What question did this study set out to answer?

To determine whether increased diastolic calcium in failing ventricular myocytes is driven by elevated cytosolic sodium and a decreased thermodynamic driving force of the Na+/Ca2+-exchanger.

March 15, 2003Cardiovascular ResearchOpen Access

Na+i and the driving force of the Na+/Ca2+-exchanger in heart failure

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Why the study?

Does increasing stimulation frequency alter cytosolic sodium, calcium transients, and NCX driving force differently in failing versus normal rabbit ventricular myocytes?

Population

Midmural left ventricular myocytes isolated from rabbits with pressure and volume overload induced heart…

Comparison

Increasing stimulation frequency (0.2-3 Hz) vs Age-matched control rabbit myocytes

Design

Preclinical

Authors

ABAntonius BaartscheerOslo University Hospital

Discussion

Member takes

Implication

May link Na+ dysregulation to diastolic Ca2+ overload in HF; leaves open translation to human therapies.

Key Points

To determine whether increased diastolic calcium in failing ventricular myocytes is driven by elevated cytosolic sodium and a decreased thermodynamic driving force of the Na+/Ca2+-exchanger.
Isolated midmural left ventricular myocytes from rabbits with pressure- and volume-overload-induced heart failure alongside age-matched controls.
Simultaneously recorded cytosolic sodium (SBFI), calcium transients (indo-1), and action potentials (perforated patch clamp) across stimulation rates from 0.2 to 3 Hz to calculate dynamic changes in exchanger driving force (DeltaG(exch)).
Across 0.2 to 3 Hz pacing, heart failure myocytes exhibited higher cytosolic sodium (6.4 to 10.8 vs. 3.8 to 6.4 mmol/L) and elevated diastolic calcium (142 to 219 vs. 47 to 98 nmol/L) compared to controls.
Calcium transient amplitude declined in heart failure (300 to 250 nmol/L) while increasing in controls (201 to 479 nmol/L), and time-averaged DeltaG(exch) decreased substantially in heart failure (6.8 to 2.8 vs. 8.7 to 6.4 kJ/mol).
Increasing stimulation rate reduced forward-mode DeltaG(exch) by ~30% in heart failure, while reverse-mode time integral increased ninefold and reverse-mode duration increased more than sixfold relative to control.

Structured PICO

Does increasing stimulation frequency alter cytosolic sodium, calcium transients, and NCX driving force differently in failing versus normal rabbit ventricular myocytes?

Population

Midmural left ventricular myocytes isolated from rabbits with pressure and volume overload induced heart failure (HF) and age-matched controls

Intervention

Increasing stimulation frequency (0.2-3 Hz)

Comparator

Age-matched control rabbit myocytes

Outcome

Cytosolic sodium ([Na+]i), calcium transients ([Ca2+]i), action potentials, and driving force of the Na+/Ca2+-exchanger (DeltaG(exch))surrogate

In a rabbit model of heart failure, increased cytosolic sodium and prolonged action potentials decrease the forward mode driving force of the Na+/Ca2+-exchanger, leading to disturbed diastolic calcium handling.

Cite This Study

Antonius Baartscheer (2003) studied this question.

synapsesocial.com/papers/6a73ff475e45dc7750a8ca57 https://doi.org/10.1016/s0008-6363(02)00848-9

Topics

Heart failure HFrEF treatment

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Na+i and the driving force of the Na+/Ca2+-exchanger in heart failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Na+i and the driving force of the Na+/Ca2+-exchanger in heart failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

Also Consider