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- Axelsson, Birger, 1957-
(författare)
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Cardiac effects of non-adrenergic inotropic drugs : clinical and experimental studies
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Myocardial failure and dysfunction is not uncommon during critical illness and following cardiac surgery. For optimal treatment, a better understanding of the effects of inotropic drugs is needed. In this thesis, two non-adrenergic mediated inotropes, milrinone and levosimendan were studied in different models of myocardial dysfunction. The study aims were to assess the following: the effects of milrinone on blood flow in coronary artery bypass grafts during CABG surgery; the effects of milrinone on left ventricular diastolic function during post-ischaemic myocardial dysfunction; whether milrinone or levosimendan are protective or injurious during acute myocardial ischaemia, and if levosimendan potentiates myocardial function when added to milrinone in an experimental model of post-ischaemic (stunned) myocardium.Material and Methods: In Study I, 44 patients undergoing coronary artery bypass surgery(CABG) were included as subjects. Milrinone or saline was administrated in a single dose during cardio-pulmonary bypass (CPB) and coronary graft flow measurements were recorded after 10 and 30 min following CPB. In Study II; 24 patients undergoing CABG had estimations of peak ventricular filling rates made before and after CPB with administration of milrinone or saline as a single dose during CPB, performed by assessment of the rate of change in diastolic cross-sectional left ventricular area. In Study III, energy-metabolic effects of milrinone and levosimendan were measured in an anaesthetized porcine model during 45 minutes of regional myocardial ischemia. Microdialysis sampling of metabolites of local ischemic metabolism allowed assessment of glycolytic activity and the degree of myocardial calcium overload. In Study IV, in a porcine model of postischaemic myocardial stunning, ventricular pressure-volume relationships were analyzed when milrinone or a combination of milrinone and levosimendan were given together.Results: In Study I, there was a clear increase in non-sequential saphenous vein graft blood flow with milrinone at 10 minutes (64.5 ± 37.4 compared to placebo 43.6 ± 25.7 ml/min (mean ± SD).). A decreasing but still measureable flow increase was seen for milrinone at 30 minutes. In Study II, an increase in early left ventricular filling rate (ventricular cross-sectional area rate of change,dA/dt) was seen in the milrinone treated group. Pre-bypass milrinone group dA/dt 22.0 ± 9.5 changed to post-bypass values dA/dt 27.8 ± 11.5 cm2/sec). Placebo group pre-bypass dA/dt was 21.0 ± 8.7 and post-bypass 17.1 ± 7.1 cm2/sec. A milrinone effect was demonstrated in an adjusted regression model (p = 0.001). In Study III, neither milrinone nor levosimendan led to a change in energy-metabolic activity during ischemia as reflected by interstitial glucose, pyruvate, lactate orglycerol. Neither drug exacerbated the relative myocardial calcium overload during ischemia. In Study IV, milrinone improved active relaxation (tau) in post-ischemic stunned myocardium, but did not markedly improve systolic function by preload recruitable stroke work. Levosimendan added to milrinone showed minimal effect on active relaxation but a positive effect on systolic function in combination with milrinone.Conclusions: We conclude that milrinone treatment leads to an increase in blood flow in newly implanted coronary saphenous vein grafts, and improves ventricular relaxation post-cardiopulmonary bypass. Neither milrinone nor levosimendan, in this porcine model, negatively influence myocardial energy metabolism or calcium overload during acute ischaemia. Addition of levosimendan to milrinone treatment during post-ischaemic ventricular dysfunction may provide additive inotropic effects on systolic function but probably not for active relaxation.
