digoxin and Intracranial-Aneurysm

Recent evidence indicates the presence of naturally occurring digitalis-like compounds in mammals, collectively known as either digitalis-like (DLF) or ouabain-like (OLF) factors, presumed to be endogenous hormones regulating the biological activity of the NA+/ K(+)-ATPase and its isoforms. This substance has been postulated to enhance renal tubular sodium excretion and to increase peripheral vascular resistance. Digoxin-like immunoreactive substance (DLIS) was observed in plasma of some patients with spontaneous subarachnoid haemorrhage (SSAH). Accumulating evidence suggests the central nervous system as a site of synthesis, but also as a site of hypertensinogenic action of endogenous cardioglycosides. The present study intends to establish the ratio of the DLIS in plasma to that in cerebrospinal fluid (CSF) in patients with SSAH and to investigate possible connection of this substance with development of arterial vasospasm. A prospective analysis of DLIS levels was performed on plasma and CSF samples obtained in 40 patients who had suffered a recent SSAH. DLIS levels were determined by the fluorescence polarisation immuno-assay method immediately after the admission to the Ward, and again seven days later. The comparison of CSF and plasma DLIS levels did not show statistically significant differences between the results--neither for the first (Z = 0.530; P = 0.591) nor for the seventh day after the disease onset (Z = 0.448; P = 0.654). Three possible hypothetical explanations of these results are offered: a) substance determined by digoxin immuno-assay has no essential likeness to digoxin; b) loss of the haemato-encephalic barrier integrity enabling free substance exchange between plasma and central nervous system; c) digoxin-like substance production within the central nervous system. Further, comparison of DLIS plasma levels (7th day from onset of SSAH) with angiography results showed that patients with multiple vasospasm had essentially higher plasma DLIS levels compared to patients with no vasospasms (Z = 2.59; P = 0.0097). The amount of extravasated blood, assessed on the basis of cranial CT scanning, was also connected with higher plasma DLIS levels (X2 = 3.29; P = 0.0305). The enhanced arterial narrowing which occurs in SSAH may be in part mediated by increased digitalis-like factor activity.

Topics: Adult; Aged; Angiography, Digital Subtraction; Cardenolides; Digoxin; Fluorescence Polarization Immunoassay; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Middle Aged; Prospective Studies; Saponins; Subarachnoid Hemorrhage; Time Factors; Tomography, X-Ray Computed

Subarachnoid haemorrhage is commonly associated with natriuresis and hyponatraemia. One possible explanation for these features is a defect in the central regulation of renal sodium reabsorption with increased secretion of a natriuretic factor. We investigated whether excess sodium secretion in patients with subarachnoid haemorrhage is related to increased secretion of natriuretic peptides or to the presence of digoxin-like immunoreactive substances.. We measured the plasma concentrations of digoxin-like immunoreactive substances (by a fluorescence polarisation immunoassay) and natriuretic peptides, aldosterone, renin, and antidiuretic hormone (by radioimmunoassay) in ten patients with aneurysmal subarachnoid haemorrhage, ten patients undergoing elective craniotomy for cerebral tumours, and 40 healthy controls of similar age and sex distribution. Samples were collected before surgery, 1 h, 4 h, and 12 h after surgery, then daily until 7 days postoperatively in the two groups of patients.. All patients with subarachnoid haemorrhage, but none of the tumour patients, showed increased urine output and urinary excretion of sodium (p = 0.018 for comparison of means of curves to 7 days). The patients with subarachnoid haemorrhage had much higher plasma concentrations of brain natriuretic peptide (BNP) than controls, on admission (mean 15.1 [SE 3.8] vs 1.6 [1.0] pmol/L, p < 0.001) and throughout the study period, accompanied by lower than normal aldosterone concentrations and normal plasma concentrations of atrial and C-type natriuretic peptides (ANP, CNP). The patients with tumours had similar plasma concentrations of ANP, BNP, and CNP to the controls. We did not detect digoxin-like immunoreactive substances in either group of patients.. Salt-wasting of central origin may induce hyponatraemia in patients with aneurysmal subarachnoid haemorrhage, possibly as a result of increased secretion of BNP with subsequent suppression of aldosterone synthesis.

Topics: Brain Neoplasms; Cardenolides; Digoxin; Enzyme Inhibitors; Female; Fluorescence Polarization Immunoassay; Humans; Hyponatremia; Intracranial Aneurysm; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Saponins; Sodium; Sodium-Potassium-Exchanging ATPase; Subarachnoid Hemorrhage

Topics: Blood Proteins; Cardenolides; Digoxin; Humans; Hyponatremia; Intracranial Aneurysm; Plasma Volume; Renin; Saponins; Sodium-Potassium-Exchanging ATPase; Subarachnoid Hemorrhage; Vasopressins