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  • American Physiological Society  (112)
  • Biology  (112)
  • 1
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 290, No. 6 ( 2006-06), p. H2516-H2521
    Abstract: A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK −/− ) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity ( V max ) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK −/− mice, both at baseline and 4 wk after myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all CK −/− mice, but ejection fraction (EF) remained normal. V max , however, was significantly reduced in the CK −/− mice [wild-type, 2.32 ± 0.09 vs. CK −/− , 1.43 ± 0.16 cm/s, P 〈 0.05; and wild-type MI, 1.53 ± 0.11 vs. CK −/− MI, 1.26 ± 0.11 cm/s, P = not significant (NS), P 〈 0.05 vs. baseline]. Myocardial perfusion was also lower in the CK −/− mice (wild-type, 6.68 ± 0.27 vs. CK −/− , 4.12 ± 0.63 ml/g·min, P 〈 0.05; and wild-type MI, 3.97 ± 0.65 vs. CK −/− MI, 3.71 ± 0.57 ml/g·min, P = NS, P 〈 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK −/− phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2006
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 2
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 285, No. 6 ( 2003-12), p. H2712-H2721
    Abstract: Our purpose was to study morphological, functional, and metabolic changes induced by chronic ischemia in myocardium supplied by the stenotic vessel and in the remote area by MR techniques. A new technique of image fusion is proposed for analysis of coronary artery stenosis involving coronary MR angiography and spectroscopic imaging. Cine-MRI was performed 2 wk after induction of coronary stenosis. Global heart function and regional wall thickening were determined in 11 Wistar rats with stenosis and compared with 7 control rats. Two weeks after stenosis was induced, spin-labeling MRI for measurement of perfusion was performed in 14 isolated hearts. In eight isolated hearts with coronary stenosis, MR spectroscopy was performed, followed by angiography. 31 P metabolite maps were fused with three-dimensional coronary angiograms. Induction of stenosis led to reduced segmental wall thickening (control: 75 ± 9%, ischemic region: 9 ± 3%, P 〈 0.05 vs. control) but also to impaired function of the remote region and lower cardiac output. Perfusion was reduced by 74.9 ± 4.0% within ischemic segments compared with a septal control region. The phosphocreatine (PCr)/ATP ratio as a marker of ischemia was reduced in the region associated with stenosis (1.09 ± 0.09) compared with remote (1.27 ± 0.08) and control hearts (1.43 ± 0.08; P 〈 0.05). The histological fraction of fibrosis within the ischemic region (12.8 ± 1.4%) correlated to ATP signal reduction from remote to the ischemic region ( r = 0.71, P 〈 0.05), but not to reduced wall thickening. Coronary narrowing caused declining function accompanied by diminished PCr/ATP, indicating impaired energy metabolism. Neither decline of function nor PCr signal decline correlated to fraction of fibrosis in histology. In contrast, reduction of ATP correlated to fibrosis and therefore to loss of viability. Impaired function within the ischemic region is associated with decreased PCr. Function of the remote region was affected as well. The fusion of PCr metabolite maps and the coronary angiogram may help to assess coronary morphology and resulting metabolic changes simultaneously.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2003
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    American Physiological Society ; 2011
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 301, No. 4 ( 2011-10), p. H1678-H1686
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 301, No. 4 ( 2011-10), p. H1678-H1686
