In dogs with acute ischemic heart failure, dofetilide prolonged repolarization (QT increased by up to 40 ms, p<0.05) without causing cardiodepressive effects.
Does dofetilide alter hemodynamics or metabolism in a canine model of acute ischemic heart failure?
Dofetilide prolongs repolarization without exerting cardiodepressive effects in a canine model of acute ischemic heart failure.
We studied the hemodynamic and metabolic effects of the novel class III antiarrhythmic agent dofetilide (UK-68,798) in acute ischemic heart failure. In pentobarbital-anesthetized dogs, heart failure was induced by microembolization of the area supplied by the main left coronary artery until a stable left ventricular (LV) end-diastolic pressure of 27 +/- 2 mm Hg was achieved. Embolization depressed LV systolic pressure, LV dP/dtmax, LV dP/dtmin, and cardiac output. None of these parameters were changed following i.v. infusion of dofetilide 5, 10, or 25 micrograms/kg, during spontaneous and paced cycle length of 300 ms (n = 9). Heart rate decreased by 12 +/- 8, 19 +/- 7, and 21 +/- 7 beats/min (p less than 0.05), while QT time increased by 23 +/- 7, 33 +/- 9, and 40 +/- 10 ms (p less than 0.05) after 5, 10, and 25 micrograms/kg, respectively. Ventricular effective refractory period increased from 128 +/- 10 to 153 +/- 11 ms after 25 micrograms/kg (n = 4). Arterial concentration and net myocardial uptake of glucose, lactate, and free fatty acids were not significantly influenced by dofetilide. In conclusion, dofetilide, at doses that prolonged repolarization, was devoid of cardiodepressive effects in acute ischemic heart failure.
Mortensen et al. (Sat,) conducted a other in Acute ischemic heart failure (n=9). Dofetilide was evaluated on Hemodynamic and metabolic effects (LV systolic pressure, LV dP/dtmax, LV dP/dtmin, cardiac output). In dogs with acute ischemic heart failure, dofetilide prolonged repolarization (QT increased by up to 40 ms, p<0.05) without causing cardiodepressive effects.