| 1. |
- Carlberg, Niclas, et al.
(författare)
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Circulating concentrations of glycocalyx degradation products in preeclampsia
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Preeclampsia is a multisystem disorder that affects maternal endothelium. The glycocalyx lines and protects the endothelial surface. In severe systemic diseases, like sepsis, it is shed and glycocalyx degradation products can be detected in increased concentrations in plasma. The aim of this study was to compare circulating concentrations of glycocalyx degradation products in degrees of preeclampsia severity. Study design: In this observational study, we included women from the South African PROVE biobank. Women were divided into normotensive controls, women with preeclampsia without end-organ complications, women with a single end-organ complication and women with multiple end-organ complications. Plasma samples taken at inclusion after diagnosis (preeclampsia cases) or at admission for delivery (normotensive controls) were analyzed with ELISA for syndecan-1, hyaluronic acid and thrombomodulin and compared between groups. Results: Women with preeclampsia (n = 47) had increased plasma concentrations of hyaluronic acid (100.3ng/ml IQR 54.2–204 vs. 27.0ng/ml IQR (13.5–66.6), p < 0,001) and thrombomodulin (4.22ng/ml IQR 3.55–5.17 vs. 3.49ng/ml IQR 3.01–3.68, p = 0.007) but not syndecan-1 compared with normotensive women (n = 10). There were no differences in plasma concentration in any of these biomarkers in women with preeclampsia with no end-organ complications (n = 10) compared with women with preeclampsia and one end-organ complication (n = 24). Women with preeclampsia with two or more end-organ complications (n = 13) had increased plasma concentrations of thrombomodulin (5.46ng/ml, IQR 4.85–7.83 vs. 4.66ng/ml, IQR 3.45–4.88, p = 0.042) compared with women with preeclampsia and no end-organ complications. Conclusion: Thrombomodulin was associated with disease severity and may be valuable for risk-stratifying women with preeclampsia.
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| 2. |
- Damén, Tor, et al.
(författare)
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Atrial natriuretic peptide does not degrade the endothelial glycocalyx: A secondary analysis of a randomized porcine model
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 65:9, s. 1305-1312
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Tidskriftsartikel (refereegranskat)abstract
- Background: The atrial natriuretic peptide (ANP) released from the heart regulates intravascular volume and is suspected to increase capillary permeability. Contradictory results regarding ANP and glycocalyx degradation have been reported. The aim of this study was to investigate if an infusion of ANP causes degradation of the endothelial glycocalyx. Methods: Twenty pigs, pretreated with 250mg methylprednisolone, were randomized to receive an infusion of either ANP (50ng/kg/min) (n=10) or 0.9% NaCl (n=10) during 60min. Endothelial glycocalyx components (heparan sulphate proteoglycan and hyaluronic acid), Hct, calculated plasma volume and colloid osmotic pressure were measured from baseline to 60min. Results: There was no difference between the control and intervention groups for heparan sulphate proteoglycan and hyaluronic acid corrected for the change in plasma volume (P=.333 and 0.197). Hct increased with 1.8±2.2% in the intervention group (P=.029) with no change −0.5±2.3% in the control group (P=.504). The plasma volume decreased in the intervention group with −8.4±10% (P=.034) with no change in the control group 3.1±12% (P=.427). Median changes in colloid osmotic pressures in the control and intervention group were −0.39 [95% CI, −1.88-0.13] and 0.9 [95% CI, 0.00-1.58], respectively (P=.012). Conclusions: In this randomized porcine study, an ANP infusion did not cause endothelial glycocalyx degradation but decreased the plasma volume most probably due to precapillary vasodilation and increased filtration. © 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
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| 3. |
- Damén, Tor
(författare)
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Blood pressure-dependent changes in plasma volume, glycocalyx and platelet function during anaesthesia -Clinical and experimental studies
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Worldwide, more than 300 million surgeries are performed each year. General anaesthesia provides the surgical patient with a state of controlled loss of sensation and awareness. It is common that general anaesthesia causes hypotension. Anaesthesia-induced hypotension is associated with haemodilution and increased plasma volume (PV). The increased PV could potentially release atrial natriuretic peptide (ANP) that is suspected to degrade the endothelial glycocalyx (EG) layer. Aims: To explore physiological and pathophysiological mechanisms resulting from anaesthesia-related hypotension we: 1) investigated the magnitude and dynamics of PV expansion secondary to anaesthesia induction; 2) assessed whether anaesthesia induction-related increase in PV could be attenuated by maintaining the mean arterial pressure (MAP) at pre-induction levels with norepinephrine (NE) infusion; 3) evaluated the consequences of anaesthesia induction-related PV expansion on the release of ANP and its effects on the EG. We also investigated whether exogenous administration of ANP caused degradation of the EG. Finally, we investigated the effect of NE infusion on platelet function and clot formation. Methods: We conducted two prospective, randomised, single-centre studies on patients that underwent elective coronary artery bypass grafting (CABG). The patients were randomised to maintain pre-induction MAP (intervention group) or MAP 60 mm Hg (control group) by titration of NE. Baseline PV was measured by 125I-albumin and the change in PV was calculated from the change in haematocrit (Hct). Changes in Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and EG-components were measured. In a prospective, randomised, blinded, experimental study, 20 pigs were randomised to receive an infusion of either ANP or NaCl. Changes in EG components, Hct, calculated PV and colloid osmotic pressure (COP) were measured. Platelet aggregation was assessed with impedance aggregometry and clot formation with rotational thromboelastometry in study IV. Results: Lower MAP, (60 mm Hg) secondary to anaesthesia induction increased the PV by 12%, while the PV increased by 2,6% in the intervention group with maintained pre-operative MAP. MR-proANP increased in the group with lower MAP but no degradation of the EG was detected. There was no increase in EG components secondary to an infusion of ANP, but the PV decreased. Intraoperative NE infusion improved platelet aggregation and clot formation. Conclusions: Haematocrit decreased and plasma volume increased shortly after anaesthesia induction caused hypotension. The increase in plasma volume could be prevented by maintaining pre-induction blood-pressure levels with a norepinephrine infusion. No ANP-induced degradation of the EG was detected. Norepinephrine could contribute to a better perioperative haemostasis.
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| 4. |
- Damén, Tor, et al.
(författare)
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Effects of different mean arterial pressure targets on plasma volume, ANP and glycocalyx-A randomized trial.
- 2021
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 65:2, s. 220-227
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Tidskriftsartikel (refereegranskat)abstract
- Arterial haematocrit (Hct) has been shown to decrease after anaesthesia induction, most probably because of an increased plasma volume (PV). The primary objective was to quantify change in PV if mean arterial pressure (MAP) was kept at baseline level or allowed to decrease to 60mm Hg. Our secondary objective was to evaluate underlying mechanisms of this response.Twenty-four coronary artery bypass patients were randomized to a higher (90mm Hg, intervention group) or lower (60mm Hg, control group) MAP by titration of norepinephrine. During the experimental procedure, no fluids were administered. Baseline PV was measured by 125 I-albumin and the change in PV was calculated from the change in Hct. Changes in MAP, plasma 125 I-albumin, colloid osmotic pressure, albumin, Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and endothelial glycocalyx components were measured from baseline to 50minutes after anaesthesia induction.The MAP during the trial was 93±9mm Hg in the intervention group and 62±5mm Hg in the control group. PV increased with up to 420±180mL in the control group and 45±130mL in the intervention group (P<.001). Albumin and colloid osmotic pressure decreased significantly more in the control group. MR-proANP increased in the control group but no shedding of the glycocalyx layer was detected in either of the groups.Allowing mean arterial pressure to fall to 60mm Hg during anaesthesia induction, increases the plasma volume due to reabsorption of interstitial water, with no ANP-induced degradation of the endothelial glycocalyx.
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| 5. |
- Damén, Tor, et al.
(författare)
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Inverted valve after initially successful transfemoral aortic valve implantation
- 2012
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Ingår i: Annals of Thoracic Surgery. - New York, USA : Elsevier. - 0003-4975 .- 1552-6259. ; 94:2, s. 636-639
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Tidskriftsartikel (refereegranskat)abstract
- A 73-year-old woman with severe aortic stenosis was accepted for transcatheter aortic valve implantation. There was minimal paravalvular leakage after the implantation, and the patient was stable. Twelve minutes after the implantation, the arterial pressure suddenly dropped. Transesophageal echocardiography showed severe left ventricular dysfunction. Cardiopulmonary resuscitation was started, and initially was successful with a systolic blood pressure of 90 mm Hg. However, despite initiation of extracorporeal circulation support, the patient deteriorated, pulmonary edema developed, and she died. Autopsy revealed an inverted aortic valve. The reasons why the patient had cardiac arrest and an inverted transfemoral aortic valve remain unclear.
