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  • 1.
    Andersson, Therese
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Low-level mechanical stimulation is sufficient to improve tendon healing in rats2012In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 113, no 9, p. 1398-1402Article in journal (Refereed)
    Abstract [en]

    Treatment of tendon injuries often involves immobilization. However, immobilization might not prevent mild involuntary isometric muscle contraction. The effect of weak forces on tendon healing is therefore of clinical interest. Studies of tendon healing with various methods for load reduction in rat Achilles tendon models show a consistent reduction in tendon strength by at least half, compared with voluntary cage activity. Unloading was not complete in any of these models, and the healing tendon was therefore still exposed to mild mechanical stimulation. By reducing the forces acting on the tendon even further, we now studied the effects of this mild stimulation. Rat Achilles tendons were transected and allowed to heal spontaneously under four different loading conditions: 1) normal cage activity; 2) calf muscle paralysis induced by botulinum toxin A (Botox); 3) tail suspension; 4) Botox and tail suspension, combined, to eliminate even mild stimulation. Healing was evaluated by mechanical testing after 8 days. Botox alone and suspension alone both reduced tendon callus size (transverse area), thereby impairing its strength compared with normal cage activity. The combination of Botox and suspension did not further reduce tendon callus size but drastically impaired the material properties of the tendon callus compared with each treatment alone. The peak force was only a fifth of that in the normal cage activity group. The results indicate that also the mild loading that occurs with either Botox or suspension alone stimulates tendon healing. This stimulation appears to affect mainly tissue quality, whereas stronger stimulation also increases callus size.

  • 2.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Editorial: Is inflammation harmless to loaded tendons?2007In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 102, no 1, p. 3-4Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 3.
    Berlin, Gösta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Challoner, KE
    Woodson, RD
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Low-O2 affinity erythrocytes improve performance of ischemic myocardium2002In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 92, no 3, p. 1267-1276Article in journal (Refereed)
    Abstract [en]

    O2 transport and O2 diffusion interact in providing O2 to tissue, but the extent to which diffusion may be critical in the heart is unclear. If O2 diffusion limits mitochondrial oxygenation, a change in blood O2 affinity at constant total O2 transport should alter cardiac O2 consumption (VO2) and function. To test this hypothesis, we perfused isolated isovolumically working rabbit hearts with erythrocytes at physiological blood-gas values and P50 (PO2 required to half-saturate hemoglobin) values at Ph of 7.4 of 17 ▒ 1 Torr (2,3-bisphosphoglycerate depletion) and 33 ▒ 5 Torr (inositol hexaphosphate incorporation). When perfused at 40 and 20% of normal coronary flow, mean VO2 decreased from the control value by 37 and 46% (P < 0.001), and function, expressed as cardiac work, decreased by 38 and 52%, respectively (P < 0.001). Perfusion at higher P50 during low-flow ischemia improved VO2 by 20% (P < 0.001) and function by 36% (P < 0.02). There was also modest improvement at basal flow (P < 0.02 and P < 0.002, respectively). The improvement in VO2 and function due to the P50 increase demonstrates the importance of O2 diffusion in this cardiac ischemia model.

  • 4.
    Eliasson, Pernilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Influence of a single loading episode on gene expression in healing rat Achilles tendons2012In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 2, p. 279-288Article in journal (Refereed)
    Abstract [en]

    Mechanical loading stimulates tendon healing via mechanisms that are largely unknown. Genes will be differently regulated in loaded healing tendons, compared to unloaded, just because of the fact that healing processes have been changed. In order to avoid such secondary effects and study the effect of loading per se, we therefore studied the gene expression response shortly after a single loading episode in otherwise unloaded healing tendons.

