Clinical Science (1979) 57,4139-415s
Objective measurement of performance during acute stress in patients with essential hypertension: assessment of the effects of propranolol and metoprolol F. G. D U N N , A. R. L O R I M E R
A N D T. D. V. L A W R I E University Dejmrlment of Medical Cardiology, Royal Iqfirmary, Glasgow. Scotland, UX.
Summary 1. A standardized method of objectively measuring performance during simulated car driving is described. 2. The effect of a single dose of propranolol and metoprolol were compared with placebo in two groups of patients with untreated essential hypertension. 3. Performance was similar after /Iadrenoreceptor-blockingagents or placebo. 4. Blood pressure response to stress persisted after administration of the blocking agents.
Key words: metoprolol, propranolol, stress. Introduction The symptoms experienced during stress are predominantly mediated through the sympathetic nervous system and therefore it is not surprising that /3-adrenoreceptor-blocking agents have been used to modify these symptoms in such circumstances as public speaking (Taggart, Carruthers & Somerville, 1973) and racing car driving (Taggart & Carruthers, 1972). However, it is not clear at present what effects &adrenoreceptor-blocking agents have on performance when measured objectively. The performance of a group of violinists was assessed after single-dose placebo and oxprenolol (James, Pearson, W i t h & Newbury, 1977) and it was found that both a subjective improvement in well-being and an objective improvement in performance O C C U K ~ . Conversely, a psychomotor test was applied to a group of normotensive volunteer subjects and it was noted Correspondence: Dr F. G.DUM,University Department of Medical Cardiology, Royal Infirmary,Glasgow G4 OSF, Scotland, U.K.
that the blockade caused a detrimental effect on performance (Glaister, Harrison & Allnutt, 1973). In view of these discrepant findings, we have assessed further a method of objectively measuring performance during stress. Patients and methods
Two groups of nine patients (1 7 males, one female) with untreated idiopathic hypertension were studied. The mean age in group 1 was 44 years and in group 2 was 40 years. There were no contraindications to padrenoreceptor blockade and no patient had previously been conversant with the stress procedure used. The stress was performed twice on each patient at weekly intervals. On one occasion they received a /3-adrenoreceptor blocker (the non-selective propranolol in group 1 and the more cardioselective metoprolol in group 2) and on the other occasion placebo. The tablets were given in a single blind randomized crossover manner. The apparatus used consisted of a cardriving simulating machine with associated auditory and visual stimuli. The machine is fitted with a steering wheel, two forward gears and an accelerator pedal. At the start of the test, the visual display shows a central car which is controlled by the steering wheel. A points score system is incorporated into the machine. These are given in response to the distance covered by the car during each run of 50 s. Other vehicles move randomly in the path of the central car and, if these are not avoided, a collision occurs causing the car to stop temporarily. Thus time is lost, less distance is covered and a lower points total is achieved. The auditory stimuli comprise firstly a motor car engine noise, which increases as the accelerator is pressed, and secondly a loud banging noise each time there is a collision.
413s
414s
F. G.Dunn,A . R . Lorimer and T. D. V . Lawrie
The protocol was as follows. Baseline heart rate and blood pressure (Roche Arteriosonde) were recorded. The patients were instructed in the use of the machine and given 10 practice runs to familiarize them with the procedure and minimize the learning effect. Two hours after active drug or placebo, stress testing was undertaken with the mean of five scores being recorded. Pre-stress and stress heart rate and blood pressure were taken. The procedure was repeated 1 week later on the alternative preparation. Results
Baseline heart rate fell from a mean of 91 to 71 b e a t s h i n with propranolol (P < 0.001) and from 88 to 67 beats/min with metoprolol (P< 0.001). It remained unchanged in both placebo groups. A significant rise in heart rate occurred during the test in both groups irrespective of whether blocking agent or placebo was given (Table 1). The rise was less with the blockers, being 6% for propranolol vs 10% for placebo and 6% for metoprolol vs 13% for placebo but not significantly so on group analysis. Resting systolic blood pressure did not change significantly after P-adrenoreceptor blocker (Table 1). A highly significant rise in systolic pressure occurred in both groups during stress (P < 0401 for all). In group 1 the placebo rise was from 164 to 194 mmHg and with propranolol from 162 to 188 mmHg. In group 2, the rise was from 160 to 187 mmHg with placebo and with metoprolol from 152 to 17 1 mmHg. The percentage rises were identical in the two placebo groups. The rise was somewhat less with the blocking agents (15% propranolol vs 17% placebo and 13% metoprolol vs 17% placebo)
