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- Lambert, Elisabeth A, et al.
(författare)
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Single-unit muscle sympathetic nervous activity and its relation to cardiac noradrenaline spillover.
- 2011
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Ingår i: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 589:Pt 10, s. 2597-605
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Tidskriftsartikel (refereegranskat)abstract
- Recent work using single-unit sympathetic nerve recording techniques has demonstrated aberrations in the firing pattern of sympathetic nerves in a variety of patient groups. We sought to examine whether nerve firing pattern is associated with increased noradrenaline release. Using single-unit muscle sympathetic nerve recording techniques coupled with direct cardiac catheterisation and noradrenaline isotope dilution methodology we examined the relationship between single-unit firing patterns and cardiac and whole body noradrenaline spillover to plasma. Participants comprised patients with hypertension (n=6), depression (n=7) and panic disorder (n =9) who were drawn from our ongoing studies. The patient groups examined did not differ in their single-unit muscle sympathetic nerve firing characteristics nor in the rate of spillover of noradrenaline to plasma from the heart. The median incidence of multiple spikes per beat was 9%. Patients were stratified according to the firing pattern: low level of incidence (less than 9% incidence of multiple spikes per beat) and high level of incidence (greater than 9% incidence of multiple spikes per beat). High incidence of multiple spikes within a cardiac cycle was associated with higher firing rates (P <0.0001) and increased probability of firing (P <0.0001). Whole body noradrenaline spillover to plasma and (multi-unit) muscle sympathetic nerve activity in subjects with low incidence of multiple spikes was not different to that of those with high incidence of multiple spikes. In those with high incidence of multiple spikes there occurred a parallel activation of the sympathetic outflow to the heart, with cardiac noradrenaline spillover to plasma being two times that of subjects with low nerve firing rates (11.0 ± 1.5 vs. 22.0 ± 4.5 ng min⁻¹, P <0.05). This study indicates that multiple within-burst firing and increased single-unit firing rates of the sympathetic outflow to the skeletal muscle vasculature is associated with high cardiac noradrenaline spillover.
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| 5. |
- Falkenberg, Cecilia, et al.
(författare)
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Cardiac autonomic function in adolescents operated by arterial switch surgery.
- 2013
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 168:3, s. 1887-1893
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Children with transposition of the great arteries, in whom an arterial switch operation (ASO) is performed, have been shown to have an increased incidence of sudden death, which may be due to cardiac autonomic imbalance and repolarisation instability. We hypothesised that i) cardiac norepinephrine (NE) kinetics and ii) arterial baroreflex sensitivity (BRS), reflecting sympathetic activity and vagal function respectively, are altered in this group. METHODS AND RESULTS: 17 children (15.8±1.5years of age) with ASO-surgery in the neonatal period were studied. 17 had cardiac BRS assessed by spontaneous fluctuations of systolic blood pressure and RR-interval, and repolarisation was measured as QT variability index. Matched healthy subjects were controls. Cardiac vagal function and repolarisation pattern were unchanged following ASO-surgery. At cardiac catheterisation, we infused tritiated NE in 8 of these children to examine total body and cardiac sympathetic function at baseline and following 5min of adenosine infusion to induce reflex sympathetic activation. Blood was sampled simultaneously from the aorta and coronary sinus. Cardiac fractional extraction of ([3H])NE was substantially lower in operated children, being 56±10 vs. 82±9% (p=0.0001). Following i.v. adenosine in the operated group, NE total body spillover doubled vs. baseline (p<0.002) and the coronary venous-arterial concentration gradient of ([3H])dihydroxyphenylglycol increased 4-fold (p=0.04). CONCLUSIONS: Arterial switch operation performed neonatally appears to leave cardiac vagal function intact and, although cardiac sympathetic activation in response to adenosine occurs, cardiac neuronal NE reuptake is impaired. This may be pro-arrhythmic by reducing removal capacity of NE from the cardiac synaptic cleft.
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- Kageyama, Masa, et al.
