Inhibition of NADPH oxidase prevents acute lung injury in obese rats following severe trauma

American Journal of Physiology-Heart and Circulatory Physiology

et al. 2014

Self Cite

Xiang L, Lu S, Mittwede PN, Clemmer JS, Husband GW, Hester RL. ␤ 2-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats. Am J Physiol Heart Circ Physiol 307: H621-H627, 2014. First published June 14, 2014; doi:10.1152/ajpheart.00208.2014.-Early hyperglycemia after trauma increases morbidity and mortality. Insulin is widely used to control posttrauma glucose, but this treatment increases the risk of hypoglycemia. We tested a novel method for early posttrauma hyperglycemia control by suppressing hepatic glycogenolysis via ␤ 2-adrenoreceptor blockade [ICI-118551 (ICI)]. We have shown that, after severe trauma, obese Zucker (OZ) rats, similar to obese patients, exhibit increased acute lung injury compared with lean Zucker (LZ) rats. We hypothesized that OZ rats exhibit a greater increase in early posttrauma glucose compared with LZ rats, with the increased posttrauma hyperglycemia suppressed by ICI treatment. Orthopedic trauma was applied to both hindlimbs in LZ and OZ rats. Fasting plasma glucose was then monitored for 6 h with or without ICI (0.2 mg·kg Ϫ1 ·h Ϫ1 iv.) treatment. One day after trauma, plasma IL-6 levels, lung neutrophil numbers, myeloperoxidase (MPO) activity, and wetto-dry weight ratios were measured. Trauma induced rapid hepatic glycogenolysis, as evidenced by decreased liver glycogen levels, and this was inhibited by ICI treatment. Compared with LZ rats, OZ rats exhibited higher posttrauma glucose, IL-6, lung neutrophil infiltration, and MPO activity. Lung wet-to-dry weight ratios were increased in OZ rats but not in LZ rats. ICI treatment reduced the early hyperglycemia, lung neutrophil retention, MPO activity, and wet-to-dry weight ratio in OZ rats to levels comparable with those seen in LZ rats, with no effect on blood pressure or heart rate. These results demonstrate that ␤ 2-adrenoreceptor blockade effectively reduces the early posttrauma hyperglycemia, which is associated with decreased lung injury in OZ rats. obesity; trauma; glucose; lung injury; ␤ 2-adrenoreceptor UNINTENTIONAL INJURIES are the leading cause of mortality in individuals under 50 yr of age in the United States, with staggering medical expenses attributable to traumatic injury (10a, 43). Obese patients with severe orthopedic trauma are at a higher risk than lean patients for increased inflammation, multiorgan failure, prolonged hospital stay, and increased mortality (5,8,10,12). Although the mechanisms responsible for the increased posttrauma complications in obese patients are unclear, intensive and specific treatments have been emphasized for these patients.Posttrauma hyperglycemia has been recognized as a risk factor that exacerbates complications, organ dysfunction, and mortality (29,41,44). Several clinical studies have suggested that, in critically ill obese patients, impaired glucose homeostasis appears to be a better predictor of increased complications and mortality than body mass index (38,41,45). In addition, there is evidence that the early hyperglycemia within the f...

Section: Significance and Clinical Relevancementioning

confidence: 62%

Section: Significance and Clinical Relevancementioning

confidence: 98%

Section: Severe Orthopedic Trauma Protocolsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

β₂-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats

Xiang

American Journal of Physiology-Heart and Circulatory Physiology

et al. 2014

Self Cite

“…We have shown that the day after orthopedic trauma, obese rats exhibit increased incidences of acute lung and acute kidney injury, the two most-frequent organ injuries observed in trauma patients. This is evidenced by the presence of greater lung inflammation and pulmonary edema, decreased glomerular filtration rate and renal plasma flow, and increased urine excretion of renal damage markers in obese Zucker rats as compared to their lean counterparts (58, 96). This is in agreement with the clinical literature, which has consistently demonstrated an increased risk of multiple organ (especial lung and kidney) dysfunction, injury, and failure in obese blunt trauma patients (11, 20).…”

Section: Obesity and Animal Models Of Critical Illnessmentioning

confidence: 99%

Obesity and Critical Illness

Clemmer

Bergin

et al. 2016

Shock

Self Cite

Critical illness is a major cause of morbidity and mortality around the world. While obesity is often detrimental in the context of trauma, it is paradoxically associated with improved outcomes in some septic patients. The reasons for these disparate outcomes are not well understood. A number of animal models have been used to study the obese response to various forms of critical illness. Just as there have been many animal models that have attempted to mimic clinical conditions, there are many clinical scenarios that can occur in the highly heterogeneous critically ill patient population that occupies hospitals and intensive care units. This poses a formidable challenge for clinicians and researchers attempting to understand the mechanisms of disease and develop appropriate therapies and treatment algorithms for specific subsets of patients, including the obese. The development of new, and the modification of existing animal models is important in order to bring effective treatments to a wide range of patients. Not only do experimental variables need to be matched as closely as possible to clinical scenarios, but animal models with pre-existing comorbid conditions need to be studied. This review briefly summarizes animal models of hemorrhage, blunt trauma, traumatic brain injury, and sepsis. It also discusses what has been learned through the use of obese models to study the pathophysiology of critical illness in light of what has been demonstrated in the clinical literature.

Glucose Homeostasis and Cardiovascular Alterations in Diabetes

Xiang

Comprehensive Physiology

Clemmer

2015

Diabetes mellitus is an increasingly prevalent disease associated with a high morbidity and mortality burden. Many of the adverse outcomes secondary to diabetes occur as a result of the impaired glucose homeostasis and pathophysiological alterations to the cardiovascular system. The purpose of this overview is to broadly discuss many of the changes that occur in the context of diabetes that affect cardiovascular function. Following a brief introduction to the classification and etiologies of the various forms of diabetes, the mechanisms of impaired glucose homeostasis will be covered. Vascular endothelial dysfunction, which has been posited to play a major role in the development of target organ pathology, will be addressed, followed by a discussion of the effects of diabetes on the renal, cardiovascular, and pulmonary systems.