but not significantly so. The rise from week to week was similar in both groups, indicating that the stress was maintained on repeat studies. Baseline diastolic blood pressure was not significantly changed by the blocking agents. The rise in diastolic pressure in group 1 was from 114 to 128 mmHg with propranolol and 116 to 122 mmHg with placebo, the extent of this rise being greater with propranolol (P< 0-05).In group 2 the rise seen with metoprolol and with placebo was very similar (Table 1). The mean performance scores for each group of patients are shown in Table 1. Within each group a wide range of driving skills was represented but in each patient the level of skill remained much the same over the two series of runs. This was particularly so in group 1, there being a greater degree of variability in group 2. No significant differences were evident in the level of performance in either group. Discussion
The car-driving simulating machine used in this study provides a standardized method of both inducing acute stress and objectively measuring performance. The constancy of the blood pressure response in the two placebo groups suggests that the stress is reproducible and the similarity in blood pressure rise from week to week suggests that the stress is maintained on repeat testing. Neither P-adrenoreceptor-blocking agent modified the blood pressure response to the stress and this is in agreement with a previous study of the effect of single-dose blocking agents during acute stress (Nicotero, Beamer, Moutsos &
TABLE1. Heart rate. systolic and diastolic pressures and peflormance scores in subjects of group 1 and group 2 Mean values k SD are shown. *P < 0.05;**P < 0.01; ***P < 0.001. Group 2
Group 1
Performance scores Heart rate (beatshin) Baseline Pre-stress Stress Systolic pressure (mmHg) Baseline Pre-stress Stress Diastolic pressure (mmHg) Baseline Pre-stress Stress
Propranolol
Placebo
Metoprolol
191 f 36
193 f 36
199 f 42
91 f 16 71 f lo*** 75 f 12.
Placebo 196 f 47
8 7 f 12 92 f 14 101 f 21..
88 f 14 67 f 1V** 71 f 9 *
9 0 f I5 8 9 2 17 99 f 16..
166 f 14 162 f 21 188 f 30.'.
170 f 20 164 f 16 194 & 24"'
160 f 18 152 f 24 171 t 30***
160 f 20 160 f 20 187 ? 24***
117 f 9 114f 15 128 f 15***
121 f 1 1 116 f 14 122 f 121
106 f 14 105 f 14 112 f IS**
113 f 15 110 f 14 117 f 15'.
Propranolol and metoprolol in stress Shapiro, 1968). We have previously shown modification of blood pressure rise by propranolol with a form of chronic industrial stress (Dunn, Melville, Jones, Lorimer & Lawrie, 1978). That study differed from the one reported here not only in that a different type of stress was used but also in that blood pressure was normalized with propranolol before re-studying. Studies are currently in progress to look at the effect of long-term blockade on blood pressure response and performance during this acute stress. The performance scores remained similar within each patient irrespective of the therapy given and as noted this was over a wide range of driving skills. Acknowledgment The authors gratefully acknowledge the support of ICI Pharmaceuticals Ltd with the apparatus used in this study.
415s
References DUNN,F.G.,MELVILLE,D.I., JONES,J.V., LORIMER, A.R. & LAWRIE,T.D.V. (1978) Standardised stress and hypertension: Comparison of effect of propranolol and methyldopa. British Journal of Clinical Pharmacology, S, 223-226. GLAISTER,N.H., HARRISON,M.A. & ALLNUIT, M.F. (1973) Experimental cardiovascular stress and the influence of oxprenolol. In: New Perspectives in Beta blockade. An International Symposium, Aarhus. Denmark, pp. 241-267. Ed. Burley, D.M.,Fryer, J.H., Rondel, R.K. & Taylor, S.H. CIBA, Horsharn, U.K. JAMES,I.M., PEARSON, R.M., GIUFFITH, D.N.W. & NEWBURY, P. (1977) Effect of oxprenolol on stage-fright in musicians. Lancet. ii, 952-954. NICOTERO, J.A., BEAMER,V., M m s o s , S.E. & SHAPIRO,J.A. (1968) Effects of propranolol on the pressor response to noxioils stimuli in hypertensive patients. American Journal of Cardiology, 22,657-666. TAGGART,P. & CARRVTHERS,M. (1972) Suppression by oxprenolol of adrenergic response to stress. Lancet, ii, 256258.
TAGGART,P., CARRUTHERS,M. & SOMERVILLE, W. (1973) Electrocardiogram, plasma catecholamines and lipids and their modification by oxprenolol when speaking before an audience. Lancet, ii, 341-346.
