Modeling Pathological Hemodynamic Responses to the Valsalva Maneuver.

The Valsalva maneuver (VM) consisting in a forced expiration against closed airways is one of the most popular clinical tests of the autonomic nervous system function. When properly performed by a healthy subject, it features four characteristic phases of arterial blood pressure (BP) and heart rate (HR) variations, based on the magnitude of which the autonomic function may be assessed qualitatively and quantitatively. In patients with some disorders or in healthy patients subject to specific conditions, the pattern of BP and HR changes during the execution of the Valsalva maneuver may, however, differ from the typical sinusoidal-like pattern. Several types of such abnormal responses are well known and correspond to specific physiological conditions. In this paper, we use our earlier mathematical model of the cardiovascular response to the Valsalva maneuver to show that such pathological responses may be simulated by changing individual model parameters with a clear physiological meaning. The simulation results confirm the adaptability of our model and its usefulness for diagnostic or educational purposes.

Mathematical modelling of cardiovascular response to the Valsalva manoeuvre.

The Valsalva manoeuvre (VM) used for clinical autonomic testing results in a complex cardiovascular response with a concomitant action of several regulatory mechanisms whose nonlinear interactions are difficult to analyse without the aid of a mathematical model. The article presents a new non-pulsatile compartmental model of the human cardiovascular system with a variable intrathoracic pressure enabling the simulation of the haemodynamic response to the VM. The model is based on physiological data and includes three baroreflex mechanisms acting on heart rate, systemic resistance and venous unstressed volume. New nonlinear functions have been proposed to model cardiac output dependence on preload and afterload. Following the individual fitting of some parameters with a clear physiological meaning, the model is able to fit clinical data from patients with both typical and abnormal haemodynamic response to the VM. The sensitivity analysis showed that the model is most sensitive to the parameters describing the vascular pressure-volume relationships (the maximal volume of systemic veins and the relative level of vascular compliance). The use of nonlinear pressure-volume relationships for systemic veins proved crucial for the accurate modelling of the VM. On the contrary, the introduction of aroreflex time delays did not change significantly the haemodynamic response to the manoeuvre. The model can be a useful tool for aiding the interpretation of patient's response to the VM and provides a framework for analysing the interactions between the cardiovascular system and autonomic regulatory mechanisms.

Antibodies to muscle and ganglionic acetylcholine receptors (AchR) in celiac disease.

BACKGROUND: About 2.5% of patients with idiopathic peripheral neuropathy or idiopathic dysautonomia have underlying celiac disease (CD). Antibodies to ganglioside have been reported in CD patients with neuropathy. No data are so far available on the presence in CD of acetylcholine receptor (AChR) antibodies. Muscle AChR antibodies are found in patients with myasthenia gravis, and ganglionic AChR antibodies in patients with autoimmune autonomic neuropathy. OBJECTIVE: To determine the frequency of AChR antibodies in CD patients and assess possible correlations with neurological manifestations. METHODS: Seventy CD patients (16 M, 54 F, mean age 36 years) underwent neurological and electrophysiological evaluation. AChR antibodies were detected with radioimmunoprecipitation assay. Sera from 15 age-matched patients with systemic lupus erythematosus (SLE) and 10 with Sjogren syndrome were studied as controls. RESULTS: None of our CD patients complained of autonomic symptoms or fatigable weakness. Borderline titres (0.03-0.05 nmol/l) of ganglionic AChR antibodies were present in 4 patients, one affected with type I diabetes and one with subclinical neuropathy. Three of the 4 patients underwent cardiovascular autonomic function tests, which showed no abnormalities. Low levels of ganglionic AChR antibodies (0.05-0.10 nmol/l) were found in 2 SLE control patients, one of whom had a severe sicca complex. Muscle AChR antibodies (>1.0 nmol/l) were found in two CD patient and one control patient with SLE. Neither had symptoms or signs of myasthenia gravis. DISCUSSION AND CONCLUSIONS: CD is occasionally associated with neurologic disease, and with antibody reactivity to neuronal antigens. None of our CD patients had autonomic failure or significant levels of ganglionic AChR antibodies. Two CD patient and one control with SLE had muscle AChR antibodies without clinical evidence of myasthenia. The presence of antibodies in CD and in SLE patients may reflect a non-specific autoimmune response in these patients or may indicate subclinical autoimmune autonomic and neuromuscular involvement.