Browsing by Author "Kohn, Tertius A"

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    Mechanisms underlying the development of weakness in idiopathic inflammatory myopathies: an in vitro single muscle fibre contractility study
    (2018) Henning, Franclo; Kohn, Tertius A; Carr, Jonathan A
    Introduction: Polymyositis (PM), dermatomyositis (DM) and necrotising autoimmune myopathy (NAM) form part of the spectrum of idiopathic inflammatory myopathies (IIMs). Although the pathogenic mechanisms are different, the unifying feature is that of weakness caused, in some way or another, by an inflammatory attack on muscle. The mechanism by which weakness develops is still unclear, but experimental animal data suggest that dysfunction of the contractile apparatus might contribute to muscle weakness in these conditions. This study investigated the contractile function of single muscle fibres from patients with IIMs in vitro. Methods: Muscle biopsies obtained from patients with IIMs and healthy controls were dissected and chemically permeabilised. Single muscle fibres were dissected out and subjected to contractility measurement based on standard protocols utilising a permeabilised single fibre system. Specific force (SF; maximum force normalised to cross-sectional area), was calculated for each fibre and compared between the two groups. In addition, maximum shortening velocity and power output were assessed in some of the fibres, and calcium sensitivity in the rest. The myosin heavy chain composition of each fibre was determined by means of gel electrophoresis. Results: A total of 178 fibres from IIM cases and 174 fibres from controls were studied. Specific (normalised) force was 23%, 24% and 29% lower in the IIM group for all fibre types combined, type I fibres, and type IIa fibres, respectively. Shortening velocity and maximum power output were significantly higher in the IIM group for both type I and IIa fibres, compared to controls, while calcium sensitivity was higher in type IIa fibres from IIM cases than controls. Discussion: The findings from this study suggest that weakness in IIMs may, at least in part, be caused by dysfunction of the contractile apparatus leading to impaired contractile force. The higher shortening velocity, power output and calcium sensitivity in fibres from IIM cases probably represents compensatory mechanisms. Although the mechanism by which contractile function is affected has not been investigated, animal studies suggest a role for TNF-α. The findings of this study provide a basis for further investigation into the mechanisms underlying weakness in IIMs.
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    Physiological responses of wild antelope to exercise training as a prospective treatment to prevent capture myopathy
    (2022) Breed, Dorothy; Kohn, Tertius A; Meyer, Leith C R
    Capture myopathy is a lethal condition associated with physiological stress in wildlife and is responsible for most deaths during game capture. Exercise training to improve fitness has been proposed as a preventative management strategy for capture myopathy but lacks scientific evidence. The aim of this study was to determine whether regular exercise training of wild antelope is indeed feasible, and whether physiological adaptations occur that could mitigate the response to capture stress. Forty wild blesbok (Damaliscus pygargus phillipsi) were habituated for two weeks to a boma. Twenty were randomly selected to be exercise trained for four weeks, consisting of thirtyminute low, medium and high intensity running sessions four or five times per week. Ten of the exercise trained and ten untrained blesbok were subjected to a twenty-minute capture stress event that included chasing by humans, a motorised quadbike, and a helicopter. Immediately following this event, the animals were immobilised, physiological variables recorded, and blood samples obtained at 0 and 40 minutes. The same sampling occurred on days 2 and 5 after the original stress event but only at 0 minutes. Untrained and unstressed animals served as controls for the effect of training and the acute stress response, respectively. The exercise trained blesbok responded physiologically better to the capture stress event , indicated by lower blood lactate concentrations [exercised: Median (Mdn) = 9.4 mmol/l , Interquartile range (IQR) = 7.9 – 12.4 mmol/l vs. non-exercised: Mdn = 11.0 mmol/l, IQR = 10.5 – 14.1 mmol/l] and reduced post-capture stress rectal temperatures [exercised: Mdn = 41.4 °C, IQR = 41.1 – 41.6 °C vs. non-exercised: Mdn: 41.8 °C, IQR = 41.6 - 41.8 °C]. Although the pH did not differ between the groups - the exercise trained blesbok group had less animals presenting acidaemic, there was an increased cHCO3 - [mean (M) ± standard deviation (SD) of exercised: 20 ± 3 vs. non-exercised: 16 ± 5 mmol/l) and BEecf (M ± SD of exercised: - 5 ± 3 vs. non-exercised: - 10 ± 6 mEq/L) that supports an increased buffering ability for the exercised group. These findings conform to previous exercise training studies in humans, horses, and rodents that indicate similar adaptations in trained groups exposed to exertional stress compared to untrained groups. The data also confirmed the severe hypoxaemia that is caused by the opioid immobilisation drugs. This is the first study showing that wild antelope can be successfully exercise trained, which led to physiological adaptations resulting in improved fitness. Whether this training programme will prevent the onset of capture myopathy and reduce fatalities still needs to be further investigated.