Search PubMed⌕ Search

Biomedical subjects

B Katzung

Publications and source records attributed to B Katzung.

5 recordsLinked to original sources
PubMed1994

Use-dependent properties of flecainide acetate in accessory atrioventricular pathways.

Flecainide acetate has been shown to have use-dependent properties. The use-dependent properties of flecainide were evaluated in 20 patients (13 men and 7 women, mean age 32 +/- 11 years) with accessory atrioventricular connections. Twenty to 30 stimulus drive trains were introduced in either the atrium or ventricle at progressively faster rates. The range of cycle lengths over which anterograde and retrograde conduction block occurred in the accessory pathway was assessed in the drug-free state and after oral loading with flecainide acetate. The block cycle length index was defined as the shortest cycle length during which 1:1 conduction was maintained in the accessory pathway minus the longest cycle length during which block in the accessory pathway occurred on the second paced beat. In the drug-free state, the (mean +/- SD) anterograde and retrograde block cycle length indexes were 20 +/- 12 and 20 +/- 9 ms, respectively. After flecainide therapy, the anterograde and retrograde block cycle length indexes increased to 80 +/- 33 and 65 +/- 29 ms, respectively (p = 0.002 compared with the drug-free state). The block cycle length index did not correlate with serum flecainide levels, but did correlate with other electrophysiologic markers of drug effect on accessory pathway conduction. The change in the block cycle length index demonstrates that flecainide has a progressive effect on accessory pathway conduction at more rapid rates, consistent with its in vitro use-dependent properties. This index is an excellent marker of drug efficacy.

Adult↗
PubMed1992

Effects of sympathetic stimulation on use dependence of lidocaine, mexiletine, and quinidine in an intact canine model.

The use- or rate-dependent effects of a continuous infusion of lidocaine (n = 6, serum level 3.1 +/- 0.34 micrograms/mL), mexiletine (n = 8, serum level 7.08 +/- 0.90 micrograms/mL), and quinidine (n = 6, serum level 6.8 +/- 1.22 micrograms/mL) were studied in an open chest canine preparation. A use-dependent effect on conduction was assessed by measuring the change in the His to surface ventricular activation (HV) time at differing atrial paced rates during drug infusion. Global sympathetic activation was achieved by nondecentralized left stellate ganglion stimulation (4-10 Hz, 6-12 V, 2 ms) and use dependence at the same cycle lengths was compared. Repolarization times were measured from epicardial monophasic action potentials recorded from the anterior left ventricle throughout the study. There was no significant change in the HV time during control studies with or without left stellate stimulation. Use-dependent slowing of conduction was seen in all studies during drug infusion. This was evident at cycle lengths of 300-190 ms for quinidine and at cycle lengths less than 250 ms for lidocaine and mexiletine. Stellate stimulation attenuated use dependence in all studies. This effect was significant from cycle lengths of 300-190 ms for lidocaine and quinidine and at cycle lengths shorter than 230 ms for mexiletine (p less than 0.05). Stellate stimulation significantly reduced use-dependent prolongation of the HV interval by an average of 60%. During stellate stimulation there was a nonsignificant trend towards cycle length independent shortening of action potential duration both at baseline and in the presence of drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1986

Use-dependent effects of lidocaine on conduction in canine myocardium: application of the modulated receptor hypothesis in vivo.

Lidocaine is a commonly used antiarrhythmic drug that causes use-dependent blockade of sodium channels in vitro and reduces conduction velocity in vitro and in vivo. According to the modulated receptor hypothesis of antiarrhythmic drug action, lidocaine has a low affinity for rested sodium channels but a high affinity for open and inactivated channels. In the present experiments, we characterized use-dependent conduction slowing and recovery from slowing by lidocaine in anesthetized dogs. The His-to-ventricular conduction interval was used as the indicator of conduction velocity. We found that prolongation of conduction time was greater as the stimulation frequency was increased. Moreover, on abruptly changing the stimulation frequency, a new steady-state conduction time was approached in two to three depolarizations. On discontinuation of stimulation, the conduction time of progressively less premature extrastimuli shortened exponentially with a terminal phase time constant of 152 +/- 115 msec. These effects by lidocaine were enhanced during acidosis and enhancement was reversed by correction of the acidosis. It is concluded that the effects in vivo of lidocaine on conduction under several conditions of rate, rhythm, and pH are similar to its effects on the maximum upstroke velocity of the action potential in vitro. Although these experiments were not designed to validate the modulated receptor hypothesis, it appears that the modulated receptor hypothesis can predict the effects of lidocaine on conduction in vivo.

Animals↗