| 1. |
- Axelsson, Karl-Jonas, et al.
(författare)
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Adaptation of ventricular repolarization time following abrupt changes in heart rate: comparisons and reproducibility of repeated atrial and ventricular pacing.
- 2021
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 320:1
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Tidskriftsartikel (refereegranskat)abstract
- Adequate adaptation of ventricular repolarization (VR) duration to changes in heart rate (HR) is important for cardiac electromechanical function and electrical stability. We studied the QT and QTpeak adaptation in response to abrupt start and stop of atrial and ventricular pacing on two occasions with an interval of at least 1 mo in 25 study subjects with permanent pacemakers. Frank vectorcardiography was used for data collection. Atrial or ventricular pacing was performed for 8min aiming at a cycle length (CL) of 500ms. We measured the immediate response (IR), the time constant (τ) of the exponential phase, and T90 End, the time to reach 90% change of QT and QTpeak from baseline to steady state during and after pacing. During atrial pacing, the CL decreased on average 45% from mean (SD) 944 (120) to 518 (46) ms and QT decreased on average 18% from 388 (20) to 318 (17) ms. For QT, T90 End was 103 (24) s and 126 (15) s after start versus stop of atrial pacing; a difference of 24 (27) s (P = 0.006). The response pattern was similar for τ but IR did not differ significantly between pacing start and stop. The response pattern was similar for QTpeak and also for QT and QTpeak following ventricular pacing start and stop. The coefficients of variation for repeated measures were 7%-21% for T90 End and τ. In conclusion, the adaptation of VR duration was significantly more rapid following increasing than decreasing HR and intraindividually a relatively reproducible process.NEW & NOTEWORTHY We studied the duration of ventricular repolarization (VR) adaptation and its hysteresis, following increasing and decreasing heart rate by abrupt start and stop of 8-min atrial or ventricular pacing in study subjects with permanent pacemakers and repeated the protocol with ≥1 mo interval, a novel approach. VR adaptation was significantly longer following decreasing than increasing heart rate corroborating previous observations. Furthermore, VR adaptation was intraindividually a reproducible and, hence, robust phenomenon, a novel finding.
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| 2. |
- Bergfeldt, Lennart, 1950, et al.
(författare)
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Non-invasive electrophysiological differences between women and men:differences in body size not an explanation.
- 2022
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 323:5
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Tidskriftsartikel (refereegranskat)abstract
- There are numerous sex-related differences in cardiac electrophysiology and arrhythmia propensity but very little knowledge about the reasons. Difference in body size has been proposed as one reason and was tested in this study of >20 cardiac electrophysiology parameters in 319 (158 women) apparently healthy 50-64 years old subjects from a randomly enrolled population sample, the SCAPIS pilot study (Swedish CArdio-Pulmonary bioImaging Study), using Frank vectorcardiography. We studied conventional conduction intervals, parameters reflecting electrical heterogeneity (dispersion) in the ventricles, QRS- and T-vector directions, spatial QRS-T angles, and T-vector loop morphology. Body surface area (BSA; two methods) and lean body mass (LBM), both estimated from body weight and height, were used as body size parameters. According to multivariable linear regression analysis adjusted for sex, there was no association between electrophysiological parameters and body size apart from QRS duration and QRSarea. In conclusion, most electrophysiological parameters assessed completely non-invasively and showing statistically significant differences between women and men on the group level show no association with BSA or LBM. Scaling (indexing) the electrophysiological parameters for body size parameters are therefore not an option. As a consequence, the explanation for the sex-related electrophysiological differences should be sought along other lines.
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| 3. |
- Bondesson, Johan, 1991, et al.
(författare)
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Quantification of True Lumen Helical Morphology and Chirality in Type B Aortic Dissections
- 2021
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 320:2, s. H901-H911
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Tidskriftsartikel (refereegranskat)abstract
- Chirality is a fundamental property in many biologic systems. Motivated by previous observations of helical aortic blood flow, aortic tissue fibers, and propagation of aortic dissections, we introduce methods to characterize helical morphology of aortic dissections. After validation on computer generated phantoms, the methods were applied to patients with type B dissection. For this cohort, there was a distinct bimodal distribution of helical propagation of the dissection with either achiral or exclusively right-handed chirality, with no intermediate cases or left-handed cases. This clear grouping indicates that dissection propagation favors these two modes, potentially due to the right-handedness of helical aortic blood flow and cell orientation. The characterization of dissection chirality and quantification of helical morphology advances our understanding of dissection pathology and lays a foundation for applications in clinical research and treatment practice. For example, the chirality and magnitude of helical metrics of dissections may indicate risk of dissection progression, help define treatment and surveillance strategies, and enable development of novel devices that account for various helical morphologies.
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| 4. |
- Bondesson, J., et al.