    Abstract: In humans, cerebrovascular responses to alterations in arterial Pco 2 and Po 2 are well documented. However, few studies have investigated human coronary vascular responses to alterations in blood gases. This study investigated the extent to which the cerebral and coronary vasculatures differ in their responses to euoxic hypercapnia and isocapnic hypoxia in healthy volunteers. Participants ( n = 15) were tested at rest on two occasions. On the first visit, middle cerebral artery blood velocity ( V̄ P ) was assessed using transcranial Doppler ultrasound. On the second visit, coronary sinus blood flow (CSBF) was measured using cardiac MRI. For comparison with V̄ P , CSBF was normalized to the rate pressure product [an index of myocardial oxygen consumption; normalized (n)CSBF] . Both testing sessions began with 5 min of euoxic [end-tidal Po 2 (Pet O 2 ) = 88 Torr] isocapnia [end-tidal Pco 2 (Pet CO 2 ) = +1 Torr above resting values]. Pet O 2 was next held at 88 Torr, and Pet CO 2 was increased to 40 and 45 Torr in 5-min increments. Participants were then returned to euoxic isocapnia for 5 min, after which Pet O 2 was decreased from 88 to 60, 52 and 45 Torr in 5-min decrements. Changes in V̄ P and nCSBF were normalized to isocapnic euoxic conditions and indexed against Pet CO 2 and arterial oxyhemoglobin saturation. The V̄ P gain for euoxic hypercapnia (%/Torr) was significantly higher than nCSBF ( P = 0.030). Conversely, the V̄ P gain for isocapnic hypoxia (%/%desaturation) was not different from nCSBF ( P = 0.518). These findings demonstrate, compared with coronary circulation, that the cerebral circulation is more sensitive to hypercapnia but similarly sensitive to hypoxia.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2011
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    American Physiological Society ; 2002
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 283, No. 6 ( 2002-12-01), p. H2411-H2419
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 283, No. 6 ( 2002-12-01), p. H2411-H2419
    Abstract: 0.1152/ajpheart. 01098.2001.—Arteriogenesis has been associated with the presence of monocytes/macrophages within the collateral vessel wall. We tested the hypothesis that arteriogenesis is functionally linked to the concentration of circulating blood monocytes. Monocyte concentrations in peripheral blood were manipulated by single injections of the antimetabolite 5-fluorouracil (5-FU), resulting in a marked rebound effect in New Zealand White rabbits. Collateral artery growth was assessed by the use of a model of acute femoral artery ligation. Seven days after ligation, collateral conductance and the number of visible collateral arteries were increased in the rebound group. This increase was accompanied by an increased monocyte accumulation as demonstrated by immunohistology in the thigh 3 days after surgery. In a second animal model (129S2/SvHsd mice), 5-FU treatment caused a remarkable decrease in blood monocyte numbers at day 4, followed by a rebound effect at day 12. Foot blood flow, assessed by laser-Doppler imaging before and at various time points after surgery, increased from day 7 through day 21 in mice from the rebound group. In contrast, ligation during the phase of monocyte depletion resulted in a reduction of blood flow reconstitution. This inhibition could be reversed by an injection of isolated monocytes. In conclusion, we have demonstrated a functional link between the monocyte concentration in the peripheral blood and the enhancement of arteriogenesis.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2002
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 5
    In: Journal of Applied Physiology, American Physiological Society, Vol. 96, No. 5 ( 2004-05), p. 1701-1713
    Abstract: Remodeling of the airway smooth muscle (ASM) cell has been proposed to play an important role in airway hyperresponsiveness. Using a functional assay, we have assessed remodeling of the cultured rat ASM cell and the role of heat shock protein (HSP) 27 in that process. To probe remodeling dynamics, we measured spontaneous motions of an individual Arg-Gly-Asp-coated microbead that was anchored to the cytoskeleton. We reasoned that the bead could not move unless the microstructure to which it is attached rearranged; if so, then its mean square displacement (MSD) would report ongoing internal reorganizations over time. Each bead displayed a random, superdiffusive motion; MSD increased with time as ∼ t 1.7 , whereas an exponent of unity would be expected for a simple passive diffusion. Increasing concentrations of cytochalasin-D or latrunculin-A caused marked increases in the MSD, whereas colchicine did not. Treatments with PDGF or IL-1β, but not transforming growth factor-β, caused decreases in the MSD, the extent of which rank-ordered with the relative potency of these agents in eliciting the phosphorylation of HSP27. The chemical stressors anisomycin and arsenite each increased the levels of HSP27 phosphorylation and, at the same time, decreased bead motions. In particular, arsenite prevented and even reversed the effects of cytochalasin-D on bead motions. Finally, ASM cells overexpressing phospho-mimicking human HSP27, but not wild-type or phosphorylation-deficient HSP27, exhibited decreases in bead motions that were comparable to the arsenite response. Taken together, these results show that phosphorylated HSP27 favors reduced bead motions that are probably due to stabilization of the actin cytoskeleton.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    RVK:
