Influence of the new class I antiarrhythmic agent diprafenone on the end-systolic pressure-volume relationship (conductance technique)

Abstract

To evaluate cordiodepressive risks of antiarrhythmic treatment with diprafenone, we monitored, in addition to conventional hemodynamic parameters, end-systolic pressure-volume relations to assess potential negative inotropic effects. Thirteen patients underwent hemodynamic analysis with and without the influence of diprafenone 1.5 mg/kg, both a) at rest (paced heart rate of 90 beats/min and b) during tachycardia (paced tachycardia of 160 beats/min). Left ventricular volumes increased under the influence of diprafenone, both at rest (end-diastolic volume by an average of 12%, end-systolic volume by 21%) and during tachycardia (by 15% and by 47%, respectively). Diprafenone induced a depression of left ventricular function during tachycardia only: Ejection fraction fell by an average of 25% and stroke work by 19%, while end-diastolic pressure increased by an average of 28% and systemic vascular resistance by 34%. Diprafenone caused the loops of the end-systolic pressure-volume relationship to move rightward and decreased the slope k, indicating negative entropy, both at rest and during tachycardia. Thus, since under the influence of diprafenone negative inotropic effects and depressed left ventricular function were found (while determinants of preload and afterload increased), diprafenone should not be used as an antiarrhythmic agent in patients with advanced cardiac failure.

Na+ channels as sites of action of the cardioactive agent DPI 201-106 with agonist and antagonist enantiomers.

“…Binding experiments using radioactively labeled toxins indicate that DPI 201-106 and its enantiomers do not interact with sites already identified for tetrodotoxin or sea anemone and scorpion toxins. (30). The positive inotropic effect of DPI appears to be due to an effect of the drug on the myocardial Na+ channel (1)(2)(3).…”

Effects of Acetate on Left Ventricular Function in Hemodialysis Patients

“…LV muscle mass was calculated according to Rackley et al [6] with the modification indicated by Trenouth [7], Simultaneous LV volume and LV pressure relations were per formed by a conductance catheter, a discriminative QRS-analysis of ECG and a signal-analysis computer system 'Orpheus IF. The method is described in detail elsewhere [8][9][10]. Since conductance correlated with hemoglobin (r=0.84), values were corrected to patients' hemo globin.…”