    The Achilles tendon was transected in 30 tail suspended rats. The animals were let down from the suspension to load their tendons on a treadmill for 30 min once, 5 days after tendon transection. Gene expression was studied by Affymetrix microarray before, and 3, 12, 24 and 48 h after loading. The strongest response in gene expression was seen 3 hours after loading, when 150 genes were up- or down-regulated (fold change≥ 2, p≤0.05). 12 hours after loading, only 3 genes were up-regulated, while 38 were down-regulated. Less than 7 genes were regulated after 24 and 48 hours. Genes involved in the inflammatory response were strongly regulated at 3 and 12 hours after loading; this included up-regulation of iNOS, PGE synthase, and IL-1β. Also genes involved in wound healing/coagulation, angiogenesis and production of reactive oxygen species were strongly regulated by loading. Microarray results were confirmed for 14 selected genes in a repeat experiment (N=30 rats) using real-time PCR. It was also confirmed that a single loading episode on day 5 increased the strength of the healing tendon on day 12. The fact that there were hardly any regulated genes 24 h after loading suggests that optimal stimulation of healing requires a mechanical loading stimulus every day.

  • 5.
    Eliasson, Pernilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, Therese
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Primary gene response to mechanical loading in healing rat Achilles tendons2013In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 114, no 11, p. 1519-1526Article in journal (Refereed)
    Abstract [en]

    Loading can stimulate tendon healing. In healing rat Achilles tendons, we have found more than 150 genes upregulated or downregulated 3 h after one loading episode. We hypothesized that these changes were preceded by a smaller number of regulatory genes and thus performed a microarray 15 min after a short loading episode, to capture the primary response to loading. We transected the Achilles tendon of 54 rats and allowed them to heal. The hind limbs were unloaded by tail-suspension during the entire experiment, except during the loading episode. The healing tendon tissue was analyzed by mechanical testing, microarray, and quantitative real-time polymerase chain reaction (qRT-PCR). Mechanical testing showed that 5 min of loading each day for 4 days created stronger tissue. The microarray analysis after one loading episode identified 15 regulated genes. Ten genes were analyzed in a repeat experiment with new rats using qRT-PCR. This confirmed the increased expression of four genes: early growth response 2 (Egr2), c-Fos, FosB, and regulation of G protein signaling 1 (Rgs1). The other genes were unaltered. We also analyzed the expression of early growth response 1 (Egr1), which is often coregulated with c-Fos or Egr2, and found that this was also increased after loading. Egr1, Egr2, c-Fos, and FosB are transcription factors that can be triggered by numerous stimuli. However, Egr1 and Egr2 are necessary for normal tendon development, and can induce ectopic expression of tendon markers. The five regulated genes appear to constitute a general activation machinery. The further development of gene regulation might depend on the tissue context.

  • 6.
    Eliasson, Pernilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Fahlgren, Anna
    Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Pasternak, Björn
    Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Unloaded rat Achilles tendons continue to grow, but lose viscoelasticity2007In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 103, no 2, p. 459-463Article in journal (Refereed)
    Abstract [en]

    Tendons can function as springs and thereby preserve energy during cyclic loading. They might also have damping properties, which, hypothetically, could reduce risk of microinjuries due to fatigue at sites of local stress concentration within the tendon. At mechanical testing, damping will appear as hysteresis. How is damping influenced by training or disuse? Does training decrease hysteresis, thereby making the tendon a better spring, or increase hysteresis and thus improve damping? Seventy-eight female 10-wk-old Sprague-Dawley rats were randomized to three groups. Two groups had botulinum toxin injected into the calf muscles to unload the left Achilles tendon through muscle paralysis. One of these groups was given doxycycline, as a systemic matrix metalloproteinase inhibitor. The third group served as loaded controls. The Achilles tendons were harvested after 1 or 6 wk for biomechanical testing. An increase with time was seen in tendon dry weight, wet weight, water content, transverse area, length, stiffness, force at failure, and energy uptake in all three groups (P < 0.001 for each parameter). Disuse had no effect on these parameters. Creep was decreased with time in all groups. The only significant effect of disuse was on hysteresis (P = 0.004) and creep (P = 0.007), which both decreased with disuse compared with control, and on modulus, which was increased (P = 0.008). Normalized glycosaminoglycan content was unaffected by time and disuse. No effect of doxycycline was observed. The results suggest that in growing animals, the tendons continue to grow regardless of mechanical loading history, whereas maintenance of damping properties requires mechanical stimulation.

