Asynchronous development of electrical remodeling and cardiac hypertrophy in the complete AV block dog.

OBJECTIVE: Left ventricular hypertrophy has been associated with the prolongation of QT-time, and an increased risk of ventricular arrhythmias. The renin angiotensin system has been implicated in the development of ventricular hypertrophy. At 5 weeks complete AV block (CAVB) in the dog, there is: (1) biventricular hypertrophy associated with a transient activation of components of the renin angiotensin system, (2) increased APD, more pronounced in the left than in the right ventricle leading to spatial dispersion of repolarization, and (3) enhanced susceptibility to drug-induced torsade de pointes arrhythmias. To investigate whether these remodeling processes develop in parallel, time dependency was assessed in absence or presence of the AT1 receptor-blocker Irbesartan. METHODS AND RESULTS: Dogs in sinus rhythm, 2 and 5 weeks CAVB were compared to dogs chronically treated with Irbesartan (30 mg/kg BID). Endocardial monophasic APD of left and right ventricle was measured and susceptibility to torsade de pointes was tested by infusing Dofetilide (0.025 mg/kg/5'). Hypertrophy was determined by relating heart-to-body weight at sacrifice. Left ventricular APD had increased more than right ventricular APD at 2 and 5 weeks CAVB, leading to an increase in spatial dispersion. At that time torsade de pointes were evocable in the majority of the dogs. Hypertrophy had only developed completely at 5 weeks CAVB. Irbesartan had no effect on electrical and structural parameters or on arrhythmogenicity. CONCLUSIONS: In the CAVB dog ventricular hypertrophy is not a prerequisite for electrical remodeling or drug-induced torsade de pointes, and the AT1-receptor has no dominant role in the completion of these remodeling processes.

The JT-area indicates dispersion of repolarization in dogs with atrioventricular block.

UNLABELLED: Heterogeneity in cardiac repolarization (Delta APD) is known to be arrhythmic. In the dog model of chronic complete AV-block and acquired long QT syndrome, an increase in Delta MAPD (defined as left ventricular monophasic action potential duration (MAPD) minus right ventricular MAPD) is often associated with changes in T-wave morphology. The purpose of this study was to correlate known changes in Delta MAPD with the planimetric total area of the T-wave on the surface ECG (integral of J-T, mVx ms). METHODS: The relationship between Delta MAPD and total area of the T-wave (i.e., JT-area) was assessed in four different protocols with different types of dispersion: (1) class III drugs followed by levcromakalim (n= 7), (2) LAD coronary artery occlusion and reperfusion (n = 6), (3) dronedarone i.v., an amiodarone like agent (n = 5) and (4) steady state pacing at cycle lengths of 1000 ms and 500 ms (n = 5). RESULTS: Class III drugs increased Delta MAPD (55 +/- 40 ms to 120 +/- 50 ms(#), P<0.05), which was correlated (r = 0.74, P < 0.001) with JT-area (50 +/- 40 mV. ms to 95 +/- 35 mV x ms(#)). Ischemia increased both Delta MAPD (30 +/- 25 ms to 90 +/- 40 ms(#)) and JT-area (60 +/- 55 mV x ms to 75 +/- 50 mV x ms(#)). Both levcromakalim and reperfusion reversed these conditions. Dronedarone had no effect on Delta MAPD or on JT-area while a faster frequency reduced both Delta MAPD and JT-area. CONCLUSION: Changes in dispersion of ventricular repolarization are reflected by alterations in JT-area. This non-invasive parameter may therefore be used to indicate changes in heterogeneity in ventricular repolarization.