The Rate- and Species-Dependence of Short-Term Memory in Cardiac Myocytes

Abstract

Short-term memory is an intrinsic property of paced cardiac myocytes that reflects the influence of pacing history, and not just the immediately preceding diastolic interval (DI), on the action potential duration (APD). Although it is recognized that shortterm memory affects the dynamics of cardiac myocytes in general, and the onset of irregular cardiac rhythm in particular, its has never been adequately quantified or measured directly in experiments or numerical simulations, mainly due to the absence of appropriate techniques. As a result, very little is known about the rate-and species dependent behavior of short-term memory. In this study, we introduce a new approach that allows one to estimate how much short-term memory, M S , is present in the cardiac myocyte at different pacing rates. The new quantification is based on the fact that pacing history affects not only the APD, but the entire dynamics of paced cardiac myocytes, in particular the restitution curve. Using the patch clamp technique and numerical simulations, we measured short-term memory restitution-the dependence of M S on the cycle length-in isolated rabbit and guinea pig ventricular myocytes. In both species, M S is rate-and species-dependent, displaying a biphasic behavior as a function of cycle length. Moreover, our results indicate that there is a significant difference in M S measured between both species at small cycle lengths. Numerical simulations suggest that the kinetics of the rapidly activating delayed rectifier potassium current I Kr is partially responsible for this difference.

Stochastic vagus nerve stimulation affects acute heart rate dynamics in rats

“…Cardiac memory is an established property of paced cardiac myocytes to reflect the influence of pacing history and adapt and respond to novel stimuli. Several experimental studies and numerical simulations have shown that memory plays a role in modulating cardiac dynamics [ 30 , 31 ]. Indeed, in future studies, we will examine post-VNS recovery after a longer time delay.…”

Sex Differences in Vagus Nerve Stimulation Effects on Rat Cardiovascular and Immune Systems

“…Our short-term results indicated that on average cardiovascular variables recover to pre-VNS level almost 60 min after VNS is terminated. One possible explanation for this delayed effect could be contribution of VNS to the phenomenon called cardiac memory in which cardiomyocytes dynamics can be adapted based on the pacing history and response to stimuli (Tolkacheva, 2007).…”

The Interrelations among Stochastic Pacing, Stability, and Memory in the Heart

“…3. There are other approaches that quantify the amount of cardiac memory, one of which is via a restitution portrait pacing protocol (8,23). Although current restitution portrait protocols are relevant only to deterministic pacing by requiring that the APD and DI values reach a constant steady state and that their steady-state sum equals the BCL, their adaptation and use in the context of stochastic pacing and memory should be investigated in future work.…”

“…The concept of short-term cardiac memory reflects the fact that a specific APD at a specific myocyte depends on the history of its electrical activity and therefore can be described as a function of its preceding activation properties, such as previous APDs, previous diastolic intervals (DIs), or previous intracellular ion concentrations. The ionic mechanisms underlying shortterm cardiac memory are not yet fully understood (8), despite some evidence in the literature pointing out the involvement of the intracellular concentration of sodium, [Na þ ] i . Both Schaeffer et al (9) and Decker et al (10) found that by holding [Na þ ] i constant, most of the cardiac memory features were eliminated.…”