105
Journal of Physiology (1990), 430, pp. 105-117 With 4 figures Printed in Great Britain
CARDIOVASCULAR RESPONSES TO STATIC EXERCISE IN MAN: CENTRAL AND REFLEX CONTRIBUTIONS BY S. C. GANDEVIA* AND S. F. HOBBS From the School of Physiology and Pharmacology and School of Medicine, University of New South Wales, Kensington, Sydney 2033, Australia (Received 14 March 1990) SUMMARY
1. To assess the contributions of muscle chemoreflexes and central signals of motor command to cardiovascular to static exercise, blood pressure and heart rate were measured during three separate conditions: (i) isometric handgrip contractions, (ii) entrapment of metabolites produced by these contractions within the contracting muscles (chemoreflex effect), and (iii) attempted contractions of acutely paralysed muscles at three levels of effort (command effect). 2. The chemoreflex was assessed during circulatory occlusion applied as the contraction ceased. Paralysis was produced by local infusion of lignocaine distal to a sphygmomanometer cuff inflated above systolic pressure. 3. Blood pressure and heart rate increased progressively during isometric contraction of 33 and 50% maximal voluntary strength (for 120 and 75 s respectively). Muscle chemoreflexes during occlusion also increased blood pressure in proportion to the duration of contraction but did not increase heart rate. During attempted contraction of paralysed muscles at three measured levels of motor command, blood pressure and heart rate increased, but only heart rate was graded with the level of command. 4. The pattern of cardiovascular response for the muscle chemoreflex (as indicated by the ratio of the changes in heart rate and blood pressure) differed from that for isometric contractions and for motor commands in isolation. The pattern for contractions and for moderate but not high intensities of motor command was similar. 5. These data suggest that cardiovascular responses to moderate intensities of static contraction can be produced primarily by motor command, but that both motor command and muscle chemoreflexes contribute to cardiovascular responses at higher intensities of static exercise. When studied in isolation, central motor command and muscle chemoreflexes do not produce the same pattern of circulatory responses. * Address for correspondence: Department of Clinical Neurophysiology, Institute of Neurological Sciences, The Prince Henry & Prince of Wales Hospitals, PO Box 233, Matraville, Sydney 2036, Australia.
MS 8350
106
S. C. GANDEVIA AND S. F. HOBBS INTRODUCTION
Fatiguing static contractions are accompanied by progressive increases in heart rate and blood pressure (Lind, Taylor, Humphreys, Kennelly & Donald, 1964; Schibye, Mitchell, Payne & Saltin, 1981; Saltin, Sjogaard, Gaffney & Rowell, 1981). These increases may be elicited by a rise in the activity of chemosensitive afferents within working muscle (e.g. Alam & Smirk, 1937, 1938; McCloskey & Mitchell, 1972; Freund, Rowell, Murphy, Hobbs & Butler, 1979; Kaufman, Longhurst, Rybicki, Wallach & Mitchell, 1983; Mense & Stahnke, 1983; Mitchell, Reeves, Rogers & Secher, 1989a; Mitchell, Reeves, Rogers, Secher & Victor, 1989b) or by centrally generated neural activity related to the motor command used to produce contraction (e.g. Krogh & Lindhard, 1913; Freyschuss, 1970; Goodwin, McCloskey & Mitchell, 1972; Hobbs, 1982; Hobbs & Gandevia, 1985; Leonard, Mitchell, Mizuno, Rube, Saltin & Secher, 1985). In human subjects, a muscle chemoreflex can be studied without the presence of command-related signals by trapping the metabolites produced during contraction and maintaining any local hypoxia with a cuff inflated above arterial pressure. The associated cardiovascular response is measured after the cuff is inflated and the contraction has ended. This chemoreflex increases blood pressure above resting values but not as much as in a static contraction (Alam & Smirk, 1937; Lind et al. 1964; Staunton, Taylor & Donald, 1964). Furthermore, this reflex increases heart rate above resting values in some subjects and decreases it below resting levels in others, but even the increases in heart rate are not as large as those during contraction (e.g. Alam & Smirk, 1938; Lind et al. 1964; Staunton et al. 1964). Presumably, neural signals other than muscle chemoreceptor activity must contribute to the increases in blood pressure and particularly heart rate during normal contractions. Centrally generated motor commands can increase heart rate and blood pressure. The cardiovascular responses due to motor command signals can be measured during attempts to contract muscles paralysed acutely (and completely) by a neuromuscular blocking agent or local anaesthesia. Both Freyschuss (1970) and Hobbs & Gandevia (1985) found that heart rate and blood pressure increased significantly during attempts to contract completely paralysed muscles at levels of effort (or command) associated with 70 and 50% of maximal voluntary contractile force, respectively. However, it is not known how the heart rate and pressor responses to central motor commands and muscle chemoreflexes