title: HBI-3000 prevents secondary sudden cardiac death.
abstract: BACKGROUND
  In postmyocardial infarction patients, transient episodes of ischemia are associated with a greater incidence of sudden cardiac death (SCD). Ventricular tachycardia and ventricular fibrillation (VF) are responsible for the majority of SCDs, but current pharmacological interventions for prevention of lethal ventricular arrhythmias are less than satisfactory. We investigated the efficacy of HBI-3000 (HBI), a novel antiarrhythmic agent, in preventing SCD in a conscious canine model.
  
  
  METHODS
  After 3 to 7 days of a surgically induced myocardial infarction (ie, 90-minute occlusion of the left anterior descending coronary artery followed by 30 minutes of reperfusion), conscious animals were administered vehicle (0.9% NaCl solution for injection) or HBI (15 mg/kg) intravenously. An occlusive thrombus at a site remote from the previous myocardial infarction was induced by electrolytic injury to the intimal surface of the left circumflex coronary artery.
  
  
  RESULTS
  Control animals developed premature ventricular complexes (PVCs) followed by ventricular tachycardia, which terminated in VF in 5 of the 8 dogs. HBI reduced the frequency of PVCs, and only 1 of the 9 HBI-treated animals developed VF (P < .05). In a separate group of postinfarcted animals, the electrical conversion threshold was assessed before and after the intravenous administration of HBI (5, 10, or 15 mg/kg) or flecainide (3 mg/kg), a class IC antiarrhythmic agent. The electrical conversion threshold was not altered by HBI, whereas the administration of flecainide increased the threshold (P < .01 vs baseline).
  
  
  CONCLUSIONS
  The data indicate that HBI is an effective antiarrhythmic and antifibrillatory agent for the prevention of VF or sudden cardiac death.
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-5632, USA. jullial@umich.edu
authors.forename: Jullia Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Benedict R
authors.initials: BR
authors.lastname: Lucchesi
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000503:physiopathology; D013463:Sulfuric Acid Esters / Q000008:administration & dosage / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control; D018879:Ventricular Premature Complexes / Q000209:etiology / Q000517:prevention & control
chemical_list: D000889:Anti-Arrhythmia Agents; D013463:Sulfuric Acid Esters; C558473:sulcardine sulfate; D005424:Flecainide
keywords: antiarrhythmic; defibrillation; myocardial ischemia; sulcardine sulfate; ventricular fibrillation