flosequinan and Arrhythmias--Cardiac

Topics: Arrhythmias, Cardiac; Electrocardiography; Female; Humans; Middle Aged; Quinolines; Vasodilator Agents

1. Flosequinan, milrinone, isoprenaline and forskolin given intravenously at similarly hypotensive doses have been evaluated in separate studies for their effect on ischaemia-induced arrhythmias and on ventricular cyclic nucleotide content following coronary artery ligation in the pentobarbitone anaesthetized rat. 2. Flosequinan did not affect mortality or arrhythmias following coronary artery ligation in either study and no change in ventricular cyclic nucleotide content was observed. 3. Isoprenaline caused a significant increase in mortality (P < 0.05) in both studies whereas milrinone and forskolin caused a significant increase in mortality in only one of the two studies conducted. All three agents caused significant increases in cyclic AMP which were associated with increased incidence of arrhythmias. 4. When compared at similarly hypotensive doses, flosequinan, in contrast to milrinone, isoprenaline and forskolin, did not influence ischaemia-induced arrhythmias or raise ventricular cyclic nucleotide levels in the anesthetized rat.

Topics: Adenylyl Cyclases; Adrenergic beta-Agonists; Anesthesia; Animals; Arrhythmias, Cardiac; Blood Pressure; Colforsin; Coronary Vessels; Cyclic AMP; Cyclic GMP; Enzyme Activation; Isoproterenol; Male; Milrinone; Myocardial Ischemia; Myocardium; Phosphodiesterase Inhibitors; Pyridones; Quinolines; Rats; Rats, Wistar; Vasodilator Agents

Topics: Arrhythmias, Cardiac; Humans; Quinolines; Vasodilator Agents

We have evaluated the acute electrophysiological effects of flosequinan in 18 patients with normal ventricular function. Following intravenous infusion of flosequinan 100 mg over 1 h, mean (SD) systolic blood pressure fell from 131 +/- 19 to 120 +/- 22 mmHg (P less than 0.02) and there was significant shortening of sinus cycle length (732 +/- 151 to 575 +/- 93 ms, P less than 0.001), AH interval (110 +/- 45 to 71 +/- 19 ms, P less than 0.01), QRS duration (98 +/- 28 to 91 +/- 26 ms, P less than 0.02) and QT interval (373 +/- 47 to 337 +/- 35 ms, P less than 0.001), but no change in sinus node recovery time, intra-atrial conduction time, HV interval or the corrected QTc interval. There was a reduction in both anterograde atrioventricular Wenckebach cycle length (299 +/- 53 to 259 +/- 52 ms, P less than 0.01) and retrograde ventriculoatrial Wenckebach cycle length (375 +/- 77 to 300 +/- 56 ms, P less than 0.01). There was no change in atrial or ventricular effective refractory period (ERP) but atrial functional refractory period (FRP) shortened (233 +/- 31 to 212 +/- 24 ms, P = 0.07) as did ventricular FRP (249 +/- 24 to 234 +/- 21 ms, P less than 0.01). Patients received an oral dose of flosequinan 50 mg 12 h later. By 24 h, sinus cycle length, QRS duration and the QT interval had all returned towards baseline values, but ventricular ERP had lengthened (199 +/- 22 to 215 +/- 26 ms, P less than 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Drug Evaluation; Electrocardiography; Electrophysiology; Female; Heart Conduction System; Hemodynamics; Humans; Male; Quinolines; Vasodilator Agents; Ventricular Function, Left