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  • 1.
    Eiken, Ola
    et al.
    Karolinska Inst, Swedish Def Res Agcy.
    Kolegard, Roger
    Karolinska Inst, Swedish Def Res Agcy.
    Mekjavic, Igor B.
    Jozef Stefan Inst, Dept Automat Biocybernet & Robot.
    Pressure-distension relationship in arteries and arterioles in response to 5 wk of horizontal bedrest2008In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 295, no 3, p. H1296-H1302Article in journal (Refereed)
    Abstract [en]

    We hypothesized that exposure to prolonged recumbency (bedrest), and thus reductions of intravascular pressure gradients, increases pressure distension in arteries/arterioles in the legs. Ten subjects underwent 5 wk of horizontal bedrest. Pressure distension was investigated in arteries and arterioles before and after the bedrest, with the subject seated or supine in a hyperbaric chamber with either one arm or a lower leg protruding through a hole in the chamber door. Increased pressure in the vessels of the arm/leg was accomplished by increasing chamber pressure. Vessel diameter and flow were measured in the brachial and posterior tibial arteries using Doppler ultrasonography. Electrical tissue impedance was measured in the test limb. Bedrest increased (P < 0.01) pressure distension threefold in the tibial artery (from 8 +/- 7% to 24 +/- 11%) and by a third (P < 0.05) in the brachial artery (from 15 +/- 9% to 20 +/- 10%). The pressure-induced increase in tibial artery flow was more pronounced (P < 0.01) after (50 +/- 39 ml/min) than before (13 +/- 23 ml/min) bedrest, whereas the brachial artery flow response was unaffected by bedrest. The pressure-induced decrease in tissue impedance in the leg was more pronounced (P < 0.01) after (16 +/- 7%) than before (10 +/- 6%) bedrest, whereas bedrest did not affect the impedance response in the arm. Thus, withdrawal of the hydrostatic pressure gradients that act along the blood vessels in erect posture markedly increases pressure distension in dependent arteries and arterioles.

  • 2.
    Holzapfel, Gerhard A.
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Sommer, Gerhard
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, Christian T.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Regitnig, P
    Determination of layer-specific mechanical properties of human coronary arteries with nonatherosclerotic intimal thickening and related constitutive modeling2005In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 289, no 5, p. H2048-H2058Article in journal (Refereed)
    Abstract [en]

    At autopsy, 13 nonstenotic human left anterior descending coronary arteries [71.5 +/- 7.3 ( mean +/- SD) yr old] were harvested, and related anamnesis was documented. Preconditioned prepared strips (n = 78) of segments from the midregion of the left anterior descending coronary artery from the individual layers in axial and circumferential directions were subjected to cyclic quasi-static uniaxial tension tests, and ultimate tensile stresses and stretches were documented. The ratio of outer diameter to total wall thickness was 0.189 +/- 0.014; ratios of adventitia, media, and intima thickness to total wall thickness were 0.4 +/- 0.03, 0.36 +/- 0.03, and 0.27 +/- 0.02, respectively; axial in situ stretch of 1.044 +/- 0.06 decreased with age. Stress-stretch responses for the individual tissues showed pronounced mechanical heterogeneity. The intima is the stiffest layer over the whole deformation domain, whereas the media in the longitudinal direction is the softest. All specimens exhibited small hysteresis and anisotropic and strong nonlinear behavior in both loading directions. The media and intima showed similar ultimate tensile stresses, which are on average three times smaller than ultimate tensile stresses in the adventitia (1,430 +/- 604 kPa circumferential and 1,300 +/- 692 kPa longitudinal). The ultimate tensile stretches are similar for all tissue layers. A recently proposed constitutive model was extended and used to represent the deformation behavior for each tissue type over the entire loading range. The study showed the need to model nonstenotic human coronary arteries with nonatherosclerotic intimal thickening as a composite structure composed of three solid mechanically relevant layers with different mechanical properties. The intima showed significant thickness, load-bearing capacity, and mechanical strength compared with the media and adventitia.

