Digoxin-specific Fab Antibody Fragments Research Articles

Beneficial effect of digoxin-specific Fab fragments in bipolar disorder- a preliminary study

A vast amount of experimental data supports the notion that Na+, K+-ATPase and endogenous cardiac steroids (ECS) such as digoxin and ouabain are involved in bipolar disorders. The aim of the study was to examine the possible beneficial effect of Digoxin-specific antibody Fab fragments Digibind, in bipolar disorder (BD) patients. In a pilot, open-label study without a control group, BD inpatient subjects received a single dose of Digibind, injected intravenously. During the 72 hrs following the intervention. the response to Digibind was measured using the Montgomery-Asberg Depression Rating Scale (MADRS). A total 6 patients with a moderate to severe bipolar depressive episode (MADRS 30.3, 24–38) participated in the study. We found a significant clinical improvement at all time points after Digibind administration, manifested by a maximal decrease in the MADRS score of 8.3 points at 24 hrs, followed by a gradual rebound to baseline scores. No control group was included, treatment was open-label, and only 6 patients were studied. This preliminary study showed that a one-time injection of Digibind resulted in a transient significant beneficial effect on depression symptoms in BD patients.

Severe digoxin intoxication: A case report of the use of digoxin-specific Fab antibody fragments

Digoxin is a cardiac glycoside that has been used for several decades to treat heart failure and atrial fibrillation. Several doctors prescribe it to their patients, although it is not the first choice for either condition. In rare cases, intoxication can occur, leading to life-threatening cardiac arrhythmias. Here we report the case of an 84-year-old Caucasian woman who presented to the emergency department with dyspnoea, cough, and bilateral lower limb oedema. Eight days prior to her presentation, she had been prescribed methyldigoxin. As the patient had undiagnosed dementia and was taking medication without supervision, she ingested toxic amounts of the drug. Electrocardiogram showed the presence of arrhythmia, which resolved after using digoxin-specific Fab antibody fragments. In elderly patients, special care should be exercised when prescribing drugs with narrow therapeutic windows.

Clinical signs and symptoms of toxic serum digoxin levels in neonates.

Mutlu M, Aslan Y, Kader Ş, Aktürk-Acar F, Dilber E. Clinical signs and symptoms of toxic serum digoxin levels in neonates. Turk J Pediatr 2019; 61: 244-249. Digoxin is widely used in the treatment of congestive heart failure and some arrhythmias. Digoxin toxicity may occur easily because digoxin has a narrow therapeutic index. This retrospective study was conducted to evaluate the clinical signs and symptoms of toxic serum digoxin levels in neonates. Medical reports of the neonates who had serum digoxin concentrations > 2 nanogram/milliliter (ng/ml) were reviewed in terms of patient demographics, serum digoxin concentrations, signs and symptoms of digoxin toxicity, serum digoxin and electrolyte levels, renal function tests, electrocardiograms, echocardiography, and treatments applied. Digoxin toxic levels were identified in the 13 neonates. Of the 13 neonates with digoxin toxic level, 9 (69%) were term and 8 (62%) were female. Twenty-three percent (3/13) of newborn infants were symptomatic. Symptomatic patients had statistically significantly higher serum digoxin levels, at 7.76±2.76 (5.4-10.8) ng/ml, than asymptomatic patients, at 3.31±1.09 (2.02-4.95) (p=0.036). Symptoms related to toxic digoxin levels were observed in the three neonates with plasma digoxin levels > 5 ng/ml. Gastrointestinal and central nervous system symptoms were the major clinic findings. Despite high digoxin levels, no digoxin-related arrhythmia was observed on electrocardiography, other than sinus bradycardia. Two premature neonates were treated with digoxin-specific antibody Fab fragments (DigiFab®) and hypokalemia developed in both of them. Our data suggests that symptoms related with digoxin toxic levels were observed in neonates with plasma digoxin levels > 5 ng/ml. Serum digoxin levels should be measured in case of signs and symptoms of digoxin toxicity or risk factors for such toxicity.

