Autonomic dysfunction in normotensive awake subjects with obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is associated with systemic arterial hypertension and cardiac arrhythmias and may lead to cardiovascular complications. Dysfunction of the autonomic nervous system (ANS) may play a role in the development of cardiovascular complications. The aim of this work was to study the ANS by spectral analysis of the heart rate variability (HRV) at rest and after stress (head-up tilt test) in a group of normotensive awake OSAS subjects. We studied 22 males with OSAS, aged 47.6 +/- 13.1 yrs, with a body mass index (BMI) 35.6 +/- 7.7 kg.m-2 and blood systolic and diastolic pressure (BSP and BDP, respectively) of 128 +/- 16 and 80 +/- 9 mmHg. Nineteen healthy males were studied as controls. Autonomic investigations were performed using the computerized power spectral analysis of HRV with autoregressive modelling which identifies low frequency (LF), as a marker of sympathetic activity and high frequency (HF), as a marker of vagal activity. OSAS patients showed greater sympathetic activity (LF) at rest than normal subjects, and an abnormal response to the head-up tilt test compared to control subjects. Five OSAS patients behaved like control subjects. Comparison of the functional parameters between these five OSAS patients and the other 17 OSAS patients showed a statistically significant difference for only basal arterial carbon dioxide tension (Pa,CO2) and minimal nocturnal oxyhaemoglobin (HbO2) saturation (NADIR). Our study shows autonomic nervous system dysfunction in patients with obstructive sleep apnoea syndrome, which may have facilitated a pathophysiological link with the cardiovascular complications observed in these patients.

Depressed baroreceptor reflex in patients with obstructive sleep apnea (OSA).

In this study we evaluated the cardiovascular autonomic function in twenty-five OSA patients and in twenty-five control healthy subjects, by computerized spectral analysis of R-R interval variation at rest and during orthostatism by head-up tilt maneuver to up-right position (80 degrees) as a sympathetic provocation. The results of our study show that most patients affected by OSA have a sympathetic overactivity and a decreased baroreflex response in comparison with normal subjects. The method here described is simple, objective and very sensitive and may be utilized to discover early signs of an autonomic dysfunction consequent to OSA leading to cardiovascular complications of the late stage of the disease.

Increased lipid peroxidation in type 2 poorly controlled diabetic patients.

An increased lipid peroxidation, due to the altered intracellular ratio between free radicals and antioxidant systems, has been recently related to diabetes. To study the possible relationship between lipid peroxidation and metabolic control, we measured the plasma concentrations of malondialdehyde (MDA), end product of the oxidation of polyunsaturated fatty acids, in poorly and well controlled Type 2 diabetic patients. A significant increase in plasma malondialdehyde concentrations was found in poorly controlled diabetics when compared to well controlled patients (p < 0.001) and to healthy normoglycaemic subjects (p < 0.001), whereas no significant difference was observed between the two latter groups. Plasma MDA/Cholesterol and MDA/triglyceride ratios were both higher in poorly controlled diabetics than in well controlled (p < 0.005) and in normal subjects (p < 0.01 and p < 0.02 for MDA/CHOL and MDA/TG respectively). In diabetic patients a positive correlation was found between plasma MDA levels and mean daily blood glucose (p < 0.01), plasma fructosamines (p < 0.001), HbA1 (p < 0.05) and plasma triglycerides (p < 0.05), while no significant correlation was shown between plasma malondialdehyde and total cholesterol. Malondialdehyde levels were followed-up for 7 days running (T1-T7) in five poorly controlled diabetics, treated with conventional insulin therapy. This group showed normalized plasma lipid peroxide values (0.486 +/- 0.13 mumol/l, T5, M +/- SEM) 72 h after the restoration of glycaemic control (145 +/- 25 mg/dl, T2, M +/- SEM). These results confirm the increase of lipid peroxidation during Type 2 diabetes. The correlation with the degree of metabolic imbalance suggests a possible role for lipid peroxidation in the occurrence of glucose-induced macromolecular changes.

[Insulin counter-regulation in multiple sclerosis]. / La controregolazione insulare nella sclerosi multipla.

Fasting hypoglycemia is frequently observed in patients with Multiple Sclerosis (S.M.) showing orthostatic hypotension and defective thermoregulation, although they never complicate in hypoglycemic coma. The aim of this study was to evaluate glucose homeostasis in S.M. patients. Both insular and counter-insular regulating mechanisms were investigated by determination of glucose, insulin, C-peptide and cortisol plasmatic levels during OGTT, and subsequently by evaluating glucagon plasmatic levels after arginine administration (30 g., i.v.). Our results suggest that the increased susceptibility of S.M. patients to undergo fasting hypoglycemia could be related to some alterations in counter-insular mechanisms, generally included among neurovegetative modifications in S.M. patients and probably due to orthosympathetic function impairment.

[Liver damage caused by psychopharmaceuticals]. / Danno epatico da psicofarmaci.

Liver plays a central role in drug metabolism, particularly in uptake, biotransformation and excretion of metabolites. Among these metabolic steps biotransformation represents the most critical factor in drug-induced liver damage, especially when hepatic protective mechanisms, such as the tripeptide glutathione (GSH), are decreased thereby predisposing to lipid peroxidation of biological membranes. The authors focus on the prevalence of hepatic damage in a population of patients chronically treated with psychotropic drugs and divided according to the therapeutic schedule and the type of drug. It is shown that the liver damage induced by psychopharmacologic treatment correlates in a group of 15 patients with a significant decrease of hepatic glutathione.

[2-3 diphosphoglycerate and tissue oxygenation in the cirrhotic]. / 2-3 difosfoglicerato ed ossigenazione tissutale nel cirrotico.

Increased 2-3 Diphosphoglycerate levels in cirrhotic patients have been reported. Previous studies did not show significant changes in 2-3 DPG in anaemic cirrhotic patients when compared to non anaemic cirrhotic patients, but the role played by alkalosis and/or hypoxia has not been investigated. To study this question, haematic 2-3 DPG was measured in 8 male patients with liver cirrhosis (histologically diagnosed) together with PO2, PCO2, pH and Hct. 2-3 DPG was also measured in 6 healthy male volunteers. We found a significant increase in blood 2-3 DPG of cirrhotic patients compared to control subjects (5,55 +/- 0,4 vs 2,18 +/- 0,3 mmol/l erythrocytes respectively, p less than 0,001) in agreement with previous studies. PO2 levels and Hct value did not show important changes, whereas PCO2 and pH resulted to be very altered when compared to normal values, even though we could not correlate these values with blood 2-3 DPG. We conclude that the genesis of 2-3 DPG increase is multifactorial, however an alteration in acid-base equilibrium seems to play a more important role than hypoxia.