Objective measurement of performance during acute stress in patients with essential hypertension: assessment of the effects of propranolol and metoprolol F. G. D U N N , A. R. L O R I M E R
A N D T. D. V. L A W R I E University Dejmrlment of Medical Cardiology, Royal Iqfirmary, Glasgow. Scotland, UX.
Summary 1. A standardized method of objectively measuring performance during simulated car driving is described. 2. The effect of a single dose of propranolol and metoprolol were compared with placebo in two groups of patients with untreated essential hypertension. 3. Performance was similar after /Iadrenoreceptor-blockingagents or placebo. 4. Blood pressure response to stress persisted after administration of the blocking agents.
Key words: metoprolol, propranolol, stress. Introduction The symptoms experienced during stress are predominantly mediated through the sympathetic nervous system and therefore it is not surprising that /3-adrenoreceptor-blocking agents have been used to modify these symptoms in such circumstances as public speaking (Taggart, Carruthers & Somerville, 1973) and racing car driving (Taggart & Carruthers, 1972). However, it is not clear at present what effects &adrenoreceptor-blocking agents have on performance when measured objectively. The performance of a group of violinists was assessed after single-dose placebo and oxprenolol (James, Pearson, W i t h & Newbury, 1977) and it was found that both a subjective improvement in well-being and an objective improvement in performance O C C U K ~ . Conversely, a psychomotor test was applied to a group of normotensive volunteer subjects and it was noted Correspondence: Dr F. G.DUM,University Department of Medical Cardiology, Royal Infirmary,Glasgow G4 OSF, Scotland, U.K.
that the blockade caused a detrimental effect on performance (Glaister, Harrison & Allnutt, 1973). In view of these discrepant findings, we have assessed further a method of objectively measuring performance during stress. Patients and methods
Two groups of nine patients (1 7 males, one female) with untreated idiopathic hypertension were studied. The mean age in group 1 was 44 years and in group 2 was 40 years. There were no contraindications to padrenoreceptor blockade and no patient had previously been conversant with the stress procedure used. The stress was performed twice on each patient at weekly intervals. On one occasion they received a /3-adrenoreceptor blocker (the non-selective propranolol in group 1 and the more cardioselective metoprolol in group 2) and on the other occasion placebo. The tablets were given in a single blind randomized crossover manner. The apparatus used consisted of a cardriving simulating machine with associated auditory and visual stimuli. The machine is fitted with a steering wheel, two forward gears and an accelerator pedal. At the start of the test, the visual display shows a central car which is controlled by the steering wheel. A points score system is incorporated into the machine. These are given in response to the distance covered by the car during each run of 50 s. Other vehicles move randomly in the path of the central car and, if these are not avoided, a collision occurs causing the car to stop temporarily. Thus time is lost, less distance is covered and a lower points total is achieved. The auditory stimuli comprise firstly a motor car engine noise, which increases as the accelerator is pressed, and secondly a loud banging noise each time there is a collision.
413s
414s
F. G.Dunn,A . R . Lorimer and T. D. V . Lawrie
The protocol was as follows. Baseline heart rate and blood pressure (Roche Arteriosonde) were recorded. The patients were instructed in the use of the machine and given 10 practice runs to familiarize them with the procedure and minimize the learning effect. Two hours after active drug or placebo, stress testing was undertaken with the mean of five scores being recorded. Pre-stress and stress heart rate and blood pressure were taken. The procedure was repeated 1 week later on the alternative preparation. Results
Baseline heart rate fell from a mean of 91 to 71 b e a t s h i n with propranolol (P < 0.001) and from 88 to 67 beats/min with metoprolol (P< 0.001). It remained unchanged in both placebo groups. A significant rise in heart rate occurred during the test in both groups irrespective of whether blocking agent or placebo was given (Table 1). The rise was less with the blockers, being 6% for propranolol vs 10% for placebo and 6% for metoprolol vs 13% for placebo but not significantly so on group analysis. Resting systolic blood pressure did not change significantly after P-adrenoreceptor blocker (Table 1). A highly significant rise in systolic pressure occurred in both groups during stress (P < 0401 for all). In group 1 the placebo rise was from 164 to 194 mmHg and with propranolol from 162 to 188 mmHg. In group 2, the rise was from 160 to 187 mmHg with placebo and with metoprolol from 152 to 17 1 mmHg. The percentage rises were identical in the two placebo groups. The rise was somewhat less with the blocking agents (15% propranolol vs 17% placebo and 13% metoprolol vs 17% placebo)
