Backx, PeterBarazi, Nour2020-11-132020-11-132020-092020-11-13http://hdl.handle.net/10315/37958Heart rate (HR) as well as adverse cardiac events (i.e. myocardial infarction, arrhythmias, stroke, and sudden cardiac death) show circadian patterns. Circadian HR fluctuations are traditionally thought to be controlled by the autonomic nervous system (ANS). However, recent studies have concluded that diurnal HR variation arise from intrinsic remodeling in SA node. To re-examine the mechanisms controlling circadian HR fluctuations, we performed surface electrocardiographic recordings (sECG) at 4 time points per day (ZT0, ZT6, ZT12 and ZT18) in CD1 mice that had been anesthetized in order to eliminate the potential confounding effects of activity on daily HR variation. We found that unconscious mice still showed diurnal HR fluctuation with peaks of HR in the dark period (ZT 18) and HR troughs in the light period (ZT 6). The amplitude of circadian HR fluctuations was reduced by ~2/3 by blockade of the cardiac parasympathetic nervous activity (PNA) with atropine while being reduced by ~1/3 by blockade of the cardiac sympathetic nerve activity (SNA) with propranolol. Complete ANS block abolished entirely the diurnal HR fluctuations. To assess the contribution of activity to diurnal HR fluctuations we also analyzed HR in telemetrized sedentary mice which showed, unexpectedly, nearly identical amplitudes of HR fluctuations to anesthetized mice. On the other hand, after mice were given access to running wheels for 1 week, the circadian HR amplitudes increased by ~150%. Conclusion: HR fluctuation requires the ANS even in the absence of physical activity with a 2:1 proportion of parasympathetic versus sympathetic control of circadian rhythm in basal HR. These results highlight the importance of taking experimental time of day into consideration when assessing HR responses to treatments and drug administration in anesthetized mice.Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.MedicineElectronic Thesis or Dissertation2020-11-13BiologyPhysiologyCardiac biologyCardiac physiologyCircadian rhythmHeartHRIntrinsicAutonomicExtrinsicBasal heart rateHeart rateIntrinsic heart rateResting heart rateMiceCD1 miceZeitgeberAutonomic nervous systemParasympathetic nervous systemSympathetic nervous systemVagal toneCircadian autonomicHeart rate fluctuationDay and night changesCVDCardiovascular diseaseArrhythmiaSudden cardiac deathSinoatrial nodeSA nodeAnimal studyHuman physiologyPacemaker potentialHeart rate variabilityHRVAutonomic remodelingAutonomic remodellingExercise adaptationsCardiac adaptationsCircadianRhythmHeart rate rhythmHeart rhythmCircadian biologyChronobiologyCircadian medicineMethodsCircadian studyCircadian researchCardiovascularCardiacCardiovascular researchCardiac research