compare in the same subject. Cardiovascular responses to static contraction of partially paralysed muscles increase when central motor commands are increased to sustain a particular force (Leonard et al. 1985; Mitchell et al. 1989b). Furthermore, the relationship between any command-induced increase in heart rate or blood pressure and the exact level of command used in the attempted contractions is unknown. This information is necessary to understand how these two signals may interact to produce the normal cardiovascular response to static exercise. The present studies were designed to measure the changes of heart rate and blood pressure to graded levels and durations of static handgrip contraction, and to measure, in isolation, both muscle chemoreflexes produced by these contractions,
CARDIOVASCULAR RESPONSES TO STATIC EXERCISE 107 and graded responses to command-related signals in the same subjects. These data are used to estimate the potential contribution of command-related signals and muscle chemoreflexes to the cardiovascular response to static contractions. A preliminary account of some findings has been published (Hobbs & Gandevia, 1987). METHODS
Six subjects (five male, one female; 21-32 years) were studied. Each subject participated in two sets of experiments. In one, the subject made static handgrip contractions for specific durations and, just before the end of each contraction, the blood supply to the contracting arm was occluded for 3 min. In the other, the muscles of the hand and forearm were acutely paralysed and anaesthetized, and the subject attempted to contract these muscles at three levels of effort. Informed consent was obtained in writing and the procedures were approved by the local institutional ethics committee. Apart from one author who was a subject in these experiments, the remaining subjects were unaware of the specific purpose of the study. In all experiments the subjects sat comfortably with both forearms and hands resting on a table. They were continuously observed to ensure that they made minimal movements of the limbs not involved in the handgrip contraction and did not hold their breath during any of the experimental procedures. The latter point was confirmed in some studies using an impedance pneumograph. In the first set of experiments each subject produced handgrip contractions with an isometric dynamometer for 45 and 75 s at 50 % of maximal voluntary contraction (MVC) on one day and 45, 75 and 120 s at 33 % MVC on another day at least 1 week later. Maximal voluntary contraction on each side was taken as the largest of the peak forces produced by three brief maximal handgrip contractions. The dynamometer was modified to produce an electrical signal proportional to force and this was displayed on an oscilloscope in front of the subjects to help them maintain the designated force. Each combination of % MVC and duration of contraction was produced 2-4 times, with a total of six to twelve contractions on a given day. Contractions alternated between the left and right sides, and the order in which the different durations were performed was randomized. Subjects rested at least 10 min between contractions and at least 25 min between contractions with the same muscle group. Five seconds before the end of each contraction, a wide sphygmomanometer cuff wrapped around the upper part of the arm was rapidly inflated to 250 mmHg. Once the cuff was inflated contraction ceased. After 3-4 min the cuff was deflated. The cuff was carefully positioned prior to the experiment so that inflation of the cuff to high pressures did not cause pain. Systolic and diastolic blood pressure were measured by auscultation using an electronic sphygmomanometer, the accuracy of which had been previously established (Hobbs & Gandevia, 1985) and was checked with a normal sphygmomanometer on the other arm in each subject. Heart rate and blood pressure were measured three or more times during rest immediately before the contraction began, during the last 15-20 s of contraction, the three times after the first 1-5 min of occlusion (Fig. 1, top panel). Measurements were not recorded before 1-5 min of occlusion to allow the response to occlusion to stabilize. In the second series of experiments the muscles of the hand and forearm on one side were paralysed and anaesthetized by the combined effects of anoxia and local anaesthetic. The arm initially wrapped in a compression bandage and then a wide sphygmomanometer cuff around the upper arm was inflated to 200-250 mmHg. The cuff remained inflated at this level until the end of the experiment, and care was again taken to ensure that the inflated cuff caused as little discomfort as possible. Lignocaine (3 mg/kg up to a maximal dose of 200 mg) in 40 ml of saline was injected retrogradely into the forearm and hand through a catheter in a superficial vein. The arm and hand were massaged to disperse the local anaesthetic. Paralysis was considered complete when the subject could no longer contract intrinsic hands muscles and the flexors and extensors of the fingers and wrist. Sensory blockade was considered complete when there was clinically complete anaesthesia below the elbow as judged by loss of pain, temperature and tactile sensation. Complete paralysis and sensory blockade occurred 25-45 min after the cuff was inflated. Subjects attempted to perform handgrip contractions with the paralysed, anaesthetized arm. Subjects made one or two attempted contractions at levels of effort associated with 33, 50 and 75 %