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2004
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 6
    Online Resource
    Online Resource
    American Physiological Society ; 2004
    In:  Journal of Applied Physiology Vol. 96, No. 5 ( 2004-05), p. 1794-1799
    In: Journal of Applied Physiology, American Physiological Society, Vol. 96, No. 5 ( 2004-05), p. 1794-1799
    Abstract: Venous occlusion plethysmography is widely used to assess forearm blood flow (FBF). We compared the established Hokanson system (HEC4) with a newly developed Filtrass 2001 system (F2001). The HEC4 uses mercury-in-Silastic strain gauges, whereas F2001 detects volume changes with a nonmercury linear displacement device. The aim of this study was to evaluate the new F2001 against the HEC4 in terms of repeatability and systematic bias. Ten subjects were studied on 4 separate days in random order using either the HEC4 on both arms, the F2001 on both arms, the HEC4 on the right arm with the F2001 on the left, or the F2001 on the right arm and the HEC4 on the left. Stroop's colored word conflict test and postocclusive hyperemia were used to increase FBF, and lower body negative pressure was used to lower FBF. Stroop's colored word conflict test and lower body negative pressure increased (24.6 ± 1.5%, n = 240, P 〈 0.0001) and decreased (18.7 ± 0.8%, n = 240, P 〈 0.0001) FBF, respectively. Postocclusive hyperemia after occlusion times of 5, 8, and 13 min substantially increased FBF by 390 ± 86, 756 ± 217, and 851 ± 132%, respectively. Repeatability was not different between the devices (0.10 ± 2.37 vs. -0.47 ± 1.92 l/min, n = 125, P 〉 0.05), and there was no systematic bias. The F2001 is a newly developed plethysmography system that does not utilize mercury and is suitable for assessing changes of FBF in physiological studies.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    RVK:
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2004
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 7
    In: Journal of Applied Physiology, American Physiological Society, Vol. 110, No. 5 ( 2011-05), p. 1432-1438
    Abstract: Many people spend an increasing amount of time in front of computer screens equipped with light-emitting diodes (LED) with a short wavelength (blue range). Thus we investigated the repercussions on melatonin (a marker of the circadian clock), alertness, and cognitive performance levels in 13 young male volunteers under controlled laboratory conditions in a balanced crossover design. A 5-h evening exposure to a white LED-backlit screen with more than twice as much 464 nm light emission {irradiance of 0,241 Watt/(steradian × m 2 ) [W/(sr × m 2 )], 2.1 × 10 13 photons/(cm 2 × s), in the wavelength range of 454 and 474 nm} than a white non-LED-backlit screen [irradiance of 0,099 W/(sr × m 2 ), 0.7 × 10 13 photons/(cm 2 × s), in the wavelength range of 454 and 474 nm] elicited a significant suppression of the evening rise in endogenous melatonin and subjective as well as objective sleepiness, as indexed by a reduced incidence of slow eye movements and EEG low-frequency activity (1–7 Hz) in frontal brain regions. Concomitantly, sustained attention, as determined by the GO/NOGO task; working memory/attention, as assessed by “explicit timing”; and declarative memory performance in a word-learning paradigm were significantly enhanced in the LED-backlit screen compared with the non-LED condition. Screen quality and visual comfort were rated the same in both screen conditions, whereas the non-LED screen tended to be considered brighter. Our data indicate that the spectral profile of light emitted by computer screens impacts on circadian physiology, alertness, and cognitive performance levels. The challenge will be to design a computer screen with a spectral profile that can be individually programmed to add timed, essential light information to the circadian system in humans.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    RVK:
