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Tovedal, Thomas
Publications (10 of 13) Show all publications
Tovedal, T., Lubberink, M., Morell, A., Estrada, S., Golla, S. S., Myrdal, G., . . . Lennmyr, F. (2017). Blood Flow Quantitation by Positron Emission Tomography During Selective Antegrade Cerebral Perfusion. Annals of Thoracic Surgery, 103(2), 610-616
Open this publication in new window or tab >>Blood Flow Quantitation by Positron Emission Tomography During Selective Antegrade Cerebral Perfusion
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2017 (English)In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 103, no 2, p. 610-616Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Perfusion strategies during aortic surgery usually comprise hypothermic circulatory arrest (HCA), often combined with selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion. Cerebral blood flow (CBF) is a fundamental parameter for which the optimal level has not been clearly defined. We sought to determine the CBF at a pump flow level of 6 mL/kg/min, previously shown likely to provide adequate SACP at 20°C in pigs.

METHODS: Repeated positron emission tomography (PET) scans were used to quantify the CBF and glucose metabolism throughout HCA and SACP including cooling and rewarming. Eight pigs on cardiopulmonary bypass were assigned to either HCA alone (n = 4) or HCA+SACP (n = 4). The CBF was measured by repeated [(15)O]water PET scans from baseline to rewarming. The cerebral glucose metabolism was examined by [(18)F]fluorodeoxyglucose PET scans after rewarming to 37°C.

RESULTS: Cooling to 20°C decreased the cortical CBF from 0.31 ± 0.06 at baseline to 0.10 ± 0.02 mL/cm(3)/min (p = 0.008). The CBF was maintained stable by SACP of 6 mL/kg/min during 45 minutes. After rewarming to 37°C, the mean CBF increased to 0.24 ± 0.07 mL/cm(3)/min, without significant differences between the groups at any time-point exclusive of the HCA period. The net cortical uptake (Ki) of [(18)F]fluorodeoxyglucose after rewarming showed no significant difference between the groups.

CONCLUSIONS: Cooling autoregulated the CBF to 0.10 mL/cm(3)/min, and 45 minutes of SACP at 6 mL/kg/min maintained the CBF in the present model. Cerebral glucose metabolism after rewarming was similar in the study groups.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-302609 (URN)10.1016/j.athoracsur.2016.06.029 (DOI)000397165400067 ()27592601 (PubMedID)
Available from: 2016-09-07 Created: 2016-09-07 Last updated: 2018-09-03Bibliographically approved
Lindblom, R. P., Tovedal, T., Norlin, B., Hillered, L., Popova, S., Alafuzoff, I. & Thelin, S. (2017). Mechanical reperfusion with leucocyte-filtered blood does not prevent injury following global cerebral ischaemia. European Journal of Cardio-Thoracic Surgery, 51(4), 773-781
Open this publication in new window or tab >>Mechanical reperfusion with leucocyte-filtered blood does not prevent injury following global cerebral ischaemia
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2017 (English)In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 51, no 4, p. 773-781Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Prolonged global cerebral ischaemia leads to irreversible injury, often with lethal outcome. Brain injuries are partly caused by the uncontrolled reperfusion that occurs once the circulation is re-established. Recent animal experiments suggest that controlled reperfusion following lengthy ischaemia might prevent severe brain injury. This study aimed at further exploring cerebral alterations and outcome following prolonged global cerebral ischaemia and mechanically manipulated reperfusion.

METHODS: Three groups of pigs were included; one sham operated (n = 3) and two that underwent 30-min global cerebral ischaemia. All vessels that supply the brain were isolated intrathoracically, after which they were occluded for 30 min in the ischaemic groups. In one of the ischaemic groups uncontrolled reperfusion was applied (URep, n = 6), i.e. normal circulation was restored 30 min after arrested cerebral circulation. The second ischaemic group received mechanical reperfusion (MRep, n = 6) with leucocyte-filtered blood at constant flow and pressure for 20 min using extracorporeal circulation following the 30-min ischaemia, after which normal blood flow resumed. All animals were monitored for 3 h after start of uncontrolled reperfusion. Haemodynamic parameters, arterial and sagittal sinus blood gases, cerebral oxygen extraction rates and intraparenchymal biomarkers using microdialysis were measured. Brain histology was performed post-mortem.

RESULTS: Global brain ischaemia led to the same extent of severe morphological changes at the level of light microscopy in the two ischaemic experimental groups, regardless of reperfusion protocol. Furthermore, no significant differences were found between the URep and MRep groups regarding cerebral blood gases or microdialysis biomarkers.

