Impaired vagus-mediated immunosuppression in microsomal prostaglandin E synthase-1 deficient mice.

The cholinergic anti-inflammatory pathway controls innate immune responses and inflammation. The prostaglandin (PG) system is involved in several neuro-processes and associated with inflammatory activation of cells in vagal nuclei. Here we aimed to investigate the potential role of PG in cholinergic neuro-regulation. The effect of vagus nerve stimulation (VNS) has been evaluated in microsomal prostaglandin E synthase-1 (mPGES-1) knockout (-/-) and wild-type (+/+) mice regarding cytokine and PG levels after lipopolysaccharides (LPS) challenge. As expected, VNS decreased the release of pro-inflammatory cytokines both in serum and spleen extracts of mPGES-1 (+/+)animals. However, the immune suppressive effect of VNS was completely abolished in mPGES-1 (-/-) mice. The PG content was not affected by VNS in the spleen of mPGES-1 (+/+) and mPGES-1 (-/-) mice but interestingly, acetylcholine (ACh) release in spleen induced by VNS confirmed an intact cholinergic pathway in mPGES-1 (+/+) whereas no VNS-induced ACh release was found in mPGES-1 (-/-) animals. Our data show that mPGES-1 and consequently PGE2 are crucial in the cholinergic anti-inflammatory pathway. Moreover, the mechanisms involved do not affect PG content in the spleen, but lack of mPGES-1 was found to strongly affect cholinergic mechanisms in the inflamed spleen. These findings illustrate previously unrecognized associations between the cholinergic and prostaglandin systems, and may be of importance for further development of therapeutic strategies directed at modulation of the inflammatory reflex, and immunosuppression in chronic inflammatory diseases.

Relationship between the internal laryngeal nerve and the triticeal cartilage: a potentially unrecognized compression site during anterior cervical spine and carotid endarterectomy operations.

OBJECTIVE: The triticeal cartilage has received scant attention in the literature. To date, its relationship to the nearby internal laryngeal nerve has not been studied. Therefore, to elucidate further this anatomic relationship and its potential surgical implications, this study was performed. METHODS: Eighty-six adult cadaveric sides underwent dissection of the internal laryngeal nerve near its penetration of the thyrohyoid membrane. The relationship of this nerve to the triticeal cartilage was documented. Measurements and histological analysis were performed on all cartilage specimens. RESULTS: We identified triticeal cartilage in 51% of the specimens and found it to be hyaline in nature. The triticeal cartilage was located in the upper, middle, and lower thirds of the thyrohyoid membrane in 14%, 66%, and 20% of sides, respectively. Regardless of the position of the triticeal cartilage within the thyrohyoid membrane, the internal laryngeal nerve crossed directly over the triticeal cartilage on 59% of sides. CONCLUSION: When present, the internal laryngeal nerve will cross over the triticeal cartilage in the majority of individuals. This relationship should be borne in mind during surgical manipulation in this area and when placing retractors during anterior neck operations including cervical discectomy/fusion and carotid endarterectomy. Compression of the internal laryngeal nerve against the solid triticeal cartilage can cause laryngeal nerve palsy and increase the risk of resultant postoperative aspiration.

Effect of moderate aerobic exercise on sympatho-vagal balance in Type 2 diabetic patients.

AIMS: The purpose of the study was to determine long-term cardiovascular autonomic adaptation to moderate endurance aerobic exercise in people with Type 2 diabetes in order to test the hypothesis of an enhanced vagal drive. METHODS: We analysed the power spectral density of heart rate cyclic variations at rest, while lying, and while standing in 12 sedentary, non-smoking, Type 2 diabetic individuals. Testing was performed before and after a 6-month, supervised, progressive, aerobic training programme, twice weekly. Heart rate variability was assessed by autoregressive power spectral analysis (PSA); this method allows reliable quantification of low-frequency (LF) and high-frequency (HF) components, which are considered to be under mainly sympathetic and purely parasympathetic control, respectively. RESULTS: In 10-min electrocardiogram recordings, mean RR intervals values lying and standing were similar before and after physical exercise. Likewise, total heart rate variability, expressed as total power spectral density (PSD), was not altered by exercise. In contrast, on standing, the HF component, expressed in normalized units, was significantly higher (20.1 +/- 4 vs. 30.4 +/- 5, P < 0.01), whereas the LF component was significantly lower (68.1 +/- 7 vs. 49.8 +/- 8, P < 0.01) after exercise; hence, on standing, the LF/HF ratio, reflecting the sympathetic vs. parasympathetic balance, was markedly lower (16.2 +/- 11 vs. 5.2 +/- 3.2, P = 0.003). No significant exercise-related changes in these PSA components were observed on lying. CONCLUSIONS: A twice-weekly, 6-month, moderate, aerobic exercise programme, without a concomitant weight loss diet, is associated with significant improvements in cardiovascular autonomic function in overweight, non-smoking, Type 2 diabetic individuals.

Sleep apnea: a new indication for cardiac pacing?

In the general adult population, prevalence of sleep apnea syndrome reaches 4% in men and 2% in women. Continuous positive airway pressure is the most efficient treatment. At the present time, although severe atrial bradycardias could occur during sleep apnea episodes, cardiac pacing has not been demonstrated as an efficient treatment for those bradycardias. Treating sleep apnea generally reduces the number of bradyarrhythmias. However, recent studies reported a beneficial effect of atrial pacing on the sleep apnea burden. The mechanisms rely on two phenomena: first to counteract nocturnal hypervagotonia, and second to treat heart failure. By increasing the heart rate, cardiac output improves, which mitigates pulmonary subedema. Consequently, stimulation of the pulmonary afferent vagal fibers is diminished, which reduces central sleep apnea incidence. During nocturnal hypervagotonia, snoring and obstructive apnea episodes are increased, mainly due to an excessive muscular relaxation of the upper airway area inducing cyclical substantial decreases in the airway caliper. In patients with a low heart rate, atrial pacing can counteract hypervagotonia by enhancing the sympathetic tone and modifying the degree of vigilance. Accordingly, in the near future, sleep apnea treatment might potentially rely on atrial pacing in bradycardic patients with hypervagotonia (with or without heart failure). The role of the physician would then be not only to diagnose sleep apnea, but also to identify potential responders to cardiac pacing.