Orthopedic Trauma-Induced Pulmonary Injury in the Obese Zucker Rat

Xiang, Lusha; Hester, Robert L.; Fuller, Wayne A.; Sebai, Mohamad E.; Mittwede, Peter N.; Jones, Eric T.; Aneja, Arun; Russell, George V.

doi:10.1111/j.1549-8719.2010.00061.x

Cited by 13 publications

(21 citation statements)

References 52 publications

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“…We applied lean fragments to lean animals and obese fragments to obese animals to minimize any unexpected immune responses. Our published study has demonstrated increased circulating PGE 2 and cytokine levels along with pulmonary injury in the OZT induced by this protocol (46). This trauma model does not need posttrauma treatments such as surgery or antibiotics, which allows us to focus on the impact of orthopedic trauma.…”

Section: Animalsmentioning

confidence: 81%

“…Therefore, to minimize differences in basal sympathetic tone, 11-to 13-wk-old LZ and OZ were chosen for the current study. We previously demonstrated a decreased skeletal muscle arteriolar tone in the OZ with orthopedic trauma (OZT), with the decreased arteriolar tone normalized following indomethacin administration (46). These results suggest that orthopedic trauma leads to a loss of arteriolar tone in OZT because of increased circulating levels of vasodilator prostaglandin(s).…”

mentioning

confidence: 88%

“…Approximately 90% of patients with severe trauma suffer long bone fractures along with an associated soft-tissue injury (9). Therefore, we mimicked a bilateral femur fracture in male LZ and OZ by soft tissue injury followed by the sterile injection of a bone component suspension into the injured thigh muscle as previously described (29,46). In brief, 11-to 13-wk-old LZ and OZ (bone donors) were anesthetized using pentobarbital (50 mg/kg ip), and both femur and tibia bones were harvested under sterile conditions.…”

Section: Animalsmentioning

confidence: 99%

“…These results suggest that orthopedic trauma leads to a loss of arteriolar tone in OZT because of increased circulating levels of vasodilator prostaglandin(s). For example, we found increased plasma prostaglandin E 2 (PGE 2 ) levels in the OZT but not in the LZ following orthopedic trauma (LZT) (46). This increased vasodilator prostaglandin(s) in OZT may override the vasoconstrictor effect mediated by sympathetic activation and blunt the blood pressure compensation to a mild hemorrhage.…”

mentioning

confidence: 95%

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Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

Xiang

Lu²,

Fuller

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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We have shown that obese Zucker rats with orthopedic trauma (OZT) exhibit a loss of arteriolar tone in skeletal muscle. We hypothesize that the loss of arteriolar tone in OZT blunts vasoconstrictor responses to hemorrhage, resulting in an impaired blood pressure recovery. Orthopedic trauma was induced with soft tissue injury and local injection of bone components in both hindlimbs in lean (LZT) and OZT (11–13 wk). One day after the orthopedic trauma, blood pressure responses following hemorrhage were measured in conscious control lean, control obese, LZT, and OZT. In another set of experiments, the spinotrapezius muscle of control and trauma animals was prepared for microcirculatory observation. Arteriolar responses to phenylephrine (PE) or hemorrhage were determined. Hemorrhage resulted in similar blood pressure responses in control animals and LZT, but the blood pressure recovery following hemorrhage was blunted in the OZT. In the spinotrapezius, OZT exhibited decreased arteriolar tone and blunted vasoconstrictor responses to PE and hemorrhage. Treatment with glibenclamide improved the blood pressure recovery in the conscious OZT and improved the arteriolar tone, and PE induced vasoconstriction in the spinotrapezius of the OZT. Thus, ATP-dependent K+ channel-mediated loss of arteriolar tone in OZT blunts the arteriolar constriction to hemorrhage, resulting in impaired blood pressure recovery.

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Section: Animalsmentioning

confidence: 81%

mentioning

confidence: 88%

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 95%

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Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

Xiang

Lu²,

Fuller

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…Stemming from this, the OZR becomes progressively insulinresistant, dyslipidemic (moderate hypercholesterolemia and severe hypertriglyceridemia), and moderately hypertensive (1,15,20,49). Although considerable evidence has been presented by our laboratory (5,27) and by numerous others (18,30,32,35,36,47,53) regarding the correlation between indexes of vascular dysfunction with characteristics of the metabolic syndrome in these animals at specific ages, minimal evidence has been produced regarding the temporal development of the vascular impairments in these animals, and how these correlate with the evolution of the metabolic syndrome, and other putative markers of dysfunction (e.g., markers of inflammation).…”

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confidence: 99%

Distinct temporal phases of microvascular rarefaction in skeletal muscle of obese Zucker rats

