Triggered Activity As a Possible Mechanism for Arrhythmias in Ventricular Hypertrophy FLAVIEN CHARPENTIER,* STEPHANE BAUDET,** and HERVE LE MAREC* From the * Laboratory of Cardiology and ** Laboratory of General Physiology. University of Nantes, France CHARPENTIER, F., ET AL.: Triggered Activity As a Possible Mechanism for Arrhythmias in Ventricular Hypertrophy. To study the cellular mechanisms of arrhythmias occurring in cardiac hypertrophy, we performed standard microelectrode studies on papiiiar\' muscles isolated from control (group N) and hypertrophied ferrets right ventricles. Different stages of hypertrophy, induced hy pulmonary banding, were studied: 10-22 days (group H:), 4-6 weeks IH2}, and 5^-6 months (H3j. During the development of hypertrophy, under 3-adrenergic stimulation, triggered activity {TA} induced by delayed afterdepoJari- zations appeared in 2 of 5 muscles in group Hi and 8 of 8 in group H2. This arrhythmia was absent in N muscles, as weJI as in H3, despite a pronounced prolongation of the action potentials at 50% (100 ± 9.3 msec in group H3 vs 67 ± 5.7 n:sec in H2; P < 0.01} and 90% of repolarization {225 ± 8.7 in H3 vs 185 ± 7.4 msec in H2: P < 0.02). The presence ofTA was associated with an increase in the intracellular calcium activity (144 ± 60 nM in H2 vs 47 ± 9 nM in N; P < 0.05). TA properties were as follows. Triggering frequency increased as p-adrenergic stimulation increased, as pacing cycle length (PCL) de- creased, and as duration of the prestimuiative pause increased. The duration of salvos of TA increased as duration of ihe prestimuiative pauses increased (NS]. The coupling interval of the first triggered beat decreased as PCL decreased (P < 0.001). The minimal cycle length of salvos of TA was not modified by these parameters, it is concluded that delayed afterdepoiarizations-induced TA may occur under P- adrenergic stimulation during the first stages of ventricular hypertrophy. This could partly explain the occurrence of adrenergic-dependent arrhythmias in ventricular hypertrophy. (PACE. Vol. 14, November, Part II 1991) delayed afterdepolarizations, triggered activity, cardiac hypertrophy, arrhythmias, calcium homeostasis, beta-adrenergic stimulation Introduction Patients with cardiac hypertrophy have an in- creased risk of sudden death, whether hypertro- phy results from hypertension,^ ao'tic stenosis,^ or hypertrophic c:ardiomyopathies.^ It is now well recognized that ventricular arrhythmias are one of its most frequent causes.^ The mechanisms for these arrhythmias re- main unknown. It seems that they ca:inot be attrib- This work was supported by the InstUut National de la Sante et de la Recherche M6dicale, grant C.R.E. 885011. Address for reprints: Herv6LeMarec, M,D.. LiiboratoiredeCar- diologie. UA CNRS 1340, Hopital G & R Liennec. BPtOO5. 44035 Nantes c^dex. Trance. Fax: (33] 40105024. uted to a coexistent coronary artery disease,^'^ nor to left ventricular dysfunction.'' Hypertrophy-in- duced tissue modifications may be involved as cardiac hypertrophy is associated with alterations leading to a decrease in subendocardial coronary circulation" and to structural changes, like fibro- sis.'^ But cellular electrophysiological modifica- tions induced by hypertrophy like the increase in action potential duration^"*^ or the occurrence of delayed afterdepolarizations [DADs) and triggered activity^" may be responsible for arrhythmias. We studied the electrophysiological and rhythmic properties of papillary muscles isolated from ferret hypertrophied right ventricles in nor- mal conditions and under a beta-adrenergic stimu- lation. Indeed, the importance of catecholamines PACE, Vol. 14 November 1991. Part II 1735