Beyond the Pain

Shanely Margarita Garcia is a first-generation undergraduate student at Cal State LA. Her love of the cosmos is what inspires her to be a better person. From a young age, her dream to pursue music gave her the energy to begin to place her mark on the world. Through the study of the performing arts, she wishes to heal and build a community for those who are willing to be open-minded. As she grew into a young adult, she found that chasing one’s dreams is difficult yet exhilarating. Using the lessons that life and her instructors have taught her she explores art through poetry to bridge the spoken word of the mind and spirit

Effects of vitamin E and Lipoic acid on skeletal muscle contractile properties

Initial ex- periments were conducted using an in situ rat tibialis anterior (TA) muscle preparation to assess the influence of di- etary antioxidants on muscle contractile properties. Adult Sprague-Dawley rats were divided into two dietary groups: 1) control diet (Con) and 2) supplemented with vitamin E (VE) and a-lipoic acid (a-LA) (Antiox). Antiox rats were fed the Con rats’ diet (AIN-93M) with an additional 10,000 IU VE/kg diet and 1.65 g/kg a-LA. After an 8-wk feeding period, no differences existed (P > 0.05) between the two dietary groups in maximum specific tension before or after a fatigue protocol or in force production during the fatigue protocol. However, in unfatigued muscle, maximal twitch tension and tetanic force production at stimulation frequencies <40 Hz were less (P < 0.05) in Antiox animals compared with Con. To inves- tigate which antioxidant was responsible for the depressed force production, a second experiment was conducted using an in vitro rat diaphragm preparation. Varying concentra- tions of VE and dihydrolipoic acid, the reduced form of a-LA, were added either individually or in combination to baths containing diaphragm muscle strips. The results from these experiments indicate that high levels of VE depress skeletal muscle force production at low stimulation frequencie

Effects of vitamin E deficiency on fatigue and muscle contractile properties

Radical-mediated oxidative damage of skeletal muscle membranes has been implicated in the fatigue process. Vitamin E (VE) is a major chain breaking an-tioxidant that has been shown to reduce contraction-mediated oxidative damage. We hypothesized that VE de?ciency would adversely a?ect muscle contractile function, resulting in a more rapid development of muscular fatigue during exercise. To test this postulate, rats were fed either a VE-de?cient (EDEF) diet or a control (CON) diet containing VE. Following a 12-week feeding period, animals were anesthetized and mechan-ically ventilated. Muscle endurance (fatigue) and con-tractile properties were evaluated using an in situ preparationof the tibialis anterior (TA) muscle. Con-tractile properties of the TA muscle were determined before and after a fatigue protocol. The muscle fatigue protocol consisted of 60 min of repetitive contractions (250 ms trains at 15 Hz; duty cycle=11%) of the TA muscle. Prior to the fatigue protocol, no signi?cant di?erences existed in the force-frequency curves between EDEF and CON animals. At the completion of the fa-tigue protocol, muscular force productionwas signi?-cantly (P<0.05) lower inthe EDEF group (reduced by 69%) compared to CON group (reduced by 38%). Following the fatigue protocol, a right shift existed in the force-frequency curve at low stimulation frequencies ( £ 40 Hz) inthe EDEF animals compared to the CON animals (P<0.05). The stimulated and the contralateral TA muscle from the EDEF animals had signi?cantly higher markers of lipid peroxidationcompared to the same muscles inthe CON animals (P<0.05). These data support the hypothesis that VE de?ciency impairs muscular endurance and alters muscle contractile prop-erties following a prolonged series of contractions

Trolox Attenuates Mechanical Ventilation–induced Diaphragmatic Dysfunction and Proteolysis

Prolonged mechanical ventilation results in diaphragmatic oxida-tive injury, elevated proteolysis, fiber atrophy, and reduced force-generating capacity. We tested the hypothesis that antioxidant infusion during mechanical ventilation would function as an antioxi-dant to maintain redox balance within diaphragm muscle fibers and therefore prevent oxidative stress and subsequent proteolysis and contractile dysfunction. Sprague-Dawley rats were anesthe-tized, tracheostomized, and mechanically ventilated with 21% O2 for 12 hours. The antioxidant Trolox was intravenously infused in a subset of ventilated animals. Compared with acutely anesthetized, nonventilated control animals, mechanical ventilation resulted in a significant reduction (–17%) in diaphragmatic maximal tetanic force. Importantly, Trolox completely attenuated this mechanical ventilation-induced diaphragmatic contractile deficit. Total dia-phragmatic proteolysis was increased 105% in mechanical ventila-tion animals compared with controls. In contrast, diaphragmatic proteolysis did not differ between controls and mechanical ventila-tion–Trolox animals. Moreover, 20S proteasome activity in the dia-phragm was elevated in the mechanical ventilation animals (+76%); Trolox treatment attenuated this mechanical ventilation-induced rise in protease activity. These results are consistent with the hypothesis that mechanical ventilation-induced oxidative stress is an important factor regulating mechanical ventilation-induced diaphragmatic proteolysis and contractile dysfunction. Our findings suggest that antioxidant therapy could be beneficial during pro-longed mechanical ventilatio

