Ageing and atrial electrophysiologic properties in man

International Journal of Cardiology, 5 (I 984) 75-81 Elsevier

75

IJC 00087

Ageing and atria1 electrophysiologic properties in man Antonio Michelucci, Luigi Padeletti, Giuseppe A. Fradella, Raffaele Molino Lova, Domenico Monizzi, Antonio Giomi and Fabio Fantini Cattedra di Malattie dellilpparato (Received

7 December

Cardiouascolare,

Universitti di Firenze, Ita!v

1982; second revision received 20 July 1983; accepted

20 July 1983)

Michelucci A, Padeletti L, Fradella GA, Lova RM, Monizzi D, Giomi A, Fantini F. Ageing and atria1 electrophysiologic properties in man. Int J Cardiol 1984; 5:75-81. In order to assess the influence of age on atria1 electrophysiologic properties, we studied 17 normal subjects, whose ages were homogeneously distributed between 17 and 78 years, measuring in each of them effective (ERR) and functional (FRP) refractory periods at 3 sites of the right atrium (high, middle and low in the lateral wag) at the same driven frequency (120/min). Twice threshold stimuli of 2 msec duration were applied. Dispersion of atrial refractoriness was measured as the longest minus the shortest refractory period. A significant direct correlation was observed between age and dispersion of atrial refractoriness (of ERT? r = 0.75, P < 0.001; of FRP: r = 0.82, P -c 0.001). Moreover, age showed a significant direct correlation with refractoriness at high right atrium (ERI? r = 0.66, P -e 0.01; FRP: r = 0.76, P -CO.OOl), but did not correlate with that at the other two sites. We suggest that ageing modifies atrial refractoriness in a non-uniform manner inducing a progressive increment of dispersion of atrial refractoriness. The impression is that a slow but continuous process takes place from juvenility to old age.

introduction

Previous studies on humans concerning the influence of age on atria1 electrophysiologic properties [l-4] were performed measuring refractoriness at only one atria1

Correspondence Italy.

0167-5273/84/$03.00

and reprint requests to: Dr. Antonio

0 1984 Elsevier Science Publishers

Michelucci,

B.V.

Via Bronzino,

163, 50142 Firenze,

76

site (parasinusal zone). Recent papers [5-71, however, indicated the possibility of performing a more extensive evaluation of atria1 excitability in clinical electrophysiology. Results obtained testing more than one atria1 site allowed a better definition of some pathophysiological conditions, such as sinus node dysfunction and atria1 tachyarrhythmias. If we consider that a possible implication of these studies concerns the role of ageing on clinical electrophysiologic results, it becomes necessary to further evaluate this problem, adopting the more extensive protocol of the abovementioned studies [5-71. Material

and Methods

Study Group The study group consisted of 17 normal subjects (14 males and 3 females) whose ages were homogeneously distributed between 17 and 78 years. Complete medical history was obtained and physical examination was performed by at least two of the authors. Analysis of blood, urine and chest roentgenograms did not show abnormalities in any subject. Particular attention was given to exclude latent coronary artery disease. In all subjects ECG, response to multistage treadmill stress test, systolic time intervals, echocardiogram, and Holter monitoring were normal. The electrophysiological study was carried out because of a history of vertigo (9 cases), during atria1 pacing performed for atypical chest pain (5 cases) and before cardiac catheterization performed to exclude the presence of a gradient between right or left ventricles and pulmonary artery or aorta (3 cases). All patients had: (1) normal sinus rhythm with sinus rates between 60 and lOO/min in all recorded resting electrograms; and (2) absence of documented atria1 dysrhythmias. The subjects were observed for a period of 12 to 30 months (mean 18 months). Periodic controls confirmed normal cardiac conditions. Blood pressure was normal in all subjects. The subjects were studied in the resting, nonsedated and postabsorptive state after informed consent had been obtained. None of them was receiving cardioactive drugs. Stimulation Protocol Two electrodes, number 6F USC1 quadripolar and number 6F USC1 tripolar, were inserted percutaneously via a right antecubital vein and the right femoral vein respectively. The distal pair of electrodes of the quadripolar catheter were used to stimulate the atrium and the proximal pair of electrodes to record a right atria1 electrogram (A). The tripolar catheter was positioned across the tricuspid valve and was used to record the His bundle electrogram (HBE). The A, HBE and four surface electrocardiographic leads (I, II, III and V,) were simultaneously displayed on a Hewlett-Packard eight-channel oscilloscope and were recorded on an Elema-Schonander Mingograph 62-6 channel ink-jet at a paper speed of 100 mm/set. Overdrive and premature programmed atria1 stimulation were performed using an electrically

isolated battery-powered Medtronics 5325 stimulator. The pulse width was 2 msec and the amplitude was adjusted to twice diastolic threshold. The stimulating electrodes were first positioned at the high right atrium (HRA) near its junction with the superior vena cava to determine corrected sinus node recovery time and total sinoatrial condition time as previously indicated [8,9]. Atria1 extrastimuli were applied at 10 msec decrements after eight beats of atria1 pacing at a rate of 120 beats/min until atria1 refractoriness was determined. The stimulating poles were then fluoroscopically repositioned, the threshold was reevaluated and atria1 stimulation performed at two additional right atria1 sites in the lateral wall at least 1 cm distant from the HRA: mid-lateral (MRA) and low-lateral (LRA) right atrium. Definitions Atria1 functional refractory period (FRP) was the shortest coupling interval recorded on the atria1 electrogram. Atria1 effective refractory period (ERP) was the longest interval between the stimulus artefact (atria1 pacing) and the extrastimulus failing to propagate. Dispersion of atria1 refractoriness was determined from the range of refractory periods measured in each subject at the three atria1 sites as the longest minus the shortest refractory period. Values were expressed in msec and as mean f 1 SD. Correlation coefficients for the relationship between age and atria1 refractoriness or dispersion of atria1 refractoriness were derived using standard linear regression methods.

Results Sinus cycle length ranged from 700 to 980 msec (mean 828 + 111 msec). Atrioventricular conduction, corrected sinus node recovery time and total sinoatrial conduction time proved to be normal in each subject. Mean A-H and H-V intervals were respectively 105 + 10 msec and 44 &-3 msec. Mean corrected sinus recovery time was 244 + 55 msec. Mean calculated sinoatrial conduction time was 143 + 32 AGE (Y’S-I

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Fig. 1. Age plotted

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of effective (D-ERP)

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and functional

(D-FRP)

refractoriness.

78 TABLE

1

Values of age, of atrial refractoriness each subject. Pt.

x SD

of atrial refractoriness

Sex

Age

ERP HRA

MRA

LRA

D

HRA

MRA

LRA

D

M M M M M M M F M M M F F M M M M

17 25 31 37 40 41 44 46 50 53 54 57 60 63 65 73 78

260 250 240 240 250 260 290 300 280 270 270 290 290 290 270 270 310

250 240 240 290 250 230 260 265 250 270 230 260 240 260 260 230 260

260 230 220 230 280 210 280 250 290 240 220 235 270 250 230 200 240

10 20 20 60 30 50 30 50 40 30 50 55 50 40 40 70 70

280 270 270 260 270 270 300 320 320 300 300 300 330 310 295 325 330

270 250 250 300 260 270 280 280 300 280 250 290 270 300 270 285 270

270 250 250 260 285 250 290 270 300 270 250 250 290 260 260 250 260

10 20 20 40 25 20 20 50 20 30 50 50 60 50 35 75 70

49 16

272 20

252 16

243 25

42 17

297 23

275 16

265 16

38 19

“0.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

(at the three atria1 sites) and of dispersion

in

FRP

D = dispersion of atria1 refractoriness; ERP = effective refractory period: FRP = functional period; HRA = high right atrium; LRA = low right atrium; MRA = middle right atrium.

refractory

msec. Single values of age, of atria1 refractoriness (at the three atria1 sites) and of dispersion of atria1 refractoriness are reported in Table 1. ERP ranged at HRA from 240 to 310 msec (mean 272 f 20 msec), at MRA from


Fig. 2. Age plotted (HRA).

