Apnea-induced hypoxia and reoxygenation, which generates reactive oxygen species, may activate the oxidant-sensitive, proinflammatory transcription factor nuclear factor kappaB (NF-kappaB), increasing systemic inflammation in obstructive sleep apnea. We measured NF-kappaB activity in circulating neutrophils and plasma levels of NF-kappaB-controlled gene products, soluble E (sE)-selectin and soluble vascular cell adhesion molecule-1 (sVCAM-1) in control subjects and in obstructive sleep apnea (OSA) patients. To confirm a causal link with OSA, we reassessed these parameters after nasal continuous positive airway pressure (CPAP) therapy. Twenty-two subjects undergoing evaluation for symptoms of sleep-disordered breathing were grouped by apnea hypopnea index: control, less than 5/h; mild to moderate OSA, 11-40/h; severe OSA, more than 40/h. A morning venous blood sample was obtained. Neutrophils were isolated, and NF-kappaB activity was determined by electrophoretic mobility shift assay. Plasma sE-selectin and sVCAM-1 were assayed by enzyme-linked immunosorbent assay. Neutrophils in mild to moderate and severe OSA patients showed 4.8- and 7.9-fold greater NF-kappaB binding activity compared with control subjects (p<0.0001). The degree of NF-kappaB activation was positively correlated with indices of apnea severity. In five severe OSA patients, 1 month of CPAP therapy decreased neutrophil NF-kappaB activation to control levels. sE-selectin and sVCAM concentrations were reduced by CPAP in four of these five subjects. OSA leads to NF-kappaB activation, which may constitute an important pathway linking OSA with systemic inflammation and cardiovascular disease.

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We tested the hypothesis that occlusion of the descending aorta is associated with blood volume redistribution resulting in a relative hypervolemia in organs and tissues proximal to the level of occlusion. The study was performed on splenectomized dogs anesthetized with pentobarbital. Whole body scintigraphy with a Sophy DSX rectangular large field of view gamma-camera equipped with a high resolution collimator was used; Tc99m was used to label plasma albumin. The aorta was occluded at diaphragmatic and suprarenal levels in random order. The activity was counted during different stages of the experiments in the following regions of interest: brain, left and right ventricles, left and right lungs, left and right deltoid muscles, the liver, and intestines. Cross-clamping at the suprarenal level was not associated with significant changes in blood volume in any region of interest. The aortic cross-clamping at diaphragmatic level was associated with significant increases in the gamma-emission in all organs and tissues above the level of aortic occlusion by 8%-38%. Thus, the present study supports the hypothesis by demonstrating that cross-clamping of the aorta at diaphragmatic level is associated with an increase in blood volume in the organs and tissues proximal to the level of cross-clamping. Such an increase might represent the mechanism for well-documented increases in preload and blood flow above aortic occlusion, resulting in an additional (in addition to an increase in afterload) burden to the heart.

This study was designed to test the hypothesis that activation of adrenoceptors and/or the renin-angiotensin system plays an important role in the overall hemodynamic response to aortic cross-clamping. The experiments were performed on anesthetized rats pretreated with either saline (control group), an angiotensin-converting enzyme inhibitor (enalapril maleate, 2 mg/kg), an alpha 1-adrenergic antagonist (prazosin hydrochloride, 0.5 mg/kg), a beta-adrenergic antagonist (propranolol hydrochloride, 5 mg/kg), or an alpha 2-adrenergic antagonist (atipamezole, 5 mg/kg). Cross-clamping of the thoracic aorta was associated with an expected increase in mean arterial pressure and systemic vascular resistance in all animals. During the period of cross-clamping, cardiac output gradually decreased in all groups. Animals pretreated with the alpha 1-adrenergic antagonist or the angiotensin-converting enzyme inhibitor developed hypertension of a lesser degree than the control animals, while rats pretreated with the beta-adrenergic or alpha 2-adrenergic antagonist demonstrated a greater arterial hypertension than the control animals. The possible mechanisms underlying the observed differences are discussed. In conclusion, the present study confirms the posed hypothesis that the reninangiotensin and sympathetic nervous systems play an important role in hemodynamic response to cross-clamping of the thoracic aorta.