Comparison of hemodynamic effects of 2 type 111 anti arrhythmic agents in dogs with chronic ischem1c left ventricular dysfunction

Cardiac contractile dysfunction and tachyarrhythmia frequently coexist in patients with chronic LV dysfunction. Newer Class III antiarrhythmics may have a salutory influence on control of tachyarrhythrnia by action potential prolongation. These agents may not cause further hemodynamic deterioration in patients with LV dysfunction. We compared a new agent NE 10064 with sotolol, a class III antiarrhythmic, with known LV systolic depressive actions. We studied 10 mongrel dogs with chronic LV dysfunction (LVEDP = 13mmHg, ejection fraction = 35%) induced by coronary microsphere embolization with 3 mg/kg of IV NE 10064 and IV Sotolol. Each dog was atrially paced and received a placebo injection and then either sotolol or NE 10064 with the study repeated 2 weeks later with the other drug. LV hemodynamics and cardiac outputs were obtained prior to and following the placebo and drug stages. NE 10064 increased the corrected QT interval by 29 ±, 51 msec (p < .05 vs placebo) as compared to 61 + 26 msec with sotolol (p < .05 vs NE). Sotolol depressed peak + dp/dt ( by -117 ±117), peak -dp/dt (-181 ±61), increased tau (9 ±1 msec), increased LVEDP (3.2 ±4.6 mmHg) and mean right atrial pressures (0.8 ±0.3 mmHg) all are p < .05 vs placebo). However, NE 10064 moderately increased LVEDP (2.0 i 1.4 mmHg). minimally increased tau (4 ±. 7 msec), but increased peak positive dp/dt (74 ± 117), all are p < .05 vs placebo and p < .05 vs sotolol. We conclude that NE 10064 did not demonstrate LV systolic depression as compared to sotolol but did result in further relaxation abnormalities and increased LV filling pressures (though less than sotolol) possibly due to increased calcium availability due to action potential prolongation.