What is the clinical evidence from this study?

Study design: Other. Population: Atrial fibrillation (preclinical model). Intervention: NIP-142 vs. Vehicle/Control (absence of drug). Primary outcome: Atrial action potential duration at 90% repolarization (APD90) at 100 µM (p=<0.01).

January 1, 2005Journal of Pharmacological SciencesOpen Access

Atria Selective Prolongation by NIP-142, an Antiarrhythmic Agent, of Refractory Period and Action Potential Duration in Guinea Pig Myocardium

Q: What are the key findings of this study?

NIP-142 at 100 µM significantly prolonged atrial action potential duration (APD90 from 76.5 to 93.0 ms) without prolonging ventricular APD, acting via blockade of the IKACh current.

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Key result

NIP-142 at 100 µM significantly prolonged atrial action potential duration (APD90 from 76.5 to 93.0 ms) without prolonging ventricular APD, acting via blockade of the IKACh current.

Why the study?

Does NIP-142 prolong refractory period and action potential duration in isolated guinea pig myocardium and block I(KACh) in Xenopus oocytes?

Population

Isolated left atria and right ventricular papillary muscles or free walls from Hartley strain guinea pigs…

Comparison

NIP-142 (1 to 100 µM) vs Absence of drug, E-4031, 4-aminopyridine, and…

Design

Preclinical

Authors

TMTomoyuki MatsudaChiba University KTKentaro TakedaJikei University School of Medicine MIMie ItoToho University

Discussion

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Implication

Hypothesis-generating for atrial-selective IKACh blockade in supraventricular arrhythmias; leaves open human translation and safety.

Structured PICO

Does NIP-142 prolong refractory period and action potential duration in isolated guinea pig myocardium and block I(KACh) in Xenopus oocytes?

Population

Preclinical study using isolated guinea pig atrial and ventricular myocardium and Xenopus oocytes to evaluate the electrophysiological effects of NIP-142.

Intervention

NIP-142 (1 to 100 µM)

Comparator

Absence of drug (control), E-4031, 4-aminopyridine, and tertiapin

Outcome

Refractory period and action potential duration in isolated guinea pig myocardium, and I(KACh) amplitude in Xenopus oocytessurrogate

Main Result

Absolute Event Rate: 93% vs 76.5%

p-value: p=<0.01

NIP-142 selectively prolongs atrial refractory period and action potential duration via I(KACh) blockade without reverse frequency dependence, highlighting its potential for treating supraventricular arrhythmias.

Limitations

The present results cannot rule out the contribution of Ito blockade to the antiarrhythmic activity of NIP-142.
Inhibitory effects of NIP-142 have been reported on other currents such as Ito and the Kv1.5 channel current, which have not been identified in guinea pig myocardium.
How additional mechanisms like L-type Ca2+ current inhibition affect the anti-arrhythmic activity of NIP-142 awaits further investigation.
Cannot rule out the contribution of Ito blockade to the antiarrhythmic activity of NIP-142 because the density of the current is much smaller than in human atria and atria from other experimental animal species

Cite This Study

Matsuda et al. (2005) studied Atrial fibrillation (preclinical model). NIP-142 vs. Vehicle/Control (absence of drug) was evaluated on Atrial action potential duration at 90% repolarization (APD90) at 100 µM (p=<0.01). NIP-142 at 100 µM significantly prolonged atrial action potential duration (APD90 from 76.5 to 93.0 ms) without prolonging ventricular APD, acting via blockade of the IKACh current.

synapsesocial.com/papers/6a39cd7fc5135fa86afa1e47 https://doi.org/10.1254/jphs.fpj04045x

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Atria Selective Prolongation by NIP-142, an Antiarrhythmic Agent, of Refractory Period and Action Potential Duration in Guinea Pig Myocardium

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Atria Selective Prolongation by NIP-142, an Antiarrhythmic Agent, of Refractory Period and Action Potential Duration in Guinea Pig Myocardium

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

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