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May 18, 2010The Journal of Physiological SciencesOpen Access

Late sodium current contributes to diastolic cell Ca2+ accumulation in chronic heart failure

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Why the study?

Does late sodium current blockade reduce diastolic calcium accumulation and spontaneous calcium release in a canine model of chronic heart failure?

Population

19 dogs with chronic heart failure induced by multiple coronary artery microembolizations, and 6 normal…

Comparison

Selective late Na+ current blocker ranolazine or… vs Untreated failing ventricular myocytes and…

Design

Preclinical

Authors

NUNidas A. UndrovinasNational Medical Research Center of CardiologyVMVictor A. MaltsevElectrophysiologyLBLuiz BelardinelliElectrophysiology

Discussion

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Overview

Late Na current inhibition may mitigate diastolic Ca2+ overload in failing myocytes; leaves open clinical translation in human HF.

Structured PICO

Does late sodium current blockade reduce diastolic calcium accumulation and spontaneous calcium release in a canine model of chronic heart failure?

P
Population
19 dogs with chronic heart failure induced by multiple coronary artery microembolizations, and 6 normal control dogs (ventricular myocytes)
I
Intervention
Selective late Na+ current (INaL) blocker ranolazine (10 microM) or tetrodotoxin (2 microM)
C
Comparator
Untreated failing ventricular myocytes and normal ventricular myocytes
O
Outcome
Diastolic intracellular Ca2+ accumulation, action potential duration, and spontaneous Ca2+ releasessurrogate

Late sodium current contributes to diastolic calcium accumulation and spontaneous calcium release in heart failure, which can be reversed by INaL blockers like ranolazine.

Cite This Study

Undrovinas et al. (2010) studied this question.

synapsesocial.com/papers/6a6f6370439bab0cabc2c622https://doi.org/10.1007/s12576-010-0092-0

Topics

Heart failureHFrEF treatment
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy.1992 · 183 citations
  2. 2Spontaneous and inducible ventricular arrhythmias in a canine model of chronic heart failure: relation to haemodynamics and sympathoadrenergic activation1992 · 52 citations
  3. 3Measurement of sarcoplasmic reticulum Ca2+ content and sarcolemmal Ca2+ fluxes in isolated rat ventricular myocytes during spontaneous Ca2+ release1997 · 195 citations
  4. 4Effect of Ranolazine on Infarct Size in a Canine Model of Regional Myocardial Ischemia/Reperfusion1994 · 30 citations
  5. 5Short-Term Treatment With Ranolazine Improves Mechanical Efficiency in Dogs With Chronic Heart Failure2002 · 139 citations