| 1. |
- Broomé, Michael, et al.
(författare)
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Pressure-independent cardiac effects of angiotensin II in pigs.
- 2004
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Ingår i: Acta Anaesthesiol Scand. - 0001-6772 .- 1365-201X. ; 182:2, s. 111-9
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Weinstock, Joshua S, et al.
(författare)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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Ingår i: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 3. |
- Braganca, F. M. Serra, et al.
(författare)
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Improving gait classification in horses by using inertial measurement unit (IMU) generated data and machine learning
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- For centuries humans have been fascinated by the natural beauty of horses in motion and their different gaits. Gait classification (GC) is commonly performed through visual assessment and reliable, automated methods for real-time objective GC in horses are warranted. In this study, we used a full body network of wireless, high sampling-rate sensors combined with machine learning to fully automatically classify gait. Using data from 120 horses of four different domestic breeds, equipped with seven motion sensors, we included 7576 strides from eight different gaits. GC was trained using several machine-learning approaches, both from feature-extracted data and from raw sensor data. Our best GC model achieved 97% accuracy. Our technique facilitated accurate, GC that enables in-depth biomechanical studies and allows for highly accurate phenotyping of gait for genetic research and breeding. Our approach lends itself for potential use in other quadrupedal species without the need for developing gait/animal specific algorithms.
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| 4. |
- Brandsaeter, B., et al.
(författare)
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Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy
- 2004
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Ingår i: Journal of hepatology. - : Elsevier BV. - 0168-8278. ; 40:5, s. 815-22
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Hepatobiliary malignancies are frequently seen in primary sclerosing cholangitis (PSC) and they complicate the evaluation of patients and timing of liver transplantation. METHODS: Data from all Nordic PSC patients listed for liver transplantation during 1990-2001 were recorded prospectively. Predictors of hepatobiliary malignancy and patient survival rates have been analysed. RESULTS: Hepatobiliary malignancy was found in 52/255 (20%) patients accepted to the waiting list. Recent diagnosis of PSC, no ursodeoxycholic acid (UDCA) treatment, clinical suspicion and previous colorectal-cancer were predictors of malignancy. Among 89 patients with a strong suspicion of malignancy prior to acceptance, 35 (39%) had confirmed malignancy. A clinical suspicion had been raised in 35/52 (67%) patients with malignancy. Malignancy was found in 31/223 patients who received a liver allograft. The 1-, 3- and 5-year patient survival rates following transplantation for patients with PSC and cholangiocarcinoma were 65, 35 and 35%, respectively. CONCLUSIONS: Hepatobiliary malignancy is suspected in 1/3 of the PSC patients and found in 1/5. Although cholangiocarcinoma is regarded as a contraindication to liver transplantation (LTX), PSC patients with cholangiocarcinoma had a 35% 5-year survival following transplantation.
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| 5. |
- Broman, Mikael, et al.
(författare)
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Recirculation during veno-venous extra-corporeal membrane oxygenation - a simulation study
- 2015
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Ingår i: International Journal of Artificial Organs. - : SAGE Publications. - 0391-3988 .- 1724-6040. ; 38:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Veno-venous ECMO is indicated in reversible life-threatening respiratory failure without life-threatening circulatory failure. Recirculation of oxygenated blood in the ECMO circuit decreases efficiency of patient oxygen delivery but is difficult to measure. We seek to identify and quantify some of the factors responsible for recirculation in a simulation model and compare with clinical data. Methods: A closed-loop real-time simulation model of the cardiovascular system has been developed. ECMO is simulated with a fixed flow pump 0 to 5 l/min with various cannulation sites -1) right atrium to inferior vena cava, 2) inferior vena cava to right atrium, and 3) superior+ inferior vena cava to right atrium. Simulations are compared to data from a retrospective cohort of 11 consecutive adult veno-venous ECMO patients in our department. Results: Recirculation increases with increasing ECMO-flow, decreases with increasing cardiac output, and is highly dependent on choice of cannulation sites. A more peripheral drainage site decreases recirculation substantially. Conclusions: Simulations suggest that recirculation is a significant clinical problem in veno-venous ECMO in agreement with clinical data. Due to the difficulties in measuring recirculation and interpretation of the venous oxygen saturation in the ECMO drainage blood, flow settings and cannula positioning should rather be optimized with help of arterial oxygenation parameters. Simulation may be useful in quantification and understanding of recirculation in VV-ECMO.