(författare)
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The PMIP4 contribution to CMIP6-Part 1 : Overview and over-arching analysis plan
- 2018
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 11:3, s. 1033-1057
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Tidskriftsartikel (refereegranskat)abstract
- This paper is the first of a series of four GMD papers on the PMIP4-CMIP6 experiments. Part 2 (OttoBliesner et al., 2017) gives details about the two PMIP4-CMIP6 interglacial experiments, Part 3 (Jungclaus et al., 2017) about the last millennium experiment, and Part 4 (Kageyama et al., 2017) about the Last Glacial Maximum experiment. The mid-Pliocene Warm Period experiment is part of the Pliocene Model Intercomparison Project (PlioMIP) Phase 2, detailed in Haywood et al. (2016). The goal of the Paleoclimate Modelling Intercomparison Project (PMIP) is to understand the response of the climate system to different climate forcings for documented climatic states very different from the present and historical climates. Through comparison with observations of the environmental impact of these climate changes, or with climate reconstructions based on physical, chemical, or biological records, PMIP also addresses the issue of how well state-of-the-art numerical models simulate climate change. Climate models are usually developed using the present and historical climates as references, but climate projections show that future climates will lie well outside these conditions. Palaeoclimates very different from these reference states therefore provide stringent tests for state-of-the-art models and a way to assess whether their sensitivity to forcings is compatible with palaeoclimatic evidence. Simulations of five different periods have been designed to address the objectives of the sixth phase of the Coupled Model Intercomparison Project (CMIP6): the millennium prior to the industrial epoch (CMIP6 name: past1000); the mid-Holocene, 6000 years ago (midHolocene); the Last Glacial Maximum, 21 000 years ago (lgm); the Last Interglacial, 127 000 years ago (lig127k); and the mid-Pliocene Warm Period, 3.2 million years ago (midPliocene-eoi400). These climatic periods are well documented by palaeoclimatic and palaeoenvironmental records, with climate and environmental changes relevant for the study and projection of future climate changes. This paper describes the motivation for the choice of these periods and the design of the numerical experiments and database requests, with a focus on their novel features compared to the experiments performed in previous phases of PMIP and CMIP. It also outlines the analysis plan that takes advantage of the comparisons of the results across periods and across CMIP6 in collaboration with other MIPs.
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- Malan, Leoné, et al.
(författare)
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A stress syndrome prototype reflects type 3 diabetes and ischemic stroke risk : The SABPA study
- 2021
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Ingår i: Biology. - : MDPI AG. - 2079-7737. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Type 3 diabetes (T3D) accurately reflects that dementia, e.g., Alzheimer’s disease, represents insulin resistance and neurodegeneration in the brain. Similar retinal microvascular changes were observed in Alzheimer’s and chronic stressed individuals. Hence, we aimed to show that chronic stress relates to T3D dementia signs and retinopathy, ultimately comprising a Stress syndrome prototype reflecting risk for T3D and stroke. A chronic stress and stroke risk phenotype (Stressed) score, independent of age, race or gender, was applied to stratify participants (N = 264; aged 44 - 9 years) into high stress risk (Stressed, N = 159) and low stress risk (non-Stressed, N = 105) groups. We determined insulin resistance using the homeostatic model assessment (HOMA-IR), which is interchangeable with T3D, and dementia risk markers (cognitive executive functioning (cognitiveexe-func); telomere length; waist circumference (WC), neuronal glia injury; neuron-specific enolase/NSE, S100B). Retinopathy was determined in the mydriatic eye. The Stressed group had greater incidence of HOMA-IR in the upper quartile (≥5), larger WC, poorer cognitiveexe-func control, shorter telomeres, consistently raised neuronal glia injury, fewer retinal arteries, narrower arteries, wider veins and a larger optic cup/disc ratio (C/D) compared to the non-Stressed group. Furthermore, of the stroke risk markers, arterial narrowing was related to glaucoma risk with a greater C/D, whilst retinal vein widening was related to HOMA-IR, poor cognitiveexe-func control and neuronal glia injury (Adjusted R2 0.30; p ≤ 0.05). These associations were not evident in the non-Stressed group. Logistic regression associations between the Stressed phenotype and four dementia risk markers (cognitiveexe-func, telomere length, NSE and WC) comprised a Stress syndrome prototype (area under the curve 0.80; sensitivity/specificity 85%/58%; p ≤ 0.001). The Stress syndrome prototype reflected risk for HOMA-IR (odds ratio (OR) 7.72) and retinal glia ischemia (OR 1.27) and vein widening (OR 1.03). The Stressed phenotype was associated with neuronal glia injury and retinal ischemia, potentiating glaucoma risk. The detrimental effect of chronic stress exemplified a Stress syndrome prototype reflecting risk for type 3 diabetes, neurodegeneration and ischemic stroke.
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| 8. |
- Malan, Leoné, et al.
