The prolongation of the action potential in mammalian ventricular muscle at rest

Kukushkin, N. I.; Gainullin, Ravil Z.; Sosunov, Eugene A.

doi:10.1007/bf00584299

Cited by 3 publications

(2 citation statements)

References 26 publications

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Section: Methodsmentioning

confidence: 99%

“…Stabilization required 1 to 2 hours of stimulation at cycle length (CL)ϭ1000 ms. We have previously demonstrated the stability of the transmembrane potential throughout the duration of the experiment. 13 Conventional microelectrode techniques were used to record transmembrane potentials.Predrug measurements of transmembrane potentials were made at CLϭ1000, 500, and 330 ms, with 3 minutes allowed to achieve steady state at each CL. Thirty minutes was allowed for evolution of drug effects at each concentration before measurements were made.…”

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Testosterone Diminishes the Proarrhythmic Effects of Dofetilide in Normal Female Rabbits

et al. 2002

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Background-Recent clinical and experimental data suggest that testosterone may protect males against the deleterious effects of repolarization-prolonging drugs. This study tests the hypothesis that 5␣-dihydrotestosterone (DHT) protects normal females against drug-induced excessive prolongation of repolarization. Methods and Results-We used microelectrode techniques to study isolated preparations of rabbit ventricular endocardium from age-matched normal control female rabbits and female rabbits treated with DHT for 4 weeks. Serum 17␤-estradiol levels were identical in the control and DHT-treated animals, whereas DHT levels were high (equaling those in normal males) only in the DHT-treated animals. Basal action potential duration to 90% repolarization (APD 90 ) was significantly shorter in DHT-treated (155Ϯ7.4 ms, nϭ32) than control females (178Ϯ6.7 ms, nϭ29; PϽ0.05) at cycle lengthϭ1000 ms. The increase in APD 90 induced by 10 Ϫ8 mol/L dofetilide at cycle lengthϭ1000 ms was significantly less in DHT-treated females than normal females (⌬APD 90 ϭ8Ϯ7 and 29Ϯ5 ms, respectively, PϽ0.05). At 10 Ϫ6 mol/L dofetilide, the incidence of early afterdepolarizations was 28% in DHT-treated and 55% in normal female rabbits (PϽ0.05). Conclusions-Elevating DHT levels diminishes the effects of dofetilide to increase APD and induce early afterdepolarizations in females. Moreover, treatment of females with DHT results in prolongation of APD and an incidence of early afterdepolarization equal to values previously reported by us for dofetilide-treated normal males. That serum levels of 17␤-estradiol were the same in DHT-treated and untreated females suggests that estradiol is not involved in the response to dofetilide. Thus, these data suggest that DHT and perhaps other androgenic hormones may protect normal females against the risk of dofetilide-induced arrhythmia. Key Words: arrhythmia Ⅲ sex Ⅲ dofetilide Ⅲ hormones D rugs that prolong the QT interval induce a greater incidence of arrhythmias (ie, torsades de pointes [TdP]) in women than in men. [1][2][3] The greater propensity to druginduced TdP in females is generally associated with a sex-related difference in ventricular repolarization in the heart such that the rate-corrected QT interval is longer in females than males. 4 -6 Recent clinical and experimental studies propose that gonadal steroids may modulate the sex-related differences in QT interval and propensity toward drug-induced TdP. [7][8][9][10] Bidoggia et al 7 showed that women with virilization exhibit a shorter and faster repolarization time than normal women and castrated men, suggesting that testosterone is an important modulator of ventricular repolarization. In addition, Rodriguez et al 9 demonstrated that women are at greater risk of drug-induced QT prolongation during menstruation and the ovulatory phase of the menstrual cycle, with decreased risk during the luteal phase.Given that progesterone levels are higher during the luteal than the ovulatory and menstruation phases, Rodriguez et al suggest that androgen ...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Testosterone Diminishes the Proarrhythmic Effects of Dofetilide in Normal Female Rabbits

et al. 2002

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Transient outward current and rate dependence of action potential duration in rabbit cardiac ventricular muscle

1983

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A conventional (single sucrose gap) voltage clamp technique was employed to investigate the rate dependence of ionic currents activated in the plateau range of potential in the rabbit ventricular muscle. A transient outward current of increasing amplitude was observed when the period of rest preceding the test voltage clamp pulse was increased from 0.7-60 s. The action potential duration was short when the transient outward current peak (100-150 ms after the voltage clamp pulse beginning) was high under the studied conditions of stimulation (interbeat intervals 0.7-60 s). The rate dependent transient outward current was small at low levels of depolarization above the resting potential (40 mV), had a maximum at some 90-100 mV and decreased at more positive potentials. This current was sensitive to the simultaneous application of 4-aminopyridine and calcium substitution with strontium in the Tyrode solution. It is suggested that the transient outward current is probably responsible for the changes of the action potential duration in rabbit papillary muscles when the interbeat interval varies from some 0.7-60 s.

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Activity-dependent changes in the electrical behaviour of sheep cardiac Purkinje fibres

Fedida

Boyett

1985

Proc. R. Soc. Lond. B.

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Rate-dependent changes in the electrical activity of sheep Purkinje fibres maintained at 37 °C have been investigated. The duration of the action potential is maximal at a frequency of about 60 min -1 . When the rate is increased above 60 min -1 there is a substantial shortening of the action potential; this occurs abruptly in the first beat at the higher rate although subsequently there can be further changes in duration and these can result in a small prolongation, no change, or a small further shortening of the action potential and can take up to 10 min to reach a steady-state. When the rate is reduced from 60 min -1 there is also a shortening of the action potential but it occurs gradually over several hundred seconds. Action potential duration reaches a minimum value at a rate of about 6 min -1 . 70% of preparations studied showed an increase in duration again at rates below 6 min -1 but duration is always constant at frequencies below about 0.1 min -1 . The maximum diastolic potential is more negative and the pacemaker potential is larger at higher rates of stimulation. When the frequency is raised these variables increase over a time course lasting several hundred seconds. At rates below 60 min -1 the slow changes in action potential duration, maximum diastolic potential and pacemaker potential, after a change in the stimulus frequency, all have similar monoexponential time courses (Ƭ ≈ 3 min) and are accompanied by slow changes in tension production over a similar time course. In Purkinje fibres that exhibit spontaneous activity, rapid stimulation results in overdrive excitation: an acceleration of spontaneous activity when stimulation is ceased.

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The prolongation of the action potential in mammalian ventricular muscle at rest

Cited by 3 publications

References 26 publications

Testosterone Diminishes the Proarrhythmic Effects of Dofetilide in Normal Female Rabbits

Testosterone Diminishes the Proarrhythmic Effects of Dofetilide in Normal Female Rabbits

Transient outward current and rate dependence of action potential duration in rabbit cardiac ventricular muscle

Activity-dependent changes in the electrical behaviour of sheep cardiac Purkinje fibres

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