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| 6. |
- Broome, M., et al.
(författare)
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Acute effects of angiotensin II on myocardial performance
- 2001
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 45:9, s. 1147-54
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Broome, M., et al.
(författare)
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Angiotensin II mesenteric and renal vasoregulation : dissimilar modulatory effects with nitroprusside
- 2000
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 44:10, s. 1238-45
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Broome, Michael
(författare)
-
Aplysia CorVascSim
- 2012
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Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Broomé, Michael, et al.
(författare)
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Closed-loop real-time simulation model of hemodynamics and oxygen transport in the cardiovascular system
- 2013
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Ingår i: Biomedical engineering online. - 1475-925X. ; 12:1, s. 69-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Computer technology enables realistic simulation of cardiovascular physiology. The increasing number of clinical surgical and medical treatment options imposes a need for better understanding of patient-specific pathology and outcome prediction. Methods: A distributed lumped parameter real-time closed-loop model with 26 vascular segments, cardiac modelling with time-varying elastance functions and gradually opening and closing valves, the pericardium, intrathoracic pressure, the atrial and ventricular septum, various pathological states and including oxygen transport has been developed. Results: Model output is pressure, volume, flow and oxygen saturation from every cardiac and vascular compartment. The model produces relevant clinical output and validation of quantitative data in normal physiology and qualitative directions in simulation of pathological states show good agreement with published data. Conclusion: The results show that it is possible to build a clinically relevant real-time computer simulation model of the normal adult cardiovascular system. It is suggested that understanding qualitative interaction between physiological parameters in health and disease may be improved by using the model, although further model development and validation is needed for quantitative patient-specific outcome prediction.
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| 10. |
- Broomé, Michael, et al.
(författare)
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Individualized real-time clinical decision support to monitor cardiac loading during venoarterial ECMO
- 2016
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Ingår i: Journal of Translational Medicine. - : BioMed Central. - 1479-5876. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Veno-arterial extracoporeal membrane oxygenation (VA ECMO) is increasingly used for acute and refractory cardiogenic shock. Yet, in clinical practice, monitoring of cardiac loading conditions during VA ECMO can be cumbersome. To this end, we illustrate the validity and clinical applicability of a real-time cardiovascular computer simulation, which allows to integrate hemodynamics, cardiac dimensions and the corresponding degree of VA ECMO support and ventricular loading in individual patients over time.
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| 11. |
- Broome, Michael
(författare)
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MEDIQ CorVascSim
- 2011
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Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Broome, Michael, et al.
(författare)
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Prolonged extracorporeal membrane oxygenation and circulatory support as bridge to lung transplant
- 2008
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 86:4, s. 1357-1360
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 13. |
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| 14. |
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| 15. |
- Broome, Michael
(författare)
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Simulation of Cardiovascular Physiology and Pathology : The Effects of Mitral Regurgitation on Mitral and Pulmonary Venous Flow
- 2004
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The development of simulation models and modern computers makes it possible to simulate both normal cardiovascular physiology and pathology realistically. These models can be used to aid clinicians and researchers in understanding complex phenomenon. Methods: An electrical analogue of the cardiovascular system consisting of resistances, capacitances and inductances has been constructed. The contractile function of the cardiac atria and ventricles area represented by time-varying elastances. Valvular function, pericardial volume, ventricular interaction and intrathoracic pressure are also represented by constants and functions interacting with the rest of the model. Results: A regurgitant mitral orifice of 1 cm2 during systole results in an increased volume load on the left ventricle, a decrease in cardiac output and systemic arterial blood pressures accompanied by an increase in left and right-sided cardiac filling pressures and volumes. A systolic reversal of flow in the pulmonary veins is seen. The magnitude of systolic flow reversal in the pulmonary veins is dependent on left atrial compliance. Conclusion: Simulation of cardiac normal function and pathology is a meaningful way to study the heart. Results from simulations can be used to interpret clinical invasive monitoring and echocardiography data as well as experimental research data. Left atrial compliance may be of importance for interpretation of pulmonary venous flow profiles in mitral regurgitation.
