The contribution of refractoriness to arrhythmic substrate in hypokalemic Langendorff-perfused murine hearts

Sabir, Ian N.; Fraser, James A.; Killeen, Matthew J.; Grace, Andrew A.; Huang, Christopher

doi:10.1007/s00424-007-0217-3

Cited by 48 publications

(91 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After the start of perfusion, hearts were paced at 8 Hz, by use of square-wave pulses 2 ms in duration, with a stimulation voltage set to thrice the threshold of excitation (Grass S48 stimulator; Grass-Telefactor, Berkshire, UK), enabling direct comparison with previous mouse studies of arrhythmogenesis [5,22].…”

Section: Electrophysiology Of Perfused Heartsmentioning

confidence: 99%

“…endocardial APD 90 ) -(epicardial latency ? epicardial VERP) [5], respectively; and 5 the wavelength of excitation-the product of VERP and conduction velocity.…”

Section: Measurement Of Electrophysiological Datamentioning

confidence: 99%

“…The critical intervals reflect the time periods that permit re-excitation before full action potential repolarization and can involve the APD 90 exceeding VERP either in the local epicardial region or across the myocardial wall [5]. Our experiments assessed these values before and after introduction of heptanol.…”

Section: Heptanol Induces a Concentration-dependent Increase In Verpmentioning

confidence: 99%

“…First, repolarization abnormalities alone are sufficient to induce arrhythmogenesis in hypokalaemic hearts, Scn5a ?/D hearts containing a gain-of-function mutation in the a-subunit of the sodium channel, and KCNE1 -/-hearts with deletion of the coding sequence for the b-subunit of the slow delayed rectifier potassium (I Ks ) channel. In these hearts action potential duration (commonly measured at 90% repolarization, APD 90 ) is prolonged [2][3][4], transmural repolarization gradients are altered [2][3][4], and critical intervals for re-excitation given by APD 90 -ventricular effective refractory periods (VERP) are increased [3,5,6], predisposing the hearts to triggered and re-entrant arrhythmias.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ventricular arrhythmogenesis following slowed conduction in heptanol-treated, Langendorff-perfused mouse hearts

et al. 2012

Self Cite

View full text Add to dashboard Cite

Arrhythmogenic effects of slowed action potential conduction produced by the gap junction and sodium-channel inhibitor heptanol (0.1-2 mM) were explored in Langendorff-perfused mouse hearts. Monophasic action potential recordings showed that 2 mM heptanol induced ventricular tachycardia in the absence of triggered activity arising from early or after-depolarizations during regular 8 Hz pacing and programmed electrical stimulation (PES). It also increased activation latencies and ventricular effective refractory periods (VERPs), but did not alter action potential duration (APD), thereby reducing local critical intervals for re-excitation given by APD(90) - VERP. Bipolar electrogram recordings showed that 2 mM heptanol increased electrogram duration (EGD) and ratios of EGDs obtained at the longest to those obtained at the shortest S1S2 intervals studied during PES, suggesting increased dispersion of conduction velocities. These findings show, for the first time in the mouse heart, that slowed conduction induces reversible arrhythmogenic effects despite repolarization abnormalities expected to reduce arrhythmogenicity.

show abstract

Section: Electrophysiology Of Perfused Heartsmentioning

confidence: 99%

“…endocardial APD 90 ) -(epicardial latency ? epicardial VERP) [5], respectively; and 5 the wavelength of excitation-the product of VERP and conduction velocity.…”

Section: Measurement Of Electrophysiological Datamentioning

confidence: 99%

Section: Heptanol Induces a Concentration-dependent Increase In Verpmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ventricular arrhythmogenesis following slowed conduction in heptanol-treated, Langendorff-perfused mouse hearts

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, the plant kingdom is being screened for new and effective chemotherapeutic agents . Despite all efforts made by researchers, only a few plant species have been phytochemically investigated until now (Sabir et al 2007). Plant extracts of many higher plants have been reported to exhibit antibacterial, antifungal and insecticidal properties under laboratory trials Bouamama et al 2006).…”

mentioning

confidence: 99%

Comparative studies on phytochemistry, antibacterial and antifungal properties of Alstonia scholaris and Millettia pinnata

