Heart rate changes and myocardial sodium

Figures

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  FIGURE 1. Dynamic changes in intracellular sodium with rate changes. Simultaneous Ca2+ (Fura‐2), Na+ (ANG‐2), and force tracings in rat myocardium exposed to stimulation rate changes from 60/min to 180/min and back to 60/min. The circular inlay presents a single force (black) and Ca2+ transient (gray)

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  FIGURE 2. Sodium Peak and Trough Comparison. Schematic presentation of the Na+‐peak (top) and the Na+‐trough (bottom) with box and whisker plots of the measured magnitude of peak (trough), time to peak, and peak (trough) duration. The data are presented as box and whisker plots that visualize the full range of the data

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  FIGURE 3. Force, Ca, and Na Time to Peak Comparison. Box and whisker plots of time to peak for Na+, Ca2+, and systolic force after an increase in the stimulation rate from 60/min to 180/min demonstrating the sequential temporal coupling. When the times to the Na+‐peak and the force peak were compared the time to the force peak was significantly delayed

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  FIGURE 4. Additional Increase in Stimulation Rate and Stimulation Cessation. Panel (a) demonstrates a Na+ and Ca2+ and force tracing in response to a stepwise increase in stimulation frequency from 60/min, 180/min, and 360/min demonstrating a second sodium peak and corresponding changes in Ca2+ and force. Panel (b) demonstrates the restoration of higher Na+‐levels after stimulation cessation to baseline levels followed by pacing at 60/min

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  FIGURE 5. Human Example. Simultaneous Na+ (ANG‐2), Ca2+ (Fura‐2), and force tracings in human myocardium obtained from patients with coronary artery disease and hypertension with rate changes from 60/min to 180/min and back to 60/min showing a similar but less pronounced pattern compared to rat myocardium

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  FIGURE 6. Coronary Effluent. Coronary sinus Na+‐ and K+‐levels with sinus rhythm and with pacing at 125/min. The samples were drawn at a steady state and 15 to 60 s after changing the heart rate. p‐values from paired t‐tests are provided. Error bars are +/− SEM

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  FIGURE 7. NCX dependence on intracellular Na+ and stimulation rate. Effects of changes in intracellular Na+ on NCX activity denoted as ENa/Ca–Em. (a) At 60/min, NCX activities in both diastole and systole are reduced with increasing [Na+]i due to the reduction in ENa and the resulting reduction in ENa/Ca. At concentrations higher than 10 mM, NCX activity is reversed during systole because of ENa/Ca < Em. (b) At 180/min, NCX activity is again reduced with increasing [Na+]i. However, due to systole now making up a higher fraction of the cardiac cycle, net NCX exchange over a full cycle is more sensitive to the effects of [Na+]i compared to 60 bpm. Considering that Ca2+ influx is three times higher at 180/min compared to 60/min, the effective (eff) NCX activity is nearly zero at 12.5 mM and negatively valued at 15 mM