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| 16. |
- Broome, Michael
(författare)
-
Simulation of cardiovascular physiology and pathology with CorVascSim : A PC software for advanced education and research
- 2004
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 17. |
- Broome, Michael, et al.
(författare)
-
Splanchnic vasoconstriction by angiotensin II is arterial pressure dependent
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 46:1, s. 57-63
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 18. |
- Broome, M., et al.
(författare)
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The cardiac effects of intracoronary angiotensin II infusion
- 2002
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Ingår i: Anesthesia and Analgesia. - : Ovid Technologies (Wolters Kluwer Health). - 0003-2999 .- 1526-7598. ; 94:4, s. 787-93, table of contents
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 19. |
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| 20. |
- Broomé, Sara, 1989-
(författare)
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Atlantic Water in the Nordic Seas : A satellite altimetry perspective on ocean circulation
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Atlantic Water in the Nordic Seas contributes to the mild climate of Northern Europe and is the main oceanic source of heat for the Arctic. The northward bound transport of the warm and saline Atlantic Water is mediated by a topographically constrained cyclonic boundary current along the Norwegian continental slope. The analysis within this thesis is based on satellite observations of dynamic Sea Surface Heights (SSH) from 1993 to the recent present, combined with both hydrographic observations and modelling. It provides some new perspectives and results, as well as corroborates the essential role of bottom topography for the circulation in the Nordic Seas.In the first part of the thesis, the topographic constraint is used in the analysis by examining the satellite-derived SSH along topographic contours. We find stationary along-contour anomalies that indicate deviations from strict topographic steering. However, we show that these deviations are dynamically consistent with, and can be explained by, potential vorticity conservation in an adiabatic steady-state model for flow over a topographic slope. The analysis along topographic contours is further developed to study northward-propagating, low-frequency ocean temperature signals. These signals have an expression in the SSH and their propagation speed is remarkably slow compared to the current speed. We propose a conceptual model of shear dispersion effects, in which the effective advection speed of a tracer is determined not only by the rapid current core, but by a mean velocity taken over the cross-flow extent of Atlantic Water. The model predicts a reduced effective tracer advection velocity, comparable to the one observed.The close connection between anomalies in SSH and heat content is further used to study decadal variability in the Nordic Seas. There is a shift in decadal trends in the mid-2000s, from a period of strong increase in SSH and heat content to a more stagnant period. We find this variability to be forced remotely, rather than by local air-sea heat fluxes. By developing a conceptual model of ocean heat convergence, we are able to explain the broad features of the decadal changes with the temperature variability of the inflowing Atlantic Water from the subpolar North Atlantic.In the final part of the thesis, satellite-derived surface geostrophic velocity fields are used as input to a Lagrangian trajectory model. Based on this, we study the fractionation of the Atlantic Water in the Nordic Seas between the two straits towards the Arctic Ocean: the Barents Sea Opening and the Fram Strait. This Lagrangian approach also provides insights on the origin of the water that reach the straits. We find that it is the frontal current branch, rather than the slope current, that contributes to the variability of the Barents Sea Opening inflow of warm Atlantic Water, and thus potentially to the climate of the Barents Sea and its sea ice cover.
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| 21. |
- Donker, D. W., et al.
(författare)
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Echocardiography in extracorporeal life support : A key player in procedural guidance, tailoring and monitoring
- 2018
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Ingår i: Perfusion. - : Sage Publications. - 0267-6591 .- 1477-111X. ; 33:1_suppl, s. 31-41
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Tidskriftsartikel (refereegranskat)abstract
- Extracorporeal life support (ECLS) is a mainstay of current practice in severe respiratory, circulatory or cardiac failure refractory to conventional management. The inherent complexity of different ECLS modes and their influence on the native pulmonary and cardiovascular system require patient-specific tailoring to optimize outcome. Echocardiography plays a key role throughout the ECLS care, including patient selection, adequate placement of cannulas, monitoring, weaning and follow-up after decannulation. For this purpose, echocardiographers require specific ECLS-related knowledge and skills, which are outlined here.
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| 22. |
- Donker, Dirk W., et al.