  • 7. Eriksson, H
    et al.
    Bernard, S
    Glenny, R
    Fedde, R
    polissar, N
    Basaraba, R
    Walther, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Gaughan, E
    McMurphy, R
    Hlastala, M
    Effect of furosemide on pulmonary blood flow distribution in resting and wxercising horses.1999In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 86, p. 2034-2043Article in journal (Refereed)
  • 8.
    Grönkvist, Mikael
    et al.
    Swedish Defence Research Agency, Defence Medicine, Linköping and Karolinska Institutet, Stockholm.
    Bergsten, Eddie
    Swedish Defence Research Agency, Defence Medicine, Linköping and Karolinska Institutet, Stockholm.
    Eiken, Ola
    Swedish Defence Research Agency, Defence Medicine, Linköping and Karolinska Institutet, Stockholm.
    Gustafsson, Per M
    Swedish Defence Research Agency, Defence Medicine, Linköping and Karolinska Institutet, Stockholm and Department of Pediatric Clinical Physiology, Queen Silvia Children's Hospital, Göteborg, Sweden.
    Inter- and intraregional ventilation inhomogeneity in hypergravity and after pressurization of an anti-G suit2003In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 94, no 4, p. 1353-1364Article in journal (Refereed)
    Abstract [en]

    This study assessed the effects of increased gravity in the head-to-foot direction (+Gz) and anti-G suit (AGS) pressurization on functional residual capacity (FRC), the volume of trapped gas (VTG), and ventilation distribution by using inert- gas washout. Normalized phase III slope (SnIII) analysis was used to determine the effects on inter- and intraregional ventilation inhomogeneity. Twelve men performed multiple-breath washouts of SF6 and He in a human centrifuge at +1 to +3 Gzwearing an AGS pressurized to 0, 6, or 12 kPa. Hypergravity produced moderately increased FRC, VTG, and overall and inter- and intraregional inhomogeneities. In normogravity, AGS pressurization resulted in reduced FRC and increased VTG, overall, and inter- and intraregional inhomogeneities. Inflation of the AGS to 12 kPa at +3 Gz reduced FRC markedly and caused marked gas trapping and intraregional inhomogeneity, whereas interregional inhomogeneity decreased. In conclusion, increased +Gzimpairs ventilation distribution not only between widely separated lung regions, but also within small lung units. Pressurizing an AGS in hypergravity causes extensive gas trapping accompanied by reduced interregional inhomogeneity and, apparently, results in greater intraregional inhomogeneity.

  • 9.
    Grönkvist, Mikael
    et al.
    Swedish Defense Research Agency, Department of Defense Medicine, Linköping.
    Bergsten, Eddie
    Swedish Defense Research Agency, Department of Defense Medicine, Linköping.
    Gustafsson, Per M
    Swedish Defense Research Agency, Department of Defense Medicine, Linköping and Department of Paediatrics, Central Hospital, Skövde, Sweden.
    Effects of body posture and tidal volume on inter- and intraregional ventilation distribution in healthy men2002In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 92, no 2, p. 634-642Article in journal (Refereed)
    Abstract [en]

    The influences of body posture and tidal volume (Vt) on inter- and intraregional ventilation inhomogeneity were assessed by normalized phase III slope (SnIII) analysis of multiple-breath washout recordings of SF6 and He in 11 healthy men. Washouts with target Vt of 750, 1,000, and 1,250 ml were performed standing and supine. A linear-fit method was used to establish the contributions of convection-dependent (interregional) (cdi) and diffusion-convection interaction-dependent (intraregional) inhomogeneity (dcdi). Overall inhomogeneity was defined as the sum of cdi and dcdi. The difference in first-breathSnIII for SF6 vs. He, the (SF6 − He)SnIII, served as an index of intra-acinar inhomogeneity. Multiple-regression analysis revealed greater cdi supine vs. standing (P < 0.001) but no significant effects of posture on dcdi or overall inhomogeneity. Larger Vt were associated with greater cdi (P < 0.001), particularly when supine, but reduced dcdi (P < 0.001), overall inhomogeneity (P < 0.001), and (SF6 − He)SnIII (P = 0.031). In conclusion, during resting breathing overall and intraregional ventilation inhomogeneities remain unchanged when the supine posture is assumed and improve with larger Vt, but supine posture and larger breaths result in greater interregional inhomogeneities.