(författare)
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Quantification of true lumen helical morphology and chirality in type B aortic dissections
- 2021
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Ingår i: American Journal of Physiology-Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 320:2
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Tidskriftsartikel (refereegranskat)abstract
- Chirality is a fundamental property in many biological systems. Motivated by previous observations of helical aortic blood flow, aortic tissue fibers, and propagation of aortic dissections, we introduce methods to characterize helical morphology of aortic dissections. After validation on computer-generated phantoms, the methods were applied to patients with type B dissection. For this cohort, there was a distinct bimodal distribution of helical propagation of the dissection with either achiral or exclusively right-handed chirality, with no intermediate cases or left-handed cases. This clear grouping indicates that dissection propagation favors these two modes, which is potentially due to the right-handedness of helical aortic blood flow and cell orientation. The characterization of dissection chirality and quantification of helical morphology advances our understanding of dissection pathology and lays a foundation for applications in clinical research and treatment practice. For example, the chirality and magnitude of helical metrics of dissections may indicate risk of dissection progression, help define treatment and surveillance strategies, and enable development of novel devices that account for various helical morphologies. NEW & NOTEWORTHY A novel definition of helical propagation of type B aortic dissections reveals a distinct bimodality, with the true lumen being either achiral (nonhelical) or exclusively right-handed. This right-handed chirality is consistent with anatomic and physiological phenomena such as right-handed twist during left ventricle contraction, helical blood flow, and tissue fiber direction. The helical character of aortic dissections may be useful for pathology research, diagnostics, treatment selection, therapeutic durability prediction, and aortic device design.
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| 5. |
- Bryl-Górecka, Paulina, et al.
(författare)
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Microvesicles in plasma reflect coronary flow reserve in patients with cardiovascular disease.
- 2021
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 320:5
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Tidskriftsartikel (refereegranskat)abstract
- High levels of microvesicles (MVs), a type of extracellular vesicles, are detected in several pathological conditions. We investigated the connection between coronary flow reserve (CFR), a prognostic clinical parameter that reflects blood flow in the heart, with levels of MVs and their cargo, from plasma of cardiovascular patients. The PROFLOW study consists of 220 patients with prior myocardial infarction and measured CFR with transthoracic echocardiography. The patients were divided into high and low CFR groups. Plasma MVs were captured with acoustic trapping. Platelet and endothelial-derived MVs were measured with flow cytometry and MV lysates were analyzed with proteomic panels against cardiovascular biomarkers. Flow cytometry was further applied to identify cellular origin of biomarkers. Our data shows a negative correlation between MV concentration and CFR values. Platelet and endothelial MV levels were significantly increased in plasma from the low CFR group. CFR negatively correlates with the levels of several proteomic biomarkers and the low CFR group exhibited higher concentrations of these proteins in MVs. Focused analysis of one of the MV proteins, B Cell Activating Factor (BAFF), revealed platelet and not leukocyte origin and release upon proinflammatory stimulus. Higher levels of MVs carrying an elevated concentration of proatherogenic proteins, circulate in plasma in patients with low CFR, a marker of vascular dysfunction, reduced blood flow and poor prognosis. Our findings demonstrate a potential clinical value of MVs as biomarkers and possible therapeutic targets against endothelial deterioration.
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| 6. |
- Bryl-Górecka, Paulina, et al.
(författare)
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Reply to Trimaille et al.
- 2021
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 321:4, s. 750-750
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Bäck, Sophia, et al.
(författare)
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Comprehensive left atrial flow component analysis reveals abnormal flow patterns in paroxysmal atrial fibrillation
- 2024
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6135 .- 1522-1539. ; 326:3, s. H511-H521
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Tidskriftsartikel (refereegranskat)abstract
- Left atrial (LA) blood flow plays an important role in diseases such as atrial fibrillation (AF) and atrial cardiomyopathy since alterations in the blood flow might lead to thrombus formation and stroke. Using traditional techniques, such as echocardiography, atrial flow velocities can be measured at the pulmonary veins and the mitral valve, but a comprehensive understanding of the three-dimensional atrial flow field is missing. Previously, ventricular flow has been analyzed using flow component analysis, revealing new insights into ventricular flow and function. Thus, the aim of this project was to develop a comprehensive flow component analysis method for the LA and explore its utility in 21 patients with paroxysmal atrial fibrillation compared with a control group of 8 participants. The flow field was derived from time-resolved CT acquired during sinus rhythm using computational fluid dynamics. Flow components were computed from particle tracking. We identified six atrial flow components: conduit, reservoir, delayed ejection, retained inflow, residual volume, and pulmonary vein backflow. It was shown that conduit flow, defined as blood entering and leaving the LA within the same diastolic phase, exists in most subjects. Although the volume of conduit and reservoir is similar in patients with paroxysmal AF in sinus rhythm and controls, the volume of the other components is increased in paroxysmal AF. Comprehensive quantification of LA flow using flow component analysis makes atrial blood flow quantifiable, thus facilitating investigation of mechanisms underlying atrial dysfunction and can increase understanding of atrial blood flow in disease progression and stroke risk. NEW & NOTEWORTHY We developed a new comprehensive approach to atrial blood component analysis that includes both conduit flow and residual volume and compared the flow components of atrial fibrillation (AF) patients in sinus rhythm with controls. Conduit and reservoir flow were similar between the groups, whereas components with longer residence time in the left atrium were increased in the AF group. This could add to the pathophysiological understanding of atrial diseases and possibly clinical management.
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| 8. |
- Dahlberg, Pia, et al.
