Blunting of Exercise-Induced Tachycardia and Renin Release 24 Hours After a Single Dose of Sotalol W.
KIOWSKI,
M.D.,
SINGLE daily dosing of a drug contributes to improved patient compliance for any pharmacotherapy.’ In the case of beta-adrenoceptor blockers, a receptor blockade which lasts for the entire day may be particularly important because of the cardioprotective potential of these drugs.2 The degree of beta-receptor blockade can be assessed pharmacologically by an isoproterenol bolus test3 or physiologically by measuring beta receptor-mediated functions, i.e., heart rate and renin secretion especially when activated by a sympathetic stimulus.4 Sotalol, a noncardioselective beta blocker without intrinsic sympathomimetic or membrane-stabilizing activity was found to have a plasma half-life of 15 to 17 hours5 which may be associated with a 24 hour-lasting receptor blockade, as was proved to be the case with other beta-blocking drugs.6’7 Therefore, the effects of sotalol on heart rate and renin were tested at supine rest as well as during upright ergometry both 2 and 24 hours after oral administration of a single morning dose. Material
and
Methods
Six normotensive -
From Basel,
the
Department
male of Medicine,
Switzerland.
August-September
1979
volunteers
aged
University
of Basel.
F. R. BUHIER, M.D., P. VAN and M. KONG, M.D.
BRUMMELEN, M.D. Basel, Switzerland
2’2 to 26 years were studied between 9:00 and 2:00 P.M. After 30 minutes of supine bed rest, heart rates were measured and blood samples were taken for the determination of plasma renin activity via antecubital intravenous cannula. Subjects were then exercised in the upright position on an electrically braked ergometer bicycle (Elema-Sch#{246}nander EM 370). Heart rates were measured by ECG. In order to obtain values for renin under steady-state conditions, graded exercise was carried out for 20 minutes at work loads (100-150 watts) which produced heart rates of 150-170 beats/mm. At the end, measurements of heart rates and renin were repeated. The same procedures were repeated 2 hours and 24 hours after oral administration of 200 mg sotalol. Blood samples were processed for radioimmunologic measurement of plasma renin activity.8 Statistical significance of differences in heart rate. and renin was determined by Student’s paired t-test.
A.M.
Results As shown in Fig. 1, sotalol significantly reduced resting and exercise-stimulated heart rates both 2 hours and 24 hours after administration. However, the reduction in exercise tachycardia was sig513
KIO
IN
ACTIVITY
fl5/
/
BUHLER,
VAN
4
PLASMA PEN
WSKI,
hr
1701 /
140.1 HEART
/
RATE beOI$/n,,n
1101
/
/ Control
2h OIler
200r,r
blob!
P0
Fiq. 1. Reduction of resting (0,.) and exercise-stimulated ( I plasma renin activity and heart rate before (open symbols) as u,ell as 2 hours and 24 hours after a single oral dose of 200 mg sotalol (filled symhoL) in sir normal male volunteers. Results are shown as means ± standard deviation. The significance leveLs of differences from control are indicated (0 P
KIOWSKI,
M.D.,
SINGLE daily dosing of a drug contributes to improved patient compliance for any pharmacotherapy.’ In the case of beta-adrenoceptor blockers, a receptor blockade which lasts for the entire day may be particularly important because of the cardioprotective potential of these drugs.2 The degree of beta-receptor blockade can be assessed pharmacologically by an isoproterenol bolus test3 or physiologically by measuring beta receptor-mediated functions, i.e., heart rate and renin secretion especially when activated by a sympathetic stimulus.4 Sotalol, a noncardioselective beta blocker without intrinsic sympathomimetic or membrane-stabilizing activity was found to have a plasma half-life of 15 to 17 hours5 which may be associated with a 24 hour-lasting receptor blockade, as was proved to be the case with other beta-blocking drugs.6’7 Therefore, the effects of sotalol on heart rate and renin were tested at supine rest as well as during upright ergometry both 2 and 24 hours after oral administration of a single morning dose. Material
and
Methods
Six normotensive -
From Basel,
the
Department
male of Medicine,
Switzerland.
August-September
1979
volunteers
aged
University
of Basel.
F. R. BUHIER, M.D., P. VAN and M. KONG, M.D.
BRUMMELEN, M.D. Basel, Switzerland
2’2 to 26 years were studied between 9:00 and 2:00 P.M. After 30 minutes of supine bed rest, heart rates were measured and blood samples were taken for the determination of plasma renin activity via antecubital intravenous cannula. Subjects were then exercised in the upright position on an electrically braked ergometer bicycle (Elema-Sch#{246}nander EM 370). Heart rates were measured by ECG. In order to obtain values for renin under steady-state conditions, graded exercise was carried out for 20 minutes at work loads (100-150 watts) which produced heart rates of 150-170 beats/mm. At the end, measurements of heart rates and renin were repeated. The same procedures were repeated 2 hours and 24 hours after oral administration of 200 mg sotalol. Blood samples were processed for radioimmunologic measurement of plasma renin activity.8 Statistical significance of differences in heart rate. and renin was determined by Student’s paired t-test.
A.M.
Results As shown in Fig. 1, sotalol significantly reduced resting and exercise-stimulated heart rates both 2 hours and 24 hours after administration. However, the reduction in exercise tachycardia was sig513
KIO
IN
ACTIVITY
fl5/
/
BUHLER,
VAN
4
PLASMA PEN
WSKI,
hr
1701 /
140.1 HEART
/
RATE beOI$/n,,n
1101
/
/ Control
2h OIler
200r,r
blob!
P0
Fiq. 1. Reduction of resting (0,.) and exercise-stimulated ( I plasma renin activity and heart rate before (open symbols) as u,ell as 2 hours and 24 hours after a single oral dose of 200 mg sotalol (filled symhoL) in sir normal male volunteers. Results are shown as means ± standard deviation. The significance leveLs of differences from control are indicated (0 P
