July 23, 2002Circulation303 citationsOpen Access
Rate Dependence of Na + i and Contractility in Nonfailing and Failing Human Myocardium
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Key Result
Failing human myocardium had significantly higher intracellular sodium (22.1 vs 15.9 mmol/L at 0.25 Hz, P<0.05), which was associated with diastolic calcium overload at faster pacing rates.
Key Points
- This research investigates how sodium ion levels affect heart contractility in nonfailing versus failing human myocardium.
- Measured [Na+]i in SBFI-loaded muscle strips from nonfailing (NF) and failing myocardium.
- Conducted experiments at varying stimulation rates (0.25 Hz and 2.0 Hz) to assess isometric force and sodium levels.
- Compared contractile responses and sodium ion concentrations between groups.
- In failing myocardium, [Na+]i was significantly higher than in NF myocardium at all stimulation rates (P<0.05).
- At 2.0 Hz, failing myocardium force dropped to 45% of the baseline, correlating with increased [Na+]i (P<0.05).
- Reverse-mode Na+/Ca2+ exchange resulted in significant Ca2+ influx in failing myocytes, linked to elevated [Na+]i.
Structured PICO
P
Population
Ex vivo study comparing intracellular sodium homeostasis and contractility in nonfailing and failing human myocardium.
E
Exposure
Increasing stimulation rates (from 0.25 Hz to 2.0 Hz)
C
Comparator
Nonfailing human myocardium and slow pacing rates (0.25 Hz)
O
Outcome
Intracellular sodium concentration ([Na+]i) and contractility (isometric force and diastolic tension)surrogate
In failing human myocardium, altered intracellular sodium homeostasis leads to diastolic calcium overload and contractile dysfunction at higher heart rates.
Main Result
Absolute Event Rate: 22.1% vs 15.9%
p-value: p=<0.05
Abstract
BACKGROUND: In the failing human heart, altered Ca2+ homeostasis causes contractile dysfunction. Because Ca2+ and Na+ homeostasis are intimately linked through the Na+/Ca2+ exchanger, we compared the regulation of Na+i in nonfailing (NF) and failing human myocardium. METHODS AND RESULTS: Na+i was measured in SBFI-loaded muscle strips. At slow pacing rates (0.25 Hz, 37 degrees C), isometric force was similar in NF (n=6) and failing (n=12) myocardium (6.4+/-1.2 versus 7.2+/-1.9 mN/mm2), but Na+i and diastolic force were greater in failing (22.1+/-2.6 mmol/L and 15.6+/-3.2 mN/mm2) than in NF (15.9+/-3.1 mmol/L and 3.50+/-0.55 mN/mm2; P<0.05) myocardium. In NF hearts, increasing stimulation rates resulted in a parallel increase in force and Na+i without changes in diastolic tension. At 2.0 Hz, force increased to 136+/-17% of the basal value (P<0.05), and Na+i to 20.5+/-4.2 mmol/L (P<0.05). In contrast, in failing myocardium, force declined to 45+/-3%, whereas Na+i increased to 27.4+/-3.2 mmol/L (both P<0.05), in association with significant elevations in diastolic tension. Na+i was higher in failing than in NF myocardium at every stimulation rate. Na+i predicted in myocytes from Na+ (pipette)-contraction relations was 8.0 mmol/L in NF (n=9) and 12.1 mmol/L in failing (n=57; P<0.05) myocardium at 0.25 Hz. Reverse-mode Na+/Ca2+ exchange induced significant Ca2+ influx in failing but not NF myocytes, compatible with higher Na+i in failing myocytes. CONCLUSIONS: Na+i homeostasis is altered in failing human myocardium. At slow heart rates, the higher Na+i in failing myocardium appears to enhance Ca2+ influx through Na+/Ca2+ exchange and maintain sarcoplasmic reticulum Ca(2+) load and force development. At faster rates, failing myocytes with high Na+i cannot further increase sarcoplasmic reticulum Ca2+ load and are prone to diastolic Ca2+ overload.
Cite This Study
Pieske et al. (2002) studied Heart failure. Heart failure (failing myocardium) vs. Nonfailing myocardium was evaluated on Intracellular sodium concentration ([Na+]i) at 0.25 Hz (p=<0.05). Failing human myocardium had significantly higher intracellular sodium (22.1 vs 15.9 mmol/L at 0.25 Hz, P<0.05), which was associated with diastolic calcium overload at faster pacing rates.