Free radicals alter maximal diaphragmatic mitochondrial oxygen consumption in endotoxin-induced sepsis

Callahan, Leigh Ann; Stofan, D.; Szweda, Luke I.; Nethery, David; Supinski, Gerald S.

doi:10.1016/s0891-5849(00)00454-8

Cited by 67 publications

(82 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mitochondrial respiration was determined as previously described (6). After removal from the animal, diaphragms were rinsed in cold isolation buffer (180 mM KCl, 5 mM MOPS, and 2 mM EGTA, pH 7.25 at 4°C), blotted dry, weighed, and placed in fresh isolation buffer.…”

Section: Methodsmentioning

confidence: 99%

Diaphragmatic free radical generation increases in an animal model of heart failure

Supinski

Callahan²

2005

Journal of Applied Physiology

View full text Add to dashboard Cite

Supinski, Gerald S., and Leigh A. Callahan. Diaphragmatic free radical generation increases in an animal model of heart failure. J Appl Physiol 99: 1078 -1084, 2005; doi:10.1152/japplphysiol.01145.2004.-Heart failure evokes diaphragm weakness, but the mechanism(s) by which this occurs are not known. We postulated that heart failure increases diaphragm free radical generation and that free radicals trigger diaphragm dysfunction in this condition. The purpose of the present study was to test this hypothesis. Experiments were performed using halothaneanesthetized sham-operated control rats and rats in which myocardial infarction was induced by ligation of the left anterior descending coronary artery. Animals were killed 6 wk after surgery, the diaphragms were removed, and the following were assessed: 1) mitochondrial hydrogen peroxide (H2O2) generation, 2) free radical generation in resting and contracting intact diaphragm using a fluorescent-indicator technique, 3) 8-isoprostane and protein carbonyls (indexes of free radical-induced lipid and protein oxidation), and 4) the diaphragm force-frequency relationship. In additional experiments, a group of coronary ligation animals were treated with polyethylene glycol-superoxide dismutase (PEG-SOD, 2,000 units⅐kg Ϫ1 ⅐day Ϫ1) for 4 wk. We found that coronary ligation evoked an increase in free radical formation by the intact diaphragm, increased diaphragm mitochondrial H2O2 generation, increased diaphragm protein carbonyl levels, and increased diaphragm 8-isoprostane levels compared with controls (P Ͻ 0.001 for the first 3 comparisons, P Ͻ 0.05 for 8-isoprostane levels). Force generated in response to 20-Hz stimulation was reduced by coronary ligation (P Ͻ 0.05); PEG-SOD administration restored force to control levels (P Ͻ 0.03). These findings indicate that cardiac dysfunction due to coronary ligation increases diaphragm free radical generation and that free radicals evoke reductions in diaphragm force generation. oxidative stress CONGESTIVE HEART FAILURE IS known to evoke significant changes in skeletal muscle function, inducing muscle wasting, reductions in muscle force-generating capacity, and alterations in muscle energy metabolism (9,16,20). Both limb and respiratory skeletal muscle are thought to be affected in this condition (28). Some work indicates that limb skeletal muscle dysfunction plays an important role in determining exercise capacity in patients with congestive heart failure (22). In addition, respiratory muscle dysfunction may predispose these patients to respiratory failure under conditions in which the respiratory workload increases (28).The mechanism by which congestive heart failure alters skeletal muscle function remains unclear. Importantly, evidence indicates that inactivity alone cannot fully account for congestive heart failure-induced reductions in muscle function (25). Recent work indicates, however, that congestive heart failure is associated with an increase in generation of free radicals (i.e., molecules derived from superoxide anions) an...

show abstract

Section: Methodsmentioning

confidence: 99%

Diaphragmatic free radical generation increases in an animal model of heart failure

Supinski

Callahan²

2005

Journal of Applied Physiology

View full text Add to dashboard Cite

show abstract

“…A vicious cycle can occur within the mitochondria, in which sepsis-induced increased mitochondrial production of free radicals exacerbates mitochondrial dysfunction, leading to further radical production [112,113] (fig. 3).…”

Section: Bioenergenetic Failure Oxidative Stress and Glycaemic Controlmentioning

confidence: 99%

Molecular mechanisms of intensive care unit-acquired weakness

Bloch¹,

Polkey²,

Griffiths³

et al. 2011

Eur Respir J

View full text Add to dashboard Cite

Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and important clinical consequence of critical illness. It is associated with significant morbidity and mortality. The aetiology of this disease is not well understood. The purpose of this article is to review our understanding of the molecular pathogenesis of ICUAW in the context of current knowledge of clinical risk factors and aetiology.Key features of the disease are loss of muscle mass resulting from a shift in the dynamic balance of muscle protein synthesis and breakdown and a reduction in force-generating capacity. These alternations are secondary to neuropathy, disruption of the myofilament structure and function, a disrupted sarcoplasmic reticulum, electrical inexcitability and bioenergenetic failure.As knowledge and understanding of ICUAW grows, potential therapeutic targets will be identified, hopefully leading to multiple strategies for prevention and treatment of this important condition.

show abstract

“…Two commonly used models of skeletal muscle wasting, namely the hindlimb suspension and the chronic coronary occlusion, display an 17s upregulation of iNOS, an increase in oxidative stress and a significant decrease in skeletal muscle antioxidant enzyme activity [112][113][114][115]. Muscle wasting pathologies such as cachexia also increase the production of ROS and RNS production and enhance the iNOS levels [116,117]. Generation of ROS and RNS could lead to impairment of the antioxidant protection in skeletal muscles.…”

Section: Effect and Consequences Of Systemic Oxidative Stressmentioning

confidence: 99%

Oxidant metabolism in chronic obstructive pulmonary disease

2003

View full text Add to dashboard Cite

The development and progression of chronic obstructive pulmonary disease (COPD) have been associated with increased oxidative stress or reduced antioxidant resources. Several indicators of oxidative stress, such as hydrogen peroxide exhalation, lipid peroxidation products and degraded proteins, are indeed elevated in COPD patients. As a result, the antioxidant capacity decreases in COPD patients.The fall in antioxidant capacity of blood from COPD patients should not only be regarded as a reflection of the occurrence of oxidative stress but also as evidence that oxidative stress spreads out to the circulation and can therefore generate a systemic effect.COPD is linked to weight loss and in particular to loss in fat-free mass by skeletal muscle wasting. This systemic effect can be mediated by both oxidative stress and oxidative stress-mediated processes like apoptosis and inflammation. Furthermore, COPD is a predisposition for lung cancer through several mechanisms including oxidative stress and oxidative stress-mediated processes such as inflammation and disruption of genomic integrity.Current therapeutic interventions against the far-reaching consequences of the systemic oxidative stress in chronic obstructive pulmonary disease are not yet optimised. A diet designed to reduce chronic metabolic stress might form an effective therapeutic strategy in chronic obstructive pulmonary disease.

show abstract

Free radicals alter maximal diaphragmatic mitochondrial oxygen consumption in endotoxin-induced sepsis

Cited by 67 publications

References 21 publications

Diaphragmatic free radical generation increases in an animal model of heart failure

Diaphragmatic free radical generation increases in an animal model of heart failure

Molecular mechanisms of intensive care unit-acquired weakness

Oxidant metabolism in chronic obstructive pulmonary disease

Contact Info

Product

Resources

About