Effect of propranolol on the QT intervals of normal individuals during exercise: a new method for studying interventions.

Sarma, J. S. M.; Venkataraman, Kalyanasundaram; Samant, Dinesh R.; Gadgil, Uday

doi:10.1136/hrt.60.5.434

Cited by 37 publications

(12 citation statements)

References 13 publications

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“…Studies evaluating the effect of exercise on the QT interval have uniformly demonstrated that it shortens (43,44,46). However, the imprecision of rate correction formulas, particularly in the more rapid heart rate range, has precluded a fundamental understanding of the autonomic effects of exercise (and recovery) on cardiac repolarization.…”

Section: Discussionmentioning

confidence: 99%

“…We believe that these differences are related to the different autonomic milieus present during exercise versus atrial pacing. For example, Sarma et al (46) plotted the QT-RR relationship for a subject during complete exercise tests-once with a 40-mg oral dose of propranolol administered 2 to 3 h before the test and once without drug. The QT-RR relationship appeared to be exponential.…”

Section: Discussionmentioning

confidence: 99%

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Autonomic effects on QT-RR interval dynamics after exercise

Sundaram¹,

Carnethon²,

Polito³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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This study was designed to assess autonomic effects on the QT interval during recovery from exercise. Exercise is associated with an acute increased risk of sudden cardiac death. Evidence of impaired parasympathetic activity, such as low heart rate variability and heart rate recovery, and an increased QT interval are also associated with increased mortality. However, there is no clear pathophysiological link among these findings. Bicycle exercise testing was performed serially in 33 healthy volunteers (19 men; ages, 54 Ϯ 7 yr) under four conditions: 1) baseline, 2) ␤-adrenergic blockade-intravenous propranolol (0.2 mg/kg) administered during exercise, 3) parasympathetic blockade-intravenous atropine (0.04 mg/kg) administered during exercise, and 4) double blockade with propranolol and atropine. ECGs were obtained every minute in recovery for 10 min and then at the 15th and 20th min, from which the QT and RR intervals were measured. Linear regression analyses were used to assess the individual QT-RR relationships for each subject for each condition. Relative to baseline, the QT-RR relationship with parasympathetic blockade was shifted to the left and had a steeper slope. In contrast, the QT-RR relationship with ␤-adrenergic blockade was shifted to the right and had a less steep slope. The baseline and double-blockade QT-RR relationships were in the middle and essentially superimposable. There was a negative relationship between QT-RR slope and heart rate or RR interval recoveries, but it was significant only for the 1-and 2-min RR interval recoveries with low R 2 values of 0.124 and 0.114. The main parasympathetic effect in the postexercise recovery period is to counteract the sympathetically mediated QT prolongation. These data support the concept that parasympathetic tone may provide a natural antiarrhythmic effect during this time.parasympathetic; heart rate recovery; QT interval THE PATHOPHYSIOLOGY of sudden cardiac death is not completely understood. A variety of epidemiologic findings has provided key insights into the potential roles of ventricular repolarization, autonomic tone, and exercise. Although exercise has overall salutary effects, it has been shown that the risk of sudden death is increased dramatically during and immediately after exercise (3, 36) compared with sedentary periods. Although there are several possible mechanisms for this marked increased risk of sudden cardiac death, including the induction of myocardial ischemia, it may be related to the acute changes in autonomic tone that accompany exercise. The prognostic significance of abnormalities of autonomic tone has been established in multiple studies that have evaluated autonomic control of the heart rate predominantly at rest or during daily activities. These studies have linked diminished parasympathetic control with increased mortality (8,21,24,26,39,41). Finally, population studies have linked the QT interval on a 12-lead electrocardiogram (ECG) with an increased risk of ventricular arrhythmias and sudden death both in patients wit...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Autonomic effects on QT-RR interval dynamics after exercise

Sundaram¹,

Carnethon²,

Polito³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…One would predict that handgrip, which activates the sympathetic nervous system, would lead to QT interval shortening in normal subjects, and would have little or no effect on the QT interval in subjects with down-regulated β-receptors, such as those with heart failure [3,12,21,22]. The lack of effect of handgrip on the QTc interval in heart failure is therefore not unexpected.…”

Section: Discussionmentioning

confidence: 99%

Influence of posture and handgrip on the QT interval in left ventricular hypertrophy and in chronic heart failure