Severe symptomatic bradycardia after a dinner of spicy oleander soup

Introduction: Cardiac glycosides similar to digoxin are produced by different plants in nature. Nerium oleander, commonly grown as an ornamental shrub, can be found worldwide in temperate countries. Intentional or accidental ingestion of any part of the plant can lead to clinically relevant intoxication. Case report: A 63 year old woman came to the emergency department with acute dyspeptic symptoms after eating vegetable soup flavored with unfamiliar flowers she have collected herself. However, the ECG showed abnormalities that raised suspicions for an overdose of digoxin-like cardiac glycosides. The patient was not on treatment with digoxin and a careful anamnesis revealed that she had eaten oleander leaves. Digoxin specific Fab antibody fragments were administered for marked bradycardia that was not responding to atropine administration, after counseling with the reference toxicology center. The patient was also treated with activated charcoal and magnesium sulphate, intravenous fluids and pantoprazole. Four days later she was discharged as asymptomatic, with normal sinus rhythm. Conclusion: Emergency physicians should be aware of this type of poisoning, especially in cases with typical ECG alterations in patients not treated with digoxin and medical history of plants ingestion. Cardio-active glycosides are present in different plants, often used inappropriately, with potential toxic effects and harmful drug interactions.

Thevetia peruviana

Thevetia peruviana, a poisonous shrub of the Apocynaceae family, is commonly called bastard oleander, exile oleander, tiger apple, and lucky nut. The attractive yellow flower is the reason this plant is cultivated to beautify landscapes in the tropics and subtemperate regions. The toxic glycosides contained in the plant, highly concentrated in the roots and seeds, produce digoxin-like effects and act primarily by inhibiting the Na+-K+ ATPase enzyme in the cardiovascular system. Although this plant is popularly found in the Indian subcontinent, poisoning is chiefly reported from India and Sri Lanka.1Eddleston M. Ariaratnam C.A. Meyer W.P. et al.Epidemic of self-poisoning with seeds of the yellow oleander tree (Thevetia peruviana) in northern Sri Lanka.Trop Med Int Health. 1999; 4: 266-273Crossref PubMed Scopus (99) Google Scholar, 2Puvaneswaralingam S. Yellow oleander poisoning and suicide in Sri Lanka.Scott Univ Med J. 2012; 1 (Available from: http://sumj.dundee.ac.uk/data/uploads/epub-article/002-sumj.epub.pdf. Accessed August 4, 2015): 02Google Scholar, 3Bose T.K. Basu R.K. Biswas B. De J.N. Majumdar B.C. Datta S. Cardiovascular effects of yellow oleander ingestion.J Indian Med Assoc. 1999; 97: 407-410PubMed Google Scholar, 4Saraswat D.K. Garg P.K. Saraswat M. Rare poisoning with cerebra thevetia (yellow oleander). Review of 13 cases of suicidal attempt.J Assoc Physicians India. 1992; 40: 628-629PubMed Google Scholar Accidental poisoning occurs in children who mistakenly consume the fruit either in confusion for water chestnut or out of curiosity.4Saraswat D.K. Garg P.K. Saraswat M. Rare poisoning with cerebra thevetia (yellow oleander). Review of 13 cases of suicidal attempt.J Assoc Physicians India. 1992; 40: 628-629PubMed Google Scholar, 5Camphausen C. Haas N.A. Mattke A.C. Successful treatment of oleander intoxication (cardiac glycosides) with digoxin-specific Fab antibody fragments in a 7-year-old child: case report and review of literature.Z Kardiol. 2005; 94: 817-823Crossref PubMed Scopus (28) Google Scholar Mixing the dried plant parts in herbal tea has also resulted in accidental poisoning in adults.6Driggers D.A. Solbrig R. Steiner J.F. Swedberg J. Jewell G.S. Acute oleander poisoning—a suicide attempt in a geriatric patient.West J Med. 1989; 151: 660-662PubMed Google Scholar The entire plant is poisonous, and suicidal and homicidal poisoning is frequently reported with ingestion of its kernels and leaves. Knowledge of its toxicity among the locals has increased poisoning incidences from this plant, which has no specific antidote; however, it may be treated with a Fab-specific antibody in conjunction with gastric lavage using activated charcoal.5Camphausen C. Haas N.A. Mattke A.C. Successful treatment of oleander intoxication (cardiac glycosides) with digoxin-specific Fab antibody fragments in a 7-year-old child: case report and review of literature.Z Kardiol. 2005; 94: 817-823Crossref PubMed Scopus (28) Google Scholar