(författare)
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Spatiotemporal repolarization dispersion before and after exercise in patients with long QT syndrome type 1 versus controls : probing into the arrhythmia substrate
- 2023
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - 0363-6135 .- 1522-1539. ; 325:6, s. H1279-H1289
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Tidskriftsartikel (refereegranskat)abstract
- Congenital long QT syndrome (LQTS) carries an increased risk for syncope and sudden death. QT prolongation promotes ventricular extrasystoles, which, in the presence of an arrhythmia substrate, might trigger ventricular tachycardia degenerating into fibrillation. Increased electrical heterogeneity (dispersion) is the suggested arrhythmia substrate in LQTS. In the most common subtype LQT1, physical exercise predisposes for arrhythmia and spatiotemporal dispersion was therefore studied in this context. Thirty-seven patients (57% on β-blockers) and 37 healthy controls (mean age, 31 vs. 35; range, 6-68 vs. 6-72 yr) performed an exercise test. Frank vectorcardiography was used to assess spatiotemporal dispersion as Tampl, Tarea, the ventricular gradient (VG), and the Tpeak-end interval from 10-s signal averages before and 7 ± 2 min after exercise; during exercise too much signal disturbance excluded analysis. Baseline and maximum heart rates as well as estimated exercise intensity were similar, but heart rate recovery was slower in patients. At baseline, QT and heart rate-corrected QT (QTcB) were significantly longer in patients (as expected), whereas dispersion parameters were numerically larger in controls. After exercise, QTpeakcB and Tpeak-endcB increased significantly more in patients (18 ± 23 vs. 7 ± 10 ms and 12 ± 17 vs. 2 ± 6 ms; P < 0.001 and P < 0.01). There was, however, no difference in the change in Tampl, Tarea, and VG between groups. In conclusion, although temporal dispersion of repolarization increased significantly more after exercise in patients with LQT1, there were no signs of exercise-induced increase in global dispersion of action potential duration and morphology. The arrhythmia substrate/mechanism in LQT1 warrants further study.NEW & NOTEWORTHY: Physical activity increases the risk for life-threatening arrhythmias in LQTS type 1 (LQT1). The arrhythmia substrate is presumably altered electrical heterogeneity (a.k.a. dispersion). Spatiotemporal dispersion parameters were therefore compared before and after exercise in patients versus healthy controls using Frank vectorcardiography, a novelty. Physical exercise prolonged the time between the earliest and latest complete repolarization in patients versus controls, but did not increase parameters reflecting global dispersion of action potential duration and morphology, another novelty.
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| 9. |
- Eiken, O, et al.
(författare)
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Adaptation to 5 weeks of intermittent local vascular pressure increments; mechanisms to be considered in the development of primary hypertension?
- 2021
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 320:4, s. H1303-H1312
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Tidskriftsartikel (refereegranskat)abstract
- Adaptive responses to arterial/arteriolar pressure elevation have typically been investigated in cross-sectional studies in hypertensive patients or in longitudinal studies in experimental animals. The present investigation shows that in healthy individuals, fifteen 40-min, carefully controlled, moderate transmural pressure elevations markedly increase in vivo stiffness (i.e. reduce pressure distension) in arteries and arterioles. The response is mediated via local mechanisms, and it appears that endothelin-1, angiotensin-II, and matrix metalloproteinase 7 may have key roles.
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| 10. |
- Eiken, Ola, et al.
(författare)
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Adaptation to 5 weeks of intermittent local vascular pressure increments; Mechanisms to be considered in the development of primary hypertension?
- 2021
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 320:4, s. H1303-H1312
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Tidskriftsartikel (refereegranskat)abstract
- The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150mmHg in healthy men (n = 11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressuredistension determinations were conducted by exposing the subjects' arm versus remaining part of the body to differential ambient pressure. During the pressure-distension determinations, venous samples were simultaneously obtained from pressurized and unpressurized vessels. Pressure training reduced arterial pressure distension by 40 ± 23% and pressure-induced flow by 33 ± 30% (P < 0.01), but only in the pressure-trained arm, suggesting local adaptive mechanisms. The distending pressure-diameter and distending pressure-flow curves, with training-induced increments in pressure thresholds and reductions in response gains, suggest that the increased precapillary stiffness was attributable to increased contractility and structural remodeling of the walls. Acute vascular pressure provocation induced local release of angiotensin-II (ANG II) and endothelin-1 (ET-1) (P < 0.05), suggesting that these vasoconstrictors limited the pressure distension. Pressure training increased basal levels of ET-1 and induced local pressure release of matrix metalloproteinase 7 (P < 0.05), suggesting involvement of these substances in vascular remodeling. The findings are compatible with the notion that local intravascular pressure load acts as a prime mover in the development of primary hypertension.
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| 11. |
- Jonasson, Hanna, et al.
