Intrinsic Sinus Node Function Research Articles

Point: Exercise training-induced bradycardia is caused by changes in intrinsic sinus node function

it is well known that athletes have a resting sinus bradycardia—their resting heart rate can be half the normal value ([7][1])— and this is normally attributed to high vagal tone ([3][2]). This is a logical assumption, because we have known since 1921 from the work of the physiologist Otto Loewi

Exercise training-induced bradycardia is caused by changes in intrinsic sinus node function

Exercise training-induced bradycardia is caused by changes in intrinsic sinus node function

Changes in sinus node function in a rabbit model of heart failure with ventricular arrhythmias and sudden death.

Heart failure is associated with profound changes in the balance of the autonomic nervous system, such as vagal withdrawal and increased catecholamine levels. It is not known whether the intrinsic sinus node function changes during the progression of heart failure. We implanted transmitters for Holter recording in an established rabbit model of heart failure (n=9) and observed changes in sinus cycle length and the occurrence of arrhythmias during the progression of heart failure. The in vitro sinus cycle length and the responses to acetylcholine and norepinephrine in the isolated right atria were analyzed in 12 rabbits with heart failure and in 6 control rabbits. In vivo cycle length increased in some animals and decreased in others. Sudden death occurred in 3 of 9 rabbits. These rabbits had developed a shorter cycle length than the surviving rabbits. Ventricular tachycardias developed in all but 1 rabbit. The in vitro sinus cycle length increased in heart failure. The response to acetylcholine also increased in heart failure, whereas the response to norepinephrine was unchanged. Changes in intrinsic sinus node function during the progression of heart failure cannot explain the observed decreases in heart rate variability and/or baroreflex sensitivity in this disease, because increased responsiveness to acetylcholine would be expected to cause the opposite.

The sinus node function: normal and pathological.

To determine the evolution with age, of extrinsic and intrinsic sinus node electrophysiological parameters and to assess the role of each component of the autonomic nervous system relative to age in patients with and without sick sinus syndrome, electrophysiological studies of sinus node function were performed in 223 patients subdivided into four groups according to the results of their electrophysiological testings: group I included patients with normal extrinsic and intrinsic sinus node function, group II patients with exclusive extrinsic sinus dysfunction, group III patients with exclusive intrinsic sinus dysfunction and group IV patients with extrinsic and intrinsic sinus node dysfunction. The electrophysiological study was performed twice: at basal state and after autonomic blockade. Whatever the sinus node function (normal or abnormal) the extrinsic sinus node electrophysiological variables did not correlate with age; inversely all the electrophysiological measurements of the intrinsic sinus node (normal or abnormal) lengthened progressively with age, suggesting an ageing phenomenon of the intrinsic sinus node throughout life. Moreover, the study of the percentage of chronotropy of the sinus node electrophysiological variables shows a predominance of vagal tone in young subjects, whereas sympathetic activity is most prominent in elderly patients with and without sick sinus syndrome. The sinus node (normal or pathological) represents an equilibrated system: the age-related modification of the autonomic nervous system counterbalances the senescence of the intrinsic sinus node in such a way that the basal electrophysiological characteristics remain stable throughout life.

Age-related changes of sinus node function and autonomic regulation in subjects without sinus node disease--assessment by pharmacologic autonomic blockade.

To assess the relationship between aging and autonomic regulation of sinus node function, 56 subjects of various ages (range 14-75 years, mean 43 +/- 19 years) without sinus node disease were studied. Heart rate, corrected sinus node recovery time and sinoatrial conduction time were measured before (basic) and after (intrinsic) pharmacologic autonomic blockade (propranolol + atropine i.v.). Percent chronotropies of the above parameters were calculated by a modified Jordan's method. Basic heart rate and basic corrected sinus node recovery time did not vary with age (r = -0.15, r = 0.08, respectively), while basic sinoatrial conduction time tended to increase with age (r = 0.32, p < 0.05). Intrinsic heart rate decreased (r = -0.76, p < 0.001), and intrinsic corrected sinus node recovery time and intrinsic sinoatrial conduction time both increased with age (r = 0.55, p < 0.001; r = 0.56, p < 0.001, respectively). The younger the subject, the more negative the percent chronotropies of the above parameters were, and the percent chronotropies correlated positively with age (r = 0.68, p < 0.001; r = 0.52, p < 0.001 and r = 0.34, p < 0.05, respectively). In conclusion, intrinsic sinus node functions deteriorated with age. Furthermore, parasympathetic tone on the sinus node functions decreased with age, which may compensate for age-related deterioration of intrinsic sinus node function.