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| 6. |
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| 7. |
- Kolsrud, Oscar, et al.
(författare)
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Effects of atrial natriuretic peptide on renal function during cardiopulmonary bypass: a randomized pig model.
- 2020
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X. ; 57:4, s. 652-659
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Tidskriftsartikel (refereegranskat)abstract
- Acute kidney injury is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In this experimental animal study, we evaluated the effects of atrial natriuretic peptide (ANP) on renal function, perfusion, oxygenation and tubular injury during CPB.Twenty pigs were blindly randomized to continuous infusion of either ANP (50ng/kg/min) or placebo before, during and after CPB. Renal blood flow as well as cortical and medullary perfusion was measured. Blood was repeatedly sampled from the renal vein. Glomerular filtration rate was measured by infusion clearance of 51Cr-EDTA.Glomerular filtration rate was higher (P<0.001), whereas renal blood flow or renal oxygen delivery was not affected by ANP during CPB. Renal oxygen consumption did not differ between groups during CPB, whereas renal oxygen extraction was higher in the ANP group (P=0.03). Urine flow and sodium excretion were higher in the ANP group during CPB. Blood flow in the renal medulla, but not in the cortex, dropped during CPB, an effect that was not seen in the animals that received ANP.ANP improved renal function during CPB. Despite impaired renal oxygenation, ANP did not cause tubular injury, suggesting a renoprotective effect of ANP during CPB. Also, CPB induced a selectively reduced blood flow in the renal medulla, an effect that was counteracted by ANP.
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| 8. |
- Singh, Sukhi, 1990, et al.
(författare)
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Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers
- 2019
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 119:5, s. 735-743
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo.METHODS: Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 µg/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step.RESULTS: = 0.007).CONCLUSION: Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations.TRIAL REGISTRY NUMBER: ClinicalTrials.gov NCT03441412.
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| 9. |
- Singh, Sukhi, 1990, et al.
(författare)
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Intraoperative infusion of noradrenaline improves platelet aggregation in patients undergoing coronary artery bypass grafting: a randomized controlled trial
- 2019
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 17:4, s. 657-665
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Tidskriftsartikel (refereegranskat)abstract
- Background New approaches to prevent bleeding complications during cardiac surgery are needed. Objective To investigate if noradrenaline (NA) enhances platelet aggregation in patients undergoing coronary artery bypass grafting (CABG). Patients/Methods Twenty-four patients undergoing coronary artery bypass grafting (CABG) were included in a prospective parallel-group randomized study. All patients but one were treated with acetylsalicylic acid (ASA). In the treatment group (n = 12), mean arterial blood pressure (MAP) was maintained at pre-induction levels by NA infusion. In the control group (n = 12), NA was administered only if MAP decreased below 60 mmHg. Platelet aggregation (impedance aggregometry with ADP, arachidonic acid [AA] and thrombin-receptor activating peptide [TRAP] as initiators) and clot formation (clotting time, clot formation time and maximum clot firmness by EXTEM, INTEM and FIBTEM tests with thromboelastometry) were assessed before and 50 min after anesthesia induction (before cardiopulmonary bypass was initiated). Results All patients in the treatment group received NA (median dose after 50 min 0.09 (range 0-0.26) mu g kg(-1) min(-1)). Four patients in the control group also received NA (0.03-0.12 mu g kg(-1) min(-1)). There were differences between the treatment group and the control group in ADP- and AA-induced aggregation changes (ADP, +16 [25th-75th percentiles, 5-26] vs. -7 [-19 to -1] U; AA, +12 [-4 to 16] vs. -9 [-13 to 1] U). INTEM maximum clot firmness increased in the treatment group but not in the control group. Conclusion Infusion of clinically relevant doses of NA enhanced platelet aggregation and clot firmness in ASA-treated CABG patients. NA infusion is hence a potential new method to acutely improve platelet reactivity in patients on antiplatelet therapy undergoing surgery.
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