(författare)
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Normative data and the influence of age and sex on microcirculatory function in a middle-aged cohort: results from the SCAPIS study
- 2020
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6135 .- 1522-1539. ; 318:4, s. H908-H915
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to assess normative values for comprehensive forearm skin microcirculatory function: oxygen saturation, tissue fraction of red blood cells (RBCs), and speed-resolved perfusion. Furthermore, to examine the influence of age and sex on microcirculatory function. Measurements were performed using a noninvasive probe-based system, including diffuse reflectance spectroscopy and laser-Doppler flowmetry, yielding output data in absolute units. The study was conducted within the Swedish CArdioPulmonary BioImage Study (SCAPIS) and included 1,765 men and women aged 50-65 yr from the Linkoping general population. Normative values are given at baseline, at the end of a 5-min occlusion of the brachial artery and during hyperemia after occlusion release. We found a consistent age distribution, in which the oldest individuals had the lowest peak oxygen saturation (P < 0.001) and the highest baseline low-speed perfusion (P < 0.001). Women had higher peak oxygen saturation (P < 0.001), lower RBC tissue fraction, in general (P < 0.001), lower baseline perfusion in all speed regions (P = 0.01). and lower peak high-speed perfusion at hyperemia (P < 0.001). The normative data can be used as reference values in future studies of disease-specific populations. The results show that age and sex are important aspects to consider in studies of microvascular function. Women and younger age were factors associated with higher peak oxygen saturation after ischemia. This is a novel parameter that reflects overall microcirculatory function associated with vascular dilation capacity. NEW & NOTEWORTHY This study expands experimental microcirculatory research to clinical use by providing normative values on microcirculatory function in a large population-based cohort. Women and younger age were factors associated with higher peak oxygen saturation after ischemia, which implies that age and sex are important aspects to consider in studies of micmvascular function. This study is the first step toward using microcirculatory assessment as a tool to improve diagnosis. prognosis. and treatment in disease-specific populations.
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| 12. |
- Kövamees, O, et al.
(författare)
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The protective effect of remote ischemic conditioning is lost in patients with hypercholesterolemia
- 2022
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 323:5, s. H1004-H1009
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the impact of hypercholesterolemia on the protective effect of RIC on ischemia-reperfusion injury in a well-characterized patient population with isolated hypercholesterolemia. The results show that the protective effect of RIC is absent in patients with hypercholesterolemia but is apparent in patients with hypercholesterolemic following treatment with lipid-lowering drugs. The results are of importance for the understanding of how comorbidities affect the therapeutic potential of RIC.
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| 13. |
- Ng, Henry, et al.
(författare)
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Optimal cutting temperature medium embedding and cryostat sectioning are valid for cardiac myofilament function assessment
- 2020
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6135 .- 1522-1539. ; 319:1, s. H235-H241
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Tidskriftsartikel (refereegranskat)abstract
- To maximize data obtainment from valuable cardiac tissue, we hypothesized that myocardium fixed in optimal cutting temperature (OCT) medium for histology could also be used to investigate the function of myofilament proteins in situ. We compared tissue prepared via conventional liquid nitrogen (LN) snap freezing with tissue fixed in OCT and then sectioned in fiber-parallel orientation. We found that actin-myosin Ca2+ sensitivity, activation rate by Ca2+, cooperativity along the thin filament, as well as cross-bridge cycling rate were unaffected by OCT storage and could reliably be interpreted after sectioning. Absolute values in maximum force generation per cross-sectional area, as well as passive strain, are difficult to investigate after sectioning, as myofibrillar continuity along the preparation cannot be guaranteed. We have shown that myocardial tissue stored in OCT and sectioned before analysis is available for functional analysis, a valuable means of maximizing usage of precious cardiac biopsies. NEW & NOTEWORTHY Myocardial tissue in optimal cutting temperature (OCT) fixation and cryostat sectioning was tested as a means of storing and preparing tissue for myofilament function analysis in relation to conventional liquid nitrogen freezing and dissection. Actomyosin interaction, Ca2+ force activation, and passive compliance were tested. The study concluded that OCT storage and cryostat sectioning do not interfere with the actomyosin cross-bridge dynamics or Ca2+ activation but that absolute tension values suffer and may not be investigated by this method.
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| 14. |
- Rios-Navarro, C, et al.
(författare)
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Unraveling the thread of uncontrolled immune response in COVID-19 and STEMI: an emerging need for knowledge sharing
- 2021
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 320:6, s. H2240-H2254
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Tidskriftsartikel (refereegranskat)abstract
- The outbreak of severe acute respiratory syndrome coronavirus 2 that first emerged in Wuhan in December 2019 has resulted in the devastating pandemic of coronavirus disease 2019, creating an emerging need for knowledge sharing. Meanwhile, myocardial infarction is and will probably remain the foremost cause of death in the Western world throughout the coming decades. Severe deregulation of the immune system can unnecessarily expand the inflammatory response and participate in target and multiple organ failure, in infection but also in critical illness. Indeed, the course and fate of inflammatory cells observed in severe ST-elevation myocardial infarction (neutrophilia, monocytosis, and lymphopenia) almost perfectly mirror those recently reported in severe coronavirus disease 2019. A pleiotropic proinflammatory imbalance hampers adaptive immunity in favor of uncontrolled innate immunity and is associated with poorer structural and clinical outcomes. The goal of the present review is to gain greater insight into the cellular and molecular mechanisms underlying this canonical activation and downregulation of the two arms of the immune response in both entities, to better understand their pathophysiology and to open the door to innovative therapeutic options. Knowledge sharing can pave the way for therapies with the potential to significantly reduce mortality in both infectious and noninfectious scenarios.