CONCLUSIONS: Mechanical reperfusion following the current protocol does not modify brain alterations caused by 30 min of arrested cerebral circulation.

National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-315862 (URN)10.1093/ejcts/ezw367 (DOI)000398558800026 ()28007877 (PubMedID)
Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2018-01-13Bibliographically approved
Tovedal, T., Thelin, S. & Lennmyr, F. (2016). Cerebral oxygen saturation during pulsatile and non-pulsatile cardiopulmonary bypass in patients with carotid stenosis.. Perfusion, 31(1), 72-77
Open this publication in new window or tab >>Cerebral oxygen saturation during pulsatile and non-pulsatile cardiopulmonary bypass in patients with carotid stenosis.
2016 (English)In: Perfusion, ISSN 0267-6591, E-ISSN 1477-111X, Vol. 31, no 1, p. 72-77Article in journal (Refereed) Published
Abstract [en]

Pulsatile and non-pulsatile cardiopulmonary bypass (CPB) flows may have different impact on cerebral oxygen saturation in patients with restricted cerebral arterial blood supply. Twenty patients, ten diagnosed with carotid stenosis (CS, n = 10) and ten without known carotid disease (Controls, n = 10), were subjected to one period of pulsatile and one period of non-pulsatile flow (6-8 min each) during CPB at 32°C. Cerebral oxygen saturation was registered by near-infrared light spectroscopy (NIRS). The mean arterial pressure (MAP) was significantly lowered by pulsatile CPB flow. The NIRS tissue oxygenation index (TOI) tended to decrease in the CS group and increase in the Controls during pulsatile flow compared with non-pulsatile; however, the changes were not statistically significant. No significant correlations were seen between the changes in MAP and TOI across the observation periods. In conclusion, pulsatile CPB flow caused slightly decreased mean arterial pressure while the effect on cerebral oxygenation was unclear. Pulsatile flow was not found superior to non-pulsatile flow in patients with or without carotid stenosis.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-266555 (URN)10.1177/0267659115586280 (DOI)000366585600012 ()25948696 (PubMedID)
Available from: 2015-11-10 Created: 2015-11-10 Last updated: 2017-12-01Bibliographically approved
Tovedal, T., Thelin, S. & Lennmyr, F. (2015). Cerebral oxygen saturation during pulsatile and non-pulsatile cardiopulmonary bypass in patients with carotid stenosis. Perfusion
Open this publication in new window or tab >>Cerebral oxygen saturation during pulsatile and non-pulsatile cardiopulmonary bypass in patients with carotid stenosis
2015 (English)In: Perfusion, ISSN 0267-6591, E-ISSN 1477-111XArticle in journal (Refereed) Published
Keywords
Cardiopulmonary bypass, carotid stenosis, pulsatile CPB flow, NIRS
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-248678 (URN)
Available from: 2015-04-07 Created: 2015-04-07 Last updated: 2017-12-04
Tovedal, T. (2015). Cerebral perfusion during cardiopulmonary bypass with special reference to blood flow. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Cerebral perfusion during cardiopulmonary bypass with special reference to blood flow
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiopulmonary bypass (CPB) is an important method that enables open heart surgery. There is a risk of neurological complications, and efforts to minimize those include optimization of the cerebral perfusion during CPB. This thesis focuses on such optimization of flow conditions in case of obstructed venous drainage, carotid stenosis and during selective antegrade cerebral perfusion (SACP).

In a pig model of impaired venous drainage from the superior vena cava (SVC), stepwise obstruction increased the central venous pressure (CVP) and caused impaired oxygenation. Cerebral micro-dialysis revealed ischemic responses in some but not all of the pigs.

Further experiments, using the same model, aimed to restore cerebral perfusion pressure (CPP) reduced by 75% superior venous obstruction. Both vasopressor treatment and increased venous drainage were effective in normalizing the CPP and improving the cerebral oxygenation. The intracranial pressure was elevated in the vasopressor group, but no signs of brain damage were observed.

The arterial flow during CPB can be altered between pulsatile and non-pulsatile profiles. Switching between these modes was performed during CPB in 20 patients with or without carotid stenosis. The effects on cerebral oxygenation and mean arterial pressure (MAP) were examined. The MAP was significantly lowered by pulsatile flow, but the flow profile did not affect the cerebral oxygenation. No differences were seen between patients with or without carotid stenosis.

