title: Effect of endogenous digoxin-like factor and digoxin antibody on myocardial Na+, K(+)-pump activity and ventricular arrhythmias in acute myocardial ischaemia in rats.
abstract: OBJECTIVE
  The aim was to study whether a circulating sodium pump inhibitor (endogenous digoxin-like factor) contributes to the genesis of early ventricular arrhythmias in acute myocardial ischaemia in rats.
  
  
  METHODS
  Effects of digoxin antibody (260 micrograms.kg-1) on the incidence of ventricular arrhythmias, plasma digoxin-like immunoreactivity (DELFIA immunoassay), Na+, K+, and Mg2+ ions, and activity of the ouabain sensitive Na+, K(+)-pump in different regions of myocardium have been studied in propranolol naive and propranolol pretreated rats exposed to acute coronary artery ligation. Adult male Wistar rats were divided into six experimental groups: (1) saline pretreated controls; (2) saline pretreated coronary artery ligated rats; (3) coronary artery ligated rats pretreated with 260 micrograms.kg-1 digoxin antibody; (4) propranolol pretreated controls; (5) propranolol pretreated rats with acute myocardial ischaemia; (6) rats with acute myocardial ischaemia pretreated with both propranolol and digoxin antibody.
  
  
  RESULTS
  Acute myocardial ischaemia in saline pretreated rats was associated with a twofold increase of plasma digoxin-like immunoreactivity and ventricular arrhythmias, but did not lead to changes in myocardial Na+, K(+)-pump activity. Pretreatment of coronary artery ligated rats with digoxin antibody reduced the total duration of ventricular tachycardia and ventricular fibrillation during a 15 minute postligation period from 201 (SEM 34) to 46(18) seconds (p < 0.002) but did not alter activity of the myocardial Na+, K(+)-pump. In rats pretreated with propranolol, acute myocardial ischaemia was associated with a twofold inhibition of the Na+, K(+)-pump in left atrial and left ventricular myocardium, and with a 69% increase in plasma K+ concentration. Administration of digoxin antibody to propranolol pretreated coronary artery ligated rats in parallel with the antiarrhythmic effect prevented the increase in plasma K+ concentration and inhibition of Na+, K(+)-pump in the left atrial, but not the left ventricular myocardium.
  
  
  CONCLUSIONS
  A circulating digoxin-like factor contributes to the pathogenesis of myocardial ischaemia induced ventricular arrhythmias. As propranolol pretreatment of coronary artery ligated rats inhibited the Na, K(+)-pump in myocardium, the inhibitory effect of endogenous digoxin-like factor on Na+, K(+)-ATPase was probably masked in propranolol naive animals by the stimulatory action of catecholamines on Na+, K(+)-ATPase described previously.
authors.affiliation: Division of Cardiology, II Dzhanelidze First Aid (Emergency Medicine) Research Institute, St Petersburg, Russian Federation.
authors.forename: A Y
authors.initials: AY
authors.lastname: Bagrov
authors.forename: O V
authors.initials: OV
authors.lastname: Fedorova
authors.forename: N I
authors.initials: NI
authors.lastname: Roukoyatkina
authors.forename: E P
authors.initials: EP
authors.lastname: Zhabko
mesh_terms: D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000502:physiology; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism*; D001798:Blood Proteins / Q000502:physiology*; D002298:Cardenolides; D004077:Digoxin / Q000276:immunology*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D000906:Antibodies; D001798:Blood Proteins; D002298:Cardenolides; D012503:Saponins; C034504:digoxin-like factors; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase