Heart rate changes and myocardial sodium.

Historic studies with sodium ion (Na + ) micropipettes and first-generation fluorescent probes suggested that an increase in heart rate results in higher intracellular Na + -levels. Using a dual fluorescence indicator approach, we simultaneously assessed the dynamic changes in intracellular Na + and calcium (Ca 2+ ) with measures of force development in isolated excitable myocardial strip preparations from rat and human left ventricular myocardium at different stimulation rates and modeled the Na + -effects on the sodium-calcium exchanger (NCX). To gain further insight into the effects of heart rate on intracellular Na + -regulation and sodium/potassium ATPase (NKA) function, Na + , and potassium ion (K + ) levels were assessed in the coronary effluent (CE) of paced human subjects. Increasing the stimulation rate from 60/min to 180/min led to a transient Na + -peak followed by a lower Na + -level, whereas the return to 60/min had the opposite effect leading to a transient Na + -trough followed by a higher Na + -level. The presence of the Na + -peak and trough suggests a delayed regulation of NKA activity in response to changes in heart rate. This was clinically confirmed in the pacing study where CE-K + levels were raised above steady-state levels with rapid pacing and reduced after pacing cessation. Despite an initial Na + peak that is due to a delayed increase in NKA activity, an increase in heart rate was associated with lower, and not higher, Na + -levels in the myocardium. The dynamic changes in Na + unveil the adaptive role of NKA to maintain Na + and K + -gradients that preserve membrane potential and cellular Ca 2+ -hemostasis.