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| 2. |
- Abrahamsson, Pernilla, 1972-
(författare)
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Methodological aspects on microdialysis sampling and measurements
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The microdialysis (MD) technique is widely spread and used both experimentally and in clinical practice. The MD technique allows continuous collection of small molecules such as glucose, lactate, pyruvate and glycerol. Samples are often analysed using the CMA 600 analyser, an enzymatic and colorimetric analyser. Data evaluating the performance of the CMA 600 analysis system and associated sample handling are sparse. The aim of this work was to identify sources of variability related to handling of microdialysis samples and sources of error associated with use of the CMA 600 analyser. Further, to develop and compare different application techniques of the microdialysis probes both within an organ and on the surface of an organ. Material and Methods: Papers I and II are mainly in vitro studies with the exception of the No Net Flux calibration method in paper I where a pig model (n=7) was used to examine the true concentration of glucose and urea in subcutaneous tissue. Flow rate, sampling time, vial and caps material and performance of the analyser device (CMA 600) were examined. In papers III and IV normoventilated anaesthetised pigs (n=33) were used. In paper III, heart ischemia was used as intervention to compare microdialysis measurements in the myocardium with corresponding measurements on the heart surface. In paper IV, microdialysis measurements in the liver parenchyma were compared with measurements on the liver surface in association with induced liver ischemia. All animal studies were approved by the Animal Experimental Ethics Committee at Umeå University Sweden. Results: In paper I we succeeded to measure true concentrations of glucose (4.4 mmol/L) and Urea (4.1 mmol/L) in subcutaneous tissue. Paper II showed that for a batch analyse of 24 samples it is preferred to store microdialysis samples in glass vials with crimp caps. For reliable results, samples should be centrifuged before analysis. Paper III showed a new application area for microdialysis sampling from the heart, i.e. surface sampling. The surface probe and myocardial probe (in the myocardium) showed a similar pattern for glucose, lactate and glycerol during baseline, short ischemic and long ischemic interventions. In paper IV, a similar pattern was observed as in paper III, i.e. data obtained from the probe on the liver surface showed no differences compared with data from the probe in liver parenchyma for glucose, lactate and glycerol concentrations during baseline, ischemic and reperfusion interventions. Conclusion: The MD technique is adequate for local metabolic monitoring, but requires methodological considerations before starting a new experimental serie. It is important to consider factors such as flow rate, sampling time and handling of samples in association with the analysis device chosen. The main finding in this thesis is that analyses of glucose, lactate and glycerol in samples from the heart surface and liver surface reflect concentrations sampled from the myocardium and liver parenchyma, respectively.
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| 3. |
- Hylander, Johan, 1986-
(författare)
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Prehospital medical management in Swedish road tunnel incidents
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The complexity of modern road tunnel systems may delay an efficient rescue effort. Capable decision-making is needed to limit time to care. The Swedish ambulance commander, responsible for the on-scene ambulance personnel, may lack education and experience from managing road tunnel incidents. Their competence is sometimes questioned by fellow emergency services commanders. Such marginalization may obscure the medical focus and give the ambulance commander a subservient role. The ambulance commander’s role and lack of knowledge need to be explored and addressed to potentially improve their competence in managing road tunnel incidents.Aim: The overall aim of this thesis was to explore the possibilities of strengthening the decision-making ability of ambulance commanders to create more efficient rescue efforts in road tunnel incidents.Methods: In studies I and II, interviews were conducted with ambulance commanders (n=18) in Norway and Sweden concerning their experience in managing real and simulated road tunnel incidents. In study III, interviews were conducted with participants (n=19) from organizations that collaborates with the Swedish ambulance services in road tunnel incidents, about their opinions on how the ambulance commanders can improve their incident management. In study IV, an e- learning course was created based on the findings of studies I–III. The course influence on the ambulance commander’s ability to make decisions in road tunnel incidents was tested through an intervention study (n=20) which contained two simulations of major road tunnel incidents.Results: In study I, the requirement of familiarity with the tunnel system and involved organizations tasks were highlighted as important for the Norwegian ambulance commanders in their leadership role. In study II, the Swedish ambulance commanders described their leadership role as greater than that at the incident site, e.g., caring for their colleagues and being proactive, although having limited time allocated for these tasks. Findings from study III highlighted the importance of risk management and a shared terminology when responding to road tunnel incidents to avoid time-consuming misunderstandings. In study IV, the main finding was that none of the participants entered the dual- tube road tunnel correctly at the early stage of an incident. Secondly, theiiie-learning course did not significantly impact the ambulance commanders decision-making capabilities.Conclusion: The resilience of ambulance services to road tunnel incidents requires a knowledgeable and decisive ambulance commander. Inter- and intraorganizational obstacles limit the ambulance commander to become familiar with the tunnel environment, generating ambiguous decision-making. Tailored assessment methods and educational material may improve the ambulance commander situational awareness. Findings also indicate that the ambulance services command structure may be less than optimal in its current form. A senior ambulance commander, hierarchically equal to corresponding emergency services command structures, could possibly strengthen prehospital medical management in unfamiliar and complex settings such as the currently studied.