O43: Use of digoxin-specific Fab antibody fragments in two cases of life-threatening coconut crab (Birgus latro L.) poisoning

Introduction Neriifolin is a cardenolide structurally closed to digoxin and is contained in the fruit kernel of the red-eye-sea mango tree ( Cerbera manghas ), on which the coconut crab feeds. We previously reported lethal neriifolin poisonings following the consumption of New Caledonian coconut crabs Birgus latro (Maillaud et al., Toxicon 2010). This led us to consider digoxin-specific Fab antibody fragments (Fab) as a specific treatment. This presentation focuses on two cases of successful Fab use. Methods Case #1 (Maillaud et al., Toxicon 2012): a 63-year-old female was admitted to the ER. She had eaten a coconut crab 19 hours previously. ECG showed first-degree atrio-ventricular block (AVB), specific repolarisation abnormalities and prolonged cardiac pauses. Fab (760 mg) were then administered intravenously 21 hours after the toxic meal. No more cardiac pause was reported and the patient was discharged one week later. Case #2: a 73-year-old man complained of vomiting after having eaten a coconut crab a few hours before. He was admitted to the ER. ECG monitoring showed bradycardia (32 to 45 beats/min), arrhythmia and cardiac pauses. Fab were administered (380 mg IV = 10 units). 10 other units were administered 3 hours later in the ICU. Cardiac pauses disappeared and cardiac frequency went close to normal. The patient was discharged at day 2. Different blood samples were analysed. Neriifolin was determined by LC-IT-MS/MS. Table Abstract O43. Case #1 (admission) Case #1 (ICU before Fab) Case #1 (12h after Fab) Case #2 (2h after 1 st Fab) Case #2 (5h after 2 nd Fab) Case #2 (8h after 2 nd Fab) Neriifolin Serum: 1.30 Serum: 0.59 Serum: 3.04 Serum: Plasma: Whole blood: 3.17 Serum: 5.01 Serum: 3.90 Plasma: 4.36 Results Neriifolin blood concentrations (ng/mL): In both cases, neriifolin concentrations increased after the Fab perfusions. As digoxin, neriifolin leaves cardiac receptors to be bound to Fab fragments, and is then eliminated. Surprisingly, as shown in case #2, neriifolin whole blood concentration is much higher than in serum and in plasma. Like digoxin, haemoglobin could be the neriifolin binding site in blood. This may implicates that in cardenolides poisoning, low serum and plasma concentrations should be considered with caution. Two other C. manghas cardenolides of interest: cerberigenin and cerberin, were not detected in all nine samples. Conclusion Digoxin-specific Fab antibody fragments have been effective in the treatment of two life-threatening coconut crab poisonings. Such therapy should be considered in patients showing heart conduction disturbances. As with digoxin, in each case we note a rise in total (free + bound) neriifolin blood concentrations after antidote administration. In Case #2 whole blood concentration was more than 30 times higher than serum and plasma concentrations. To avoid false negative results we suggest considering also whole blood analysis in case of suspected cardenolide intoxications. Reversibility of the RBC partitioning has been shown for digoxin and haemoglobin could be a storage compartment for neriifolin which would explain the need for the supplemental Fab dose in Case #2.

