What question did this study set out to answer?

To evaluate the class III electrophysiological actions and antiarrhythmic efficacy of dofetilide across normal, ischemic, and reperfused myocardial border zones.

January 4, 2000Circulation

Electrophysiological Effects of Dofetilide in an In Vitro Model of “Border Zone” Between Normal and Ischemic/Reperfused Myocardium

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Why the study?

Does dofetilide alter electrophysiological properties and arrhythmia incidence in an in vitro model of the border zone between normal and ischemic/reperfused myocardium?

Population

Guinea pig ventricular strips submitted partly to normoxia and partly to simulated severe ischemia, then…

Comparison

Dofetilide at 5, 10, and 50 nmol/L vs Control

Design

Preclinical

Authors

RRRené RouetNormandie Université SPSandra PicardPorsolt (France)CLChristian LibersaUniversité de Lille

Discussion

Member takes

Implication

Low-dose dofetilide may reduce early ischemic dispersion while higher doses increase late arrhythmias in vitro; leaves open dose-specific effects pending clinical studies.

Key Points

To evaluate the class III electrophysiological actions and antiarrhythmic efficacy of dofetilide across normal, ischemic, and reperfused myocardial border zones.
Tested guinea pig ventricular strips exposed partly to normoxia (normal zone) and partly to simulated severe ischemia followed by reperfusion (altered zone).
Administered dofetilide at concentrations of 5, 10, and 50 nmol/L to measure action potential duration at 90% repolarization (APD90) dispersion and incidence of induced or spontaneous arrhythmias.
At 10 minutes of early ischemia, 5 nmol/L dofetilide reduced APD90 dispersion between normal and altered zones (ratio of 1.68 ± 0.22 vs 2.82 ± 0.17 in control, P < 0.05), whereas 50 nmol/L increased dispersion during late ischemia at 30 minutes (ratio of 4.62 ± 0.76 vs 2.57 ± 0.21 in control, P < 0.05).
Dofetilide abolished early extrastimulus-induced arrhythmias across all tested doses (5, 10, and 50 nmol/L).
Late spontaneous repetitive responses occurred significantly more often with 10 nmol/L (86%) and 50 nmol/L (75%) dofetilide compared to control (25%, P < 0.05), without altering arrhythmia incidence during reperfusion.

Structured PICO

Does dofetilide alter electrophysiological properties and arrhythmia incidence in an in vitro model of the border zone between normal and ischemic/reperfused myocardium?

Population

Guinea pig ventricular strips submitted partly to normoxia (normal zone) and partly to simulated severe ischemia, then reperfusion (altered zone)

Intervention

Dofetilide at 5, 10, and 50 nmol/L

Comparator

Control

Outcome

Dispersion of the action potential duration at 90% repolarization (APD90) between normal and altered zones, and incidence of arrhythmiassurrogate

In an in vitro model, low-dose dofetilide reduced early ischemic arrhythmias and APD dispersion, while higher doses worsened APD dispersion and increased late spontaneous arrhythmias.

Cite This Study

Rouet et al. (2000) studied this question.

synapsesocial.com/papers/6a76b6317ecc675f86adfd41 https://doi.org/10.1161/01.cir.101.1.86

Topics

Women and heart disease

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Implication

Low-dose dofetilide may reduce early ischemic dispersion while higher doses increase late arrhythmias in vitro; leaves open dose-specific effects pending clinical studies.

Electrophysiological Effects of Dofetilide in an In Vitro Model of “Border Zone” Between Normal and Ischemic/Reperfused Myocardium

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Electrophysiological Effects of Dofetilide in an In Vitro Model of “Border Zone” Between Normal and Ischemic/Reperfused Myocardium

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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