Short-Duration Mechanical Ventilation Enhances Diaphragmatic Fatigue Resistance but Impairs Force Production

Study objectives: Mechanical ventilation (MV) is a life-support measure for patients who cannot maintain adequate alveolar ventilation. Following prolonged MV, difficulty in weaning patients from the ventilator canoccur, and it has been postulated that difficult weaning is linked to respiratory muscle dysfunction. We tested thehypothesis that 18 h of controlled MV will diminish diaphragmatic maximal tetanic specific tension (force percross-sectional area of muscle) without impairing diaphragmatic fatigue resistance.Design: To test this postulate, adult Sprague-Dawley rats were randomly classified into one of two experimentalgroups: (1) control group (n = 8), and (2) 18-h MV group (n = 6). MV-treated animals were anesthetized,tracheostomized, and received room air ventilation. Animals in the control group were acutely anesthetized butdid not receive MV. Muscle strips from the mid-costal diaphragm were removed from both experimental groups,and contractile properties were studied in vitro to determine the effects of MV on diaphragmatic endurance andmaximal force production. Diaphragmatic endurance was investigated by measuring tension development duringrepeated contractions throughout a 30-min fatigue protocol.Results: MV resulted in a reduction (p 0.05) in diaphragmatic maximal specific tension (control group, 26.8 ± 0.2Newtons/cm2 vs MV group, 21.3 ± 0.6 Newtons/cm2). Compared to the control group, diaphragms from MVtreatedanimals maintained higher (p 0.05) percentages of the initial force production throughout the fatigueprotocol. The observed improvement in fatigue resistance was associated with an increase in diaphragmaticoxidative and antioxidant capacity as evidenced by increases (p 0.05) in both citrate synthase and superoxidedismutase activities. However, by comparison to the control group, diaphragms from MV-treated animalsgenerated less (p 0.05) absolute specific force throughout the fatigue protocol.Conclusions: These data indicate that 18 h of MV enhances diaphragmatic fatigue resistance but impairsdiaphragmatic specific tension

Correction of the Enzymatic and Functional Deficits in a Model of Pompe Disease Using Adeno-associated Virus Vectors

Pompe disease is a lysosomal storage disease caused by the absence of acid -1,4 glucosidase (GAA). The pathophysiology of Pompe disease includes generalized myopathy of both cardiac and skeletal muscle. We sought to use recombinant adeno-associated virus (rAAV) vectors to deliver functional GAA genes in vitro and in vivo. Myotubes and fibroblasts from Pompe patients were transduced in vitro with rAAV2-GAA. At 14 days postinfection, GAA activities were at least fourfold higher than in their respective untransduced controls, with a 10-fold increase observed in GAA-deficient myotubes. BALB/c and Gaa–/– mice were also treated with rAAV vectors. Persistent expression of vector-derived human GAA was observed in BALB/c mice up to 6 months after treat-ment. In Gaa–/– mice, intramuscular and intramyocardial delivery of rAAV2-Gaa (carrying the mouse Gaa cDNA) resulted in near-normal enzyme activities. Skeletal muscle contractility was partially restored in the soleus muscles of treated Gaa–/– mice, indicating the potential for vec-tor-mediated restoration of both enzymatic activity and muscle function. Furthermore, intra-muscular treatment with a recombinant AAV serotype 1 vector (rAAV1-Gaa) led to nearly eight times normal enzymatic activity in Gaa–/– mice, with concomitant glycogen clearance as assessed in vitro and by proton magnetic resonance spectroscopy

Mechanical ventilation-induced oxidative stress in the diaphragm

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Improved cardiac performance after ischemia in aged rats supplemented with vitamin E and a-lipoic acid

