Sympathoadrenal activity and sleep: in the search for a marker of hyperarousal in insomnia

Objective. To assess subjective and objective sleep characteristics and urinary metanephrine levels in patients with insomnia. Design and methods. We included patients with insomnia complaints and those without sleep– related complaints (control group) 18–75 years old. Subjective evaluation of the main sleep characteristics during the last month was assessed by the Pittsburgh Sleep Quality questionnaire, daytime sleepiness — by the Epworth Sleepiness Scale. For objective sleep evaluation we performed one-night polysomnography (PSG). Within 1 week after the PSG, daily urine was collected to determine the level of metaepinephrine. Results. The groups did not differ by age, mean sleep duration over the past month, number of night awakenings by the Pittsburgh Questionnaire, and level of daytime sleepiness. Sleep latency in insomnia group was 15 minutes longer than in the control group. PSG showed higher apnea-hypopnea and desaturation indices in the control group. There were no differences in daily urinary metanephrine excretion in the main and control groups. Correlation analysis showed no significant association between the metanephrine levels and the severity of somnolence and the index of periodic limb movements. Conclusions. Our analysis showed no significant differences in the daily urine metanephrine levels and the main PSG sleep characteristics among subjects with and without insomnia. Further work is required to clarify markers of insomnia and their negative health effects.

A COMPARATIVE STUDY OF THREE DIFFERENT DOSES OF DEXMEDETOMIDINE ON HAEMODYNAMIC RESPONSE TO LARYNGOSCOPY AND INTUBATION- A CLINICAL STUDY

Direct laryngoscopy and endotracheal intubation are associated with increase in sympathoadrenal activity results in hemodynamic instability. Many strategies were used to attenuate this response. Dexmedetomidine is one of the primary drug being used for this purpose. This study was designed to compare the effect of intravenous 0.5μg/kg, 0.75μg/kg, 1μg/kg dexmedetomidine to laryngoscopy and intubation. This study was conducted on 75 patients allotted into 3 groups 25 patients each. Group A -Inj. Dexmedetomidine 0.5 µg/kg. B - 0. 75µg/kg. C- 1µg/kg. vitals, sedation score were observed. After giving Inj. dexmedetomidine in a dose of 0.5,0.75 and 1 μg/kg change in HR at 10 minutes after laryngoscopy and intubation was 5.47%, 10.80% and 18.38% respectively, change in the SBP was 7.71%,14.69%,16.96% respectively, change in the DBP was 6.96%,13.40%,18.01%. We have found that effective dose to blunt the hemodynamic response to laryngoscopy &intubation is 0.5 μg/kg.

Overnight/first-morning urine free metanephrines and methoxytyramine for diagnosis of pheochromocytoma and paraganglioma: is this an option?

Objective Sympathoadrenal activity is decreased during overnight rest. This study assessed whether urinary-free normetanephrine, metanephrine and methoxytyramine in overnight/first-morning urine collections might offer an alternative to measurements in 24-h collections or plasma for diagnosis of pheochromocytoma and paraganglioma (PPGL). Design and methods Prospective multicenter cross-sectional diagnostic study involving 706 patients tested for PPGL, in whom tumors were confirmed in 79 and excluded in 627 after follow-up. Another 335 age- and sex-matched volunteers were included for reference purposes. Catecholamines and their free O-methylated metabolites were measured in 24-h collections divided according to waking and sleeping hours and normalized to creatinine. Plasma metabolites from blood sampled after supine rest were measured for comparison. Results Urinary outputs of norepinephrine, normetanephrine, epinephrine and metanephrine in the reference population were respectively 50 (48–52)%, 35 (32–37)%, 76 (74–78)% and 15 (12–17)% lower following overnight than daytime collections. Patients in whom PPGLs were excluded showed 28 (26–30)% and 6 (3–9)% day-to-night falls in normetanephrine and metanephrine, while patients with PPGLs showed no significant day-to-night falls in metabolites. Urinary methoxytyramine was consistently unchanged from day to night. According to receiver-operating characteristic curves, diagnostic accuracy of metabolite measurements in overnight/first-morning urine samples did not differ from measurements in 24-h urine collections, but was lower for both than for plasma. Using optimized reference intervals, diagnostic specificity was higher for overnight than daytime collections at similar sensitivities. Conclusions Measurements of urinary-free catecholamine metabolites in first-morning/overnight urine collections offer an alternative for diagnosis of PPGL to 24-h collections but remain less accurate than plasma measurements.