Electrophysiologic evaluation of sinus node dysfunction in postoperative children and young adults utilizing combined autonomic blockade–B. Marcus Et Al.: Postoperative intrinsic sinus node evaluation

Sinus node dysfunction is a recognized problem following surgery for congenital heart disease. Seven postoperative patients with sinus node dysfunction (5 Mustard, 1 tetralogy of Fallot, 1 Fontan) underwent electrophysiology study of sinus node function during combined autonomic blockade (CAB) utilizing propranolol 0.2 mg/kg i.v. and atropine 0.04 mg/kg i.v. to evaluate intrinsic sinus node function isolated from autonomic control. During CAB, intrinsic heart rate, intrinsic corrected sinus node recovery time, and intrinsic sinoatrial recovery time were measured. These results were compared with age-matched normal intrinsic data from our lab [normal (n = 7, mean age 9 years) IHR 128 +/- 24, intrinsic corrected sinus node recovery time 135 +/- 40 ms, intrinsic sinoatrial conduction time 86 +/- 19 ms]. Among postoperative Mustard patients (n = 5, mean age 13 years, mean years postoperative 11) 2 of 5 had clearly abnormal intrinsic sinus node function with nonsinus rhythm during CAB; 3 of 5 had sinus rhythm during CAB with normal or mildly abnormal intrinsic sinus node function. The postoperative case of tetralogy of Fallot (age 20 years, postoperative 14 years) had mildly abnormal intrinsic sinus node electrophysiology study. The postoperative case of Fontan (age 16 years, postoperative 1.5 years) had sinus rhythm at rest but left atrial rhythm during CAB. Different aspects of sinus node dysfunction may be expressed during resting electrophysiology study vs. electrophysiology study utilizing CAB. The pathophysiology of sinus node dysfunction among postoperative pediatric patients is not homogeneous with regard to the contribution of intrinsic sinus node dysfunction. In those patients with normal or mildly abnormal intrinsic sinus node function, an important pathophysiologic influence of the autonomic nervous system is implicated.

Heart rate responses to autonomic drugs in sick sinus syndrome. Correlation with syncope and electrophysiologic data.

To assess the influence of autonomic regulation on automaticity in patients with intrinsic sinus node dysfunction, heart rate responses to autonomic drugs were evaluated in 28 patients with sick sinus syndrome and in 8 normal subjects. Heart rates before and after intravenous administration of isoproterenol (Isp), propranolol, atropine, and methoxamine were measured. To compare the results with electrophysiologic data, heart rate and automaticity recovery time (ART) before and after pharmacologic autonomic blockade (AB) were evaluated. Seventeen patients without syncope showed a similar heart rate response after administration of Isp to that of normal subjects, but 11 patients with syncope showed a significantly lower response than patients without syncope. Responses to atropine and methoxamine were lower and response to propranolol was larger in patients as compared to normal subjects. However, no significant difference was observed between patients with and without syncope. Twelve patients showed severely prolonged max ART exceeding 5000 msec after AB. Seven of them showed preserved response to Isp and max ART before AB was significantly shorter than that after AB. The other 5 patients with lower response to Isp showed no significant change in max ART before and after AB. In conclusion, sympathetic regulation in patients with preserved response to Isp might compensate for the impaired intrinsic automaticity in preventing syncope even in patients with severely impaired intrinsic sinus node function.

The heart rate alternative sequence during pharmacologic total autonomic blockade in patients with sick sinus syndrome: differential effects in relation to age

To study the age-related changes of the sinus node function and the variations of influence of autonomic nervous system, pharmacologic total autonomic blockade (TAB) was conducted in 35 patients with symptomatic sinus bradycardia (21 men and 14 women, 50 +/- 21 years, mean +/- SD). Twenty-one patients [Group I, consisting of 14 patients younger than 60 years (group IY) nd 7 patients 60 years or older (group IE)] had a normal intrinsic heart rate (IHRo), and 14 patients had an abnormal IHRo [Group II, consisting of 8 patients younger than 60 years (group IIY) and 5 patients 60 years or older (group IIE)]. The basic cycle length was significantly longer in group II than in group I, suggesting that intrinsic sinus node function was more seriously deteriorated in group II in spite of the compensatory effect of autonomic regulation. In group II it was characteristic that the cycle length (CL) after atropine sulfate administration was longer than the CL of the predicted intrinsic heart rate (IHRp). Otherwise, some group II patients might be regarded as normal by atropine sulfate administration alone. Parasympathetic tone showed a negative correlation with age, and it was most enhanced in group IIY, suggesting that parasympathetic negative chronotropy was stronger in this group. In the course of propranolol administration, prolongation of CL was significantly larger in group IIE than in group IIY, but there was no age-related difference in group I. In group II, beta-adrenergic blockade with propranolol administration showed that sympathetic positive chronotropy was a critical compensatory factor around the upper limit of the CL of IHRp.(ABSTRACT TRUNCATED AT 250 WORDS)