against

effective

(ERP)


and functional

(FRP)

refractoriness

at high right

atrium

79

230 to 290 msec (mean 252 + 16 msec), at LRA from 200 to 290 msec (mean 256 f 14 msec). FRP ranged at HRA from 260 to 330 msec (mean 297 k 23 msec), at MRA from 250 to 300 msec (mean 275 k 16 msec), at LRA from 250 to 300 msec (mean 279 f 14 msec). Dispersion of atria1 refractoriness of ERP and of FRP ranged respectively from 10 to 70 msec (mean 42 5 17 msec) and from 10 to 75 msec (mean 38 f 19 msec). A significant direct correlation (Fig. 1) was observed between age and dispersion of atria1 refractoriness (of ERP: r = 0.75, P -c0.001; of FRP: r = 0.82, P < 0.001). Moreover, age showed a significant direct correlation (Fig. 2) with refractoriness at HRA (ERP: r = 0.66, P < 0.01; FRP: r = 0.76, P < 0.001) but did not correlate with that at MRA and LRA.

Discussion Previous studies [5-71 have shown that length of refractoriness varies physiologically along the atria1 myocardium and that some pathophysiological conditions can induce an abnormal increase of the observed differences (less homogeneous recovery of atria1 excitability, i.e. greater dispersion). Our results indicate that ageing in itself also influences the behaviour of atria1 refractoriness. In fact, a significant direct correlation was observed between age and dispersion of atria1 refractoriness. This finding can be interpreted considering that ageing induces structural changes of myocardial tissue [lo-141. Catecholamines [15] and vagal stimulation [16,17] have been demonstrated to influence the length of refractory periods. Structural changes could make their influence less uniform upon the atria1 myocardium, accounting for the progressive increment of dispersion of atria1 refractoriness observed from juvenility to old age. In this regard, it should be remembered that senile hearts are less sensitive to isoproterenol[18] and vagal stimulation [19] and that structural changes in themselves have been shown to play a role in inducing inequality of refractoriness and conduction [20]. In evaluating our,. results however, it should be considered that we controlled the cycle length variable by pacing our subjects at the same driven cycle length. There is evidence that atria1 pacing induces a release of autonomic mediators in cardiac tissue [21,22]. This may have made our results more evident. If we consider separately the three tested atria1 sites, only refractoriness at HRA (parasinusal zone) showed a significant correlation with age. A progressive increase of refractoriness from juvenility to old age was observed at this site. This area would seem to be more affected by ageing. The progressive lengthening of refractoriness could be interpreted as a progressive reduction in the effect of catecholamines and the vagus, both being capable of producing a reduction in refractoriness. The presence of diminished formation of acetylcholine in the atria of old animals [23] and of a minor increase of heart rate after administration of isoproterenol [18] or atropine [24] in older subjects could sustain this hypothesis. We cannot explain fully why only the parasinusal zone showed this progressive lengthening of refractoriness. This area has a high concentration of cholinesterase [25,26], and nerve and ganglia [27], and appears to be most affected by vagal stimulation [17]. These

80

particular characteristics could explain why the effects of the reduction of the production of acetylcholine and the lesser sensitivity to isoproterenol and to the vagus were more evident at this site. The lack of correlation between age and refractoriness at MRA and LRA (older subjects showed values of refractoriness similar to those of younger ones at these sites) did not contradict previous studies [l-4] as they utilized only the parasinusal zone in order to evaluate the influence of age. On this basis it cannot be simply affirmed, as previously done [l-4], that ageing induces a lengthening of atria1 refractoriness. The impression is that a non-homogeneous process takes place from juvenility to old age. Therefore, it can be suggested that ageing modifies atria1 refractoriness in a non-uniform manner, inducing a progressive increment of dispersion of atria1 refractoriness. Even if it is not easy to establish the clinical significance of our data, they should be taken into account when considering the differences in susceptibility to arrhythmias and electrophysiologic manifestations of arrhythmias at various ages. Atria1 arrhythmias have many predisposing factors [7,28-301 and ageing inducing a progressive increase of dispersion of atria1 refractoriness could be one of them. Finally, we would emphasize that our data should also be taken into account when performing clinical electrophysiologic diagnosis and research.

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