  • 3.
    Johnson, Jonas
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering.
    Håkansson, Felicia
    Shahgaldi, Kambiz
    KTH, School of Technology and Health (STH), Medical Engineering.
    Manouras, Aristomenis
    KTH, School of Technology and Health (STH), Medical Engineering.
    Norman, Mikael
    Sahlén, Anders
    Impact of tachycardia and sympathetic stimulation by cold pressor test on cardiac diastology and arterial function in elderly females2013In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 304, no 7, p. H1002-H1009Article in journal (Refereed)
    Abstract [en]

    Johnson J, Hakansson F, Shahgaldi K, Manouras A, Norman M, Sahlen A. Impact of tachycardia and sympathetic stimulation by cold pressor test on cardiac diastology and arterial function in elderly females. Am J Physiol Heart Circ Physiol 304: H1002-H1009, 2013. First published January 25, 2013; doi:10.1152/ajpheart.00837.2012.-Abnormal vascular-ventricular coupling has been suggested to contribute to heart failure with preserved ejection fraction in elderly females. Failure to increase stroke volume (SV) during exercise occurs in parallel with dynamic changes in arterial physiology leading to increased afterload. Such adverse vascular reactivity during stress may reflect either sympathoexcitation or be due to tachycardia. We hypothesized that afterload elevation induces SV failure by transiently attenuating left ventricular relaxation, a phenomenon described in animal research. The respective roles of tachycardia and sympathoexcitation were investigated in n = 28 elderly females (70 +/- 4 yr) carrying permanent pacemakers. At rest, during atrial tachycardia pacing (ATP; 100 min(-1)) and during cold pressor test (hand immersed in ice water), we performed Doppler echocardiography (maximal untwist rate analyzed by speckle tracking imaging of rotational mechanics) and arterial tonometry (arterial stiffness estimated as augmentation index). Estimation of arterial compliance was based on an exponential relationship between arterial pressure and volume. We found that ATP produced central hypovolemia and a reduction in SV which was larger in patients with stiffer arteries (higher augmentation index). There was an associated adverse response of arterial compliance and vascular resistance during ATP and cold pressor test, causing an overall increase in afterload, but nonetheless enhanced maximal rate of untwist and no evidence of afterload-dependent failure of relaxation. In conclusion, tachycardia and cold provocation in elderly females produces greater vascular reactivity and SV failure in the presence of arterial stiffening, but SV failure does not arise secondary to afterload-dependent attenuation of relaxation.

  • 4.
    Keramidas, Michail E.
    et al.
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Kölegård, Roger
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Mekjavic, Igor B.
    Eiken, Ola
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    PlanHab: Hypoxia exaggerates the bedrest-induced reduction in peak oxygen uptake during upright cycle-ergometry2016In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539Article in journal (Refereed)
    Abstract [en]

    The study examined the effects of hypoxia and horizontal bedrest, separately and in combination, on peak oxygen uptake (VO2peak) during upright cycle-ergometry. Ten male lowlanders underwent three 21-day confinement periods, in a counterbalanced order: i) normoxic bedrest (NBR; PIO2 = 133.1 ± 0.3 mmHg), ii) hypoxic bedrest (HBR; PIO2 = 90.0 ± 0.4 mmHg), and iii) hypoxic ambulation (HAMB; PIO2 = 90.0 ± 0.4 mmHg). Before and after each confinement, subjects performed two incremental-load trials to exhaustion, while inspiring either room-air (AIR), or a hypoxic gas (HYPO; PIO2 = 90.0 ± 0.4 mmHg). Changes in regional oxygenation of the vastus lateralis muscle and the frontal cerebral cortex were monitored with near-infrared spectroscopy. Cardiac output (CO) was recorded using a bioimpedance method. The AIR VO2peak was decreased by both HBR (~13.5%; p ≤ 0.001) and NBR (~8.6%; p ≤ 0.001), with greater drop after HBR (p = 0.01). The HYPO VO2peak was also reduced by HBR (-9.7%; p ≤ 0.001) and NBR (-6.1%; p ≤ 0.001). Peak CO was lower after both bedrest interventions, and especially after HBR (HBR: ~13%, NBR: ~7%; p ≤ 0.05). Exercise-induced alterations in muscle and cerebral oxygenation were blunted in a similar manner after both bedrest confinements. No changes were observed in HAMB. Hence, the bedrest-induced decrease in VO2peak was exaggerated by hypoxia, most likely due to a reduction in convective O2 transport, as indicated by the lower peak values of CO.

