Abstract
With the aim of evaluating whether and how rate-dependent changes of QT interval are conditioned by the autonomic nervous system, 28 healthy subjects, with no heart disease and normal basal QT interval, were electrophysiologically evaluated. The QT interval was calculated at 6 paced cycle lengths in a range between 600 and 400 ms during basal state, after beta-blockade (propranolol 0.2 mg/kg) and after autonomic blockade (propranolol 0.2 mg/kg and atropine 0.04 mg/kg). Due to A-V nodal conduction limits intra-subject cross-comparisons were evaluable in 10 subjects (age 42 ± 15 yrs). A good correlation between cycle length shortening and QT shortening was observed in all 3 conditions. The mean slope of regression curves showing such correlation was significantly lower after autonomic blockade (̄b = .10 ± .04) than both in the basal state (̄b = .22 ± .12, p <0.05) and after beta-blockade (̄b = .23 ± .08, p <0.05), thus suggesting a significant vagal prevalence and an almost inconsistent effect of sympathetic tone on rate-related changes of QT. This observation has clinical implications in that various antiarrhythmic agents possess some vagolytic activity, that may interfere with vagal conditioning on ventricular repolarization. With the aim of assessing whether such interactions exist in the clinical setting, 15 more patients, with no ischemic heart disease and normal basal QT interval, who suffered supraventricular tachyarrhythmias, were electrophysiologically evaluated with the same method as above (1st study). Oral quinidine was then administered at a daily dosage of 1200 mg for 3-4 days, after which a 2nd study was performed in all patients. Due to A-V nodal conduction limits, intra-patient cross-comparison after beta-blockade was not evaluable, but in 6 in the 1st study and in any patient after quinidine. In the 1st study, similarly to what was observed in healthy subjects, the mean slope of regression curves showing correlation between cycle length and QT was significantly lower after autonomic blockade (̄b = .15 ± .04) than in the basal state (̄b = .27 ± .10, p <0.05), whereas in the 2nd study, after quinidine, the mean slopes of the regression curves in the basal state (̄b = .20 ± .07) and after autonomic blockade (̄b = .19 ± .05) did not differ (p = NS). These results suggest that, besides prolonging QT duration: 1) quinidine counteracts the vagal conditioning on rate-related changes of QT, very likely by means of its vagolytic activity; 2) the QT prolongation induced by quinidine direct depressant effect increases as cycle length is prolonged, thus exhibiting reverse use dependence on human ventricular fibers. These two mechanisms may favour the proarrhythmic effect of the drug, when given chronically.
| Original language | English |
|---|---|
| Pages (from-to) | 1047-1056 |
| Number of pages | 10 |
| Journal | New Trends in Arrhythmias |
| Volume | 7 |
| Issue number | 4 |
| Publication status | Published - 1991 |
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ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Effects of vagal tone on rate-dependent changes of QT interval and role of quinidine on such phenomenon. / Cappato, R.; Alboni, P.; Percoco, G. F.; Ansani, L.; Antonioli, G. E.
In: New Trends in Arrhythmias, Vol. 7, No. 4, 1991, p. 1047-1056.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of vagal tone on rate-dependent changes of QT interval and role of quinidine on such phenomenon
AU - Cappato, R.
AU - Alboni, P.
AU - Percoco, G. F.
AU - Ansani, L.
AU - Antonioli, G. E.