S. C. GANDEVIA AND S. F. HOBBS
108
MVC. The order in which different levels of effort were attempted was varied. No level of effort was repeated until each level had been performed once. Before each attempted contraction the effort required was indicated to the subject by having him produce a brief 'control' contraction for less than 5 s with the normal arm at the nominated % MVC (Fig. 1, lower panel; see Results). Visual
+
+ Rest
+
ontraction
Attempt
Rest C
,4 +_
+
+
+ l
Occlusion
.X B
60s-
Fig. 1. Protocol used to measure the cardiovascular responses to contraction and to occlusion at the end of contraction (top panel) and to attempted contraction of paralysed muscles (bottom panel). The arrows indicate when both heart rate and blood pressure were measured. In the top panel the dashed line and the arrows indicate that contractions lasted for 45, 75 or 120 s and that heart rate and blood pressure were measured at the end of the contraction. In the bottom panel, 'C' shows when the brief 'control' contraction was made with the normal arm (and visual feedback) to indicate to the subject the level of effort to be used during the following attempted contraction, and 'B' indicates when the 'blind' contraction was made with the normal arm (without visual feedback) to indicate the level of effort actually used during the attempt.
feedback was provided for this contraction. Once heart rate and blood pressure had returned to the control values measured, prior to the 'control' contraction the attempted contraction began. Each attempted contraction lasted 1-15 min and blood pressure and heart rate were measured twice during each attempted contraction. Throughout each attempted contraction the subject was continuously encouraged to maintain the desired level of effort. To asses the actual level of effort used during an attempted contraction, the subject used the same effort that accompanied the attempted contraction to produce a 'blind' contraction with the normal arm (Fig. 1). The % MVC produced during this 'blind' contraction indicated the level of effort used during the previous attempted contraction. During 'blind' contractions the subject received no visual or auditory feedback about the force of contraction. Control experiments in three subjects showed that the % MVC elicited by a given level of effort was not significantly different for the two arms. Similar results have been observed in other studies (McCloskey, Ebeling & Goodwin, 1974). Thus the % MVC produced during 'blind' contractions was taken as an indicator of effort during the attempted contractions. In both sets of experiments mean arterial pressure (calculated as the diastolic pressure plus onethird of the pulse pressure) was used as the indicator of blood pressure. Statistical significance (P < 0 05) was assessed by Student's paired t tests (two-tailed), analysis of variance and Newman-Keuls tests. Averages are reported as mean + S.E.M. RESULTS
Control responses In the six subjects, the maximal voluntary force (MVC) with the handgrip dynamometer was 44 + 5 and 42+5 kg on the right and left sides, respectively. Resting heart rate and blood pressure averaged 65 + 2 beats/min and 85 + 3 mmHg during the studies involving the responses to contraction and occlusion. During anaesthetic paralysis of the lower arm, resting blood pressure steadily increased (over
109 CARDIOVASCULAR RESPONSES TO STATIC EXERCISE 1-2 h) so that at the time of attempted contractions heart rate and blood pressure averaged 71 + 6 beats/min and 98 + 5 mmHg. Blood pressure but not heart rate was significantly higher (P < 0-05) before attempted contractions compared to real contractions. However, in subjects who made two attempted contractions at the B
A
Occ
50- Con E E
40
MVC
U
EQ50 %
*
0
Con
Occ
MVC
50 % U * 0 0 33%
33%
25-
-5 7 ~ ~ ~~~~~0 ~~~~~~~~~~~0 C~~~~~~~~~ C) ~ onrcto duain()Cnrcindrtots
0
45
75
120
2
c
120 0 4575 Contraction duration (s)
0
75 ~~~~45 Contraction duration (s)
120
Fig. 2. The relationships between the increment (mean+ S.E.M.) in mean arterial pressure (A) and heart rate (B) to handgrip contractions (Con) held for 45, 75 or 120 s at 33 and 50 % of maximal voluntary contraction (MVC) and to occlusion (Occ) at the end of these contractions. The pressor and heart rate responses to occlusion were significantly smaller (P < 0 01 and P < 0 05, respectively) than those to the corresponding contractions. The pressor responses to contraction and to occlusion increased in parallel as the duration of contraction increased. Heart rate increased with increasing durations of contraction. For the group of subjects heart rate did not increase with the duration of contraction. See also Fig. 4.