(författare)
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Left ventricular unloading during veno-arterial ECMO : a review of percutaneous and surgical unloading interventions
- 2019
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Ingår i: Perfusion. - : Sage Publications. - 0267-6591 .- 1477-111X. ; 34:2, s. 98-105
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 23. |
- Donker, Dirk W., et al.
(författare)
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Left Ventricular Unloading During Veno-Arterial ECMO : A Simulation Study
- 2019
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Ingår i: ASAIO journal (1992). - : Lippincott Williams and Wilkins. - 1058-2916 .- 1538-943X. ; 65:1, s. 11-20
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Tidskriftsartikel (refereegranskat)abstract
- Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is widely used in cardiogenic shock. It provides systemic perfusion, but left ventricular (LV) unloading is suboptimal. Using a closed-loop, real-time computer model of the human cardiovascular system, cardiogenic shock supported by peripheral VA ECMO was simulated, and effects of various adjunct LV unloading interventions were quantified. After VA ECMO initiation (4 L/min) in cardiogenic shock (baseline), hemodynamics improved (increased to 85 mm Hg), while LV overload occurred (10% increase in end-diastolic volume [EDV], and 5 mm Hg increase in pulmonary capillary wedge pressure [PCWP]). Decreasing afterload (65 mm Hg mean arterial pressure) and circulating volume (-800 mL) reduced LV overload (12% decrease in EDV and 37% decrease in PCWP) compared with baseline. Additional intra-aortic balloon pumping only marginally decreased cardiac loading. Instead, adjunct Impella T enhanced LV unloading (23% decrease in EDV and 41% decrease in PCWP). Alternative interventions, for example, left atrial/ventricular venting, yielded substantial unloading. We conclude that real-time simulations may provide quantitative clinical measures of LV overload, depending on the degree of VA ECMO support and adjunct management. Simulations offer insights into individualized LV unloading interventions in cardiogenic shock supported by VA ECMO as a proof of concept for potential future applications in clinical decision support, which may help to improve individualized patient management in complex cardiovascular disease.
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| 24. |
- Frenckner, B., et al.
(författare)
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Platelet-derived growth factor inhibition : a new treatment of pulmonary hypertension in congenital diaphragmatic hernia?
- 2008
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 43:10, s. 1928-1931
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 25. |
- Holzgraefe, B., et al.
(författare)
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Extracorporeal membrane oxygenation for pandemic H1N1 2009 respiratory failure
- 2010
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Ingår i: Minerva Anestesiologica. - 0375-9393 .- 1827-1596. ; 76:12, s. 1043-1051
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 26. |
- Larsson, M., et al.
(författare)
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Experimental extracorporeal membrane oxygenation reduces central venous pressure : an adjunct to control of venous hemorrhage?
- 2010
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Ingår i: Perfusion. - : SAGE Publications. - 0267-6591 .- 1477-111X. ; 25:4, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 27. |
- Lindfors, M., et al.
(författare)
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Venous Cannula Positioning in Arterial Deoxygenation During Veno-Arterial Extracorporeal Membrane Oxygenation-A Simulation Study and Case Report
- 2016
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Ingår i: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594.
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Tidskriftsartikel (refereegranskat)abstract
- Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is indicated in reversible life-threatening circulatory failure with or without respiratory failure. Arterial desaturation in the upper body is frequently seen in patients with peripheral arterial cannulation and severe respiratory failure. The importance of venous cannula positioning was explored in a computer simulation model and a clinical case was described. A closed-loop real-time simulation model has been developed including vascular segments, the heart with valves and pericardium. ECMO was simulated with a fixed flow pump and a selection of clinically relevant venous cannulation sites. A clinical case with no tidal volumes due to pneumonia and an arterial saturation of below 60% in the right hand despite VA-ECMO flow of 4 L/min was described. The case was compared with simulation data. Changing the venous cannulation site from the inferior to the superior caval vein increased arterial saturation in the right arm from below 60% to above 80% in the patient and from 64 to 81% in the simulation model without changing ECMO flow. The patient survived, was extubated and showed no signs of hypoxic damage. We conclude that venous drainage from the superior caval vein improves upper body arterial saturation during veno-arterial ECMO as compared with drainage solely from the inferior caval vein in patients with respiratory failure. The results from the simulation model are in agreement with the clinical scenario.
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| 28. |
- Maksuti, Elira, et al.
