Plasma and cerebrospinal fluid endogenous digoxin-like immunoreactivity in patients with aneurysmal subarachnoid haemorrhage.

Abstract

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.