Focus on digitalis intoxication in the elderly Report of a case treated with digoxin-specific Fab antibody fragments

The indications for digoxin are currently limited to rare cases of heart failure and/or atrial fibrillation. Its use should be even more rare in geriatrics its pharmacological characteristics, associated with age-related changes and comorbidities, particularly increase the risk of digoxin poisoning in the elderly. However, at least a third of aged patients suffering from heart failure and/or atrial fibrillation is treated by digitalis. Digoxin intoxication can provoke gastrointestinal troubles, neurological disturbances and, above all, cardiac conduction impairment and dysrythmias, which explain its severity and high mortality rate. Presently, first-line therapy is the administration of digoxin specific antibodies. Poor prognosis factors, frequently found in digoxin intoxications in the elderly, have been established for guiding the prescription of antibodies and their dosage. It is important for geriatricians to be able to recognize poisoning signs and the conditions in which an antidote treatment is necessary. This will permit a more effective management of the case, with the support of a poison control center and possible referral of the patient to an intensive care unit.

First successful curative use of digoxin-specific Fab antibody fragments in a life-threatening coconut crab (Birgus latro L.) poisoning

We wish to report the first curative use of digoxin-specific Fab antibody fragments in a coconut crab Birgus latro L. poisoning in New Caledonia. The female patient, aged sixty-three with a previous history of cardiovascular and metabolic dysfunctions, showed marked first-degree atrio-ventricular block and several atrial pauses, and was given 760 mg of digoxin-specific Fab antibody fragments. Shortly after the perfusion her electrocardiogram returned to close to normal with only slight first-degree atrio-ventricular block and no more atrial pauses. Neriifolin LC-MS/MS tests performed on the patient's serum and urine samples confirmed cardenolide poisoning. Another, younger patient, with high neriifolin levels in her serum and urine samples only experienced gastro-intestinal symptoms and was discharged without specific treatment. The consumption of coconut crab in New Caledonia should be avoided even though the first of the two cases reported suggests that digoxin-specific Fab antibody fragments can be effective in the treatment of life-threatening poisoning caused by the ingestion of this crustacean.

Prognostic Utility of Serum Potassium in Chronic Digoxin Toxicity

In contrast to patients with acute digoxin overdose, the prognostic utility of the serum potassium concentration for patients with chronic digoxin toxicity is unclear. In such patients, we aimed to evaluate the relationship between pre-treatment serum potassium and survival. This was a case-control study at an urban Poison Control Center affiliated with a large urban medical center. We compared the serum potassium concentration between patients with chronic digoxin toxicity resulting in fatality (cases) over a 7-year period (2000-2006) versus survivors (controls) over a 1-year period (2007-2008). During the study period, there were 13 fatalities (cases) and 13 survivors (controls), of whom seven cases and five controls received appropriately dosed digoxin-specific antibody Fab fragments (Fab). There were no statistically significant differences between cases and controls with respect to serum digoxin concentration, creatinine, age, or sex. Serum potassium elevation pre-Fab was significantly associated with fatality both in mean difference (p < 0.03) and using a dichotomous cutoff of 5.0 mEq/L (p < 0.001), which performed with 92% sensitivity (95% CI 67, 99). In 86% of deaths despite appropriate Fab administration, the clinical presentation included the combination of bradycardia plus hyperkalemia. In these patients with chronic digoxin toxicity, elevated serum potassium was associated with fatality. The combination of bradycardia and hyperkalemia strongly predicted fatality even in cases with appropriate Fab administration.

The plasma disposition of sheep antibody (Fab) fragments in the guinea-pig and rabbit.