  • 10.
    Gustafsson, Per M
    et al.
    Swedish Defense Research Agency, Department of Defense Medicine, Linköping and Department of Paediatrics, Central Hospital, Skövde, Sweden.
    Eiken, Ola
    Swedish Defense Research Agency, Department of Defense Medicine, Linköping.
    Grönkvist, Mikael
    Swedish Defense Research Agency, Department of Defense Medicine, Linköping.
    Effects of hypergravity and anti-G suit pressure on intraregional ventilation distribution during VC breaths2001In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 31, no 2, p. 637-644Article in journal (Refereed)
    Abstract [en]

    The effects of increased gravity in the head-to-foot direction (+Gz) and pressurization of an anti-G suit (AGS) on total and intraregional intra-acinar ventilation inhomogeneity were explored in 10 healthy male subjects. They performed vital capacity (VC) single-breath washin/washouts of SF6 and He in +1, +2, or +3 Gz in a human centrifuge, with an AGS pressurized to 0, 6, or 12 kPa. The phase III slopes for SF6 and He over 25–75% of the expired VC were used as markers of total ventilation inhomogeneity, and the (SF6 − He) slopes were used as indicators of intraregional intra-acinar inhomogeneity. SF6 and He phase III slopes increased proportionally with increasing gravity, but the (SF6 − He) slopes remained unchanged. AGS pressurization did not change SF6 or He slopes significantly but resulted in increased (SF6 − He) slope differences at 12 kPa. In conclusion, hypergravity increases overall but not intraregional intra-acinar inhomogeneity during VC breaths. AGS pressurization provokes increased intraregional intra-acinar ventilation inhomogeneity, presumably reflecting the consequences of basilar pulmonary vessel engorgement in combination with compression of the basilar lung regions.

  • 11.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Microtrauma stimulates rat Achilles tendon healing via an early gene expression pattern similar to mechanical loading2014In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 116, no 1, p. 54-60Article in journal (Refereed)
    Abstract [en]

    Mechanical loading increases the strength of healing tendons, but also induces small localized bleedings. Therefore, it is unclear if increased strength after loading is a response to mechanotransduction or microtrauma. We have previously found only five genes to be up-regulated 15 min after a single loading episode, of them four were transcription factors. These genes are followed by hundreds of genes after 3 h, many of them involved in inflammation. We now compared healing in mechanically unloaded tendons with or without added microtrauma induced by needling of the healing tissue. Nineteen rats received Botox into the calf muscle to reduce loading, and the Achilles tendon was transected. Ten rats were randomized to needling days 2-5. Mechanical testing on day 8 showed increased strength by 45% in the needling group. Next, another 24 rats were similarly unloaded, and 16 randomized to needling on day 5 after transection. Nineteen characteristic genes, known to be regulated by loading in this model, were analyzed by qRT-PCR. Four of these genes were regulated 15 min after needling. Three of them (Egr1, c-Fos, Rgs1) were among the five regulated genes after loading in a previous study. Sixteen of the 19 genes were regulated after 3 h, in the same way as after loading. In conclusion, needling increased strength, and there was a striking similarity between the gene expression response to needling and mechanical loading. This suggests that the response to loading in early tendon healing can, at least in part, be a response to microtrauma.

  • 12.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Dansac, Arie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Different gene response to mechanical loading during early and late phases of rat Achilles tendon healing2017In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 123, no 4, p. 800-815Article in journal (Refereed)
    Abstract [en]

    Mechanical loading stimulates tendon healing both when applied in the inflammatory phase and in the early remodeling phase of the process, although not necessarily via the same mechanisms. We investigated the gene response to mechanical loading in these two phases of tendon healing. The right Achilles tendon in rats was transected, and the hindlimbs were unloaded by tail suspension. The rats were exposed to 5 min of treadmill running 3 or 14 days after tendon transection. Thereafter, they were resuspended for 15 min or 3 h until euthanasia. The controls were suspended continuously. Gene analysis was first performed by microarray analysis followed by quantitative RTPCR on selected genes, focusing on inflammation. Fifteen minutes after loading, the most important genes seemed to be the transcription factors EGR1 and C-FOS, regardless of healing phase. These transcription factors might promote tendon cell proliferation and differentiation, stimulate collagen production, and regulate inflammation. Three hours after loading on day 3, inflammation was strongly affected. Seven inflammation-related genes were upregulated according to PCR: CCL20, CCL7, IL-6, NFIL3, PTX3, SOCS1, and TLR2. These genes can be connected to macrophages, T cells, and recruitment of leukocytes. According to Ingenuity Pathway Analysis, the recruitment of leukocytes was increased by loading on day 3, which also was confirmed by histology. This inflammation-related gene response was not seen on day 14. Our results suggest that the immediate gene response after mechanical loading is similar in the early and late phases of healing but the late gene response is different. NEW amp; NOTEWORTHY This study investigates the direct effect of mechanical loading on gene expression during different healing phases in tendon healing. One isolated episode of mechanical loading was studied in otherwise unloaded healing tendons. This enabled us to study a time sequence, i.e., which genes were the first ones to be regulated after the loading episode.