(författare)
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Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke : the SABPA study
- 2021
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Ingår i: Cardiovascular Journal of Africa. - 1995-1892. ; 32:1, s. 7-18
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Low or high sympatho-adrenal-medullary axis (SAM) and hypothalamic-pituitary-adrenal axis (HPA) dysregulation reflect chronic stress. Retinal vessel dynamics may relate to SAM, HPA activity and stroke risk. Our objectives were therefore to assess the relationships between retinal vessel, SAM and HPA responses, and to determine stroke risk.METHODS: A prospective bi-ethnic gender cohort (n = 275, 45 ± 9 years) was included. Urine/serum/saliva samples for SAM [norepinephrine:creatinine ratio (u-NE)] and HPA [adrenocorticotrophic hormone (ACTH), cortisol] were obtained at baseline, three-year follow up and upon flicker light-induced provocation. Diastolic ocular perfusion pressure was measured as a marker of hypo-perfusion. Retinal arterial narrowing and venous widening calibres were quantified from digital images in the mydriatic eye. A validated stress and stroke risk score was applied.RESULTS: An interaction term was fitted for venous dilation in u-NE tertiles (p ≤ 0.05) and not in u-NE median/quartiles/quintiles. Independent of race or gender, tertile 1 (low u-NE) had a 112% increase in u-NE, decreases in cortisol, and no changes in ACTH over three years (positive feedback). Tertile 3 (high u-NE) contradictorily had decreases in u-NE and cortisol, and increases in ACTH (negative feedback). In tertile 1, reduced arterial dilation, and faster arterial vasoconstriction and narrowing were related to higher SAM activity and hypo-perfusion (p ≤ 0.05), whereas delayed venous dilation, recovery and widening were related to cortisol hypo-secretion (p ≤ 0.05). In tertile 1, delayed venous recovery responses predicted stress and stroke risk [odds ratio 4.8 (1.2-19.6); p = 0.03]. These associations were not found in u-NE tertiles 2 and 3.CONCLUSIONS: In response to low norepinephrine, a reflex increase in SAM activity occurred, enhancing arterial vasoconstriction and hypo-perfusion. Concomitant HPA dysregulation attenuated retinal vein vasoactivity and tone, reflecting delayed vein recovery responses and non-adaptation to stress. These constrained vein recovery responses are indicative of increased chronic stress and stroke risk.
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| 10. |
- Plan, Anders, et al.
(författare)
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Exceptional preservation of reidite in the Rochechouart impact structure, France: New insights into shock deformation and phase transition of zircon
- 2021
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Ingår i: Meteoritics and Planetary Science. - : Wiley. - 1086-9379 .- 1945-5100. ; 56:10, s. 1795-1828
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Tidskriftsartikel (refereegranskat)abstract
- Reidite, the high-pressure zircon (ZrSiO4) polymorph, is a diagnostic indicator of impact events. Natural records of reidite are, however, scarce, occurring mainly as micrometer-sized lamellae, granules, and dendrites. Here, we present a unique sequence of shocked zircon grains found within a clast from the Chassenon suevitic breccia (shock stageIII) from the ~200 Ma, 20–50 km wide Rochechouart impact structure in France. Our study comprises detailed characterization with scanning electron microscopy coupled with electron backscatter diffraction with the goal of investigating the stability and response of ZrSiO4 under extreme P–T conditions. The shocked zircon grains have preserved various amounts of reidite ranging from 4% up to complete conversion. The grains contain various variants of reidite, including the common habits: lamellae and granular reidite. In addition, three novel variants have been identified: blade, wedge, and massive domains. Several of these crosscut and offset each other, revealing that reidite can form at multiple stages during an impact event. Our data provide evidence that reidite can be preserved in impactites to a much greater extent than previously documented. We have further characterized reversion products of reidite in the form of fully recrystallized granular zircon grains and minute domains of granular zircon in reidite-bearing grains that occur in close relationship to reidite. Neoblasts in these grains have a distinct crystallography that is the result of systematic inheritance of reidite. We interpret that the fully granular grains have formed from prolonged exposure of temperatures in excess of 1200 °C. Reidite-bearing grains with granular domains might signify swift quenching from temperatures close to 1200 °C. Grains subjected to these specific conditions therefore underwent partial zircon-to-reidite reversion, instead of full grain recrystallization. Based on our ZrSiO4 microstructural constraints, we decipher the grains evolution at specific P–T conditions related to different impact stages, offering further understanding of the behavior of ZrSiO4 during shock.
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