The purpose of these experiments was to examine the effects of dietary antioxidant supplementation with vitamin E (VE) and a-lipoic acid (a-LA) on biochemical and physiological responses to in vivo myocardial ischemia-reperfusion (I-R) in aged rats. Male Fischer-334 rats (18 mo old) were assigned to either1) a control diet (CON) or 2)aVEanda-LA supplemented diet (ANTIOX). After a 14-wk feeding period, animals in each group underwent an in vivo I-R protocol (25 min of myocardial ischemia and 15 min of reperfusion). During reperfusion, peak arterial pressure was significantly higher (P,0.05) in ANTIOX animals compared with CON diet animals. I-R resulted in a significant increase ( P,0.05) in myocardial lipid peroxidation in CON diet animals but not in ANTIOX animals. Compared with ANTIOX animals, heart homogenates from CON animals experienced significantly less (P,0.05) oxidative damage when exposed to five different in vitro radical producing systems. These data indicate that dietary supplementation with VE and a-LA protects the aged rat heart from I-R-induced lipid peroxidation by scavenging numerous reactive oxygen species. Importantly, this protection is associated with improved cardiac performance during reperfusion

Cumulative Effects of Aging and Mechanical Ventilation on In Vitro Diaphragm Function

Study objective: Unloading the diaphragm, via mechanical ventilation (MV), results in significant diaphragmaticatrophy, contractile dysfunction, and oxidative stress in young adult animals. Since aging increases skeletal musclesusceptibility to atrophy and injury, we tested the hypothesis that MV-induced diaphragmatic contractiledysfunction would be exacerbated in aging rats.Methods: Fisher 344/Brown Norway hybrid rats (4 months old [young] and 30 months old [old]) were assigned toeither control or MV groups. MV rats were anesthetized, tracheostomized, and ventilated with 21% O2 for 12 h.Arterial BP, pH, and blood gas homeostasis were maintained in the MV animals throughout the experimental period. Animals in the control group were acutely anesthetized, and the diaphragms were immediately removed.Muscle strips from the mid-costal diaphragm were removed from each experimental animal, and contractile properties were studied in vitro.Results: Compared to young control animals, aging (old control animals) was associated with a 13% decrease inmaximal isometric tension (24.5 N/cm2 vs 21.3 N/cm2). Although, MV induced similar relative losses (24%) indiaphragmatic isometric tension in both young and old animals receiving MV, the combined effects of aging andMV resulted in a 34% decrement in diaphrag- matic isometric tension compared to young control animals (24.5N/cm2 vs 16.1 N/cm2).Conclusions: These data do not support the hypothesis that aging exacerbates the relative MV-inducedimpairment in diaphragmatic isometric tension. Nonetheless, the additive effects of aging and MV have dramaticeffects on diaphragmatic force reserve. This could exacerbate weaning difficulties in older individuals receivingM

Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat

These experiments examined the independent effects of short-term exercise and heat stress on myocardial responses during in vivo ischemia-reperfusion (I/R). Female Sprague-Dawley rats (4 mo old) were randomly assigned to one of four experimen- tal groups: 1) control, 2) 3 consecutive days of treadmill exercise [60 min/day at 60–70% maximal O2 uptake (V? O2 max)], 3) 5 consecutive days of treadmill exercise (60 min/day at 60–70% V? O2 max), and 4) whole body heat stress (15 min at 42°C). Twenty-four hours after heat stress or exercise, animals were anesthetized and mechanically venti- lated, and the chest was opened by thoracotomy. Coronary occlusion was maintained for 30-min followed by a 30-min period of reperfusion. Compared with control, both heat- stressed animals and exercised animals (3 and 5 days) main- tained higher (P < 0.05) left ventricular developed pressure (LVDP), maximum rate of left venticular pressure develop- ment (+dP/dt), and maximum rate of left ventricular pres- sure decline (-dP/dt) at all measurement periods during both ischemia and reperfusion. No differences existed between heat-stressed and exercise groups in LVDP, +dP/dt, and -dP/dt at any time during ischemia or reperfusion. Both heat stress and exercise resulted in an increase (P < 0.05) in the relative levels of left ventricular heat shock protein 72 (HSP72). Furthermore, exercise (3 and 5 days) increased (P < 0.05) myocardial glutathione levels and manganese superoxide dismutase activity. These data indicate that 3–5 consecutive days of exercise improves myocardial contractile performance during in vivo I/R and that this exercise-induced myocardial protection is associated with an increase in both myocardial HSP72 and cardiac antioxidant defense