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| 15. |
- Sandstedt, Mikael, 1990, et al.
(författare)
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Regional transcriptomic profiling reveals immune system enrichment in nonfailing atria as well as all chambers of the failing human heart
- 2023
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 325:6, s. H1430-H1445
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Tidskriftsartikel (refereegranskat)abstract
- The different chambers of the human heart demonstrate regional physiological traits and may be differentially affected during pathologic remodeling, resulting in heart failure. Few previous studies have, however, characterized the different chambers at a transcriptomic level. We therefore conducted whole-tissue RNA sequencing and gene set enrichment analysis of biopsies collected from the four chambers of adult failing (n = 8) and nonfailing (n = 11) human hearts. Atria and ventricles demonstrated distinct transcriptional patterns. Compared to nonfailing ventricles, the transcriptional pattern of nonfailing atria was enriched for a large number of gene sets associated with cardiogenesis, the immune system and bone morphogenetic protein (BMP), transforming growth factor beta (TGF beta), MAPK/JNK and Wnt signaling. Differences between failing and nonfailing hearts were also determined. The transcriptional pattern of failing atria was distinct compared to that of nonfailing atria and enriched for gene sets associated with the innate and adaptive immune system, TGF beta/SMAD signaling, and changes in endothelial, smooth muscle cell and cardiomyocyte physiology. Failing ventricles were also enriched for gene sets associated with the immune system. Based on the transcriptomic patterns, upstream regulators associated with heart failure were identified. These included many immune response factors predicted to be similarly activated for all chambers of failing hearts. In summary, the heart chambers demonstrate distinct transcriptional patterns that differ between failing and nonfailing hearts. Immune system signaling may be a hallmark of all four heart chambers in failing hearts, and could constitute a novel therapeutic target.
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| 16. |
- Sjöberg, Pia, et al.
(författare)
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Changes in left and right ventricular longitudinal function after pulmonary valve replacement in patients with Tetralogy of Fallot
- 2020
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 318:2, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- Timing and indication for pulmonary valve replacement (PVR) in patients with repaired Tetralogy of Fallot (rToF) and pulmonary regurgitation (PR) are uncertain. To improve understanding of pumping mechanics, we investigated atrioventricular coupling before and after surgical PVR. Cardiovascular magnetic resonance (CMR) were performed in patients (n=12) with rToF and PR>35% before and after PVR and in healthy controls (n=15). Atrioventricular plane displacement (AVPD), global longitudinal peak systolic strain (GLS), atrial and ventricular volumes and caval blood flows were analysed. Right ventricular (RV) AVPD and RV free wall GLS were lower in patients before PVR compared to controls (p<0.0001; p<0.01) and decreased after PVR (both p<0.0001 for both). Left ventricular (LV) AVPD was lower in patients before PVR compared to controls (p<0.05) and decreased after PVR (p<0.01). Left ventricular GLS did not differ between patients and controls (p>0.05). Right atrial reservoir volume and RV stroke volume (SV) generated by AVPD correlated in controls (r=0.93; p<0.0001) and patients before PVR (r=0.88; p<0.001) but not after PVR. In conclusion, there is a clear atrioventricular coupling in patients before PVR that is lost after PVR, possibly due to loss of pericardial integrity. Impaired atrioventricular coupling complicates assessment of ventricular function after surgery using measurements of longitudinal function. Changes in atrioventricular coupling seen in patients with rToF may be energetically unfavourable and long-term effects of surgery on atrioventricular coupling is therefore of interest. Also, AVPD and GLS cannot be used interchangeably to assess longitudinal function in rToF.
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| 17. |
- Uurasmaa, Tytti Maria, et al.
(författare)
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Subcutaneous B16 melanoma impairs intrinsic pressure generation and relaxation of the heart, which are not restored by short-term voluntary exercise in mice
- 2022
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - Rockville : American Physiological Society. - 0363-6135 .- 1522-1539. ; 322:6, s. H1044-H1056
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether subcutaneous melanoma impairs intrinsic cardiac function and hypoxia tolerance in mice. In addition, it was investigated whether these changes could be prevented by voluntary wheel-running exercise. The roles of different molecular pathways were also analyzed. Male mice (C57Bl/6NCrl) were divided into unexercised tumor-free group, unexercised melanoma group, and exercised melanoma group. The experiment lasted 2.7 ± 0.1 wk (determined by the tumor size) after which the heart function was measured in different oxygen levels ex vivo using Langendorff method. All the melanoma mice had lower pressure amplitude (50.3%), rate of pressure production (54.1%), and decline (52.5%) in hearts ex vivo when compared with tumor-free group. There were no functional differences between the two melanoma groups. All the groups had similar weight changes, heart weights, cardiomyocyte sizes, levels of Ca2+ channels, energy metabolism enzyme activities, lipid peroxidation, and reactive oxygen species in their cardiac tissue homogenates. However, all the melanoma mice had 7.4% lower superoxidase dismutase activity compared with the control animals, which might reduce the ability of the heart to react to changes in oxidative stress. The exercising melanoma group had a 28.6% higher average heart capillary density compared with the unexercised melanoma group. Short-term wheel running did not affect the tumor growth. In conclusion, subcutaneous melanoma seems to impair intrinsic heart function even before cachexia, and these functional alterations were not caused by any of the measured molecular markers. Short-term voluntary wheel-running exercise was insufficient to alleviate the intrinsic cardiac impairments caused by melanoma.NEW & NOTEWORTHY Melanoma has been shown to induce cardiac atrophy and impair cardiac function in vivo, however, it has not been investigated how melanoma affects the intrinsic heart function. Here, we showed that subcutaneous melanoma can impair intrinsic heart function in noncachectic mice, decreasing the heart's pressure production and relaxation. In addition, we investigated whether short-term voluntary wheel-running exercise could attenuate the impairment of intrinsic cardiac function. However, our results do not seem to support this hypothesis. © 2022 the American Physiological Society.
