Reduced Fatigue Resistance Research Articles

ZIDOVUDINE-MEDIATED NEONATAL DIAPHRAGM CONTRACTILE DYSFUNCTION

Zidovudine (AZT, 3'-azido-3'deoxythymidine) is a primary drug used to treat HIV/AIDS patients worldwide including the prevention of HIV vertical transmission in pregnant women. While AZT effectively inhibits HIV reverse transcriptase and thus viral replication, studies have also shown AZT to induce a drug-specific muscle myopathy and increased oxidative stress via inhibition of mitochondrial DNA γ polymerase. Previously we have shown that AZT treatment produces respiratory muscle contractile dysfunction in adults rodents (Herb et al., 1997, 2000). To determine if neonatal respiratory muscle was susceptible to AZT toxicity, adult, Sprague-Dawley dams (n = 12) were randomly assigned to a control group or treated with AZT (10mg/kg/day) administered via drinking water ad libitum 28 days prior to and throughout gestation (21 days). Following birth, adult females and pups were maintained on oral AZT for 28 days post-partum prior to contractile experiments. Respiratory muscle function was assessed using two costal diaphragm strips removed from each neonate and evaluated for force-frequency relationship, maximal isometric specific tension, and fatigue resistance (30 min test) using a field stimulation preparation. In vitro studies indicated that neonatal AZT treatment significantly altered the F-F relationship, decreased specific tension development (21%) and reduced fatigue resistance (min 20+) when compared to controls. To our knowledge, this study is the first to address the impact of AZT on neonatal respiratory muscle function. These data support the hypothesis that in utero and post-partum exposure to AZT deleteriously impacts neonatal diaphragm function in a manner similar to that seen in adult diaphragms. We conclude that these data provide evidence indicating the need for an improved understanding of the mechanism(s) responsible for the observed results as well as clinical therapies that can ameliorate the impact of AZT on neonatal respiratory muscle function. Supported by the American Lung Association, NAU Hooper Undergraduate Research Grant, & GlaxoSmithKline

Contractile properties of in situ perfused skeletal muscles from rats with congestive heart failure.

We hypothesized that in congestive heart failure (CHF) slow-twitch but not fast-twitch muscles exhibit decreased fatigue resistance in the sense of accelerated reduction of muscle force during activity. Experiments were carried out on anaesthetized rats 6 weeks after induction of myocardial infarction or a sham operation (Sham). Animals with left ventricular end-diastolic pressure (LVEDP) > 15 mmHg under anaesthesia were selected for the CHF group. There was no muscle atrophy in CHF. Force generation by in situ perfused soleus (Sol) or extensor digitorum longus (EDL) muscles was recorded during stimulation (trains at 5 Hz for 6 s (Sol) or 10 Hz for 1.5 s (EDL) at 10 or 2.5 s intervals, respectively) for 1 h in Sol and 10 min in EDL at 37 degrees C. Initial force was almost the same in Sol from CHF and Sham rats, but relaxation was slower in CHF. Relaxation times (95-5 % of peak force) were 177 +/- 55 and 131 +/- 44 ms in CHF and Sham, respectively, following the first stimulation train. After 2 min of stimulation the muscles transiently became slower and maximum relaxation times were 264 +/- 71 and 220 +/- 45 ms in CHF and Sham, respectively (P < 0.05). After 60 min they recovered to 204 +/- 60 and 122 +/- 55 ms in CHF and Sham, respectively (P < 0.05). In CHF but not in Sham rats the force of contraction of Sol declined from the second to the sixtieth minute to 70 % of peak force. The EDL of both CHF and Sham fatigued to 24-28 % of initial force, but no differences in contractility pattern were detected. Thus, slow-twitch muscle is severely affected in CHF by slower than normal relaxation and significantly reduced fatigue resistance, which may explain the sensation of both muscle stiffness and fatigue in CHF patients.

初期養生条件がモルタルの疲労およびそれに起因する中性化に及ぼす影響

Mortar specimens cured at various conditions were first subjected to bending repeated loads, and it was made clear that insufficient cure reduced fatigue resistance of them. Next, fatigue tests that the stress levels are lower than the ones of fatigue rupture were carried out, and the improved scale based on the Gompertz curve was proposed for expressing fatigue of specimens. The effect of curing conditions in early age on carbonation was furthermore studied using the scale, and it was made clear that insufficient cure is also susceptible to their carbonation. Finally, the reason for rapid carbonation of fatigued mortars insufficiently cured was discussed from the view point of changes in pore structure of them.

