Our aim was to investigate the sympathetic hyperactivity of systemic sclerosis that may lead to greater morbidity and mortality from cardiovascular events. We analysed the sympathetic (low-frequency) and vagal (high-frequency) components of heart rate variability, in supine and upright positions, in 10 patients with systemic sclerosis, 12 patients with primary Raynaud's phenomenon and 14 controls. We also analysed lung function in order to evaluate a possible link between heart rate variability and ventilation parameters. Heart rate variability was reduced in the supine position in subjects with systemic sclerosis both in comparison with primary Raynaud's phenomenon (total power: 1103±156 versus 3302±486 ;ms 2 , P < 0.004) and control subjects (3148±422 ;ms 2 , P < 0.002). Low-frequency power was higher in patients with systemic sclerosis than in the controls (54.5±4.5 versus 42.5±3.5 normalized units, P < 0.01). During tilt, the change in heart rate was +44% in controls, +24% in subjects with primary Raynaud's phenomenon, and only +17% in the patients with systemic sclerosis ( P < 0.01 versus controls). In patients with systemic sclerosis we found a significant correlation between high-frequency power and the indices of lung function (residual volume: r 2 = 0.5143, P < 0.01; total lung capacity: r 2 = 0.5142, P < 0.01, vital capacity: r 2 = 0.3789, P < 0.05). Heart rate variability was reduced and sympathetic output increased in patients with systemic sclerosis. Subjects with primary Raynaud's phenomenon were characterized by normal heart rate variability and by some degree of sympathetic hyperactivity. During tilting, subjects with systemic sclerosis maintained an unmodified heart rate variability, thus suggesting an impaired baroceptor modulation of the autonomic control. The negative correlation between high-frequency power and indices of respiratory insufficiency in patients with systemic sclerosis suggests that the pulmonary structure plays an important role in the modulation of heart rate variability.

1. Scleroderma is a systemic autoimmune disorder characterized by fibrosis affecting the skin, lung, kidney and other organs. The 70 kDa heat-shock protein has been implicated as essential for cell function during cell growth and differentiation. To study the molecular basis of intracellular events in sclerotic fibroblasts, we compared the expression of the hsp 70 gene in sclerotic and normal control fibroblasts by a run on nuclear transcription assay and a Northern blot assay. 2. In the run on nuclear transcription assay, sclerotic fibroblasts expressed an approximately eightfold higher level of hsp 70 transcription than normal fibroblasts in the quiescent condition after serum starvation. After stimulation with serum, the transcription level of the hsp 70 gene was almost similar in sclerotic and normal control fibroblasts. 3. In the Northern blot assay, the hsp 70 gene transcript, which was present in increased amounts in sclerotic fibroblasts, exhibited normal size.

1. Filterability (deformability) of erythrocytes of patients with Raynaud's phenomenon together with progressive systemic sclerosis (PSS) was decreased compared with the filtration of erythrocytes from normal subjects. 2. PSS erythrocytes showed lower electrophoretic velocity and about 23% less neuraminidase-removable sialic acid density on their surface than the normal erythrocytes. 3. PSS erythrocytes showed more adherence to cultured endothelial cells than the control normal erythrocytes. 4. It is concluded that the increased rigidity and adherence of PSS erythrocytes-5-have pathological significance in the mechanism of vascular abnormalities in PSS.