Majed Odeh

Sublingual electrical stimulation of the tongue during wakefulness and sleep.

Pharyngeal obstruction in patients with obstructive sleep apnea (OSA) is thought to result from decreased upper airway muscle tone during sleep. The goal of the present study was to estimate the role of the tongue muscles in maintaining pharyngeal patency during sleep. Using non-invasive, sub-lingual surface electrical stimulation (ES), we measured tongue protrusion force during wakefulness and upper airway resistance during sleep in seven healthy subjects and six patients with OSA. During wakefulness, ES produced similar protrusion forces in healthy subjects and patients with OSA. ES of the anterior sublingual surface, causing preferential contraction of the genioglossus, resulted in smaller effects than combined ES of the anterior and lateral surface, which also stimulated tongue retractors. During sleep, trans-pharyngeal resistance decreased and peak inspiratory flow rate increased from 319+/-24 to 459+/-27 and from 58+/-16 to 270+/-35 ml/sec for healthy subjects and OSA patients, respectively (P<0.001). However, ES was usually unsuccessful in reopening the upper airway in the presence of complete apneas. We conclude that non-invasive ES of the tongue improves flow dynamics during sleep. Combined activation of tongue protrusors and retractors may have a beneficial mechanical effect. The magnitude of responses observed suggests that in addition to the stimulated muscles, other muscles and/or forces have a substantial impact on pharyngeal patency.

Myocardial bridge: evaluation on MDCT.

OBJECTIVE The correlation between myocardial bridge and atherosclerotic changes has been controversial. The aim of this study was to evaluate the relation between myocardial bridge and atheromatous coronary artery disease (CAD). MATERIALS AND METHODS Three hundred consecutive subjects who underwent coronary CT angiography (CTA) were included in this study. The prevalence, length, depth, precise location, and concomitant atheromatous changes were evaluated. The group of subjects with myocardial bridge was compared with another subgroup, the control group, which included subjects without myocardial bridge. RESULTS From a total of 300 subjects, 78 subjects (26%) were found to have one myocardial bridge each. The mid left anterior descending artery (LAD) was the most common coronary artery involved (48/78). A significant difference was found between the LAD myocardial bridge group and the control group regarding presence of atheromatous changes in a similar LAD segment proximal to the myocardial bridge (p < 0.0001) and in the severity of atheromatous changes in these segments (mild, p < 0.0001; moderate, p < 0.02; and severe, p < 0.0001). The presence of stenosis in the LAD proximal to the myocardial bridge correlated with the thickness and length of the bridge. CONCLUSION Myocardial bridge predisposes to the development of atherosclerosis in the coronary artery segment proximal to the bridge. This may indicate that myocardial bridge should be considered an anatomic risk factor in the evaluation of CAD.

Serum levels of tumor necrosis factor-alpha correlate with severity of hepatic encephalopathy due to chronic liver failure.

Background: Several studies have shown that serum levels of tumor necrosis factor‐α (TNF) are significantly elevated in patients with acute and chronic liver diseases, where these elevations are independent of the etiology of the underlying disease. Serum levels of TNF are significantly higher in patients with cirrhosis than in those without cirrhosis, reaching the highest levels in decompensated cirrhosis. It has also been shown that plasma levels of TNF correlate with the severity of hepatic encephalopathy (HE) in fulminant hepatic failure. However, still there are no published data regarding the relationship between blood levels of TNF and the presence or severity of HE in patients with chronic liver failure.

Effect of genioglossus contraction on pharyngeal lumen and airflow in sleep apnoea patients

The purpose of the present study was to quantify the mechanical effect of genioglossus stimulation on flow mechanics and pharyngeal cross-sectional area in patients with obstructive sleep apnoea, and to identify variables that determine the magnitude of the respiratory effect of tongue protrusion. The pressure/flow and pressure/cross-sectional area relationships of the velo- and oropharynx were assessed in spontaneously breathing propofol-anaesthetised subjects before and during genioglossus stimulation. Genioglossus contraction decreased the critical pressure significantly from 1.2±3.3 to -0.7±3.8 cmH2O, with individual decreases ranging -0.6–5.9 cmH2O. Pharyngeal compliance was not affected by genioglossus contraction. The pharyngeal response to genioglossus stimulation was related to the magnitude of advancement of the posterior side of the tongue, but not to the severity of sleep apnoea, critical pressure, compliance or the shape and other characteristics of the velopharynx. Genioglossus contraction enlarges both the velo- and the oropharynx and lowers the critical pressure without affecting pharyngeal stiffness. The response to genioglossus stimulation depends upon the magnitude of tongue protrusion achieved rather than on inherent characteristics of the patient and their airway.