but not significantly so. The rise from week to week was similar in both groups, indicating that the stress was maintained on repeat studies. Baseline diastolic blood pressure was not significantly changed by the blocking agents. The rise in diastolic pressure in group 1 was from 114 to 128 mmHg with propranolol and 116 to 122 mmHg with placebo, the extent of this rise being greater with propranolol (P< 0-05).In group 2 the rise seen with metoprolol and with placebo was very similar (Table 1). The mean performance scores for each group of patients are shown in Table 1. Within each group a wide range of driving skills was represented but in each patient the level of skill remained much the same over the two series of runs. This was particularly so in group 1, there being a greater degree of variability in group 2. No significant differences were evident in the level of performance in either group. Discussion
The car-driving simulating machine used in this study provides a standardized method of both inducing acute stress and objectively measuring performance. The constancy of the blood pressure response in the two placebo groups suggests that the stress is reproducible and the similarity in blood pressure rise from week to week suggests that the stress is maintained on repeat testing. Neither P-adrenoreceptor-blocking agent modified the blood pressure response to the stress and this is in agreement with a previous study of the effect of single-dose blocking agents during acute stress (Nicotero, Beamer, Moutsos &
TABLE1. Heart rate. systolic and diastolic pressures and peflormance scores in subjects of group 1 and group 2 Mean values k SD are shown. *P < 0.05;**P < 0.01; ***P < 0.001. Group 2
Group 1
Performance scores Heart rate (beatshin) Baseline Pre-stress Stress Systolic pressure (mmHg) Baseline Pre-stress Stress Diastolic pressure (mmHg) Baseline Pre-stress Stress
Propranolol
Placebo
Metoprolol
191 f 36
193 f 36
199 f 42
91 f 16 71 f lo*** 75 f 12.
Placebo 196 f 47
8 7 f 12 92 f 14 101 f 21..
88 f 14 67 f 1V** 71 f 9 *
9 0 f I5 8 9 2 17 99 f 16..
166 f 14 162 f 21 188 f 30.'.
170 f 20 164 f 16 194 & 24"'
160 f 18 152 f 24 171 t 30***
160 f 20 160 f 20 187 ? 24***
117 f 9 114f 15 128 f 15***
121 f 1 1 116 f 14 122 f 121
106 f 14 105 f 14 112 f IS**
113 f 15 110 f 14 117 f 15'.
Propranolol and metoprolol in stress Shapiro, 1968). We have previously shown modification of blood pressure rise by propranolol with a form of chronic industrial stress (Dunn, Melville, Jones, Lorimer & Lawrie, 1978). That study differed from the one reported here not only in that a different type of stress was used but also in that blood pressure was normalized with propranolol before re-studying. Studies are currently in progress to look at the effect of long-term blockade on blood pressure response and performance during this acute stress. The performance scores remained similar within each patient irrespective of the therapy given and as noted this was over a wide range of driving skills. Acknowledgment The authors gratefully acknowledge the support of ICI Pharmaceuticals Ltd with the apparatus used in this study.
415s
References DUNN,F.G.,MELVILLE,D.I., JONES,J.V., LORIMER, A.R. & LAWRIE,T.D.V. (1978) Standardised stress and hypertension: Comparison of effect of propranolol and methyldopa. British Journal of Clinical Pharmacology, S, 223-226. GLAISTER,N.H., HARRISON,M.A. & ALLNUIT, M.F. (1973) Experimental cardiovascular stress and the influence of oxprenolol. In: New Perspectives in Beta blockade. An International Symposium, Aarhus. Denmark, pp. 241-267. Ed. Burley, D.M.,Fryer, J.H., Rondel, R.K. & Taylor, S.H. CIBA, Horsharn, U.K. JAMES,I.M., PEARSON, R.M., GIUFFITH, D.N.W. & NEWBURY, P. (1977) Effect of oxprenolol on stage-fright in musicians. Lancet. ii, 952-954. NICOTERO, J.A., BEAMER,V., M m s o s , S.E. & SHAPIRO,J.A. (1968) Effects of propranolol on the pressor response to noxioils stimuli in hypertensive patients. American Journal of Cardiology, 22,657-666. TAGGART,P. & CARRVTHERS,M. (1972) Suppression by oxprenolol of adrenergic response to stress. Lancet, ii, 256258.
TAGGART,P., CARRUTHERS,M. & SOMERVILLE, W. (1973) Electrocardiogram, plasma catecholamines and lipids and their modification by oxprenolol when speaking before an audience. Lancet, ii, 341-346.
