Electrophysiologic actions of BRB-I-28 in ischemically injured canine myocardium.

Abstract

We examined the electrophysiologic actions of BRB-I-28 using two in vivo and two in vitro models of myocardial ischemic injury. In intact canine heart studied 4 days after anterior descending coronary artery occlusion, BRB-I-28 (3 and 6 mg/kg, i.v.) prolonged refractoriness in ischemically injured epicardium to an extent similar to that caused by lidocaine (3 and 6 mg/kg i.v.). BRB-I-28 produced less rate-dependent epicardial delay and, unlike lidocaine, failed to facilitate reentrant arrhythmia formation. Lidocaine and BRB-I-28 (3 and 6 mg/kg i.v.) produced similar rate-dependent prolongation of HV intervals in the normal His-Purkinje system, and produced both tonic and use-dependent conduction block in the ischemically injured His-Purkinje system studied 2 h after anteroseptal coronary artery ligation. In isolated superfused ventricular epicardium studied 1-4 days after anterior descending coronary artery ligation, BRB-I-28 reduced action potential amplitude (APA) and maximum phase 0 upstroke (Vmax) in normal (3.2 mg/L) and ischemically injured (1 and 3.2 mg/L) tissue, with marked tonic and use-dependent conduction block (3.2 mg/L). AP potential duration (APD) was unaltered. In isolated, superfused, ischemically injured canine endocardium studied 24 h after anterior descending coronary artery occlusion, BRB-I-28 (3.2 and 10 ml/L) reduced APA and Vmax and prolonged refractoriness and conduction times in ischemically injured tissue without altering APD. Tonic block was more prominent, and use-dependent block was observed at lower drug concentrations in ischemically injured tissue. The data demonstrate selective conduction depression and prolongation of refractoriness for BRB-I-28 in ischemically injured tissues. Both use-dependent and tonic conduction block contribute to the decrease in conduction observed with BRB-I-28 in ischemically injured myocardium, with more prominent tonic conduction block present in ischemically injured epicardium and His-Purkinje tissue at 2-24 h after coronary artery occlusion than in ischemically injured left ventricular (LV) epicardium studied 4 days after coronary artery occlusion.

• Authors: E Patterson, B J Scherlag, K D Berlin, R Lazzara
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 21 Issue 4 Pg. 637-46 (Apr 1993) ISSN: 0160-2446 [Print] United States
• PMID: 7681911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Arrhythmia Agents
• Bridged Bicyclo Compounds
• Bridged Bicyclo Compounds, Heterocyclic
• 7-benzyl 3-thia-7-azabicyclo(3.3.1)nonane
• Lidocaine

Topics

• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Bridged Bicyclo Compounds (pharmacology)
• Bridged Bicyclo Compounds, Heterocyclic
• Dogs
• Electrophysiology
• Heart (drug effects, physiology)
• Heart Conduction System (drug effects)
• Heart Rate (drug effects)
• Lidocaine (pharmacology)
• Myocardial Infarction (physiopathology)
• Myocardial Ischemia (physiopathology)