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| 18. |
- Wernly, B, et al.
(författare)
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More purinergic receptors deserve attention as therapeutic targets for the treatment of cardiovascular disease
- 2020
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 319:4, s. H723-H729
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease is a major cause of morbidity and mortality worldwide. Innovative new treatment options for this cardiovascular pandemic are urgently needed. Activation of purinergic receptors (PRs) is critically involved in the development and progression of cardiovascular disease including atherosclerosis, ischemic heart disease, hypertension, and diabetes. PRs have been targeted for the treatment of several cardiovascular diseases in a clinical setting. The P2Y12R antagonists such as clopidogrel, ticagrelor, and others are the most successful class of purinergic drugs targeting platelets for the treatment of acute coronary syndrome. In addition to targeting platelets, ticagrelor may exert P2Y12R-independent effect by targeting erythrocyte-mediated purinergic activation. The partial A1R agonist neladenoson and the A2AR agonist regadenoson have been applied in cardiovascular medicine. In experimental studies, many other PRs have been shown to play a significant role in the development and progression of cardiovascular diseases, and targeting these receptors have resulted in promising outcomes. Therefore, many of these PRs including A2BR, A3R, P2X3R, P2X4R, P2X7R, P2Y1R, P2Y4R, P2Y6R, and P2Y11R can be considered as therapeutic targets. However, the multitude of PR subtypes expressed in different cells of the cardiovascular system may constitute a challenge whether single or multiple receptors should be targeted at the same time for the best efficacy. The present review discusses the promising purinergic drugs used in clinical studies for the treatment of cardiovascular disease. We also update experimental evidence for many other PRs that can be considered as therapeutic targets for future drug development.
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| 19. |
- Wernly, B, et al.
(författare)
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Ticagrelor: a cardiometabolic drug targeting erythrocyte-mediated purinergic signaling?
- 2021
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 320:1, s. H90-H94
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Tidskriftsartikel (refereegranskat)abstract
- Cardiometabolic diseases lead to vascular complications, which cause increasing morbidity and mortality worldwide. The underlying mechanisms are multifactorial and complex but may involve altered purinergic signaling that significantly contributes to cardiovascular dysfunction. Ticagrelor is a successful purinergic drug directly targeting ADP-mediated P2Y12R signaling for platelet aggregation and is widely used in patients with acute coronary syndrome. In addition, ticagrelor can target red blood cells (RBCs) to release ATP and inhibit adenosine uptake by RBCs, which subsequently activate purinergic signaling. This involvement in purinergic signaling may allow ticagrelor to mediate pleiotropic effects and contribute to the beneficial cardiovascular outcomes observed in clinical studies. Recent studies have established a novel function of RBCs, which is that RBCs act as disease mediators for the development of cardiovascular complications in type 2 diabetes (T2D). RBC-released ATP is defective in T2D, which has implications for the induction of vascular dysfunction by dysregulating purinergic signaling. Ticagrelor might target RBCs and restore the bioavailability of ATP and adenosine, thereby attenuating cardiovascular complications. The present perspective discusses the pleiotropic effect of ticagrelor, with a focus on the possibility of ticagrelor for the treatment of cardiometabolic complications by targeting RBCs and initiating purinergic activation. A better understanding of the proposed cardiometabolic effects could support novel clinical indications for ticagrelor application.
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| 20. |
- Winbo, Annika, et al.