same % MVC but at different resting blood pressures, the responses measured at the higher pressures were not different from those measured at the lower ones. Thus, the change in basal blood pressure was not considered to affect systematically the response to attempted contractions.
Responses to real contractions and circulatory occlusion At a particular contraction intensity, blood pressure increased progressively with the duration of handgrip contraction in all subjects. The average responses for the group of subjects are shown in Fig. 2. During circulatory occlusion blood pressure remained above resting values, but always below that during contractions (Fig. 2A). This pressor response during occlusion was directly related to the duration of contraction in all subjects. Furthermore, the pressor responses to contraction and to occlusion increased in parallel. The difference between the pressor response to contraction and to occlusion was highly significant (P < 0-01), and this difference averaged 7-9 + 1-9 and 11-9 + 1-3 mmHg at 33 and 50 % MVC, respectively. During handgrip contractions at 33 and 50 % MVC, heart rate increased consistently in five of six subjects. In one subject heart rate did not change or fell at 45 and 75 s of contraction at 33 % MVC and at 45 s of 50 % MVC. The mean changes
S. C. GANDEVIA AND S.
110
F.
HOBBS
in heart rate for the group of subjects are shown in Fig. 2B. The rise in heart rate was directly related to the duration of contraction. The increment in heart rate was also directly related to the rise in blood pressure. For example, contractions at 50 % MVC for 45 s and at 33 % MVC for 120 s produced similar increments in blood pressure and A
12
B
2
EE
16
-
~~~~~~~~E co
co
C
0)0
MV (%)
MVC ()
Fig. 3. The relationship between the fraction of the maximal voluntary handgrip contraction (% MVC) at which subjects indicated that attempted contractions were made and the changes in mean arterial pressure (A) and heart rate (B). The blood pressure and heart rate responses at all three levels of % MVC were significantly greater than zero (P < 0-01). The rise in heart rate was positively correlated (P < 005) to the % MVC attempted, but the pressor responses were not.
heart rate. This also indicates that the force of contraction did not increase heart rate independent of blood pressure. Compared to resting levels, the chemoreflexes increased heart rate in two subjects, did not changed heart rate in two subjects, and decreased it in the remaining two subjects. The average response for the six subjects was no change in heart rate from resting values regardless of the duration or the force of contraction (Fig. 2B). The average difference between the heart rat response to contraction and to occlusion was significant (P < 0 01) for every combination of force and duration.