SACP is used to ensure the cerebral perfusion during deep hypothermic circulatory arrest (HCA). The cerebral blood flow (CBF) was examined using positron-emission tomography (PET) technique in 8 pigs divided into HCA and HCA+SACP groups. The CBF was downregulated by 70% to 0.10 ml/cm3/min by 20°C hypothermia. A pump flow of 6 ml/kg/min preserved the CBF level without signs of cerebral desaturation. The fluorodeoxyglucose (FDG) uptake after re-warming to 37°C was similar after SACP compared with HCA alone.

In conclusion, experimental SVC obstruction may impair the cerebral perfusion. Vasopressors can restore the CPP during SVC obstruction and improve cerebral oxygenation. In patients, pulsatile flow can lower the MAP in absence of effects on the cerebral oxygenation. During experimental HCA, SACP at 6 ml/kg/min can preserve the CBF at 0.10 ml/cm3/min.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. p. 61
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1108
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-248686 (URN)978-91-554-9257-1 (ISBN)
Public defence
2015-06-11, Robergsalen, Ingång 40, 4 tr, Akademiska sjukhuset, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2015-05-21 Created: 2015-04-07 Last updated: 2015-07-07Bibliographically approved
Morell, A., Lennmyr, F., Jonsson, O., Tovedal, T., Pettersson, J., Bergquist, J., . . . Bjørnerud, A. (2015). Influence of blood/tissue differences in contrast agent relaxivity on tracer based MR perfusion measurements. Magnetic Resonance Materials in Physics, Biology and Medicine, 28(2), 135-147
Open this publication in new window or tab >>Influence of blood/tissue differences in contrast agent relaxivity on tracer based MR perfusion measurements
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2015 (English)In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 28, no 2, p. 135-147Article in journal (Refereed) Published
Abstract [en]

PURPOSE:

Perfusion assessment by monitoring the transport of a tracer bolus depends critically on conversion of signal intensity into tracer concentration. Two main assumptions are generally applied for this conversion; (1) contrast agent relaxivity is identical in blood and tissue, (2) change in signal intensity depends only on the primary relaxation effect. The purpose of the study was to assess the validity and influence of these assumptions.

MATERIALS AND METHODS:

Blood and cerebral tissue relaxivities r1, r2, and r2* for gadodiamide were measured in four pigs at 1.5 T. Gadolinium concentration was determined by inductively coupled plasma atomic emission spectroscopy. Influence of the relaxivities, secondary relaxation effects and choice of singular value decomposition (SVD) regularization threshold was studied by simulations.

RESULTS:

In vivo relaxivities relative to blood concentration [in s-1 mM-1 for blood, gray matter (GM), white matter (WM)] were for r1 (2.614 ± 1.061, 0.010 ± 0.001, 0.004 ± 0.002), r2 (5.088 ± 0.952, 0.091 ± 0.008, 0.059 ± 0.014), and r2* (13.292 ± 3.928, 1.696 ± 0.157, 0.910 ± 0.139). Although substantial, by a nonparametric test for paired samples, the differences were not statistically significant. The GM to WM blood volume ratio was estimated to 2.6 ± 0.9 by r1, 1.6 ± 0.3 by r2, and 1.9 ± 0.2 by r2*. Secondary relaxation was found to reduce the tissue blood flow, as did the SVD regularization threshold.

CONCLUSION:

Contrast agent relaxivity is not identical in blood and tissue leading to substantial errors. Further errors are introduced by secondary relaxation effects and the SVD regularization.

