David H. P. Streeten

Role of Impaired Lower-Limb Venous Innervation in the Pathogenesis of the Chronic Fatigue Syndrome

BACKGROUND In patients with acute orthostatic hypotension, there is excessive pooling of blood in the legs, which may result from the strikingly subnormal compliance that is demonstrable in the pedal veins during norepinephrine infusion. The common occurrence of delayed orthostatic hypotension and/or tachycardia in the chronic fatigue syndrome (CFS) led to the present studies of foot vein compliance in CFS patients with a linear variable differential transformer. METHODS Seven patients with CFS were compared with 7 age- and gender matched healthy control subjects in their blood pressure, heart-rate, and plasma norepinephrine responses to prolonged standing and in measurements of their foot vein contractile responses to intravenous norepinephrine infusions with the linear variable differential transformer. RESULTS Excessive, delayed (usually after 10 min) orthostatic reductions in systolic and diastolic blood pressure (P < 0.01) and inconsistently excessive increases in heart rate were found in the CFS patients, in whom venous compliance in response to infused norepinephrine was significantly reduced (P < 0.05). CONCLUSIONS In these patients with CFS, delayed orthostatic hypotension was clearly demonstrable, and, as in previously reported patients with orthostatic hypotension of acute onset, this was associated with reduced pedal vein compliance during norepinephrine infusion, implying impaired sympathetic innervation of foot veins. The rapid symptomatic improvement demonstrated in previous studies of CFS patients during correction of orthostatic venous pooling by inflation of military antishock trousers (MAST) to 35 mm Hg may suggest that excessive lower body venous pooling, perhaps by reducing cerebral perfusion, is involved in the orthostatic component of fatigue in these patients.

Idiopathic intracranial hypertension and orthostatic edema may share a common pathogenesis

Our aim was to determine the frequency of orthostatic edema (OE) in patients with idiopathic intracranial hypertension (IIH). We evaluated 30 women with IIH for evidence of OE by comparing sodium and water excretion in the recumbent and standing postures and morning and evening body weights. Data were compared with findings in 30 women with OE, 22 weight-matched obese normal subjects, and 20 lean normal subjects. The effect of treatment with diuretics or diuretics plus sympathomimetic agents was compared. Seventy-seven percent of IIH patients had evidence of peripheral edema and 80% had significant orthostatic retention of sodium or water. Excretion of a standard saline load and of a tap water load was significantly impaired in the upright posture in the IIH and OE patients compared with the lean and obese normal subjects. Diuretic therapy induced weight loss (up to 9 kg) and decreased mean weight gain from morning to evening in 5 of 12 patients treated. In seven patients also treated with diuretics plus sympathomimetic drugs, the diuretic-induced morning weight loss and morning to evening weight gain were both significantly improved with the addition of sympthomimetic agents. Therapy reduced the frequency or severity of headaches in seven patients and reduced papilledema in four patients who received no other concurrent treatment for IIH. The orthostatic retention of sodium and water and the consequent edema is very similar in IIH and OE patients, suggesting a common pathogenesis for both disorders. Diuretic therapy, dietary salt and water restriction, and planned periods of recumbency merit study as a treatment for these patients.

Action of L-epinephrine on the renin-aldosterone system and on urinary electrolyte excretion in man.

The effect of L-epinephrine infusions (0.5-6.5 micrograms/min for up to 24 hr) in recumbency, on the renin-aldosterone system was studied in normal volunteers on diets containing 200 mEq sodium. Urinary sodium excretion was increased, potassium excretion was decreased, aldosterone excretion was suppressed while blood pressure and heart rate were minimally affected by epinephrine (1 microgram/min). Inulin and para-aminohippurate clearances changed transiently and slightly during epinephrine infusions over 10 hr in normal subjects. In separate experiments, epinephrine lowered serum K, raised serum Na, raised plasma renin activity and, usually lowered plasma aldosterone concentrations. There was an excellent correlation between epinephrine-induced changes in serum K and plasma aldosterone concentrations (r = +0.85, p less than 0.001). Significant dose-response relationships were found between L-epinephrine infusion rates of 0.5-6.5 micrograms/min and observed serum K concentrations. We conclude that L-epinephrine infusions at rates probably well within the physiological range, induce hypokalemia (by increased cellular uptake of K) which lowers aldosterone secretion depsite concomitant elevation of PRA and causes natriuresis for up to 24 hr.