(författare)
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Cardiac remodeling in aortic and mitral valve disease : a simulation study with clinical validation
- 2019
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Ingår i: Journal of Applied Physiology. - Stockholm : Karolinska Institutet, Dept of Physiology and Pharmacology. - 8750-7587 .- 1522-1601.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Remodeling is an important long-term determinant of cardiac function throughout the progression of heart disease. Numerous biomolecular pathways for mechanosensing and transduction are involved. However, we hypothesize that biomechanical factors alone can explain changes in myocardial volume and chamber size in valve disease. Methods: A validated model of the human vasculature and the four cardiac chambers was used to simulate aortic stenosis, mitral regurgitation and aortic regurgitation. Remodeling was simulated with adaptive feedback preserving myocardial fiber stress and wall shear stress in all four cardiac chambers. Briefly, the model used myocardial fiber stress to determine wall thickness and cardiac chamber wall shear stress to determine chamber volume. Results: Aortic stenosis resulted in the development of concentric left ventricular hypertrophy. Aortic and mitral regurgitation resulted in eccentric remodeling and eccentric hypertrophy, with more pronounced hypertrophy for aortic regurgitation. Comparisons with published clinical data showed the same direction and similar magnitudes of changes in end-diastolic volume index and left ventricular diameters. Changes in myocardial wall volume and wall thickness were within a realistic range both in stenotic and regurgitant valvular disease. Conclusions: Simulations of remodeling in left-sided valvular disease support, in both a qualitative and quantitative manner, that left ventricular chamber size and hypertrophy are primarily determined by preservation of wall shear stress and myocardial fiber stress.
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| 29. |
- Maksuti, Elira, et al.
(författare)
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Contribution of the Arterial System and the Heart to Blood Pressure during Normal Aging : A Simulation Study
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- During aging, systolic blood pressure continuously increases over time, whereas diastolic pressure first increases and then slightly decreases after middle age. These pressure changes are usually explained by changes of the arterial system alone (increase in arterial stiffness and vascular resistance). However, we hypothesise that the heart contributes to the age-related blood pressure progression as well. In the present study we quantified the blood pressure changes in normal aging by using a Windkessel model for the arterial system and the time-varying elastance model for the heart, and compared the simulation results with data from the Framingham Heart Study. Parameters representing arterial changes (resistance and stiffness) during aging were based on literature values, whereas parameters representing cardiac changes were computed through physiological rules (compensated hypertrophy and preservation of end-diastolic volume). When taking into account arterial changes only, the systolic and diastolic pressure did not agree well with the population data. Between 20 and 80 years, systolic pressure increased from 100 to 122 mmHg, and diastolic pressure decreased from 76 to 55 mmHg. When taking cardiac adaptations into account as well, systolic and diastolic pressure increased from 100 to 151 mmHg and decreased from 76 to 69 mmHg, respectively. Our results show that not only the arterial system, but also the heart, contributes to the changes in blood pressure during aging. The changes in arterial properties initiate a systolic pressure increase, which in turn initiates a cardiac remodelling process that further augments systolic pressure and mitigates the decrease in diastolic pressure.
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| 30. |
- Maksuti, Elira, 1986-, et al.
(författare)
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Hydraulic forces contribute to left ventricular diastolic filling
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Myocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75-100% of diastole. The hydraulic force was the same order of magnitude as the peak driving force of LV (1-3N vs 5-10N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the resulting hydraulic forces, should be considered when characterizing diastolic function and dysfunction.
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| 31. |
- Maksuti, Elira, et al.
(författare)
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Hydraulic forces contribute to left ventricular diastolic filling
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7, s. 43505-43505
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75-100% of diastole. The hydraulic force was estimated to be 10-60% of the peak driving force of LV filling (1-3 N vs 5-10 N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the associated hydraulic force, should be considered when characterizing diastolic function and dysfunction.