(författare)
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Functional hyperactivity in long OT syndrome type 1 pluripotent stem cell-derived sympathetic neurons
- 2021
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 321:1, s. H217-H227
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Tidskriftsartikel (refereegranskat)abstract
- Sympathetic activation is an established trigger of life-threatening cardiac events in long QT syndrome type 1 (LQT1). KCNQ1 loss-of-function variants, which underlie LQT1, have been associated with both cardiac arrhythmia and neuronal hyperactivity pathologies. However, the LQT1 sympathetic neuronal phenotype is unknown. Here, we aimed to study human induced pluripotent stem cell (hiPSC)-derived sympathetic neurons (SNs) to evaluate neuronal functional phenotype in LQT1. We generated hiPSC-SNs from two patients with LQT1 with a history of sympathetically triggered arrhythmia and KCNQ1 loss-of-function genotypes (c.781_782delinsTC and p.S349W/p.R518X). Characterization of hiPSC-SNs was performed using immunohistochemistry, enzyme-linked immunosorbent assay, and whole cell patch clamp electrophysiology, and functional LQT1 hiPSC-SN phenotypes compared with healthy control (WT) hiPSC-SNs. hiPSC-SNs stained positive for tyrosine hydroxylase, peripherin, KCNQ1, and secreted norepinephrine. hiPSC-SNs at 60 +/- 2.2 days in vitro had healthy resting membrane potentials (-60 +/- 1.3 mV), and fired rapid action potentials with mature kinetics in response to stimulation. Significant hyperactivity in LQT1 hiPSC-SNs was evident via increased norepinephrine release, increased spontaneous action potential frequency, increased total inward current density, and reduced afterhyperpolarization, compared with age-matched WT hiPSC-SNs. A significantly higher action potential frequency upon current injection and larger synaptic current amplitudes in compound heterozygous p.S349W/p.R518X hiPSC-SNs compared with heterozygous c.781_782delinsTC hiPSC-SNs was also observed, suggesting a potential genotype-phenotype correlation. Together, our data reveal increased neurotransmission and excitability in heterozygous and compound heterozygous patient-derived LQT1 sympathetic neurons, suggesting that the cellular arrhythmogenic potential in LQT1 is not restricted to cardiomyocytes. NEW & NOTEWORTHY Here, we present the first study of patient-derived LQT1 sympathetic neurons that are norepinephrine secreting, and electrophysiologically functional, in vitro. Our data reveal a novel LQT1 sympathetic neuronal phenotype of increased neurotransmission and excitability. The identified sympathetic neuronal hyperactivity phenotype is of particular relevance as it could contribute to the mechanisms underlying sympathetically triggered arrhythmia in LQT1.
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| 21. |
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| 22. |
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| 23. |
- Bryl-Górecka, Paulina, et al.
(författare)
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Microvesicles in plasma reflect coronary flow reserve in patients with cardiovascular disease
- 2021
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - 0363-6135. ; 320:5, s. 2147-2160
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Tidskriftsartikel (refereegranskat)abstract
- High levels of microvesicles (MVs), a type of extracellular vesicles, are detected in several pathological conditions. We investigated the connection between coronary flow reserve (CFR), a prognostic clinical parameter that reflects blood flow in the heart, with levels of MVs and their cargo, from plasma of patients with cardiovascular disease. The PROFLOW study consists of 220 patients with prior myocardial infarction and measured CFR with transthoracic echocardiography. The patients were divided into high and low CFR groups. Plasma MVs were captured with acoustic trapping. Platelet- and endothelial-derived MVs were measured with flow cytometry, and vesicle lysates were analyzed with proteomic panels against cardiovascular biomarkers. Flow cytometry was further applied to identify cellular origin of biomarkers. Our data show a negative correlation between MV concentration and CFR values. Platelet and endothelial MV levels were significantly increased in plasma from the low CFR group. CFR negatively correlates with the levels of several proteomic biomarkers, and the low CFR group exhibited higher concentrations of these proteins in MVs. Focused analysis of one of the MV proteins, B cell activating factor (BAFF), revealed platelet and not leukocyte origin and release upon proinflammatory stimulus. Higher levels of MVs carrying an elevated concentration of proatherogenic proteins circulate in plasma in patients with low CFR, a marker of vascular dysfunction, reduced blood flow, and poor prognosis. Our findings demonstrate a potential clinical value of MVs as biomarkers and possible therapeutic targets against endothelial deterioration.
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| 24. |
- Dahlberg, Pia, et al.
(författare)
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Spatio-temporal repolarization dispersion before and after exercise in patients with long QT syndrome type 1 vs controls - probing into the arrhythmia substrate.
- 2023
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Ingår i: American journal of physiology. Heart and circulatory physiology. - 1522-1539. ; 325:6
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Tidskriftsartikel (refereegranskat)abstract
- Congenital long QT syndrome (LQTS) carries an increased risk for syncope and sudden death. QT prolongation promotes ventricular extrasystoles which in the presence of an arrhythmia substrate might trigger ventricular tachycardia degenerating into fibrillation. Increased electrical heterogeneity (dispersion) is the suggested arrhythmia substrate in LQTS. In the most common subtype LQT1, physical exercise predisposes for arrhythmia and spatio-temporal dispersion was therefore studied in this context. Thirty-seven patients (57% on beta-blockers) and 37 healthy controls (mean age 31 vs 35, range 6-68 vs 6-72 years) performed an exercise test. Frank vectorcardiography was used to assess spatio-temporal dispersion as Tamplitude, Tarea, the ventricular gradient (VG), and the Tpeak-end interval from 10s-signal averages before and 7±2 min after exercise; during exercise too much signal disturbance excluded analysis. Baseline and maximum heart rates as well as estimated exercise intensity were similar, but heart rate recovery was slower in patients. At baseline QT and heart rate corrected QT (QTcB) were significantly longer in patients (as expected), while dispersion parameters were numerically larger in controls. After exercise QTpeakcB and Tpeak-endcB increased significantly more in patients (18±23 vs 7±10ms and 12±17 vs 2±6ms; p<0.001 and p<0.01). There was, however, no difference in the change in Tamplitude,Tarea and VG between groups. In conclusion, while temporal dispersion of repolarization increased significantly more after exercise in LQT1 patients, there were no signs of exercise-induced increase in global dispersion of action potential duration and morphology. The arrhythmia substrate/mechanism in LQT1 warrants further study.