Relationship between tumor necrosis factor-alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure

BACKGROUND. We have recently demonstrated that in humans, circulating levels of tumor necrosis factor‐α (TNF) correlate positively with severity of hepatic encephalopathy (HE) due to chronic liver failure. AIM. The main aim of this larger population study is to determine the relationship between TNF and ammonia in patients with HE and chronic liver failure due to liver cirrhosis. METHODS. Circulating levels of TNF and ammonia were measured in 108 patients with liver cirrhosis due to various etiologies in various clinical grades of HE (grades 0–4). TNF concentrations were measured in venous serum using commercially available solid‐phase high sensitivity enzyme‐linked immunosorbent assay. Ammonia levels were determined in venous plasma by the enzymatic method, using the glutamate dehydrogenase reaction. RESULTS. The mean±SEM values of circulating levels of TNF and ammonia at presentation in patients with grade 0 of HE (n = 30) were 3.89±0.2 pg/mL and 49.8±2.8 µg/mL respectively, in patients with grade 1 of HE (n = 26) were 8.56±0.34 pg/mL and 101.6±6.5 µg/mL respectively, in patients with grade 2 of HE (n = 22) were 11.59±0.48 pg/mL and 160.3±10.7 µg/mL respectively, in patients with grade 3 of HE (n = 20) were 19.98±0.94 pg/mL and 228.8±16.1 µg/mL respectively, and in patients with grade 4 of HE (n = 10) were 51.53±8.59 pg/mL and 284.2±20.3 µg/mL respectively. A significant positive correlation was found between circulating levels of TNF and those of ammonia (r = 0.62, P<0.0001), and also between circulating levels of both substances and severity of HE in these patients (r = 0.95, P<0.0001, and r = 0.9, P<0.0001 respectively). TNF and ammonia were both significant independent predictors of severity of HE (P<0.0001 for both variables). CONCLUSION. The results of this study demonstrate a significant relationship between TNF and ammonia in patients with chronic liver failure and HE, and so strengthen the suggestion that TNF could be strongly involved in the pathogenesis of HE in these patients. Hence, we suggest a new theory in the pathogenesis of HE, the ‘TNF theory’.

Tumor necrosis factor-α as a myocardial depressant substance

Abstract Most patient with sepsis and septic shock develop significant derangements of myocardial function. The presence of a circulating myocardial depressant substance (MDS) has been suggested to be the major cause of myocardial depression in sepsis and septic shock. MDS is still not fully characterized by chemical means, and there is no consensus regarding its identity. Nevertheless, high levels of MDS activity can be found in sera from patients with sepsis and septic shock. Furthermore, MDS has been shown to have a number of specific characteristics. These characteristics have also been described with tumor necrosis factor-α (TNF), a cytokine that is well recognized to be a primary mediator in the pathogenesis of infection, tissue injury, inflammation and shock. In this review it is suggested that TNF is an MDS, and that the cardiovascular injury and myocardial depression during sepsis and septic shock involve a final common pathway, where TNF may have an important role in this common pathway.

Coronary artery disease among asymptomatic diabetic and nondiabetic patients undergoing coronary computed tomography angiography.

ObjectivesThe aim of this study was to determine the prevalence and severity of coronary artery disease (CAD) and the plaque composition in asymptomatic diabetic and nondiabetic patients undergoing coronary computed tomography angiography (CCTA). BackgroundCAD is the major cause of death among patients with diabetes. The true prevalence of CAD in asymptomatic diabetic patients, however, remains unknown. Materials and methodsA total of 328 consecutive patients (each with at least one risk factor or abnormal stress-test results) were referred for cardiac evaluation, 42 with diabetes and 286 without diabetes, all asymptomatic for cardiac-related symptoms. Groups were matched for age, sex, and CAD risk factors. CAD was defined as coronary atherosclerosis, with obstructive or nonobstructive lesions. CCTA was performed and findings compared between patients with diabetes and those without. ResultsCAD was present in 39 (93%) diabetic patients and in 211 (73%) nondiabetic patients (P=0.006). Obstructive CAD was more common in diabetic patients than in nondiabetic patients (29 vs. 6.6%, respectively; P<0.0001). In diabetic patients, more coronary segments with atherosclerosis per patient were detected (5.5 segments/patient vs. 2.8 segments/patient in nondiabetics; P<0.0001). The total Agatston score was significantly higher in diabetic patients vs. nondiabetic patients (370±96 and 79.9±16, respectively; P<0.0001). ConclusionOur results indicate a high prevalence (93%) of CAD in asymptomatic diabetic patients with either nonobstructive or obstructive lesions. CCTA may be a useful imaging modality for selecting patients at high risk who would benefit most from further evaluation for subclinical ischemia.

