The Effects of Sleep Hypoxia on Coagulant Factors and Hepatic Inflammation in Emphysematous Rats

OBJECTIVES: To develop a sleep hypoxia (SH) in emphysema (SHE) rat model and to explore whether SHE results in more severe hepatic inflammation than emphysema alone and whether the inflammation changes levels of coagulant/anticoagulant factors synthesized in the liver. METHODS: Seventy-five rats were put into 5 groups: SH control (SHCtrl), treated with sham smoke exposure (16 weeks) and SH exposure (12.5% O(2), 3 h/d, latter 8 weeks); emphysema control (ECtrl), smoke exposure and sham SH exposure (21% O(2)); short SHE (SHEShort), smoke exposure and short SH exposure (1.5 h/d); mild SHE (SHEMild), smoke exposure and mild SH exposure (15% O(2)); standard SHE (SHEStand), smoke exposure and SH exposure. Therefore, ECtrl, SHEShort, SHEMild and SHEStand group were among emphysematous groups. Arterial blood gas (ABG) data was obtained during preliminary tests. After exposure, hepatic inflammation (interleukin -6 [IL-6] mRNA and protein, tumor necrosis factor α [TNFα] mRNA and protein) and liver coagulant/anticoagulant factors (antithrombin [AT], fibrinogen [FIB] and Factor VIII [F VIII]) were evaluated. SPSS 11.5 software was used for statistical analysis. RESULTS: Characteristics of emphysema were obvious in emphysematous groups and ABGs reached SH criteria on hypoxia exposure. Hepatic inflammation parameters and coagulant factors are the lowest in SHCtrl and the highest in SHEStand while AT is the highest in SHCtrl and the lowest in SHEStand. Inflammatory cytokines of liver correlate well with coagulant factors positively and with AT negatively. CONCLUSIONS: When SH is combined with emphysema, hepatic inflammation and coagulability enhance each other synergistically and produce a more significant liver-derivative inflammatory and prothrombotic status

Modeling the Afferent Dynamics of the Baroreflex Control System

In this study we develop a modeling framework for predicting baroreceptor firing rate as a function of blood pressure. We test models within this framework both quantitatively and qualitatively using data from rats. The models describe three components: arterial wall deformation, stimulation of mechanoreceptors located in the BR nerve-endings, and modulation of the action potential frequency. The three sub-systems are modeled individually following well-established biological principles. The first submodel, predicting arterial wall deformation, uses blood pressure as an input and outputs circumferential strain. The mechanoreceptor stimulation model, uses circumferential strain as an input, predicting receptor deformation as an output. Finally, the neural model takes receptor deformation as an input predicting the BR firing rate as an output. Our results show that nonlinear dependence of firing rate on pressure can be accounted for by taking into account the nonlinear elastic properties of the artery wall. This was observed when testing the models using multiple experiments with a single set of parameters. We find that to model the response to a square pressure stimulus, giving rise to post-excitatory depression, it is necessary to include an integrate-and-fire model, which allows the firing rate to cease when the stimulus falls below a given threshold. We show that our modeling framework in combination with sensitivity analysis and parameter estimation can be used to test and compare models. Finally, we demonstrate that our preferred model can exhibit all known dynamics and that it is advantageous to combine qualitative and quantitative analysis methods

Lack of flow mediated dilation and enhanced angiotensin II-induced constriction in skeletal muscle arterioles of lupus-prone autoimmune mice

Systemic lupus erythematosus (SLE) is associated with disturbances in the microcirculation of various tissues, yet the nature of arteriolar dysfunction has not been characterized. Thus, changes in diameter of isolated, pressurized skeletal muscle arterioles of mice with systemic autoimmune disease (lupus prone, MRL/lpr four-month old female) and control (MRL) mice were investigated by video-microscopy. Arteriolar responses to changes in intraluminal pressure, flow, and to vasoactive agents with known mechanisms of action were compared. The active and passive (in Ca(2+) free solution) diameter of MRL/lpr arterioles were not significantly different compared to MRL and morphometric changes were not apparent. Compared to MRL mice the endothelium-dependent dilations to increase in flow, acetylcholine and bradykinin were markedly reduced in arterioles of MRL/lpr mice. Endothelium-independent dilations to sodium-nitroprusside and adenosine were similar in MRL and MRL/lpr arterioles. Furthermore, angiotensin II elicited greater constrictions in MRL/lpr arterioles, whereas serotonin-induced constrictions were similar in both groups. Thus, in arterioles of MRL/lpr mice endothelium-dependent dilator mechanisms are impaired and constriction to angiotensin II is enhanced, suggesting specific alterations in the vasomotor function of microvessels that are likely contribute to the disturbance of skeletal muscle blood flow observed in systemic lupus erythematosus