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| 4. |
- Shahgaldi, Kambiz, 1978-
(författare)
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Assessment of Left Ventricular Function and Hemodynamics Using Three-dimensional Echocardiography
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Left ventricular (LV) volumes and ejection fraction (EF) are important predictors of cardiac morbidity and mortality. LV volumes provide valuable prognostic information which isparticularly useful in the selection of therapy or determination of the optimal time for surgery. Two-dimensional (2D) echocardiography is the most widely used non-invasive method forassessment of cardiac function, 2D echocardiography has however several limitations inmeasuring LV volumes and EF since the formulas for quantifications are based on geometricalassumptions. Three-dimensional (3D) echocardiography has been available for almost twodecades, although the use of this modality has not gained wide spread acceptance. 3D echocardiography can overcome the above mentioned limitation in LV volume and EF evaluation since it is not based on geometrical assumption. 3D echocardiography has been shownin several studies to be more accurate and reproducible with low inter- and intraobservervariability in comparison to 2D echocardiography regarding the measurements of LV volumesand EF. The overall aim of the thesis was to evaluate the feasibility and accuracy of 3D echocardiography based-methods in the clinical context. In Study I the feasibility of 3D echocardiography was investigated for determination of LV volumes and EF using parasternal, apical and subcostal approaches. The study demonstrated that the apical 3D echocardiography view offers superior visualization. Study II tested the possibility of creating flow-volume loops to differentiate patients with valvular abnormalities from normal subjects. There were significant differences in the pattern from flow-volume loops clearly separating the groups. In Study III the visual estimation, “eyeballing” of EF was evaluated with two- and tri-plane echocardiography in comparison to quantitative 3D echocardiography. The study confirmed that an experienced echocardiographer can, with a high level of agreement estimate EF both with two- and tri-plane echocardiography. Study IV exposed the high accuracy of stroke volume and cardiac output determination using a3D biplane technique by planimetrically tracing the left ventricular outflow tract and indicating that an assumption of circular left ventricular outflow tract is not reliable. In Study V, two 3D echocardiography modalities, single-beat and four-beat ECG-gated 3D echocardiography were evaluated in patients having sinus rhythm and atrial fibrillation. Thesingle-beat technique showed significantly lower inter-and intraobserver variability in LV volumes and EF measurements in patients having atrial fibrillation in comparison to four-beat ECG-gated acquisition due to absence of stitching artifact. All studies demonstrated good results suggesting 3D echocardiography to be a feasible andaccurate method in daily clinical settings.
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| 5. |
- Söderqvist, Emil, 1972-
(författare)
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New approaches to monitoring of cardiac function
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Left ventricular pumping performance may be described by intraventricular pressure and volume variables, usually presented as a pressure-volume plot. However, on-line monitoring of left ventricular pressure and volume with high temporal resolution requires the use of an invasive catheter technique such as, for example, the conductance catheter method. On the other hand, the very invasiveness and complexity of this approach makes it less suitable for clinical use. It is then not surprising that there has been long-felt need to make the conductance method less invasive and attempts have been made to adjust the method to clinical demands and routine in order to extract more information from pressure-volume interplay and possibly translate relevant data to their non-invasive estimates. In the present studies, a standard five segmental conductance catheter was used in animal (pig) experiments. Segmental conductances were compared to global conductance. Since the mid-ventricular segment was shown to reflect global volume, which was also shown on theoretical basis, it was concluded that a single segmental catheter most probably could be used to estimate global left ventricular volume. Subsequently, a thin and flexible single segmental conductance catheter was constructed and applied to an animal (pig) experimental model. Results were reproducible and very few arrythmias were detected. At the next stage, left ventricular isovolumic phases were investigated using the standard conductance catheter method, as well as echocardiographically derived tissue velocity doppler. Conductance was shown to decrease during isovolumic contraction, and an adjustment method was proposed in order to account for the subsequent decrease in pressure-volume loop area. In separate experiments, the left ventricular pressure wave form during left ventricular systole was examined, and an algorithm was proposed to discriminate between the changes in afterload, preload and contractility. Results showed clearly discernible patterns of the respective load and contractility alternation. Finally, the left ventricular continuous area was monitored continuously during the entire cardiac cycle as a measure of left ventricular volume dynamics in normal subjects and three patients with left ventricular abnormalities using echocardiographic automatic boundary detection. The left ventricular area thus obtained was plotted against its first derivative, to form a flow-volume estimates loop, in accordance with the flow-volume examinations used in respiratory physiology. Data obtained from the abnormal ventricles were presented as flow-volume estimates loops, exemplifying the possible use of the method.
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