808-2 Sudden Heart Rate Speeding and Slowing Facilitates the Inducibility of Ventricular Tachycardia in Dogs

Clinically, torsades de pointes (TdP) often occurs when the heart rate suddenly slows (eg. atrial fibrillation to sinus rhythm). We investigated whether the dose of cesium chloride (CsCI) required to induce early afterdepolarizations (EADs), the putative mechanism of TdP. and ventricular tachycardia (VT) was different in dogs with a paced left ventricular cycle length (PCL) of 1,000 msec for a 1 week versus dogs with a PCL of 1,000msec for 1 week and 500 msec for 1 hour prior to a PCL of 1,000msec. All dogs had atrioventricular (AV) block induced by radiofrequency ablation and were studied closed chest. While recording surface ECG leads I.II.III and LV endocardlal monophasic action potential (MAP), CsCI was injected Incrementally (0.25, 0.5, 0.625, 0.75, 1.0mM/kg) until sustained VT was induced. In group 1 (n=6), CsCI was injected during PCL=1,000 msec. In group 2 (n=7), CsCI was injected during PCL=1,000msec after PCL=500msec for 1 hour. In group 1, VT was induced at 0.75 mM/kg in 3 dogs and at 1.0mM/kg in 3 dogs. VT was induced at 0.75 mM/kg in all 7 dogs in group 2(p<0.05). The area of EAD as a percentage of LV MAP area (%EAD) in group 2 dogs exceeded that of group 1 at 0.5, 0.625, 0.75 mM/kgCsCI (mM/kg)0.250.50.6250.75Group 1 (%EAD)108±2.4115±39119±5.4129±5.1Group 2 (%EAD)108±3.6118±2.1127±3.9135±5.4pns<0.05<0.01<0.05We conclude that only 1 hour of rapid pacing after 1week of bradycardia is sufficient to produce a change in myocardial responsiveness to the K+ channel blocker, CsCI, and increases the susceptibility of VT induction, possibly via an increase in EAD amplitud