  • 13.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Ramstedt, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Health Sciences.
    COX-2 inhibition impairs mechanical stimulation of early tendon healing in rats by reducing the response to microdamage2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 5, p. 534-540Article in journal (Refereed)
    Abstract [en]

    Early tendon healing can be stimulated by mechanical loading and inhibited by cyclooxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs). Therefore, we investigated if impairment of tendon healing by a COX-2 inhibitor (parecoxib) is related to loading. Because loading might infer microdamage, which also stimulates healing, we also investigated if this effect is inhibited by parecoxib. The Achilles tendon was transected in 114 rats. Three degrees of loading were used: full loading, partial unloading, and unloading (no unloading, Botox injections in the plantar flexor muscles, or Botox in combination with tail suspension). For each loading condition, the rats received either parecoxib or saline. In a second experiment, rats were unloaded with Botox, and the tendon was subjected to microdamage by needling combined with either saline or parecoxib. Mechanical testing day 7 showed that there was a significant interaction between loading and parecoxib for peak force at failure (P less than 0.01). However, logarithmic values showed no significant interaction, meaning that we could not exclude that the inhibitory effect of parecoxib was proportionate to the degree of loading. Microbleeding was common in the healing tissue, suggesting that loading caused microdamage. Needling increased peak force at failure (P less than 0.01), and this effect of microdamage was almost abolished by parecoxib (P less than 0.01). Taken together, this suggests that COX-2 inhibition impairs the positive effects of mechanical loading during tendon healing, mainly by reducing the response to microdamage.

  • 14.
    Lanne, T.
    et al.
    Länne, T., Division of Physiology, Department of Medicine and Care, University Hospital, Linköping, Sweden.
    De, Basso R.
    De Basso, R., Division of Physiology, Department of Medicine and Care, University Hospital, Linköping, Sweden.
    Powell, J.T.
    Imperial College, Charing Cross, London, United Kingdom.
    Reply [20]2006In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 100, no 4, p. 1431-1432Other (Other academic)
    Abstract [en]

    [No abstract available]

  • 15.
    Länne, Toste
    et al.
    Linköping University, Department of Medicine and Care, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Debasso, Rachel
    Linköping University, Department of Medicine and Care, Physiology. Linköping University, Faculty of Health Sciences.
    Powell, J. T.
    Imperial Coll Charing Cross, London, UK.
    Influence of fibrillin-1 genotype on aortic stiffness in men: a note of caution - Reply2006In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 100, no 4, p. 1431-1432Article in journal (Other academic)
  • 16.
    Löf, Marie
    et al.
    Linköping University, Department of Biomedicine and Surgery, Nutrition. Linköping University, Faculty of Health Sciences.
    Forsum, Elisabet
    Linköping University, Department of Biomedicine and Surgery, Nutrition. Linköping University, Faculty of Health Sciences.
    Evaluation of bioimpedance spectroscopy for measurements of body water distribution in healthy women before, during, and after pregnancy2004In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 96, no 3, p. 967-973Article in journal (Refereed)
    Abstract [en]