Fat metabolism during exercise: a review--part III: effects of nutritional interventions.

By changes in nutrition it is possible to manipulate fat oxidation. It is often theorized that increasing fat oxidation may reduce glycogen breakdown and thus enhance performance. Therefore, the effects of acute, short-term and long-term fat feeding have been subjects of investigation for many years. Ingestion of long-chain triacylglycerols (LCT) during exercise may reduce the gastric emptying rate and LCT will appear in the plasma only slowly. Medium-chain triacylglycerols (MCT) do not have these disadvantages and they are rapidly oxidized. However, the contribution of MCT to energy expenditure is only small because they can only be ingested in small amounts without causing gastrointestinal distress. So at present, fat supplementation in the hours preceding to or during exercise (either long chain or medium chain triacylglycerols) cannot be recommended. High-fat diets and fasting have been suggested to increase fatty acid availability and spare muscle glycogen resulting in improved performance. Both fasting and short term high-fat diets will decrease muscle glycogen content and reduce fatigue resistance. Chronic high-fat diets may provoke adaptive responses preventing the decremental effects on exercise performance. However, at present, there is little evidence to support this hypothesis. Also from a health perspective, caution should be exercised when recommending high-fat diets to athletes.

Na+, K+‐pump activity and skeletal muscle contractile deficits in the spontaneously hypertensive rat

Skeletal muscles in an animal model of genetic hypertension (the spontaneously hypertensive rat. SHR) exhibit significant deficits in contractile performance. These deficits appear to be unrelated to the rise in blood pressure. Slow-twitch soleus muscles show a decrease in specific muscle tension and a reduced resistance to muscle fatigue during prolonged contractile activity. We tested the hypothesis that the reduced fatigue resistance occurs as a consequence of an impaired ability to maintain or restore Na+ and K+ balance across the sarcolemma during repeated contractions. This may result from a genetically based increase in the Na+ permeability of SHR muscles, coupled with a reduction Na+, K+ pump capacity as the animals mature. Soleus muscles in adult SHR exhibit a significant increase in intracellular Na+ content and a significant decrease in intracellular K+ content at rest. B6RB+ uptake in Na(+)-loaded hypertensive muscles is 45% less than predicted from the number of ouabain-binding sites available. Activation of Na+, K+ pumps using adrenaline or insulin produces a significantly smaller hyperpolarization in hypertensive soleus than in control muscles. Control soleus muscles are hyperpolarized for at least 10 min after a 4 min period of high-frequency activity, but hypertensive soleus muscles remain at resting polarity. Nonetheless, the number of ouabain-binding sites in hypertensive muscle is significantly greater than in control soleus, and binding affinities are similar. This apparent deficit in pump capacity might lead to a greater and more prolonged increase in extracellular K+ during repetitive contractions,and an associated decline in tension. Recently, we have been able to prevent the abnormal decrease in hypertensive soleus fatigue resistance by long-term treatment (8 weeks) with the Ca2+ blocker amlodipine. The therapy prevented or reversed the contractile deficits, but did not restore the responsiveness of the Na+, K+ pump to hormonal stimulation. The current data suggest that both a reduction in Na+, K(+)-pump capacity and changes in Ca2+ distribution play a role in the development of contractile deficits in hypertensive muscles.

Tensile and Fatigue Behavior of Aluminum Oxide Fiber Reinforced Magnesium Composites: Part I. Fiber Fraction and Orientation

The mechanical behavior of commercially pure magnesium reinforced with FP aluminum oxide fibers has been studied as a function of fiber fraction and orientation. Test specimens included material of two different volume fractions of fiber and four different fiber orientations. Axial properties were dependent on the fiber content and generally followed the rule of mixtures. Of the off-axis properties, only the elastic modulus exhibited a significant dependence on fiber content. Off-axis loading resulted in large reductions in both the tensile and fatigue properties. The reductions coincided with a change in fracture morphology from fracture across fibers during axial loading to fracture along the fiber direction for off-axis loading. A weak fiber/matrix interface was found to be responsible for the drop in tensile properties, and a combination of a weak matrix and a weak fiber/matrix interface were responsible for the reduced fatigue resistance.

Formation of fillet transitions in cast iron crankshafts by the action of local contact

Automatic electric arc welding is currently used extensively for restoring worn pins on automobile engine crankshafts [i, 2]. However, the efficiency of the restoration technique used depends mainly on article material. In a number of cases use of electric arc welding or another restoration method associated with thermal effects on the article material may markedly reduce fatigue resistance characteristics.