Delayed afterdepolarizations and triggered arrhythmias in hypertrophic cardiomyopathic hearts.
Hypertrophic cardiomyopathy is known to be associated with increased risk of sudden cardiac death. The mechanism is unknown but ventricular tachyarrhythmia is believed to be a major contributing cause. Using standard microelectrode techniques, we examined the propensity of delayed afterdepolarizations (DADs) and triggered activity development in isolated ventricular myocardium from Syrian hamsters with hereditary hypertrophic cardiomyopathy (BIO 14.6) and control hamsters (BIO RB). Induction of DAD was facilitated by burst pacing (15-beat trains with decremental cycle lengths) and with isoproterenol (2 x 10(-7) mol/L). Under baseline conditions with Tyrode's solution containing 2.0 mmol/L CaCl2, no DADs were inducible in eight preparations of myocardium from normal hamsters by burst pacing with or without isoproterenol. In contrast, 2 out of 6 preparations of ventricular myocardium from BIO 14.6 hamsters had inducible DADs by burst pacing alone, and 5 out of 6 preparations had inducible DADs or triggered activity in the presence of isoproterenol (p < 0.05 compared with control). Increasing the extracellular Ca++ to 4.0 mmol/L resulted in enhancement of inducible DADs: in 2 out of 8 preparations with pacing alone, in an additional 2 preparations with isoproterenol in control myocardium, and in 5 out of 6 preparations of BIO 14.6 by burst pacing alone (p < 0.05 compared with control). Exposure to the protein kinase C (PKC)-activating phorbol ester phorbol 12-myristate 13-acetate resulted in suppression of the beta-adrenergic-induced triggered activity in hypertrophic cardiomyopathic preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
Samson
R A
RA
Department of Pediatrics, College of Medicine, University of Iowa, Iowa City.
Lee
H C
HC
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D002118:Calcium / Q000032:analysis / Q000494:pharmacology; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000503:physiopathology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008647:Mesocricetus; D008839:Microelectrodes; D011493:Protein Kinase C / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D011493:Protein Kinase C; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium