Table 1.

Studies investigating relationship between atrial electrophysiological changes and ageing.

Authors	Species	Characteristics	Key findings
Brembilla-Perrot et al. [96]	Human	Patients aged >70 years versus younger	Decreased AF inducibility due to increased atrial ERP
Centurión et al. [89]	Human	Patients with paroxysmal AF during sinus rhythm aged >60 years versus younger	Greater mean number of abnormal right atrial electrograms defined as ≥100 msec duration and, or showing eight fragmented deflections
Roberts-Thomson et al. [87]	Human	Patients aged >60 years versus younger	Greater number of complex fractionated electrograms
Sakabe et al. [94]	Human	Patients without a history of AF or structural heart disease	No relationship between age and inducibility of AF
Calcium mishandling
El-Armouche et al. [99]	Human	Western blotting used to assess phosphorylation levels of Ca handling proteins in right atrial appendage	Hyperphosphorylation of phospholamban could be contributory to leaky ryanodine receptors and thus abnormal calcium handling in chronic AF patients
Hove-Madsen et al. [97]	Human	Age > 66 years	Higher calcium spark frequency and higher incidence of spontaneous calcium waves in comparison to patients with sinus rhythm
Ono et al. [88]	Rats	Old versus young rats	Glycolytic inhibition has been shown to result in spontaneous AF due to calcium mishandling and early after depolarisation-induced triggered activity
Wongcharoen et al. [90]	Rabbits	Responses of pulmonary vein tissues to rapamycin, FK-506, and ouabain in young and aged rabbits	Increased pulmonary vein arrhythmogenesis secondary to ryanodine receptor dysfunction-resultant calcium mis-handling
Atrial ERP
Kistler et al. [100]	Human	Electrophysiological and electroanatomical studies in 3 age groups (≥60 years, 31–59 years, and ≤30 years)	Age-associated electrical and structural remodeling (regional conduction slowing, increase in atrial ERP, impaired sinus node function, conduction delay at crista terminalis, and areas of low voltage)
Brembilla-Perot et al. [96]	Human	734 patients (age 16–85 years, mean 61 ± 15 years)	Increased atrial ERP and age >70 years independently predicted reduced AF inducibility
Brorson and Olsson [101]	Human	Right atrial monophasic action potentials recorded in 40 healthy males	No age correlation
Anyukhovsky et al. [92]	Dogs	Young versus old canine atrial	Age-related differences in action potential contour, decreased I CaL, and slower conduction of early premature beats
Huang et al. [106]	Rats	Adult, middle aged versus aged rats	Age-associated prolongation of the monophasic action potential (mAP) and ERP in the right atrium, but a decrease in mAP and ERP in the left atrium, suggesting a potential reentrant mechanism for AF
Kojodjojo et al. [107]	Humans	Most study subjects suffered from atrioventricular reentrant arrhythmias, syncope, or palpitations and hence these atria were not “healthy”	No change in left atrial ERP with ageing
Michelucci et al. [105]	Humans	17 normal subjects (age range 17–78 years)	Age-related increase in right atrial ERP
Su et al. [103]	Rats	Adults versus aged rats	In response to muscarinic stimulation, ageing-related prolongation of atrial maximum diastolic potential but not of APD
Toda [102]	Rabbit	Rabbit ages varied from 2–360 days old	Age-related prolongation of APD
Ion channel remodelling in ageing and AF
I CaL Anyukhovsky et al. [92]	Canine atria		Reduced I CaL
I Na Baba et al. [108]	Canine atria		(i) Peak current unchanged at low stimulation frequencies but reduced at stimulation frequencies relevant to AF
Wu et al. [110]	Rabbit atria		(ii) Decreased in hyperlipidemic aged rabbits
I to Dun et al. [109]	Canine atrium		Increased in the left atrium
I KAch Su et al. [103]	Rat		Indirect evidence of increase [104]