The effects of rate and irregularity on sympathetic nerve activity in human subjects

Irregular rhythm and atrial metabolism are key for the evolution of proarrhythmic atrial remodeling in atrial fibrillation

“…An irregular pacing interval causes decreased cardiac output, as well as increased pulmonary wedge and right atrial pressure compared to regular pacing at the same rate in patients [7]. In another cohort, greater degrees of irregularity have been associated with increased sympathoexcitation [26]. While it is likely that the effects of irregular activation in vivo are at least partly a macroscopic phenomenon, resulting from restitution properties (i.e., the dependence of electrical and mechanical properties of the heart on the preceding diastolic interval), filling times and baroreflex mechanisms, there is evidence that isolated cardiomyocytes are also modulated by the degree of irregularity of pacing rhythm.…”

“…For example, irregular pacing of a co-culture of atrial cardiomyocytes and intrinsic cardiac adrenergic cells causes increased expression of catecholamine-synthesizing enzymes compared to regular pacing [24]. This increase can be abrogated by endothelin-A receptor blockade and inhibition of the CnA/NFAT pathway [24], providing a potential calcium-dependent mechanism for the increased sympathoexcitation observed in patients [26]. Furthermore, irregular pacing of neonatal rat ventricular cardiomyocytes (NRVM) results in decreased calcium-transient amplitude compared to regular pacing, possibly due to reduced expression of the sarcoplasmic reticulum (SR) calcium ATPase (SERCA2a) [16].…”

Restoring Sinus Rhythm Improves Baroreflex Function in Patients With Persistent Atrial Fibrillation

“…The postulated mechanism was that the long RR coupling intervals commonly observed in AF resulted in unloading of the arterial baroreceptors and reflex increase in SNA despite the absence of a significant decrease in mean BP. In a subsequent study, we demonstrated that the magnitude of sympathoexcitation correlated with the degree of variability in RR intervals 15. After controlling for the hemodynamic changes, there was a 6.1% increase in SNA for every 1% increase in irregularity.…”

Contemporary Management of Atrial Fibrillation: Update on Anticoagulation and Invasive Management Strategies

“…32,33 In certain patients, increased sympathetic tone brings on episodes of AF, and it is likely that sympathovagal balance also plays a role in initiating AF. [34][35][36] ALCOHOL AND CAFFEINE Binge drinking of alcohol has been associated with AF, producing what is called the holiday heart syndrome. Observational studies have also found an association between sustained heavy use of alcohol and AF.…”