digoxin and Ischemic-Attack--Transient

The prevalence of stroke is increased in individuals with heart failure (HF). The stroke mechanism in HF may be cardiogenic embolism or cerebral hypoperfusion. Stroke risk increases with decreasing ejection fraction and low cardiac output is associated with hypotension and poor survival. We examine the relationship among blood pressure level, history of stroke/transient ischemic attack (TIA), and HF.. We compared the prevalence of self-reported history of stroke or TIA in the REasons for Geographic And Racial Differences in Stroke (REGARDS) participants with HF (as defined by current digoxin use) and without HF. We excluded participants with atrial fibrillation or missing data. We examined the relationship between HF and history of stroke/TIA within tertiles of systolic blood pressure (SBP) adjusting for patient demographic and health characteristics.. Prevalent stroke/TIA were reported by 66 (26.3%) of 251 participants with and 1805 (8.5%) of 21 202 participants without HF (P<0.0001). Within each tertile of SBP, the unadjusted OR (95% CI) for prior stroke/TIA among those with HF compared with those without HF (the reference group) was, 4.0 (2.8 to 5.8) for SBP <119.5 mm Hg, 2.7 (1.8 to 3.9) for SBP >or=119.5 but <131.5 mm Hg, and 2.3 (1.6 to 3.2) for SBP >or=131.5 mm Hg. After adjustment, the relationship between prior stroke/TIA and HF remained significant only within the lowest tertile of SBP (<119.5 mm Hg; 3.0; 1.5 to 6.1).. The odds of prevalent self-reported stroke/TIA are increased in participants with HF and most markedly increased in participants with low SBP. Longitudinal data are needed to determine whether this reflects stroke/TIA secondary to thromboembolism from poor cardiac function or secondary to cerebral hypoperfusion.

Topics: Aged; Aged, 80 and over; Biomarkers; Black People; Blood Pressure; Cohort Studies; Comorbidity; Digoxin; Female; Geography; Heart Failure; Humans; Hypotension; Ischemic Attack, Transient; Male; Medical History Taking; Middle Aged; Odds Ratio; Prevalence; Racial Groups; Risk Factors; Stroke; Surveys and Questionnaires; White People

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

24 h after ligation of the left middle cerebral artery in cats (sham operation in the control group), a constant intravenous infusion of digoxin was begun and continued to toxicity (ventricular rhythm) and death. We found that the lethal dose of digoxin was significantly less in the stroke group than in the control group, but the lethal plasma digoxin concentration was significantly greater in the stroke group than in the control group. In a subsequent study, we demonstrated that ischemic stroke caused a significant prolongation in the elimination half-life of digoxin and an increase in the volume of distribution. The mean plasma clearance of the stroke group was approximately three fourths of that of the control group. We concluded that the decreased tolerance to digoxin after ischemic stroke was due to the prolonged half-life and decreased clearance of digoxin.

Topics: Animals; Blood Gas Analysis; Blood Pressure; Cats; Cerebrovascular Disorders; Digoxin; Electrocardiography; Hematocrit; Ischemic Attack, Transient; Kinetics

Topics: Aged; Arrhythmias, Cardiac; Bradycardia; Coronary Disease; Digoxin; Electrocardiography; Heart Block; Humans; Hypertension; Ischemic Attack, Transient; Middle Aged; Rheumatic Heart Disease; Syncope; Tachycardia