Table 1.

Electrophysiological properties and proarrhythmic potential of 8 mg kg⁻¹ moxifloxacin (n=6), 8 mg kg⁻¹ azithromycin (n=5) and 25 μg kg⁻¹ dofetilide (n=5) in isoflurane-anaesthetized dogs with CAVB (mean±s.d.)

	Control 1	Moxifloxacin	Control 2	Azithromycin	Control 3	Dofetilide
RR (ms)	1162±238	1436±167*†	1021±182	1044±149	1159±198	1251±252
QT (ms)	480±95	594±75*	452±49	420±52†	478±84	622±143*
QTc (ms)	466±78	556±63*	450±42	416±48†	464±73	600±126*
LV MAPD (ms)	394±86	515±89*	369±36	345±57†	418±75	607±139*
RV MAPD (ms)	350±61	451±99*	323±37	315±37†	352±82	479±156*
ΔMAPD (ms)	43±40	64±63	46±13	30±37	66±42	128±43*
STVLV (ms)	2.0±0.9	3.0±1.3	2.2±0.6	2.3±0.5	1.8±0.7	3.8±1.5*
PP (ms)	597±137	681±112*	531±53	521±38†	573±46	666±82*
Couplets	0.3±0.5	9.5±14	0.0±0.0	1.2±1.6	2.4±3.6	77±75
Multiples	0.3±0.8	0.0±0.0	0.0±0.0	0.0±0.0	0.0±0.0	2.5±3.5
TdP incidence	0	0	0	0	0	100%
[Drug]pl (μg ml−1)a	0±0	8.0±0.8	0±0	4.7±0.8	0±0	0.035±0.005b

Abbreviations: CAVB, chronic atrioventricular block; MAP, monophasic action potentials; MAPD, MAP to 90% repolarization; STV, short-term variability; TdP, torsades de pointes.

Analyses of experiments with moxifloxacin or azithromycin were performed before and 10 min after start of infusion of 8 mg kg⁻¹, whereas dofetilide experiments were analysed before administration and before the first TdP (3±1 min). No statistically significant differences were identified within the control data. Singles and multiples, mean frequency of single and coupled (>2) extrasystoles, respectively, determined over 20 min. TdP incidence is relative to group size.

^*P<0.05 versus control; ^†P<0.05 versus dofetilide-induced change.

^aConcentrations at 10 min are not peak-plasma concentrations (see text for details);

^bPlasma concentrations of dofetilide were acquired from another study performed under comparable conditions Thomsen et al. (2003).