    Bioimpedance spectroscopy (BIS) is a technique of interest in the study of human pregnancy because it can assess extracellular (ECW), intracellular (ICW), and total body water (TBW) as ECW plus ICW. The technique requires appropriate resistivity coefficients and has not been sufficiently evaluated during the reproductive cycle. Therefore, in a methodological study, we estimated ECW, ICW, and TBW, by means of BIS, and compared the results with the corresponding estimates obtained by using reference methods. Furthermore, results obtained by means of population-specific resistivity coefficients were compared with results obtained by means of general resistivity coefficients. These comparisons were made before pregnancy, in gestational weeks 14 and 32, as well as 2 wk postpartum in 21 healthy women. The reference methods were isotope and bromide dilution. Average ICW, ECW, and TBW, estimated by means of BIS, were in agreement with reference data before pregnancy, in gestational week 14, and postpartum. The corresponding comparison in gestational week 32 showed good agreement for ICW, whereas estimates by means of BIS were significantly (P < 0.001) lower than the corresponding reference values for ECW and TBW. Thus the BIS technique, which was based on a model developed for the nonpregnant body, estimated increases in ICW accurately, whereas increases in ECW and TBW tended to be underestimated. Estimates obtained by using population-specific and general resistivity coefficients were very similar. In conclusion, the results indicated that BIS is potentially useful for studies during pregnancy but that further work is needed before it can be generally applied in such studies.

  • 17.
    Powell, J T
    et al.
    University Hospitals of Coventry and Warwickshire, Walsgrave, Coventry, UK.
    Turner, R J
    University Hospitals of Coventry and Warwickshire, Walsgrave, Coventry, UK.
    Sian, M
    University Hospitals of Coventry and Warwickshire, Walsgrave, Coventry, UK.
    Debasso, Rachel
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Influence of fibrillin-1 genotype on the aortic stiffness in men2005In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 99, no 3, p. 1036-1040Article in journal (Refereed)
    Abstract [en]

    Aortic stiffness is a predictor of cardiovascular mortality. The mechanical properties of the arterial wall depend on the connective tissue framework, with variation in fibrillin-1 and collagen I genes being associated with aortic stiffness and/or pulse pressure elevation. The aim of this study was to investigate whether variation in fibrillin-1 genotype was associated with aortic stiffness in men. The mechanical properties of the abdominal aorta of 79 healthy men (range 28-81 yr) were investigated by ultrasonographic phase-locked echo tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in intron 28, and collagen type I alpha 1 genotype characterized by the 2,064 OT polymorphism, were determined by using DNA from peripheral blood cells. Three common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10 (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or 2-4 genotype (P = 0.005). Pulse pressure also was increased in the 2-3 genotype (P = 0.04). There was no significant association between type 1 collagen genotype and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype in men was associated with increased aortic stiffness and pulse pressure, indicative of an increased risk for cardiovascular disease. Copyright © 2005 the American Physiological Society.

  • 18.
    Rosendal, Lars
    et al.
    Östergötlands Läns Landsting, Pain and Occupational Centre.
    Sogaard, Karin
    National Institute of Occupational Health, Copenhagen.
    Kjaer, Michael
    Bispebjerg Hospital.
    Sjogaard, Gisela
    National Institute of Occupational Health, Copenhagen.
    Langberg, Henning
    Bispebjerg Hospital.
    Kristiansen, Jesper
    1National Institute of Occupational Health, Copenhagen.
    Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise2005In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 98, no 2, p. 477-481Article in journal (Refereed)
    Abstract [en]

    Interleukin (IL)-6, which is released from muscle tissue during intense exercise, possesses important metabolic and probably anti-inflammatory properties. To evaluate the IL-6 response to low-intensity exercise, we conducted two studies: 1) a control study with insertion of microdialysis catheters in muscle and determination of interstitial muscle IL-6 response over 2 h of rest and 2) an exercise study to investigate the IL-6 response to 20 min of repetitive low-force exercise. In both studies, a microdialysis catheter (cutoff: 3,000 kDa) was inserted into the upper trapezius muscle of six male subjects, and the catheters were perfused with Ringer-acetate at 5 mul/min. Venous plasma samples were taken in the exercise study. The insertion of microdialysis catheters into muscle resulted in an increase in IL-6 from 8 +/- 0 to 359 +/- 171 and 484 +/- 202 pg/ml after 65 and 110 min, respectively (P less than 0.001). Similarly, in the exercise study, IL-6 increased to 289 +/- 128 pg/ml after a 55-min rest (P less than 0.001). During the subsequent repetitive low-force exercise, muscle IL-6 further increased to 1,246 +/- 461 pg/ml and reached 2,132 +/- 477 pg/ml after a 30-min recovery ( all P less than 0.001). In contrast to this, plasma IL-6 did not significantly change in response to exercise. We conclude that upper extremity, low-intensity exercise results in a substantial increase in IL-6 in the interstitium of the stabilizing trapezius muscle, whereas no change is seen for plasma IL-6.

