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Alpha and beta adrenergic interactions with ouabain-induced delayed afterdepolarizations
Abstract:
Standard microelectrode techniques were used to study the effect of alpha and beta adrenergic agonists and antagonists on ouabain-induced delayed afterdepolarizations (DADs) in isolated canine Purkinje fibers. The Purkinje fibers were superfused with ouabain (2 X 10(-7) M) for approximately 30 min to produce afterdepolarizations before superfusion with appropriate adrenergic agonists and antagonists. Propranolol (2 X 10(-7) M), a beta blocking concentration, had no effect on DAD amplitude; higher concentrations of propranolol (2 X 10(-6) reduced DAD and eliminated triggered rhythms. Isoproterenol (5 X 10(-6) M) increased DAD amplitude and triggered activity, an effect which was abolished by pretreatment with propranolol (2 X 10(-7) M). Neither alpha adrenergic blockade with phentolamine nor superfusion with the alpha adrenergic receptor agonist methoxamine had an effect on DAD amplitude or triggered activity. It is concluded that the beta adrenergic stimulation can enhance DAD amplitude and triggered activity in the ouabain-toxic Purkinje fiber. In contrast, alpha adrenergic agonists and blockers do not appear to have significant effects on DAD amplitude or triggered activity.
Insights
Beta-adrenergic stimulation enhances ouabain-induced delayed afterdepolarizations (DADs) and triggered rhythms in canine Purkinje fibers. Alpha-adrenergic agents showed no significant effect on DADs or triggered activity.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Pharmacology
Background:
- Ouabain toxicity can induce dangerous cardiac arrhythmias.
- Delayed afterdepolarizations (DADs) are implicated in arrhythmogenesis.
- Adrenergic signaling plays a role in cardiac function and arrhythmogenesis.
Purpose of the Study:
- To investigate the role of alpha and beta-adrenergic signaling in ouabain-induced DADs.
- To determine the effects of adrenergic agonists and antagonists on canine Purkinje fiber DADs.
Main Methods:
- Standard microelectrode techniques were employed.
- Isolated canine Purkinje fibers were superfused with ouabain to induce DADs.
- Fibers were subsequently exposed to alpha and beta-adrenergic agonists and antagonists.
Main Results:
- Beta-adrenergic stimulation (isoproterenol) increased DAD amplitude and triggered activity.
- Higher concentrations of propranolol (beta-blocker) reduced DADs and eliminated triggered rhythms.
- Alpha-adrenergic blockade (phentolamine) and agonist (methoxamine) had no significant effect.
Conclusions:
- Beta-adrenergic stimulation can exacerbate DADs and triggered activity in ouabain-toxic Purkinje fibers.
- Alpha-adrenergic agents do not appear to significantly influence ouabain-induced DADs or triggered rhythms.