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| 25. |
- Holm, Hannes, et al.
(författare)
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Ventricular-arterial coupling and cardiovascular risk among young adults : The African-PREDICT study
- 2023
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - 1522-1539. ; 325:2, s. 362-371
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Tidskriftsartikel (refereegranskat)abstract
- Ventricular-arterial coupling (VAC) has independent diagnostic and prognostic value for cardiovascular (CV) risk stratification, but studies on its association with anthropometric and CV factors are sparse in young individuals without overt CV disease. We aim to provide descriptive data regarding VAC and its associations with CV risk factors in young adults without overt CV disease. For 631 (mean age, 24 ± 3 yr; 51% female) individuals, VAC was determined by carotid-femoral pulse wave velocity (PWV)/global longitudinal strain (GLS). Multivariable logistic and linear regression models were performed to explore the association between PWV/GLS and CV risk factors. A P-value < 0.05 was considered statistically significant. The mean PWV/GLS was 0.33 ± 0.07 m/s%. Higher ratios of PWV/GLS associated with older age, male sex, and a higher prevalence of CV risk factors (i.e., higher blood pressure, prevalent hypertension, higher waist circumference, active smoking, higher plasma triglycerides, lower high-density lipoprotein cholesterol, and an adverse urine albumin/creatinine ratio). Furthermore, higher PWV/GLS was associated with echocardiographic measures such as lower ejection fraction and higher left ventricle mass index. In expanded logistic regression models, higher ratios of PWV/GLS were significantly associated with the prevalence of active smoking [odds ratio (OR), 1.88; confidence interval (CI) 1.36-2.58, P < 0.001] and hypertension (OR 1.98; CI 1.40-2.80, P < 0.001). We demonstrated that worse VAC reflected by higher values of PWV/GLS are significantly associated with CV risk factors in young adults. The results suggest that PWV/GLS might serve as a tool to improve the profiling of cardiovascular risk in young adults. NEW & NOTEWORTHY Assessing VAC is especially useful in heart failure and valvular heart disease, but less is known about VAC in the pathophysiology of CV disease risk in younger individuals. In young individuals without overt CV disease, we showed descriptive data regarding VAC, determined by PWV/GLS ratio, and explored the associations of VAC with clinical CV disease risk factors. Worse VAC, reflected by higher values of PWV/GLS, associated with high blood pressure and smoking in young adults.
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| 26. |
- Möller, Ulrika Olsson, et al.
(författare)
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Using Cards to Facilitate Conversations About Wishes and Priorities of Patients in Palliative Care
- 2020
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Ingår i: Journal of Hospice and Palliative Nursing. - : Lippincott Williams and Wilkins Ltd.. - 1522-2179 .- 1539-0705. ; 22:1, s. 33-39
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Tidskriftsartikel (refereegranskat)abstract
- To avoid discomfort, health care professionals may hesitate to pursue conversations about end of life with patients. Certain tools have the potential to facilitate smoother conversations in this matter. The objective was to explore the experiences of patients in palliative care in using statement cards to talk about their wishes and priorities. Forty-six cards with statements of wishes and priorities were developed and tested for feasibility with 40 participants, who chose the 10 most important cards and shared their thoughts about the statements and conversation. Data from individual interviews and field notes were analyzed using content analysis. One category describes practical aspects of using the cards including the relevance of the content and the process of sorting the cards. The second category describes the significance of using the cards including becoming aware of what is important, sharing wishes and priorities, and reflecting on whether wishes and priorities change closer to death. The cards helped raise awareness and verbalize wishes and priorities. All statements were considered relevant. The conversations focused not only on death and dying, but also on challenges in the participants' current life situation. For the most ill and frail participants, the number of cards needs to be reduced.
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| 27. |
- Olsson Möller, Ulrika, et al.
(författare)
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A Reduced Deck of Conversation Cards of Wishes and Priorities of Patients in Palliative Care
- 2022
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Ingår i: Journal of Hospice and Palliative Nursing. - : Lippincott Williams and Wilkins Ltd.. - 1522-2179 .- 1539-0705. ; 24:3, s. 175-180
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Tidskriftsartikel (refereegranskat)abstract
- The individual wishes and priorities of patients with advanced disease are too often neglected, making a deck of cards with statements reflecting potential wishes and priorities a useful conversation tool. However, in the most ill patients, the card selection and sorting process may be too strenuous. The aims of this study were to explore the wishes and priorities of patients receiving palliative care and to reduce a deck of statement cards to be clinically useable even for the most ill patients. In interviews, participants selected their top 10 from a deck of 46 statement cards. Descriptive and analytical statistics were used. Thirty-nine patients from 5 specialized palliative care units in Sweden participated. Six participants died within 1 month of the interviews. "To be free from pain"was ranked as the highest priority by the majority, and "To have staff I feel comfortable with"was ranked highest by the 6 most ill participants. A deck of cards with the 20 statements most chosen by patients receiving palliative care was created. The cards cover physical, psychological, social, existential, and practical aspects and are helpful for formulating goals of care for patients and informing the development of a core outcome set for palliative care.
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