Keywords
MRI, relaxivity, contrast agent, perfusion
National Category
Radiology, Nuclear Medicine and Medical Imaging Analytical Chemistry
Research subject
Radiology; Medical Radiophysics
Identifiers
urn:nbn:se:uu:diva-170528 (URN)10.1007/s10334-014-0452-5 (DOI)000352149200004 ()
Available from: 2012-03-28 Created: 2012-03-12 Last updated: 2017-12-07Bibliographically approved
Tovedal, T. (2013). Cerebral Perfusion during Cardiopulmonary Bypass. (Licentiate dissertation). Uppsala: Uppsala University, Department of Surgical Sciences
Open this publication in new window or tab >>Cerebral Perfusion during Cardiopulmonary Bypass
2013 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Impaired superior vena cava (SVC) cannula outflow during cardiopulmonary bypass (CPB) is a frequent issue, often manifested by only marginal changes in routine monitoring parameters. Nevertheless, significant impact on cerebral perfusion may result. When detected, remedial actions involve cannula repositioning, raising the operating table, increasing the mean arterial pressure (MAP) and adding vacuum-assisted venous drainage to the CPB system. Increased venous outflow enables increased arterial flow and thereby also increased MAP and cerebral perfusion pressure (CPP). Although representing a common clinical problem, controlled studies on SVC obstruction are few and the phenomenon has not been satisfactorily characterized. This licentiate thesis is based on two animal studies. The first (I) study describes the effects on cerebral perfusion and oxygen saturation by stepwise SVC cannula obstruction in increments of 25% until fully occluded. The second (II) study describes the effects on CPP and cerebral perfusion of two different strategies for dealing with restricted cerebral venous outflow. In Study I, ten pigs during 34 ºC CPB were examined. The animals were divided into two groups receiving either low CPB blood flow (LQ), or normal CPB blood flow (HQ). Cerebral perfusion and oxygen saturation were monitored by blood gases, near-infrared light spectroscopy (NIRS) of tissue oxygen saturation (TOI), and cerebral micro-dialysis. SVC obstruction caused increased CVP and deteriorated cerebral oxygen saturation parameters, but no metabolic effects were detectable at the group level by the micro-dialysis. However, four of ten animals showed a combined pattern of decreased TOI and SVC oxygen saturation along with increased lactate/pyruvate ratio. The phenomenon appeared in both groups and in connection with both obstruction and release of obstruction, indicating the presence of individual sensitivity to impaired cerebral perfusion. CPB tubing flow measurements revealed that the total venous drainage was preserved even with the SVC completely clamped, indicating that the drainage, but not the CVP elevation, could be fully compensated by the inferior vena cava. In Study II, intracranial pressure monitoring, NIRS, and cerebral laser-Doppler flow measurements were used for surveillance along with blood gases and analysis of the glial cellmarker S100ß in sagittal sinus blood. A SVC obstruction of 75% was applied in order to achieve a distinct CPP reduction in fourteen pigs subjected to 34 ºC CPB. Two randomly assigned strategies for restoration of the CPP were examined; vasopressor treatment (VP)and partial release of obstruction (PR) mimicking a successful repositioning of the SVC cannula. Both strategies successfully restored the CPP to baseline levels, without immediate signs of severe ischemia, although intracranial and central pressures remained elevated in the VP group throughout the experiments. The analysis of S100ß showed no signs of brain damage. In conclusion, SVC congestion may impair cerebral perfusion during CPB. Reduced SVC cannula flow may pass undetected during bi-caval CPB due to a compensatory increase in IVC flow. Experimental SVC obstruction during CPB may reduce the CPP, resulting in impaired cerebral perfusion. Both vasopressor therapy and improved venous drainage can in the short term individually restore the CPP during these circumstances.

Place, publisher, year, edition, pages
Uppsala: Uppsala University, Department of Surgical Sciences, 2013
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-204734 (URN)
Presentation
2013-08-27, Klassrummet, Inst f kir vet, Akademiska sjukhuset, ing 70, Uppsala, 14:00 (Swedish)
Supervisors
Available from: 2013-08-14 Created: 2013-08-09 Last updated: 2014-07-24Bibliographically approved
Tovedal, T., Myrdal, G., Jonsson, O., Bergquist, M., Zemgulis, V., Thelin, S. & Lennmyr, F. (2013). Experimental treatment of superior venous congestion during cardiopulmonary bypass. European Journal of Cardio-Thoracic Surgery, 44(3), E239-E244
Open this publication in new window or tab >>Experimental treatment of superior venous congestion during cardiopulmonary bypass
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2013 (English)In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 44, no 3, p. E239-E244Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES:

Superior venous outflow obstruction affects cerebral perfusion negatively by reducing cerebral perfusion pressure (CPP). We present a randomized study designed to compare two alternative strategies to preserve the CPP during superior vena cava (SVC) congestion and cardiopulmonary bypass (CPB).

METHODS:

Fourteen pigs on bi-caval CPB were subjected to 75% occlusion of the SVC flow. CPP was restored either by vasopressor treatment (VP, n = 7) or by partial relief (PR) of the congestion (n = 7). The cerebral effects of the interventions were studied for 60 min with intracranial pressure (ICP) monitoring, cerebral blood flow measurement, the near-infrared light spectroscopy tissue oxygen saturation index (StO2), arterial and venous blood gas analyses and serial measurements of the glial cell damage marker protein S100β.