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2011
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 8
    Online Resource
    Online Resource
    American Physiological Society ; 2012
    In:  Journal of Applied Physiology Vol. 112, No. 1 ( 2012-01-01), p. 159-166
    In: Journal of Applied Physiology, American Physiological Society, Vol. 112, No. 1 ( 2012-01-01), p. 159-166
    Abstract: Utilizing micro-X-ray CT (μCT) imaging, we sought to generate an atlas of in vivo and intact/ex vivo lungs from normal murine strains. In vivo imaging allows visualization of parenchymal density and small airways (15–28 μm/voxel). Ex vivo imaging of the intact lung via μCT allows for improved understanding of the three-dimensional lung architecture at the alveolar level with voxel dimensions of 1–2 μm. μCT requires that air spaces remain air-filled to detect alveolar architecture while in vivo structural geometry of the lungs is maintained. To achieve these requirements, a fixation and imaging methodology that permits nondestructive whole lung ex vivo μCT imaging has been implemented and tested. After in vivo imaging, lungs from supine anesthetized C57Bl/6 mice, at 15, 20, and 25 cmH 2 O airway pressure, were fixed in situ via vascular perfusion using a two-stage flushing system while held at 20 cmH 2 O airway pressure. Extracted fixed lungs were air-dried. Whole lung volume was acquired at 1, 7, 21, and 〉 70 days after the lungs were dried and served as validation for fixation stability. No significant shrinkage was observed: +8.95% change from in vivo to fixed lung ( P = 0.12), −1.47% change from day 1 to day 7 ( P = 0.07), −2.51% change from day 1 to day 21 ( P = 0.05), and −4.90% change from day 1 to day 70 and thereafter ( P = 0.04). μCT evaluation showed well-fixed alveoli and capillary beds correlating with histological analysis. A fixation and imaging method has been established for μCT imaging of the murine lung that allows for ex vivo morphometric analysis, representative of the in vivo lung.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    RVK:
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2012
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 9
    Online Resource
    Online Resource
    American Physiological Society ; 2000
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 279, No. 6 ( 2000-12-01), p. H2587-H2592
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 279, No. 6 ( 2000-12-01), p. H2587-H2592
    Abstract: A close relationship exists between regional myocardial blood flow (RMBF) and function during acute coronary inflow restriction (perfusion-contraction matching). However, the relationship of flow and function during coronary microvascular obstruction is unknown. In 12 anesthetized dogs, the left circumflex coronary artery was perfused from an extracorporeal circuit. After control measurements, 3,000 microspheres (42 μm diameter) per milliliter per minute inflow were injected to cause a microembolism (ME, n = 6). With unchanged systemic hemodynamics and RMBF, posterior systolic wall thickening (PWT) decreased from 19.8 ± 1.9% SD at control to 13.3 ± 4.0, 10.3 ± 3.8, and 6.9 ± 4.7% ( P 〈 0.05 vs. control) at 1, 4, and 8 h, respectively. For comparison, inflow was progressively reduced to match PWT to that of the ME group at 1, 4, and 8 h (stenosis, STE, n = 6). RMBF in the STE group was reduced in proportion to PWT. Infarct size was not different among groups (6.5 ± 4.5 vs. 3.4 ± 3.2%). However, the number of leukocytes infiltrating the area at risk was significantly greater in the ME group than in the STE group. Coronary microembolization results in perfusion-contraction mismatch and is associated with an inflammatory response.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2000
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    American Physiological Society ; 2003
    In:  Physiological Reviews Vol. 83, No. 1 ( 2003-01-01), p. 253-307
    In: Physiological Reviews, American Physiological Society, Vol. 83, No. 1 ( 2003-01-01), p. 253-307
    Abstract: Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.
    Type of Medium: Online Resource
    ISSN: 0031-9333 , 1522-1210
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2003
    detail.hit.zdb_id: 1471693-8
    SSG: 12
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