Clinical Efficiency of Bisoprolol in Patients with Coronary Heart Disease Depending on Polymorphous Marker Type of ADRB-1 Gene

At present, in order to influence the indices of the global contractions of the left ventricles in patients with coronary heart disease effectively, genetic characteristics in receptor structure and particularly adrenoreceptors responsible for sympathoadrenal activity should be considered. Patients division depending on the type of polymorphism gives prerequisites for new efficient algorithms for individual selection of medicines, including β-blockers. Taking into consideration the type of polymorphous marker of ADRB- 1 receptor, it is possible to maximize the effect of β-adrenoceptor, thereby to influence effectively the pathogenic mechanism of the disease.

Short-term sympathoadrenal inhibition augments the thermogenic response to β-adrenergic receptor stimulation

Sedentary behavior is associated with an attenuated thermogenic response to β-adrenergic receptor (β-AR) stimulation, an important regulator of energy expenditure (EE) in humans. Chronic stimulation of β-ARs, via heightened activity of the sympathoadrenal system, leads to diminished β-AR function. We have investigated the hypothesis that the thermogenic response of sedentary adults to β-AR stimulation will be increased during short-term sympathoadrenal inhibition. Using a randomly ordered, repeated measures study design, resting EE (REE; indirect calorimetry, ventilated hood technique) and the % increase in EE above REE (%ΔEE) during acute i.v. isoproterenol administration (nonselective β-AR agonist; 6, 12, and 24 ng/kg fat-free mass per min) were determined in 16 sedentary adults (nine females and seven males, 25±1 years, body mass index: 26.1±0.9 kg/m2, maximal oxygen uptake: 40±2 ml/kg per min (mean±s.e.m.)) in the basal state and on the 6th day of transdermal clonidine administration (centrally acting α2-AR agonist; 0.2 mg/day). Relative to baseline, clonidine inhibited sympathoadrenal activity, as evidenced by decreased plasma norepinephrine concentration (1.04±0.13 vs 0.34±0.03 nmol/l; P<0.001), skeletal muscle sympathetic nerve activity (22.5±3.8 vs 8.5±1.9 bursts/min; P=0.003), and resting heart rate (63±2 vs 49±1 beats/min; P<0.001). Sympathoadrenal inhibition decreased REE (6510±243 vs 5857±218 kJ/day; P<0.001), increased respiratory exchange ratio (0.84±0.01 vs 0.86±0.01; P=0.03), and augmented the thermogenic response to β-AR stimulation (%ΔEE: 11±2, 16±2, and 24±2 vs 14±1, 20±2, and 31±2; P=0.04). These data demonstrate that in sedentary humans, short-term inhibition of sympathoadrenal activity increases the thermogenic response to β-AR stimulation, an important determinant of EE and hence energy balance.

Differential therapeutic approach to hypertensive urgencies

Design and methods. Effi cacy and safety of several antihypertensive medications were evaluated in 473 cases of nonthreatening hypertensive crisis. Blood pressure (BP) was measured by (Korotkov) method, hemodynamic parameters were evaluated by reographic investigation, and heart rhythm variability was recorded according to the guideline of International Society of Electrophysiology. Results. It was shown that antihypertensive therapy decreasing sympathoadrenal activity are preferable in emergency. In this situation clonidine and moxonidine were the most effective. Captopril was active if high diastolic blood pressure was registered. Nifedipine effi cacy decreased in patients with high sympathoadrenal activity and high increase of BP. Conclusion. Our results showed that the most effective and safe medication in case of the non-threatening hypertensive crisis was moxonidine