RESULTS:

Both strategies restored the CPP to baseline levels and no signs of severe ischaemia were observed. In the PR group, the venous and ICPs were normalized in response to the intervention, while in the VP group those parameters remained elevated throughout the experiment. The haemoglobin oxygen saturation in the sagittal sinus (SsagO2) was increased by both VP and PR, while significant improvement in the StO2 was observed only in the PR group. The S100β concentrations were similar in the two groups.

CONCLUSIONS:

Experimental SVC obstruction during CPB may reduce the CPP, resulting in impaired cerebral perfusion. Both vasopressor treatment and improved venous drainage can, in the short term, individually restore the CPP during these circumstances.

Keywords
cerebral protection, cardiopulmonary bypass, venous obstruction
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-199823 (URN)10.1093/ejcts/ezt311 (DOI)000323350400018 ()23766424 (PubMedID)
Available from: 2013-05-15 Created: 2013-05-15 Last updated: 2017-12-06Bibliographically approved
Lubberink, M., Tovedal, T., Morell, A., Golla, S., Estrada, S., Asplund, V., . . . Lennmyr, F. (2012). Measurement of absolute cerebral blood flow during cardiopulmonary bypass and selective cerebral perfusion using [O-15]water and PET. Paper presented at 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM), AUG 09-11, 2012, Baltimore, MD. Journal of Cerebral Blood Flow and Metabolism, 32(S1), S157-S158
Open this publication in new window or tab >>Measurement of absolute cerebral blood flow during cardiopulmonary bypass and selective cerebral perfusion using [O-15]water and PET
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2012 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 32, no S1, p. S157-S158Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-182334 (URN)10.1038/jcbfm.2012.80 (DOI)000307138000164 ()
Conference
9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM), AUG 09-11, 2012, Baltimore, MD
Available from: 2012-10-09 Created: 2012-10-09 Last updated: 2017-12-07Bibliographically approved
Jonsson, O., Morell, A., Zemgulis, V., Lundström, E., Tovedal, T., Myrdal Einarsson, G., . . . Lennmyr, F. (2011). Minimal Safe Arterial Blood Flow During Selective Antegrade Cerebral Perfusion at 20° Centigrade. Annals of Thoracic Surgery, 91(4), 1198-1205
Open this publication in new window or tab >>Minimal Safe Arterial Blood Flow During Selective Antegrade Cerebral Perfusion at 20° Centigrade
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2011 (English)In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 91, no 4, p. 1198-1205Article in journal (Refereed) Published
Abstract [en]

Background

Selective antegrade cerebral perfusion (SACP) enables surgery on the aortic arch, where cerebral ischemia may cause neurologic sequels. This study aims to identify the minimum arterial flow level to maintain adequate cerebral perfusion during SACP in deep hypothermia in the pig.

Methods

Two groups of pigs were subjected to SACP at 20°C α-stat. In group 1 (n = 6), flow was stepwise adjusted from 8-6-4-2-8 mL · kg−1 · min−1 and in group 2 (n = 5), flow was kept constant at 6 mL · kg−1 · min−1. Magnetic resonance imaging and spectroscopy were performed at each flow level together with hemodynamic monitoring and blood gas analysis. The biochemical marker of cerebral damage protein S100β was measured in peripheral blood.

Results

Decreased mixed venous oxygen saturation and increased lactate in magnetic resonance spectroscopy was seen as a sign of anaerobic metabolism below 6 mL · kg−1 · min−1. No ischemic damage was seen on diffusion-weighted imaging, but the concentrations of S100β were significantly elevated in group 1 compared with group 2 at the end of the experiment (p < 0.05). Perfusion-weighted imaging showed coherence between flow setting and cerebral perfusion, increase of blood volume across time, and regional differences in perfusion during SACP.

Conclusions

The findings suggest an ischemic threshold close to 6 mL · kg−1 · min−1 in the present model. Regional differences in perfusion during SACP may be of pathogenic importance to focal cerebral ischemia.

Keywords
cerebral perfusion
National Category
Physiology
Research subject
Thorax Surgery
Identifiers
urn:nbn:se:uu:diva-147480 (URN)10.1016/j.athoracsur.2010.12.066 (DOI)000288785800057 ()21353198 (PubMedID)
Funder
Swedish Research Council, k2010-64x-08268-23-3
Available from: 2011-02-25 Created: 2011-02-25 Last updated: 2018-01-12Bibliographically approved
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