The plasma elimination of sheep digoxin-specific Fab (fragment antigen-binding) antibody fragments has been studied after intravenous injection (1 mg kg-1) in guinea-pigs and rabbits using an enzyme-linked immunosorbent assay. The log concentration versus time profiles were best described by biexponential and triexponential functions for the response in the guinea-pig and rabbit, respectively. However, the elimination half-lives and apparent volumes of distribution were similar in both species (about 140 min and 120 mL kg-1, respectively). The value for the Fab distribution volume suggests that the antibody fragments distribute out of the vascular compartment but do not fully occupy the extracellular space. Our estimates of the latter, using thiocyanate as a marker, ranged from 220 to 327 mL kg-1 (rabbits and guinea-pigs, respectively). The distribution of Fab fragments in these two species differs significantly from that in the rat, where our earlier studies have shown that these antibody fragments are confined to the intravascular compartment with a distribution volume approximately equivalent to that of plasma (about 40 mL kg-1).

Digitalis must be banished from the table: a rare case of acute accidental Digitalis intoxication of a whole family

Advanced Digitalis intoxication is a rare event, mainly associated with overdose in patients with Digitalis therapy. We report an unusual case of acute 'familiar' digitalis poisoning in three patients who had eaten potato dumplings flavoured with leaves of Borago officinalis L. unconsciously mixed with leaves of Digitalis purpurea L. A complicated clinical course with marked bradyarrhythmias was presented, with good evolution thanks to the use of digoxin-specific antibody Fab fragments. The theme of the domestic use of plants with medicinal effects has been treated and discussed.

Erfolgreiche Therapie einer schweren Oleander-Vergiftung (Herzglykosid) mit Digitalis-Antidot bei einem 7-jährigen Kind—Fallbericht mit Literaturübersicht

A 7-year-old girl presented six hours after ingestion of a yellow oleander seed (Thevetia peruviana) with severe emesis, change in colour vision and complete heart block. Initial treatment with phenytoin and isoprenalin infusion led to intermittent supraventricular and ventricular tachycardia. The patient was then treated with two intravenous doses of 190 mg of digoxin-specific Fab antibody fragments (Digibind). Subsequently the patient's rhythm reverted to sinus rhythm and the symptoms resolved within 2 hours. administration of digoxin-specific Fab antibody fragments in an otherwise healthy child after oleander intoxication is safe and without adverse reactions.

Traitement par anticorps antidigitalique d'une intoxication volontaire par laurier rose

A chronically depressed 44-year-old man was rescued by the French medicalised ambulance service four hours after the ingestion of Nerium oleander leaves in a suicide attempt. Cardiotoxicity was evidenced by the presence of bradycardia with mental confusion and vomiting. The patient was empirically treated in the prehospital phase with a single dose of digoxin-specific Fab antibody fragments (Digidot ®). In spite of this treatment, the patient presented a new episode of important bradycardia (25 b/minute). Thereafter, the patient's rhythm stabilized and neurological signs and vomiting resolved. The patient recovered uneventfully and was discharged from the intensive care unit two days later.

Late rebound digoxin toxicity after digoxin-specific antibody fab fragments therapy in anuric patient

Late rebound digoxin toxicity after digoxin-specific antibody fab fragments therapy in anuric patient