  • 19.
    Rullman, E.
    et al.
    Karolinska Institutet, Stockholm, Sweden .
    Rundqvist, H.
    Karolinska Institutet, Stockholm, Sweden .
    Wågsäter, Dick
    Karolinska Institutet, Stockholm, Sweden .
    Fischer, H.
    Karolinska Institutet, Stockholm, Sweden .
    Eriksson, P.
    Karolinska Institutet, Stockholm, Sweden .
    Sundberg, C. J.
    Karolinska Institutet, Stockholm, Sweden .
    Jansson, E.
    Karolinska Institute, Stockholm, Sweden.
    Gustafsson, T.
    Karolinska Institutet, Stockholm, Sweden .
    A single bout of exercise activates matrix metalloproteinase in human skeletal muscle2007In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 102, no 6, p. 2346-2351Article in journal (Refereed)
    Abstract [en]

    The aims of this study were 1) to characterize changes in matrix metalloproteinase (NIMP), endostatin, and vascular endothelial growth factor (VEGF)-A expression in skeletal muscle in response to a single bout of exercise in humans; and 2) to determine if any exchange of endostatin and VEGF-A between circulation and the exercising leg is associated with a change in the tissue expression or plasma concentration of these factors. Ten healthy males performed 65 min of cycle exercise, and muscle biopsies were obtained from the vastus lateralis muscle at rest and immediately and 120 min after exercise. In the muscle biopsies, measurements of mRNA expression levels of MMP-2, MMP-9, MMP-14, and tissue inhibitor of metalloproteinase; VEGF and endostatin protein levels; and NIMP activities were performed. Femoral arterial and venous concentrations of VEGF-A and endostatin were determined before, during, and 120 min after exercise. A single bout of exercise increased MMP-9 mRNA and activated MMP-9 protein in skeletal muscle. No measurable increase of endostatin was observed in the skeletal muscle or in plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels was induced by exercise, with no signs of peripheral uptake from the circulation. However, a decrease in plasma VEGF-A concentration occurred following exercise. Thus 1) a single bout of exercise activated the MMP system without any resulting change in tissue endostatin protein levels, and 2) the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Other mechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.

  • 20.
    Rullman, Eric
    et al.
    Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Norrbom, Jessica
    Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Strömberg, Anna
    Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Wågsäter, Dick
    Karolinska Institute, Stockholm, Sweden.
    Rundqvist, Helene
    Karolinska Institute, Stockholm, Sweden.
    Haas, Tara
    York University,Toronto, Ontario, Canada .
    Gustafsson, Thomas
    Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Endurance exercise activates matrix metalloproteinases in human skeletal muscle2009In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 106, no 3, p. 804-812Article in journal (Refereed)
    Abstract [en]

    In the present study, the effect of exercise training on the expression and activity of matrix metalloproteinases (MMPs) in the human skeletal muscle was investigated. Ten subjects exercised one leg for 45 min with restricted blood flow and then exercised the other leg at the same absolute workload with unrestricted blood flow. The exercises were conducted four times per week for 5 wk. Biopsies were taken from the vastus lateralis muscles of both legs at rest before the training period, after 10 days and 5 wk of training, and 2 h after the first exercise bout for analysis of MMP and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA, enzyme activity, and protein expression. Levels of MMP-2, MMP-14, and TIMP-1 mRNA in muscle tissue increased after 10 days of training regardless of blood flow condition. MMP-2 mRNA level in laser-dissected myofibers and MMP-2 activity in whole muscle increased with training. The level of MMP-9 mRNA and activity increased after the first bout of exercise. Although MMP-9 mRNA levels appeared to be very low, the activity of MMP-9 after a single bout of exercise was similar to that of MMP-2 after 10 days of exercise. MMP-2 and MMP-9 protein was both present throughout the extracellular matrix of the muscle, both around fibers and capillaries, but MMP-2 was also present within the skeletal muscle fibers. These results show that MMPs are activated in skeletal muscle in nonpathological conditions such as voluntary exercise. The expression and time pattern indicate differences between the MMPs in regards of production sites as well as in the regulating mechanism