Akram

Anjum

Ahmad

et al. 2014

Australasian Plant Dis. Notes

View full text Add to dashboard Cite

Phytochemical profiles and antimicrobial activities of A. scholaris and M. pinnata extracts have been assessed. Test microorganisms were evaluated for their susceptibility against aqueous, methanol, ethanol, n-hexane and chloroform extracts from leaves of both plant species. Antibacterial effects were evaluated against eight bacterial species (three gram positive and five gram negative) of high economic importance, whereas antifungal effects were evaluated against three devastating fungal pathogens. Maximum number of phytochemical groups was noted in methanol and aqueous extracts of both plant species which showed the best antibacterial activities. This indicates that methanol extract contained a wide range of antibiotic compounds, whereas ethanol extract was least effective against tested bacterial and fungal species. This study supports the use of plant origin pesticides against pathogenic microbes.

show abstract

A quantitative analysis of the effect of cycle length on arrhythmogenicity in hypokalaemic Langendorff-perfused murine hearts

Sabir

Fraser

Cass

et al. 2007

Pflugers Arch - Eur J Physiol

Self Cite

View full text Add to dashboard Cite

The clinically established proarrhythmic effect of bradycardia and antiarrhythmic effect of lidocaine (10 μM) were reproduced in hypokalaemic (3.0 mM K + ) Langendorffperfused murine hearts paced over a range (80-180 ms) of baseline cycle lengths (BCLs). Action potential durations (at 90% repolarization, APD 90 s), transmural conduction times and ventricular effective refractory periods (VERPs) were then determined from monophasic action potential records obtained during a programmed electrical stimulation procedure in which extrasystolic stimuli were interposed following regular stimuli at successively decreasing coupling intervals. A novel graphical analysis of epicardial and endocardial, local and transmural relationships between APD 90 , corrected for transmural conduction time where appropriate, and VERP yielded predictions in precise agreement with the arrhythmogenic findings obtained over the entire range of BCLs studied. Thus, in normokalaemic (5.2 mM K + ) hearts a statistical analysis confirmed that all four relationships were described by straight lines of gradients not significantly (P>0.05) different from unity that passed through the origin and thus subtended constant critical angles, θ with the abscissa (45.8°±0.9°, 46.6°±0.5°, 47.6°±0.5°and 44.9°± 0.8°, respectively). Hypokalaemia shifted all points to the left of these reference lines, significantly (P<0.05) increasing θ at BCLs of 80-120 ms where arrhythmic activity was not observed (∼63°, ∼54°, ∼55°and ∼58°, respectively) and further significantly (P<0.05) increasing θ at BCLs of 140-180 ms where arrhythmic activity was observed (∼68°, ∼60°, ∼61°and ∼65°, respectively). In contrast, the antiarrhythmic effect of lidocaine treatment was accompanied by a significant (P<0.05) disruption of this linear relationship and decreases in θ in both normokalaemic (∼40°, ∼33°, ∼39°and ∼41°, respectively) and hypokalaemic (∼40°, ∼44°, ∼50°and ∼48°, respectively) hearts. This extended a previous approach that had correlated alterations in transmural repolarization gradients with arrhythmogenicity in murine models of the congenital long QT syndrome type 3 and hypokalaemia at a single BCL. Thus, the analysis in terms of APD 90 and VERP provided a more sensitive indication of the effect of lidocaine than one only considering transmural repolarization gradients and may be particularly applicable in physiological and pharmacological situations in which these parameters diverge.

show abstract

The contribution of refractoriness to arrhythmic substrate in hypokalemic Langendorff-perfused murine hearts

Cited by 48 publications

References 52 publications

Ventricular arrhythmogenesis following slowed conduction in heptanol-treated, Langendorff-perfused mouse hearts

Ventricular arrhythmogenesis following slowed conduction in heptanol-treated, Langendorff-perfused mouse hearts

Comparative studies on phytochemistry, antibacterial and antifungal properties of Alstonia scholaris and Millettia pinnata

A quantitative analysis of the effect of cycle length on arrhythmogenicity in hypokalaemic Langendorff-perfused murine hearts

Contact Info

Product

Resources

About