An unusual electrocardiographic pattern of cardiac glycoside poisoning

The electrocardiogram (ECG) presented in Fig. 1 probably linked to the development of late cardiac was registered about 24 h after the deliberate ingespotentials, are also evident. The association of tion of a vague dose of digoxin (probably 5–10 mg) bradycardia and delayed afterdepolarizations due to in a 46-year-old female affected by human immunodigoxin-induced intracellular calcium overload, is deficiency virus infection. probably responsible of this pattern of repolarization. No signs or symptoms related to cardiac inThe more pronounced abnormalities recorded in the volvement were documented before the event; the index beat (*) compared with the following beat, patient declared drug ingestion during the daily were probably due to a longer R–R preceding medical interview. By this time plasma digoxin level interval. was .4 ng/ml (normal range 0.8–2 ng/ml). She was This patient without cardiac symptoms confirm asymptomatic. No significant plasma electrolyte abthat, in subjects with excessive serum digitalis connormalities were found. The patient was treated with centrations, the likelihood of having clinical signs of digoxin-specific FAB antibody fragments. A control intoxication is lesser if the electrocardiogram records ECG obtained 24 h later, with a digoxin plasma level a slow rhythm compared with signs of increased of 1.85 ng/ml, is illustrated in Fig. 2. The remaining automaticity [1]. hospital stay was uneventful. The initial ECG (Fig. 1) shows some peculiar and References unusual abnormalities of ventricular repolarization characterized by an apparent QT-interval prolonga[1] Abdad-Santos F, Carcas AJ, Ibanez C, Frias J. Digoxin level and tion (not confirmed by the calculation of the QTc) clinical manifestations as determinants in the diagnosis of digoxin and a QT-interval dispersion. Prominent U-waves, toxicity. Ther Drug Monit 2000;22:163–8.

Intoxication digitalique en période néonatale: rôle de la déshydratation

Despite the great progress which has been made in the treatment of acute digitalis intoxication by digoxin-immune Fab, it still remains a severe complication of cardiotonic therapy. A neonate with ventricular septal defect and large left-to-right shunt was treated with digitalis and diuretics at the usual starting doses. An intensive phototherapy was also required because of a hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Toxic digoxin accumulation (plasma level 14 ng/mL) was diagnosed three days after the initiation of treatment by the presence of sinus bradycardia and bursts of ventricular fibrillation. Intravenous administration of digoxin-specific antibody Fab fragments (Digidot) was effective, with a rapid improvement of the digitalis poisoning. Because of the particularities concerning drug distribution, metabolism and elimination of drugs in the neonatal period, the digoxin therapeutic index is narrow. This case report suggests the involvement of phototherapy and diuretics, which might induce a significant decrease in extracellular water and drug distribution volumes, ultimately promoting the occurrence of an intoxication.

Role of ouabain-like compound in the rostral ventrolateral medulla in rats.

To determine whether ouabain-like compound (OLC) exerts modulatory influences on the activity of vasomotor neurons in the rostral ventrolateral medulla (RVLM), we examined the effects of microinjecting ouabain, digoxin-specific antibody Fab fragments, and mAb against ouabain on the rat RVLM. Microinjection of ouabain into the unilateral RVLM of anesthetized normotensive rats elicited dose-dependent increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). The pressor and sympathoexcitatory effects of ouabain in the RVLM were reversed by microinjections of an M2 muscarinic antagonist, gallamine, or digoxin-specific antibody Fab fragments. Furthermore, a prior microinjection in the RVLM of gallamine, digoxinspecific antibody Fab fragments, or kainic acid or intravenous injection of hexamethonium all prevented the pressor and sympathoexcitatory effects induced by a subsequent microinjection of ouabain. Microinjections of either digoxinspecific antibody Fab fragments or gallamine per se significantly decreased baseline MAP and RSNA. Injection of digoxin-specific antibody Fab fragments attenuated the effects of a subsequent injection of gallamine. Microinjection of mAb against ouabain, but not nonspecific IgG, also significantly decreased baseline MAP and RSNA. These results suggest that OLC in the RVLM contributes to the tonic activity of vasomotor neurons in anesthetized normotensive rats, and the action of OLC in the RVLM is at least partly mediated by M2 muscarinic mechanisms.