Frisbee

Goodwill

Frisbee

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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lution of metabolic syndrome is associated with a progressive reduction in skeletal muscle microvessel density, known as rarefaction. Although contributing to impairments to mass transport and exchange, the temporal development of rarefaction and the contributing mechanisms that lead to microvessel loss are both unclear and critical areas for investigation. Although previous work suggests that rarefaction severity in obese Zucker rats (OZR) is predicted by the chronic loss of vascular nitric oxide (NO) bioavailability, we have determined that this hides a biphasic development of rarefaction, with both early and late components. Although the total extent of rarefaction was well predicted by the loss in NO bioavailability, the early pulse of rarefaction developed before a loss of NO bioavailability and was associated with altered venular function (increased leukocyte adhesion/rolling), and early elevation in oxidant stress, TNF-␣ levels, and the vascular production of thromboxane A2 (TxA2). Chronic inhibition of TNF-␣ blunted the severity of rarefaction and also reduced vascular oxidant stress and TxA 2 production. Chronic blockade of the actions of TxA2 also blunted rarefaction, but did not impact oxidant stress or inflammation, suggesting that TxA 2 is a downstream outcome of elevated reactive oxygen species and inflammation. If chronic blockade of TxA 2 is terminated, microvascular rarefaction in OZR skeletal muscle resumes, but at a reduced rate despite low NO bioavailability. These results suggest that therapeutic interventions against inflammation and TxA 2 under conditions where metabolic syndrome severity is moderate or mild may prevent the development of a condition of accelerated microvessel loss with metabolic syndrome. skeletal muscle perfusion; vascular remodeling; vascular reactivity; rodent models of obesity; nitric oxide bioavailability; chronic inflammation EPIDEMIOLOGICAL STUDIES HAVE clearly and consistently demonstrated that both the incidence and prevalence of the metabolic syndrome is continuing to increase in Western society and in most developed economies worldwide (4, 9, 24). Although each of the constituent systemic pathologies (e.g., impaired glycemic control, atherogenic dyslipidemia, hypertension, obesity) have been well documented to increase the risk for development of impaired vascular structure/function and peripheral vascular disease (PVD) (10,11,13,14,16,25,29,45), the significance of this multi-pathology state is that it increases the risk for individuals to develop PVD well beyond that for any single contributing element. Given the impact of PVD on life expectancy, quality of life, depression, and the direct (health care) and indirect (lost productivity) economic costs to society (3, 41, 44), considerable emphasis has been placed on not only the study of PVD and its contributing elements in human subjects but also for the detailed investigation of appropriate animal models of vasculopathy in the metabolic syndrome (1, 49, 51). However, although the existing literature is replet...

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Ethyl pyruvate protects rats from phosgene‐induced pulmonary edema by inhibiting cyclooxygenase2 and inducible nitric oxide synthase expression

Chen

Bai

et al. 2011

J of Applied Toxicology

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Phosgene is a poorly water-soluble gas penetrating the lower respiratory tract which can induce acute lung injury characterized by a latent phase of fatal pulmonary edema. Pulmonary edema caused by phosgene is believed to be a consequence of oxidative stress and inflammatory responses. Ethyl pyruvate (EP) has been demonstrated to have anti-inflammatory and anti-oxidative properties in vivo and in vitro. The potential therapeutic role of EP in phosgene-induced pulmonary edema has not been addressed so far. In the present study, we aim to investigate the protective effects of EP on phosgene-induced pulmonary edema and the underlying mechanisms. Rats were administered with EP (40 mg kg(-1)) and RAW264.7 cells were also incubated with it (0, 2, 5 or 10 µm) immediately after phosgene (400 ppm, 1 min) or air exposure. Wet-to-dry lung weight ratio (W:D ratio), nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production, cyclooxygenase2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, and mitogen-activated protein kinases activities (MAPKs) were measured. Our results showed that EP treatment attenuated phosgene-induced pulmonary edema and decreased the level of NO and PGE(2) dose-dependently. Furthermore, EP significantly reduced COX-2 expression, iNOS expression and MAPK activation induced by phosgene. Moreover, specific inhibitors of MAPKs reduced COX-2 and iNOS expression induced by phosgene. These findings suggested that EP has a protective role against phosgene-induced pulmonary edema, which is mediated in part by inhibiting MAPK activation and subsequently down-regulating COX-2 and iNOS expression as well as decreasing the production of NO and PGE(2).

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Orthopedic Trauma-Induced Pulmonary Injury in the Obese Zucker Rat

Cited by 13 publications

References 52 publications

Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

Distinct temporal phases of microvascular rarefaction in skeletal muscle of obese Zucker rats

Ethyl pyruvate protects rats from phosgene‐induced pulmonary edema by inhibiting cyclooxygenase2 and inducible nitric oxide synthase expression

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