Davey

1999

Clinical Science

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In certain disease states prolongation of the QT interval has been shown to be arrhythmogenic. Whether QTc interval changes with position and thus whether certain positions are more arrhythmogenic than others is not known for different diseases that predispose to arrhythmias, and was therefore studied. Patients with left ventricular hypertrophy and heart failure, and the appropriate matched controls, were recruited. Subjects were studied in the lying, sitting, standing and squatting positions and had QT intervals determined by computer algorithm 2 min after each position change. After resting, QT interval was determined while the subjects performed maximum handgrip exercise with their dominant hand. QT intervals were rate-corrected using Bazett's method. QTc interval is prolonged in heart failure patients compared with either left ventricular hypertrophy or control subjects in the lying and sitting position, but not in the standing or squatting position. The QTc intervals for heart failure and control subjects were, respectively, 443+/-7 ms versus 421+/-6 ms when lying (P<0.05), 451+/-10 ms versus 419+/-6 ms when sitting (P<0.05), 429+/-10 versus 414+/-7 ms when standing (P not significant) and 437+/-10 versus 419+/-8 ms when squatting (P not significant). The values for patients with hypertrophy did not differ from control values. Maximum handgrip does not affect the QTc interval in heart failure, but prolongs it in both the hypertrophy and control groups. Position and static exercise are important modifiers of QTc interval and their effect depends on the condition of the left ventricle.

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“…Recent studies have suggested that a monoexponential formula best fit the QT-versus-RR relation in humans. 33,34 Thus, the use of Bazett's formula might have biased the analysis of Wang et al 3 The present study was designed to assess the rate and concentration dependence of QT prolongation with three different dosages of sotalol in normal volunteers. Two other objectives were to confirm that a monoexponential formula fits the QT-versus-RR relation better than Bazett's formula and to deter-.…”

mentioning

confidence: 99%

Rate dependence of sotalol-induced prolongation of ventricular repolarization during exercise in humans.

et al. 1991

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Studies in animals have shown that drug-induced action potential prolongation with class III antiarrhythmic agents increases with slow pacing rates. We studied the physiological rate dependence of sotalol effects on ventricular repolarization, measured as QT interval duration on the surface electrocardiogram at rest and during a maximal exercise test, in 10 normal volunteers. In a randomized, crossover study, three dosages of sotalol (160 mg/24 hr, 320 mg/24 hr, and 640 mg/24 hr) were administered during 4 days to each subject. In a control period, no drug was administered. During each period, 50-100 QT intervals were measured over a wide range of RR intervals recorded at rest and during the course of a maximal exercise test. Plasma sotalol concentration and beta-adrenoceptor blockade (percent reduction in peak exercise heart rate from control) were also measured. The QT-versus-RR relation was fitted to several formulas, and the overall best fit was used to calculate QT interval duration normalized for a heart rate of 60 beats/min (QTc) and to analyze the rate dependence of QT prolongation with sotalol. Sotalol-induced beta-adrenoceptor blockade and QTc prolongation were dose and concentration dependent. Sotalol reduced peak exercise heart rate by 13.8 +/- 7% at the dosage of 320 mg/24 hr and by 25.4 +/- 8% at the dosage of 640 mg/24 hr (both p less than 0.01). Sotalol prolonged QTc interval by 5.8 +/- 3.7% and 11.8 +/- 3% at these respective dosages (both p less than 0.01). The concentration of sotalol required to produce minimal (mean QTc prolongation, 5.6%; confidence interval, 0-11.2%) QTc prolongation (680 ng/ml) tended to be lower than that required for minimal (mean percent reduction in maximal exercise heart rate, 13.9%; confidence interval, 0-27.8%) beta-blockade (840 ng/ml). QT prolongation with sotalol increased with increasing RR intervals (i.e., decreasing heart rate) at all dosages. QT prolongation became statistically significant for RR of 800 msec or more at all dosages and for RR intervals of 600 msec or more at the dosage of 640 mg/24 hr. This rate dependence altered the relation between QT interval duration and sotalol plasma concentrations. These results suggest that sotalol prolongs QTc interval in humans at dosages and concentrations similar to those required to produce beta-adrenoceptor blockade, QT prolongation with sotalol is more pronounced when heart rate decreases and is not apparent during exercise-induced tachycardia, and the relation between QT prolongation with sotalol and plasma concentrations of the drug depends on the heart rate at which measurements are made.

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Effect of propranolol on the QT intervals of normal individuals during exercise: a new method for studying interventions.

Cited by 37 publications

References 13 publications

Autonomic effects on QT-RR interval dynamics after exercise

Autonomic effects on QT-RR interval dynamics after exercise

Influence of posture and handgrip on the QT interval in left ventricular hypertrophy and in chronic heart failure

Rate dependence of sotalol-induced prolongation of ventricular repolarization during exercise in humans.

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