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| 32. |
- Maksuti, Elira, 1986-
(författare)
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Imaging and modeling the cardiovascular system
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Understanding cardiac pumping function is crucial to guiding diagnosis, predicting outcomes of interventions, and designing medical devices that interact with the cardiovascular system. Computer simulations of hemodynamics can show how the complex cardiovascular system is influenced by changes in single or multiple parameters and can be used to test clinical hypotheses. In addition, methods for the quantification of important markers such as elevated arterial stiffness would help reduce the morbidity and mortality related to cardiovascular disease.The general aim of this thesis work was to improve understanding of cardiovascular physiology and develop new methods for assisting clinicians during diagnosis and follow-up of treatment in cardiovascular disease. Both computer simulations and medical imaging were used to reach this goal.In the first study, a cardiac model based on piston-like motions of the atrioventricular plane was developed. In the second study, the presence of the anatomical basis needed to generate hydraulic forces during diastole was assessed in heathy volunteers. In the third study, a previously validated lumped-parameter model was used to quantify the contribution of arterial and cardiac changes to blood pressure during aging. In the fourth study, in-house software that measures arterial stiffness by ultrasound shear wave elastography (SWE) was developed and validated against mechanical testing.The studies showed that longitudinal movements of the atrioventricular plane can well explain cardiac pumping and that the macroscopic geometry of the heart enables the generation of hydraulic forces that aid ventricular filling. Additionally, simulations showed that structural changes in both the heart and the arterial system contribute to the progression of blood pressure with age. Finally, the SWE technique was validated to accurately measure stiffness in arterial phantoms.
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| 33. |
- Maksuti, Elira, et al.
(författare)
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Modelling the heart with the atrioventricular plane as a piston unit
- 2015
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Ingår i: Medical Engineering and Physics. - : Elsevier BV. - 1350-4533 .- 1873-4030. ; 37:1, s. 87-92
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Tidskriftsartikel (refereegranskat)abstract
- Medical imaging and clinical studies have proven that the heart pumps by means of minor outer volume changes and back-and-forth longitudinal movements in the atrioventricular (AV) region. The magnitude of AV-plane displacement has also shown to be a reliable index for diagnosis of heart failure. Despite this, AV-plane displacement is usually omitted from cardiovascular modelling. We present a lumped-parameter cardiac model in which the heart is described as a displacement pump with the AV plane functioning as a piston unit (AV piston). This unit is constructed of different upper and lower areas analogous with the difference in the atrial and ventricular cross-sections. The model output reproduces normal physiology, with a left ventricular pressure in the range of 8-130 mmHg, an atrial pressure of approximatly 9 mmHg, and an arterial pressure change between 75 mmHg and 130 mmHg. In addition, the model reproduces the direction of the main systolic and diastolic movements of the AV piston with realistic velocity magnitude (similar to 10 cm/s). Moreover, changes in the simulated systolic ventricular-contraction force influence diastolic filling, emphasizing the coupling between cardiac systolic and diastolic functions. The agreement between the simulation and normal physiology highlights the importance of myocardial longitudinal movements and of atrioventricular interactions in cardiac pumping.
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| 34. |
- Maksuti, Elira, 1986-, et al.
(författare)
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Physical modeling of the heart with the atrioventricular plane as a piston unit
- 2013
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Cardiac models do not often take the atrioventricular (AV) interactioninto account, even though medicalimaging and clinical studies have shown that the heart pumps with minorouter volume changes throughout the cardiac cycle and with backand forthlongitudinal movements in the AVregion. We present a novel cardiac model based on physical modeling of the heart withthe AV-plane asa piston unit. Model simulationsgeneratedrealistic outputsforpressures and flows as well asAV-piston velocity, emphasizing the relevance of myocardial longitudinal movements in cardiac function
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| 35. |
- Steding-Ehrenborg, Katarina, et al.