Reproducibility of electrophysiological parameters of sinus node following autonomic blockade

We investigated the reproducibility of sinus node cycle length (SCL), corrected sinus node recovery time (CSRT) and sino-atrial conduction time (SACT) during the control state and following autonomic blockade in 25 patients (mean age: 56.9 ± 13.8 years). Autonomic blockade was induced by i.v. administration of propranolol (0.2 mg/kg) and atropine (0.04 mg/kg). The electrophysiological study was repeated after 24 hr and the results were compared. The patients were divided into two groups: Group 1 (15) with normal and Group 2 (10) with abnormal intrinsic sinus node function. Following autonomic blockade in Group 1 the daily variations in SCL, CSRT and SACT were very slight whereas in Group 2 there was far greater variability in these parameters. However, in the latter group there were no patients who changed their status from prolonged to normal intrinsic CSRT on the second study, whereas SACT changed its status in 2 patients. In Group 1 the daily variations in sinus node parameters were much slighter following autonomic blockade than during the control state. In Group 2 the variations were very similar during control and following autonomic blockade. These data suggest that: (1) following autonomic blockade the reproducibility of sinus node parameters is very good in Group 1, whereas in Group 2 several patients show marked daily variations in sinus node parameters; (2) following autonomic blockade the sinus node electrophysiological parameters are meaningful in diagnosing an involvement of intrinsic sinus node function; and (3) in patients with abnormal sinus node parameters during control state, but with normal intrinsic sinus node function, the daily variations are mainly due to change in autonomic tone, whereas when the intrinsic sinus node function is abnormal, the day to day variations during control state appear due predominantly to intrinsic sinus node abnormalities.

Influence of digoxin on sinus node function after pharmacologic autonomic blockade.

The effect of iv digoxin on normal sinus node function was studied after pharmacologic autonomic blockade (AB) in ten patients. Sinus cycle length (SCL), sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) were determined before and after AB with propranolol (0.2 mg/kg body weight) and atropine sulfate (0.04 mg/kg body weight) iv, and 15 min, 30 min, and 45 min after 1 mg iv digoxin. AB resulted in a significant decrease (P less than 0.01) in SCL (916 +/- 158 to 716 +/- 120 ms), in SNRT (1,229 +/- 221 to 871 +/- 190 ms), and in SACT (79 +/- 34 to 44 +/- 10 ms). Fifteen minutes after iv digoxin there was no significant change observed in SCL (716 +/- 120 to 708 +/- 92 ms), in SNRT (871 +/- 190 to 864 +/- 148 ms), or in SACT (44 +/- 10 to 46 +/- 15 ms). Similar results were obtained 30 min after digoxin administration. It is concluded that a single therapeutic dose of digoxin has no direct effect on electrophysiologic parameters of normal intrinsic sinus node function.

Electrophysiologic effects on combined autonomic blockade in patients with sinus node disease.

Thirty-two patients were studied before and after i.v. administration of 0.15-0.20 mg/kg of propranolol. Twenty-one of the 32 underwent combined autonomic blockade with the additional infusion of 0.04 mg of atropine. Twenty other patients with sinus node disease underwent electrophysiologic studies both before and after i.v. administration of 0.04 mg of atropine alone. Spontaneous cycle length, maximal corrected sinus node recovery time, sinoatrial conduction time, secondary pauses and intrinsic heart rate were measured. Secondary pauses were more common in those with abnormal intrinsic heart rates, and they did not correlate with changes in maximal corrected sinus node recovery time or sinoatrial conduction time. In patients with normal intrinsic heart rate, abnormal test measurements usually returned to normal after combined blockade (hypervagotonia); however, some patients showed a new abnormality after propranolol that was not reversible with atropine (catecholamine-dependent). Abnormal test responses in patients with abnormal intrinsic heart rate persisted or increased after combined blockade. We conclude that patients with sinus node disease may be categorized as (1) those with intrinsic sinus node disease; (2) those with normal intrinsic sinus node function but either relative hypervagotonia or catecholamine dependency; and (3) those with abnormal intrinsic sinus node function affected by vagal or catecholamine factors.