What is the clinical evidence from this study?

Study design: Other. Population: Heart failure. Intervention: Pacing tachycardia heart failure model vs. Control (normal hearts). Primary outcome: Intracellular Ca(2+) concentration transients and molecular determinants.

What question did this study set out to answer?

To identify the cellular and molecular mechanisms responsible for abnormal intracellular calcium handling and contractile dysfunction in heart failure.

November 23, 2006AJP Heart and Circulatory PhysiologyOpen Access

Cellular and molecular determinants of altered Ca2+handling in the failing rabbit heart: primary defects in SR Ca2+uptake and release mechanisms

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Key result

In a rabbit heart failure model, abnormal sarcoplasmic reticulum Ca2+ uptake and release synergistically contribute to depressed intracellular Ca2+ transients and altered action potential profiles.

Population

Rabbit pacing tachycardia heart failure model (myocytes isolated from failing and control hearts)

Comparison

Pacing-induced heart failure vs Myocytes from normal/control rabbit hearts

Design

Preclinical

Authors

AAAntonis A. ArmoundasElectrophysiology JRJochen RoseJohns Hopkins University RARajesh AggarwalUniversity College Dublin

Discussion

Member takes

Implication

Does not yet alter HF management; hypothesis-generating for SR Ca2+ targets in larger models.

Key Points

To identify the cellular and molecular mechanisms responsible for abnormal intracellular calcium handling and contractile dysfunction in heart failure.
Used a rabbit pacing tachycardia model of heart failure to isolate failing and control ventricular myocytes.
Measured action potential duration, L-type calcium channel current density, sodium-calcium exchanger currents, and intracellular calcium transients.
Quantified mRNA and protein expression of calcium-handling proteins, including SERCA2a, phospholamban, ryanodine receptor, and the sodium-calcium exchanger.
Peak intracellular calcium was significantly depressed in failing vs. control myocytes (0.56 ± 0.04 µM vs. 0.72 ± 0.07 µM, P < 0.05), with slowed decay rates and reduced calcium spark amplitudes (P < 0.0001).
Protein expression of SERCA2a, phospholamban, and ryanodine receptor was significantly downregulated (P < 0.05), whereas sodium-calcium exchanger protein was significantly upregulated (P < 0.05).

Structured PICO

Population

Rabbit pacing tachycardia heart failure model (myocytes isolated from failing and control hearts)

Intervention

Pacing-induced heart failure

Comparator

Myocytes from normal/control rabbit hearts

Outcome

Intracellular Ca2+ concentration ([Ca2+]i) transients and expression of Ca2+ handling proteinssurrogate

In a rabbit model of pacing-induced heart failure, abnormal sarcoplasmic reticulum Ca2+ uptake and release due to altered expression of key Ca2+ handling proteins synergistically contribute to depressed Ca2+ transients and altered action potentials.

Cite This Study

Armoundas et al. (2006) studied Heart failure. Pacing tachycardia heart failure model vs. Control (normal hearts) was evaluated on Intracellular Ca(2+) concentration transients and molecular determinants. In a rabbit heart failure model, abnormal sarcoplasmic reticulum Ca2+ uptake and release synergistically contribute to depressed intracellular Ca2+ transients and altered action potential profiles.

synapsesocial.com/papers/6a135f8071369867e4937d70 https://doi.org/10.1152/ajpheart.00525.2006

Topics

Heart failure HFrEF treatment

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Cellular and molecular determinants of altered Ca2+handling in the failing rabbit heart: primary defects in SR Ca2+uptake and release mechanisms

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Cellular and molecular determinants of altered Ca2+handling in the failing rabbit heart: primary defects in SR Ca2+uptake and release mechanisms

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

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