(författare)
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Hydraulic force is a novel mechanism of diastolic function which may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF
- 2021
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 130:4, s. 993-1000
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A hydraulic force generated by blood moving the atrio-ventricular plane is a novel mechanism of diastolic function. The direction and magnitude of the force is dependent on the geometrical relationship between the left atrium and ventricle and is measured as the short-axis atrio-ventricular area difference (AVAD). In short, the net hydraulic force acts from a larger area towards a smaller. It is currently unknown how cardiac remodeling affects this mechanism. The aim of the study was therefore to investigate this diastolic mechanism in patients with pathological or physiological remodeling.METHODS: 70 subjects (n=11 heart failure with preserved ejection fraction (HFpEF), n=10 heart failure with reduced ejection fraction (HFrEF), n=7 signs of isolated diastolic dysfunction, n=10 hypertrophic cardiomyopathy (HCM), n=10 cardiac amyloidosis, n=18 triathletes and n=14 controls) were included. Subjects underwent Cardiac MR and short-axis images of the left atrium and ventricle were delineated. AVAD was calculated as ventricular area minus atrial area and used as an indicator of net hydraulic force.RESULTS: At the onset of diastole, AVAD in HFpEF was median -9.2 cm2 versus -4.4 cm2 in controls, p=0.02). The net hydraulic force was directed towards the ventricle for both, but larger in HFpEF. HFrEF was the only group with a positive median value 11.6 cm2 and net hydraulic force was throughout diastole directed towards the atrium.CONCLUSION: The net hydraulic force may impede cardiac filling throughout diastole in HFpEF, worsening diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles and aid ventricular filling.
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| 36. |
- Sundbom, Per, 1981-
(författare)
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Acoustic and afterload evaluation of left ventricular assist devices
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Heart Failure is a serious condition with consequences not only for the individual patient but also for the society with a 5-year mortality rate of 45-60%, and a substantial economic burden. The estimated prevalence in Sweden is 2.2% and the age adjusted prevalence increases with higher age. The fundamental treatment for heart failure is pharmaceutical in combination with life-style changes, and physiotherapy. For patients with advanced heart failure, the use of long-term circulatory support can be an option as a bridge to transplantation, or as destination therapy. However, this treatment entails a risk of multiple adverse events. The incidence of pump thrombosis increased as a clinical problem in 2012 and the need for diagnostic methods were desired. The aim of this thesis was to develop and to evaluate the use of a mock loop circuit to study the acoustics of left ventricular assist devices, to evaluate different recording devices and to study the effect of afterload on pump function.Methods: Two different mock loops, with the possibility to insert artificial thrombus and to adjust preload and afterload were created to facilitate recording of the left ventricular assist devices. An iPhone/iPodTM was used as recording device since remote monitoring is desirable. The sounds from HeartMate IITM during different conditions were studied. The iPhone/iPod was evaluated in comparison to dedicated recording equipment, and the mock loop recordings to clinical situation. The sound from HeartMate 3TM was studied, compared between in vivo and in vitro recordings, and the use of an electronic stethoscope was evaluated. The impact of afterload on left ventricular assist devices was studied in a mock loop circuit with different changes in preload and afterload.Results: Mock loop circuit is a promising method to safely change the surrounding conditions as the pump is working. The sound from both HeartMate IITM and HeartMate 3TM can be recorded and analyzed in frequency and time domain. When inserting artificial thrombus in a HeartMate IITM the frequency spectrum is altered. The use of dedicated recording devices is superior to both electronic stethoscope and iPhone/iPodTM, but these handheld devices can be used in clinical settings. The recordings from mock loop circuit and patients appear similar for both HeartMate IITM and HeartMate 3TM. The flow of the devices is affected by the afterload. The HeartMate 3TM is more resistant to increased clot analogs within the pump. For both pumps, best efficacy is seen for clean circuits. The flow rate from the monitor might be misleading since the measured flow rate and the flow rate from monitor can differ due to surrounding conditions. The estimated flow might be adjusted by fitting a parabolic curve.Conclusion: The use of mock loop circuit to study both flow and sound under different conditions is valid. It is possible to record and study the sound from both HeartMate IITM and HeartMate 3TM. The sound holds information of pump function and appears similar in vivo and in vitro. All recording devices can be used, but dedicated equipment is superior to the more handheld devices, although these might have a function as a screening device. The flow measurement on the monitor might not be valid and optimization of fluid status and afterload can further increase pump efficiency.
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| 37. |
- Sundeman, H., et al.
(författare)
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Effects of desflurane on the pig intestinal circulation during hypotension
- 1999
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 43:10, s. 1069-77
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 38. |
- Sundeman, H., et al.
(författare)
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The effects of desflurane on cardiac function as measured by conductance volumetry in swine
- 1998
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Ingår i: Anesthesia and Analgesia. - : Ovid Technologies (Wolters Kluwer Health). - 0003-2999 .- 1526-7598. ; 87:3, s. 522-8
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Tidskriftsartikel (refereegranskat)abstract
- 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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