Beneficial Effect of Digoxin-Specific Fab Antibody Fragments in Oleander Intoxication

A 24-year-old man presented to the emergency department with nausea, vomiting, abdominal pain, and an acute confusional state of 6 hours' duration. Ten hours before admission, he had ingested a mixture of orange juice and six ground leaves, later identified as Nerium oleander (common pink oleander) leaves. His blood pressure was 100/80 mm Hg, and his pulse rate was irregular at 40/min. He was disoriented and his speech was dysarthric. Twelve-lead electrocardiography revealed a complete atrioventricular block, with a nodal escape rhythm of 40/min and diffuse ST depression. The presumptive diagnosis of acute oleander intoxication was confirmed by the detection of digoxin (1.0 nmol/L [0.8 ng/mL]) on radioimmunoassay. Despite intensive therapy, the patient's hemodynamic condition deteriorated. His blood pressure decreased to 70/40 mm Hg; he became oliguric and nonresponsive to external stimuli; and his potassium concentration rose to 6.8 mmol/L. Eighteen hours after admission, an empiric 480-mg dose of digoxin-specific Fab antibody fragments was administered intravenously over 30 minutes. Within minutes of the initiation of immunotherapy, the patient woke up; his blood pressure rose to 90/50 mm Hg; and he regained a sinus rhythm of 68/min with a prolonged PR interval. His potassium concentration decreased to 5.1 mmol/L within 15 minutes and normalized within 1 hour of therapy initiation. One day later, the 1 degree atrioventricular block disappeared, but the ST depression persisted for an additional 6 days. The value of digoxin-specific Fab antibody fragments in the treatment of plant glycoside and, in particular, oleander intoxication is discussed.

Beneficial effect of digoxin-specific Fab antibody fragments in oleander intoxication

Beneficial effect of digoxin-specific Fab antibody fragments in oleander intoxication

Brain "ouabain" mediates the sympathoexcitatory and hypertensive effects of high sodium intake in Dahl salt-sensitive rats.

To assess whether brain ouabain-like activity (OLA) mediates the hypertensive effects of high sodium intake in Dahl salt-sensitive (Dahl S) rats, the effects of blockade of brain OLA on mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were evaluated in conscious Dahl salt-resistant (Dahl R) and Dahl S rats on a regular (120 mumol/g) or high sodium (1370 mumol/g) diet from 4 to 7 weeks of age. Dahl S rats given high sodium showed higher basal MAP and augmented responses of MAP and RSNA to air stress and to intracerebroventricular injection of the alpha 2-adrenergic receptor agonist guanabenz as compared with Dahl R rats or Dahl S rats given regular sodium. In contrast, the sympathoexcitatory and pressor responses to intracerebroventricular injection of ouabain (0.3 and 1.0 microgram) were markedly attenuated in Dahl S rats given high sodium. Intracerebroventricular preinjection of 0.3 microgram ouabain significantly enhanced blood pressure and RSNA responses to air stress and intracerebroventricular guanabenz in Dahl S rats given regular sodium to the levels observed in Dahl S rats given high sodium. Intracerebroventricular digoxin-specific antibody Fab (DAF) fragments (132 micrograms/8 microL for 5 minutes) did not change basal MAP and RSNA during the first 4 hours after administration in Dahl S rats on a high sodium diet for 3 weeks. However, 18 hours after the injection of DAF fragments, basal MAP and RSNA were significantly decreased, reaching values for Dahl S rats on a regular sodium diet. The magnitude of increases or decreases in MAP and RSNA to air stress or intracerebroventricular guanabenz were significantly attenuated by the DAF fragments in Dahl S rats on a high sodium but not regular sodium diet. Concomitant intracerebroventricular infusion of DAF fragments (200 micrograms per day) prevented the development of hypertension after a high sodium diet in Dahl S rats and prevented an augmentation in pressor and sympathoexcitatory responses to air stress. After discontinuing the infusion of DAF fragments, resting MAP gradually increased to the high levels found in Dahl S rats given high sodium treated with gamma-globulins. These results support the concept that high sodium intake may cause hypertension in Dahl S rats by increasing endogenous brain OLA, thereby enhancing sympathetic outflow and basal blood pressure as well as sympathoexcitatory and pressor responses to stress.