  • 21.
    Walther, Sten M
    et al.
    Department of Intensive Care, Ulleva°l University Hospital, Oslo, Norway.
    Johansson, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Flatebø, Torun
    Department of Physiology, University of Oslo, Oslo, Norway.
    Nicolaysen, Anne
    Department of Physiology, University of Oslo, Oslo, Norway.
    Nicolaysen, Gunnar
    Department of Physiology, University of Oslo, Oslo, Norway.
    Marked differences between prone and supine sheep in effect of PEEP on perfusion distribution in zone II lung2005In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 99, no 3, p. 909-914Article in journal (Refereed)
    Abstract [en]

    The classic four-zone model of lung blood flow distribution has been questioned. We asked whether the effect of positive end-expiratory pressure (PEEP) is different between the prone and supine position for lung tissue in the same zonal condition. Anesthetized and mechanically ventilated prone (n = 6) and supine (n = 5) sheep were studied at 0, 10, and 20 cmH2O PEEP. Perfusion was measured with intravenous infusion of radiolabeled 15-μm microspheres. The right lung was dried at total lung capacity and diced into pieces (≈1.5 cm3), keeping track of the spatial location of each piece. Radioactivity per unit weight was determined and normalized to the mean value for each condition and animal. In the supine posture, perfusion to nondependent lung regions decreased with little relative perfusion in nondependent horizontal lung planes at 10 and 20 cmH2O PEEP. In the prone position, the effect of PEEP was markedly different with substantial perfusion remaining in nondependent lung regions and even increasing in these regions with 20 cmH2O PEEP. Vertical blood flow gradients in zone II lung were large in supine, but surprisingly absent in prone, animals. Isogravitational perfusion heterogeneity was smaller in prone than in supine animals at all PEEP levels. Redistribution of pulmonary perfusion by PEEP ventilation in supine was largely as predicted by the zonal model in marked contrast to the findings in prone. The differences between postures in blood flow distribution within zone II strongly indicate that factors in addition to pulmonary arterial, venous, and alveolar pressure play important roles in determining perfusion distribution in the in situ lung. We suggest that regional variation in lung volume through the effect on vascular resistance is one such factor and that chest wall conformation and thoracic contents determine regional lung volume. Copyright © 2005 the American Physiological Society.

  • 22.
    Åstrand, Håkan
    et al.
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Stålhand, Jonas
    Linköping University, Department of Management and Engineering, Mechanics. Linköping University, The Institute of Technology.
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Sonesson, B.
    Malmö University Hospital.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Karlsson, J
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    In vivo estimation of the contribution of elastin and collagen on the mechanical properties in the abdominal aorta of man: effect of age and gender2011In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 110, no 1, p. 8750-8757Article in journal (Refereed)
    Abstract [en]

    The mechanical properties of the aorta affect cardiac function and are related to cardiovascular morbidity/mortality. This study was designed to evaluate the isotropic (mainly elastin, elastiniso) and anisotropic (mainly collagen, collagenani) material parameters within the human aorta in vivo. Thirty healthy men and women in three different age categories (23–30, 41–54, and 67–72 yr) were included. A novel mechanical model was used to identify the mechanical properties and the strain field with aid of simultaneously recorded pressure and radius in the abdominal aorta. The magnitudes of the material parameters relating to both the stiffness of elastiniso and collagenani were in agreement with earlier in vitro studies. The load-bearing fraction attributed to collagenani oscillated from 10 to 30% between diastolic and systolic pressures during the cardiac cycle. With age, stiffness of elastiniso increased in men, despite the decrease in elastin content that has been found due to elastolysis. Furthermore, an increase in stiffness of collagenani at high physiological pressure was found. This might be due to increased glycation, as well as changed isoforms of collagen in the aortic wall with age. A marked sex difference was observed, with a much less age-related effect, both on elastiniso and collagenani stiffness in women. Possible factors of importance could be the effect of sex hormones, as well as differing collagen isoforms, between the sexes.

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