PY - 1991
Y1 - 1991
N2 - With the aim of evaluating whether and how rate-dependent changes of QT interval are conditioned by the autonomic nervous system, 28 healthy subjects, with no heart disease and normal basal QT interval, were electrophysiologically evaluated. The QT interval was calculated at 6 paced cycle lengths in a range between 600 and 400 ms during basal state, after beta-blockade (propranolol 0.2 mg/kg) and after autonomic blockade (propranolol 0.2 mg/kg and atropine 0.04 mg/kg). Due to A-V nodal conduction limits intra-subject cross-comparisons were evaluable in 10 subjects (age 42 ± 15 yrs). A good correlation between cycle length shortening and QT shortening was observed in all 3 conditions. The mean slope of regression curves showing such correlation was significantly lower after autonomic blockade (̄b = .10 ± .04) than both in the basal state (̄b = .22 ± .12, p <0.05) and after beta-blockade (̄b = .23 ± .08, p <0.05), thus suggesting a significant vagal prevalence and an almost inconsistent effect of sympathetic tone on rate-related changes of QT. This observation has clinical implications in that various antiarrhythmic agents possess some vagolytic activity, that may interfere with vagal conditioning on ventricular repolarization. With the aim of assessing whether such interactions exist in the clinical setting, 15 more patients, with no ischemic heart disease and normal basal QT interval, who suffered supraventricular tachyarrhythmias, were electrophysiologically evaluated with the same method as above (1st study). Oral quinidine was then administered at a daily dosage of 1200 mg for 3-4 days, after which a 2nd study was performed in all patients. Due to A-V nodal conduction limits, intra-patient cross-comparison after beta-blockade was not evaluable, but in 6 in the 1st study and in any patient after quinidine. In the 1st study, similarly to what was observed in healthy subjects, the mean slope of regression curves showing correlation between cycle length and QT was significantly lower after autonomic blockade (̄b = .15 ± .04) than in the basal state (̄b = .27 ± .10, p <0.05), whereas in the 2nd study, after quinidine, the mean slopes of the regression curves in the basal state (̄b = .20 ± .07) and after autonomic blockade (̄b = .19 ± .05) did not differ (p = NS). These results suggest that, besides prolonging QT duration: 1) quinidine counteracts the vagal conditioning on rate-related changes of QT, very likely by means of its vagolytic activity; 2) the QT prolongation induced by quinidine direct depressant effect increases as cycle length is prolonged, thus exhibiting reverse use dependence on human ventricular fibers. These two mechanisms may favour the proarrhythmic effect of the drug, when given chronically.
AB - With the aim of evaluating whether and how rate-dependent changes of QT interval are conditioned by the autonomic nervous system, 28 healthy subjects, with no heart disease and normal basal QT interval, were electrophysiologically evaluated. The QT interval was calculated at 6 paced cycle lengths in a range between 600 and 400 ms during basal state, after beta-blockade (propranolol 0.2 mg/kg) and after autonomic blockade (propranolol 0.2 mg/kg and atropine 0.04 mg/kg). Due to A-V nodal conduction limits intra-subject cross-comparisons were evaluable in 10 subjects (age 42 ± 15 yrs). A good correlation between cycle length shortening and QT shortening was observed in all 3 conditions. The mean slope of regression curves showing such correlation was significantly lower after autonomic blockade (̄b = .10 ± .04) than both in the basal state (̄b = .22 ± .12, p <0.05) and after beta-blockade (̄b = .23 ± .08, p <0.05), thus suggesting a significant vagal prevalence and an almost inconsistent effect of sympathetic tone on rate-related changes of QT. This observation has clinical implications in that various antiarrhythmic agents possess some vagolytic activity, that may interfere with vagal conditioning on ventricular repolarization. With the aim of assessing whether such interactions exist in the clinical setting, 15 more patients, with no ischemic heart disease and normal basal QT interval, who suffered supraventricular tachyarrhythmias, were electrophysiologically evaluated with the same method as above (1st study). Oral quinidine was then administered at a daily dosage of 1200 mg for 3-4 days, after which a 2nd study was performed in all patients. Due to A-V nodal conduction limits, intra-patient cross-comparison after beta-blockade was not evaluable, but in 6 in the 1st study and in any patient after quinidine. In the 1st study, similarly to what was observed in healthy subjects, the mean slope of regression curves showing correlation between cycle length and QT was significantly lower after autonomic blockade (̄b = .15 ± .04) than in the basal state (̄b = .27 ± .10, p <0.05), whereas in the 2nd study, after quinidine, the mean slopes of the regression curves in the basal state (̄b = .20 ± .07) and after autonomic blockade (̄b = .19 ± .05) did not differ (p = NS). These results suggest that, besides prolonging QT duration: 1) quinidine counteracts the vagal conditioning on rate-related changes of QT, very likely by means of its vagolytic activity; 2) the QT prolongation induced by quinidine direct depressant effect increases as cycle length is prolonged, thus exhibiting reverse use dependence on human ventricular fibers. These two mechanisms may favour the proarrhythmic effect of the drug, when given chronically.
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UR - http://www.scopus.com/inward/citedby.url?scp=0026377759&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:0026377759
VL - 7
SP - 1047
EP - 1056
JO - New Trends in Arrhythmias
JF - New Trends in Arrhythmias
SN - 0393-5302
IS - 4
ER -