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Pharmacological effects on oscillatory afterpotentials in partially depolarized ventricular myocardium
1Julius Bernstein Institute of Physiology, Martin-Luther University Halle-Wittenberg, GDR, Saale.
Abstract:
Oscillatory afterpotentials induced by toxic concentrations of ouabain were studied in isolated papillary muscles from the right ventricular myocardium of guinea pigs. In partially depolarized muscles (22 mM extracellular K+) oscillatory afterpotentials (OAP) that follow action potentials can be described as nearly harmonic, periodical damped oscillation using a five parameter model. We measured the time course of the appearance and disappearance of ouabain-induced OAP under control conditions and modified by different pharmacological tools. Changes were quantified by the parameters of the model used. Adriamycin (50 microM) significantly delayed the time to the first OAP after administration of ouabain but also shortened the time necessary for recovery after a 30 min application of ouabain. Adriamycin also reduced the damping ratio of OAP but unlike caffeine (2 mM) it did not completely suppress OAP. The reduction of the extracellular Na+ concentration from 126 to 63 mM strikingly depressed OAP both in damping ratio and amplitude. Dexamethasone (2 microM) transiently depressed already developed OAP. The effects of adriamycin as well as Na+ reduction point to a contribution of a Na/Ca exchange in the generation of OAP. The effect of dexamethasone may refer to an involvement of eicosanoides in the generation of arrhythmogenic OAP.
Insights
Ouabain-induced oscillatory afterpotentials (OAP) in guinea pig heart muscle were investigated. Adriamycin and reduced sodium levels suggest sodium-calcium exchange involvement in OAP generation, while dexamethasone may involve eicosanoids.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Cardiac Electrophysiology
Background:
- Ouabain induces toxic oscillatory afterpotentials (OAP) in cardiac muscle.
- OAP can be modeled as damped oscillations, providing parameters for quantitative analysis.
Purpose of the Study:
- To investigate the time course and modulation of ouabain-induced OAP using pharmacological agents.
- To elucidate the ionic mechanisms underlying OAP generation.
Main Methods:
- Isolated guinea pig right ventricular papillary muscles were used.
- Muscles were partially depolarized with elevated extracellular potassium (22 mM).
- Effects of ouabain, adriamycin, caffeine, dexamethasone, and varying sodium concentrations on OAP were quantified using a five-parameter model.
Main Results:
- Adriamycin delayed OAP onset but accelerated recovery, reducing damping ratio without suppression.
- Reduced extracellular sodium significantly decreased OAP amplitude and damping.
- Dexamethasone transiently depressed OAP, suggesting eicosanoid involvement.
Conclusions:
- Results suggest a role for sodium-calcium exchange in ouabain-induced OAP.
- Dexamethasone's effect indicates potential involvement of eicosanoids in arrhythmogenic OAP.