Improved Upper Airway Patency Elicited by Electrical Stimulation of the Hypoglossus Nerves

The present study evaluated the mechanisms by which upper airway (UAW)-dilating muscle contraction, elicited by hypoglossus nerve (HGN) stimulation, improved UAW patency. Pressure-flow (P-V) relationships of the isolated UAW as well as the negative intraluminal pressures required to cause UAW collapse were assessed before and during electrical stimulation of the HGN in 8 anesthetized, ventilated dogs. Sectioning of the HGN shifted the P-V relationship to the left, while electrical stimulation resulted in a substantial shift of the curve to the right, indicating UAW dilatation. UAW resistance decreased from 9.0 +/- 1.5 to 0.3 +/- 0.1 cm H2O.1(-1).s during HGn stimulation (p < 0.01). The magnitude of negative intraluminal pressure at which UAW collapse occurred (the critical pressure) increased from -2.7 +/- 0.7 to -13.2 +/- 2.1 cm H2O (p < 0.002). The increase in UAW conductance and stability raised the maximal flow which could be sustained without collapse from 0.28 +/- 0.07 to 2.07 +/- 0.35 l/s during HGN stimulation (p < 0.001). These findings indicate that in the anesthetized dog, UAW muscle contraction improves UAW patency both by dilating the UAW and by stiffening its walls.

Effect of upper airway muscle contraction on supraglottic resistance and stability

The activation of upper airway (UAW) muscles is believed to increase UAW patency to air flow. To evaluate the mechanisms by which UAW muscles act to prevent UAW collapse, pressure-flow relationships of the isolated UAW as well as the negative pressure required to cause UAW collapse (Pcrit) were assessed before and during electrical stimulation of four UAW muscle pairs in anesthetized dogs. Stimulation of each of the muscles shifted the pressure-flow curve toward lower pressures for any given flow rate, indicating UAW dilatation. UAW resistance decreased from 7.9 +/- 0.6 to 0.4 +/- 0.1, 2.7 +/- 0.6, 2.3 +/- 0.8 and to 4.8 +/- 1.5 cmH2O.L-1.sec during genioglossus, geniohyoid, sternothyroid and sternohyoid stimulation respectively (P < 0.01 in all cases). However, only genioglossus stimulation significantly increased Pcrit (from -3.4 +/- 0.6 to -12.0 +/- 1.8 cmH2O, P < 0.001). Relaxation of the genioglossus thus appears to produce the main impediment to air flow through the UAW, and contraction of this muscle improves UAW patency both by dilating the supraglottic airway and by stiffening its walls.

Dependency of upper airway patency on head position: the effect of muscle contraction.

In the present study we examined the effect of flexion and extension of the head on upper airway (UAW) patency in anesthetized dogs, and compared the dilatory and stabilizing effects of electrically stimulated UAW muscles at the different head positions. Flexion of the head increased UAW resistance (Ruaw) and reduced maximal flow (Vmax), but had little effect on the negative pressure at which UAW collapse occurred (Pcrit). Extension of the head, on the other hand, resulted in more negative Pcrit values and increased Vmax without significantly affecting Ruaw. Electrically induced UAW muscle contraction affected the pressure-flow curve and Ruaw, as well as Pcrit. Changing head position had a substantial effect on the dilatory and stabilizing effect of the various UAW muscles. However, independent of head position, genioglossus stimulation was most effective in reducing Ruaw and increasing Pcrit. We conclude that in the anesthetized, supine dog, head position affects the mechanical properties of the UAW and the effects of UAW muscle contraction.