at 4% and 6% DES. Isovolumetric relaxation time increased only at 6% DES. We conclude that smaller doses of DES have a significant cardiodepressive effect in the setting of barbiturate infusion, as measured by conductance volumetry. IMPLICATIONS: Desflurane, in very small doses, depressed cardiac function during pentobarbital anesthesia with ketamine and benzodiazepine premedication in swine, as assessed by conductance volumetry and left ventricular pressure and volume relationship analysis. These results suggest that desflurane, in combination with certain anesthetics, can be cardiodepressive even in very small doses.

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