Dataset Information

Enoxaparin sodium prevents intestinal microcirculatory dysfunction in endotoxemic rats.

ABSTRACT:

Introduction

During severe sepsis or septic shock, activation of the inflammatory and coagulatory systems can result in microcirculatory dysfunction as well as microvascular thrombosis, culminating in multiple organ dysfunction and death. Enoxaparin can inhibit factor Xa and attenuate endothelial damage. The primary purpose of this study was to investigate the effect of enoxaparin on intestinal microcirculation in endotoxemic rats.

Methods

Thirty male Wistar rats were divided into the following three groups: sham operated (OP); lipopolysaccharide (LPS); and LPS + Enoxaparin group. The rats received a midline laparotomy to exteriorize a segment of terminal ileum for microcirculation examination by full-field laser perfusion imager and sidestream dark field video microscope on mucosa, muscle, and Peyer's patch. In the LPS and LPS + Enoxaparin groups, 15 mg/kg LPS was administered intravenously to induce endotoxemia, and 400 IU/kg enoxaparin sodium was also administered in the LPS + Enoxaparin group.

Results

At 240 minutes, the mean arterial pressure was higher in the LPS + Enoxaparin group than in the LPS group (93 ± 9 versus 64 ± 16 mm Hg, P < 0.001). Microcirculatory blood flow intensity was higher in the LPS + Enoxaparin group than in the LPS group as follows: mucosa (1085 ± 215 versus 617 ± 214 perfusion unit [PU], P < 0.001); muscle (760 ± 202 versus 416 ± 223 PU, P = 0.001); and Peyer's patch (1,116 ± 245 versus 570 ± 280 PU, P < 0.001). Enoxaparin inhibited LPS-induced reduction in perfused small vessel density and increase in heterogeneity of microcirculation.

Conclusions

Enoxaparin can prevent intestinal microcirculatory dysfunction in endotoxemic rats by preventing microvascular thrombosis formation and maintaining normal mean arterial pressure.

SUBMITTER: Yeh YC

PROVIDER: S-EPMC3681388 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

Enoxaparin sodium prevents intestinal microcirculatory dysfunction in endotoxemic rats.

Yeh Yu-Chang YC Wang Ming-Jiuh MJ Lin Chih-Peng CP Fan Shou-Zen SZ Tsai Jui-Chang JC Sun Wei-Zen WZ Ko Wen-Je WJ

Critical care (London, England) 20121212 2

<h4>Introduction</h4>During severe sepsis or septic shock, activation of the inflammatory and coagulatory systems can result in microcirculatory dysfunction as well as microvascular thrombosis, culminating in multiple organ dysfunction and death. Enoxaparin can inhibit factor Xa and attenuate endothelial damage. The primary purpose of this study was to investigate the effect of enoxaparin on intestinal microcirculation in endotoxemic rats.<h4>Methods</h4>Thirty male Wistar rats were divided into ...[more]

PMID: 22507823

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Project description:Although women are more susceptible to pulmonary arterial hypertension (PAH) than men, their right ventricular (RV) function is better preserved. Estrogen receptor-α (ERα) has been identified as a likely mediator for estrogen protection in the RV. However, the role of ERα in preserving RV function and remodeling during pressure overload remains poorly understood. We hypothesized that loss of functional ERα removes female protection from adverse remodeling and is permissive for the development of a maladapted RV phenotype. Male and female rats with a loss-of-function mutation in ERα (ERαMut) and wild-type (WT) littermates underwent RV pressure overload by pulmonary artery banding (PAB). At 10 wk post-PAB, WT and ERαMut demonstrated RV hypertrophy. Analysis of RV pressure waveforms demonstrated RV-pulmonary vascular uncoupling and diastolic dysfunction in female, but not male, ERαMut PAB rats. Similarly, female, but not male, ERαMut exhibited increased RV fibrosis, comprised primarily of thick collagen fibers. There was an increased protein expression ratio of TIMP metallopeptidase inhibitor 1 (Timp1) to matrix metalloproteinase 9 (Mmp9) in female ERαMut compared with WT PAB rats, suggesting less collagen degradation. RNA-sequencing in female WT and ERαMut RV revealed kallikrein-related peptidase 10 (Klk10) and Jun Proto-Oncogene (Jun) as possible mediators of female RV protection during PAB. In summary, ERα in females is protective against RV-pulmonary vascular uncoupling, diastolic dysfunction, and fibrosis in response to pressure overload. ERα appears to be dispensable for RV adaptation in males. ERα may be a mediator of superior RV adaptation in female patients with PAH.NEW & NOTEWORTHY Using a novel loss-of-function mutation in estrogen receptor-α (ERα), we demonstrate that female, but not male, ERα mutant rats display right ventricular (RV)-vascular uncoupling, diastolic dysfunction, and fibrosis following pressure overload, indicating a sex-dependent role of ERα in protecting against adverse RV remodeling. TIMP metallopeptidase inhibitor 1 (Timp1), matrix metalloproteinase 9 (Mmp9), kallikrein-related peptidase 10 (Klk10), and Jun Proto-Oncogene (Jun) were identified as potential mediators in ERα-regulated pathways in RV pressure overload.

Dataset Information

Enoxaparin sodium prevents intestinal microcirculatory dysfunction in endotoxemic rats.

Introduction

Methods

Results

Conclusions

Publications

Enoxaparin sodium prevents intestinal microcirculatory dysfunction in endotoxemic rats.

Similar Datasets

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