  • 5. Sahlen, Anders
    et al.
    Abdula, Göran
    Norman, Mikael
    Manouras, Aristomenis
    KTH, School of Technology and Health (STH), Medical Engineering.
    Brodin, Lars-Ake
    KTH, School of Technology and Health (STH), Medical Engineering.
    Lund, Lars H.
    Shahgaldi, Kambiz
    KTH, School of Technology and Health (STH), Medical Engineering.
    Winter, Reidar
    KTH, School of Technology and Health (STH), Medical Engineering.
    Arterial vasodilatory and ventricular diastolic reserves determine the stroke volume response to exercise in elderly female hypertensive patients2011In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 301, no 6, p. H2433-H2441Article in journal (Refereed)
    Abstract [en]

    Sahlen A, Abdula G, Norman M, Manouras A, Brodin LA, Lund LH, Shahgaldi K, Winter R. Arterial vasodilatory and ventricular diastolic reserves determine the stroke volume response to exercise in elderly female hypertensive patients. Am J Physiol Heart Circ Physiol 301: H2433-H2441, 2011. First published September 16, 2011; doi:10.1152/ajpheart.00555.2011.-Elderly female hypertensives with arterial stiffening constitute a majority of patients with heart failure with preserved ejection fraction (HFpEF), a condition characterized by inability to increase cardiac stroke volume (SV) with physical exercise. As SV is determined by the interaction between the left ventricle (LV) and its load, we wished to study the role of arterial hemodynamics for exertional SV reserve in patients at high risk of HFpEF. Twenty-one elderly (67 +/- 9 yr) female hypertensive patients were studied at rest and during supine bicycle stress using echocardiography including pulsed-wave Doppler to record flow in the LV outflow tract and arterial tonometry for central arterial pressure waveforms. Arterial compliance was estimated based on an exponential relationship between pressure and volume. The ratio of aortic pressure-to-flow in early systole was used to derive characteristic impedance, which was subsequently subtracted from total resistance (mean arterial pressure/cardiac output) to yield systemic vascular resistance (SVR). It was found that patients with depressed SV reserve (NoRes; reserve <15%; n = 10) showed decreased arterial compliance during exercise, while patients with SV reserve >= 15% (Res; n = 11) showed increased compliance. Exercise produced parallel increases in LV end-diastolic volume and arterial volume in Res patients while NoRes patients exhibited a lesser decrease in SVR and a drop in effective arterial volume. Poor SV reserve in elderly female hypertensives is due to simultaneous failure of LV preload and arterial vasodilatory reserves. Abnormal arterial function contributes to a high risk of HFpEF in these patients.

  • 6.
    Siebenmann, Christoph
    et al.
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Rasmussen, P.
    Sorensen, H.
    Bonne, T. C.
    Zaar, M.
    Aachmann-Andersen, N. J.
    Nordsborg, N. B.
    Secher, N. H.
    Lundby, C.
    Hypoxia increases exercise heart rate despite combined inhibition of beta-adrenergic and muscarinic receptors2015In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 308, no 12, p. H1540-H1546Article in journal (Refereed)
    Abstract [en]

    Hypoxia increases the heart rate response to exercise, but the mechanism(s) remains unclear. We tested the hypothesis that the tachycardic effect of hypoxia persists during separate, but not combined, inhibition of beta-adrenergic and muscarinic receptors. Nine subjects performed incremental exercise to exhaustion in normoxia and hypoxia (fraction of inspired O-2 = 12%) after intravenous administration of 1) no drugs (Cont), 2) propranolol (Prop), 3) glycopyrrolate (Glyc), or 4) Prop + Glyc. HR increased with exercise in all drug conditions (P < 0.001) but was always higher at a given workload in hypoxia than normoxia (P < 0.001). Averaged over all workloads, the difference between hypoxia and normoxia was 19.8 +/- 13.8 beats/min during Cont and similar (17.2 +/- 7.7 beats/min, P = 0.95) during Prop but smaller (P < 0.001) during Glyc and Prop + Glyc (9.8 +/- 9.6 and 8.1 +/- 7.6 beats/min, respectively). Cardiac output was enhanced by hypoxia (P < 0.002) to an extent that was similar between Cont, Glyc, and Prop + Glyc (2.3 +/- 1.9, 1.7 +/- 1.8, and 2.3 +/- 1.2 l/min, respectively, P > 0.4) but larger during Prop (3.4 +/- 1.6 l/min, P = 0.004). Our results demonstrate that the tachycardic effect of hypoxia during exercise partially relies on vagal withdrawal. Conversely, sympathoexcitation either does not contribute or increases heart rate through mechanisms other than beta-adrenergic transmission. A potential candidate is beta-adrenergic transmission, which could also explain why a tachycardic effect of hypoxia persists during combined beta-adrenergic and muscarinic receptor inhibition.

