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.
In failing human myocardium, altered intracellular sodium homeostasis leads to diastolic calcium overload and contractile dysfunction at higher heart rates.
Absolute Event Rate: 22.1% vs 15.9%
p-value: p=<0.05
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.
Pieske et al. (Tue,) conducted a other in 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.