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Effect of coronary perfusion of heptanol or potassium on conduction and ventricular arrhythmias
D J Callans1, R S Kieval, B G Hook
1Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Insights
Cellular coupling abnormalities, influenced by gap junctions, contribute to arrhythmias. Heptanol, affecting cellular coupling, increased ventricular tachycardia susceptibility more than potassium, which impacts membrane properties.
Area of Science:
- Cardiovascular Physiology
- Electrophysiology
Background:
- Cellular coupling, modulated by intracellular gap junctions, is implicated in reentrant arrhythmias following myocardial infarction.
- Understanding the distinct effects of agents targeting cellular coupling versus active membrane properties is crucial for arrhythmia research.
Purpose of the Study:
- To investigate the differential arrhythmogenic effects of heptanol (gap junction modulator) and potassium (affecting active membrane properties) in normal canine myocardium in vivo.
- To determine if agents affecting cellular coupling have different arrhythmogenic consequences compared to those altering active membrane properties.
Main Methods:
- Localized intracoronary infusion of heptanol and potassium in 11 normal dogs.
- Assessment of dose-related effects on conduction velocity.
- Programmed electrical stimulation to induce arrhythmias during agent infusion.
Main Results:
- Both heptanol and potassium caused dose-related slowing of conduction.
- Potassium infusion led to ventricular fibrillation in a dose-dependent manner.
- Heptanol infusion induced uniform ventricular tachycardia in a significant proportion of animals.
- Heptanol, but not potassium, increased susceptibility to reentrant ventricular tachycardia in normal myocardium.
Conclusions:
- Agents affecting cellular coupling, such as heptanol, can increase susceptibility to ventricular tachycardia through reentrant mechanisms.
- Agents primarily altering active membrane properties, like potassium, induce arrhythmias through different pathways.
- The distinct effects highlight the importance of targeting specific mechanisms in antiarrhythmic strategies.
Abstract:
Abnormalities in cellular coupling, modulated in part by intracellular gap junctions, have an important role in the genesis of reentrant arrhythmias in the setting of chronic myocardial infarction. The effects of heptanol, which has a relatively selective action on gap junctional resistance at low concentrations, and potassium, which primarily affects active membrane properties, were assessed using a localized intracoronary infusion system in 11 normal dogs in vivo. Both agents caused a dose-related slowing of conduction. Programmed stimulation during potassium infusion resulted in ventricular fibrillation in two of six animals treated with a low dose (5.0-5.5 meq/l) and five of six animals treated with a high dose (7.0-7.5 meq/l). During the infusion of 1.0 mM heptanol, uniform ventricular tachycardia was induced in four of eight animals. Infusion of heptanol, but not potassium, increased the susceptibility to presumably reentrant ventricular tachycardia in normal myocardium. This suggests that agents that affect cellular coupling may have markedly different arrhythmogenic consequences than agents that primarily alter active membrane properties.