  • 7. Sommer, G.
    et al.
    Regitnig, P.
    Költringer, L.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Biaxial mechanical properties of intact and layer-dissected human carotid arteries at physiological and supraphysiological loadings2010In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 298, no 3, p. H898-H912Article in journal (Refereed)
    Abstract [en]

    Sommer G, Regitnig P, Koltringer L, Holzapfel GA. Biaxial mechanical properties of intact and layer-dissected human carotid arteries at physiological and supraphysiological loadings. Am J Physiol Heart Circ Physiol 298: H898-H912, 2010. First published December 24, 2009; doi:10.1152/ajpheart.00378.2009.-Specimens of intact wall tubes of human common carotid arteries (CCA), internal carotid arteries (ICA) (n = 11, age 77.6 yr, SD 6.3), and related adventitia and media-intima tubes are mechanically examined. Cyclic, quasi-static extension-inflation tests at different axial stretches are performed on preconditioned tube specimens. Stress-free configurations show significant stress releases in the circumferential direction of the intact CCA and ICA walls and in the axial directions of the intact CCA walls and the CCA and ICA adventitias. All investigated tissues exhibit strong nonlinear, pseudoelastic mechanical behavior with small hysteresis. The "inversion" feature, where the pressure/axial stretch relationship becomes a vertical line, is found only for intact walls. Axial "inversion stretches" are 1.15 (SD 0.06) for CCA and 1.14 (SD 0.06) for ICA, and related external axial forces are 0.43 N (SD 0.15) and 0.30 N (SD 0.22), respectively. Significant negative correlations between age and axial inversion stretches for CCA (r = -0.67, P = 0.03) and ICA (r = -0.29, P = 0.04) are identified. Adventitias are very compliant at low pressures, but change into stiff tubes at high pressures. The burst pressure of the adventitia is beyond 250 kPa. A relatively low burst pressure of similar to 60 kPa is found in the media-intima tubes, in which the pressure/circumferential stretch relationships are almost independent of the axial stretches. Stress analyses indicate a high degree of material anisotropy for all investigated tissues. High circumferential and axial stresses occur in the media-intima tubes at physiological conditions. The obtained data are intended to serve for an improvement of constitutive laws, determination of constitutive parameters, and enhancing our knowledge of the mechanical functions of arteries and their associated layers in specific pathophysiological and clinical problems, such as hypertension and angioplasty with stenting.

  • 8.
    Sundblad, Patrik
    et al.
    KTH, School of Technology and Health (STH), Environmental Physiology (Closed 20130701).
    Wranne, B
    Influence of posture on left ventricular long- and short-axis shortening.2002In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 283, no 4, p. H1302-1306Article in journal (Refereed)
    Abstract [en]

    End-diastolic volume and left ventricular stroke volume are increased in the supine compared with upright position, but the contribution of long-axis (LAS) and short-axis shortening (SAS) to these changes with change in posture has not been established. We examined long- and short-axis motion and dimensions with echocardiography in 10 healthy subjects in the upright and supine position. Long-axis length at end diastole was almost identical, whereas the diastolic short-axis diameter was increased in the supine position. At end systole, there was a decreased long-axis length and increased short-axis length in the supine vs. upright position. Both LAS and SAS were enhanced in supine vs. upright positions [LAS: 9.3 +/- 2.2 vs. 15.1 +/- 3.1 mm (P < 0.001); SAS: 12.7 +/- 3.2 vs. 16.3 +/- 2.8 mm (P < 0.001)], presumably via Starling mechanisms. LAS increased more in the lateral part of the mitral annulus than in the septal part [7.7 +/- 2.6 vs. 4.0 +/- 2.8 mm (P < 0.006)], which implies that the more spherical form, in the supine position, induces more stretch at the lateral free wall than in the ventricular septum. These findings support the notion that Starling mechanisms affect systolic LAS.

  • 9. Wandt, B.
    et al.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Lundback, S.
    Misinterpretation about the contribution of the left ventricular long-axis shortening to the stroke volume2006In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 291, no 5, p. H2550-H2550Article in journal (Refereed)
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