Quantitative Assessment of the SR Ca 2+ Leak-Load Relationship
Key result
Addition of 1 mmol/L tetracaine to intact ventricular myocytes reduced resting intracellular Ca2+ by 25% (126 vs 94 nmol/L; P<0.05), indicating a diastolic SR Ca2+ leak of 12 micromol/L per second.
Population
Intact, isolated ventricular myocytes
Comparison
Exposure to 0 Na+, 0 Ca2+ solution +/- 1 mmol/L… vs Baseline/without tetracaine
Design
Preclinical
Authors
Discussion
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Implication
SR Ca2+ leak quantification in intact myocytes should not change practice; leaves open its role in human HF contractility.
Structured PICO
P
Population
Intact, isolated ventricular myocytes
I
Intervention
Exposure to 0 Na+, 0 Ca2+ solution +/- 1 mmol/L tetracaine (to block resting leak) after stimulation
C
Comparator
Baseline/without tetracaine
O
Outcome
Sarcoplasmic reticulum (SR) Ca2+ leak (J(leak)) magnitude and relationship with SR Ca2+ loadsurrogate
Main Result
Absolute Event Rate: 94% vs 126%
p-value: p=<0.05
The study quantifies diastolic SR Ca2+ leak in intact ventricular myocytes, demonstrating it is steeply dependent on SR Ca2+ load and accounts for 30% of SR diastolic efflux.
Cite This Study
Shannon et al. (2002) studied Normal, intact ventricular myocytes. Tetracaine in 0 Na+, 0 Ca2+ solution vs. Without tetracaine was evaluated on Resting [Ca2+]i (p=<0.05). Addition of 1 mmol/L tetracaine to intact ventricular myocytes reduced resting intracellular Ca2+ by 25% (126 vs 94 nmol/L; P<0.05), indicating a diastolic SR Ca2+ leak of 12 micromol/L per second.