Responses to attempted contractions of paralysed muwcles For attempted contraction of paralysed hand and forearm muscles, the subjects were instructed to use the levels of effort associated with the brief trial contraction at 33, 50 or 75 % MVC. After the attempted contractions 'blind' contractions were made with the normal arm, and in these the subjects produced forces equivalent to 29 + 2, 46 + 1, and 73 +1 % MVC. Thus subjects were able to sustain and grade their effort during complete paralysis, a finding supported by direct recording from motor axons (Gandevia, Macefield, Burke & McKenzie, 1990). Blood pressure increased in all subjects in response to attempted contractions. The first and second measurements of blood pressure during the attempted contractions were not different as
III CARDIOVASCULAR RESPONSES TO STATIC EXERCISE the pressor response was sustained throughout the attempted contraction. The rises in pressure were significant (P < 001) at each level of effort, but a dependence on the intensity of effort could not be demonstrated (Fig. 3A). Attempts to contract paralysed muscles increased heart rate throughout the attempted contraction in each subject at each intensity of effort. These increments
3571A ~2
Journal of Physiology (1990), 430, pp. 105-117 With 4 figures Printed in Great Britain
CARDIOVASCULAR RESPONSES TO STATIC EXERCISE IN MAN: CENTRAL AND REFLEX CONTRIBUTIONS BY S. C. GANDEVIA* AND S. F. HOBBS From the School of Physiology and Pharmacology and School of Medicine, University of New South Wales, Kensington, Sydney 2033, Australia (Received 14 March 1990) SUMMARY
1. To assess the contributions of muscle chemoreflexes and central signals of motor command to cardiovascular to static exercise, blood pressure and heart rate were measured during three separate conditions: (i) isometric handgrip contractions, (ii) entrapment of metabolites produced by these contractions within the contracting muscles (chemoreflex effect), and (iii) attempted contractions of acutely paralysed muscles at three levels of effort (command effect). 2. The chemoreflex was assessed during circulatory occlusion applied as the contraction ceased. Paralysis was produced by local infusion of lignocaine distal to a sphygmomanometer cuff inflated above systolic pressure. 3. Blood pressure and heart rate increased progressively during isometric contraction of 33 and 50% maximal voluntary strength (for 120 and 75 s respectively). Muscle chemoreflexes during occlusion also increased blood pressure in proportion to the duration of contraction but did not increase heart rate. During attempted contraction of paralysed muscles at three measured levels of motor command, blood pressure and heart rate increased, but only heart rate was graded with the level of command. 4. The pattern of cardiovascular response for the muscle chemoreflex (as indicated by the ratio of the changes in heart rate and blood pressure) differed from that for isometric contractions and for motor commands in isolation. The pattern for contractions and for moderate but not high intensities of motor command was similar. 5. These data suggest that cardiovascular responses to moderate intensities of static contraction can be produced primarily by motor command, but that both motor command and muscle chemoreflexes contribute to cardiovascular responses at higher intensities of static exercise. When studied in isolation, central motor command and muscle chemoreflexes do not produce the same pattern of circulatory responses. * Address for correspondence: Department of Clinical Neurophysiology, Institute of Neurological Sciences, The Prince Henry & Prince of Wales Hospitals, PO Box 233, Matraville, Sydney 2036, Australia.
MS 8350
106
S. C. GANDEVIA AND S. F. HOBBS INTRODUCTION
Fatiguing static contractions are accompanied by progressive increases in heart rate and blood pressure (Lind, Taylor, Humphreys, Kennelly & Donald, 1964; Schibye, Mitchell, Payne & Saltin, 1981; Saltin, Sjogaard, Gaffney & Rowell, 1981). These increases may be elicited by a rise in the activity of chemosensitive afferents within working muscle (e.g. Alam & Smirk, 1937, 1938; McCloskey & Mitchell, 1972; Freund, Rowell, Murphy, Hobbs & Butler, 1979; Kaufman, Longhurst, Rybicki, Wallach & Mitchell, 1983; Mense & Stahnke, 1983; Mitchell, Reeves, Rogers & Secher, 1989a; Mitchell, Reeves, Rogers, Secher & Victor, 1989b) or by centrally generated neural activity related to the motor command used to produce contraction (e.g. Krogh & Lindhard, 1913; Freyschuss, 1970; Goodwin, McCloskey & Mitchell, 1972; Hobbs, 1982; Hobbs & Gandevia, 1985; Leonard, Mitchell, Mizuno, Rube, Saltin & Secher, 1985). In human subjects, a muscle chemoreflex can be studied without the presence of command-related signals by trapping the metabolites produced during contraction and maintaining any local hypoxia with a cuff inflated above arterial pressure. The associated cardiovascular response is measured after the cuff is inflated and the contraction has ended. This chemoreflex increases blood pressure above resting values but not as much as in a static contraction (Alam & Smirk, 1937; Lind et al. 1964; Staunton, Taylor & Donald, 1964). Furthermore, this reflex increases heart rate above resting values in some subjects and decreases it below resting levels in others, but even the increases in heart rate are not as large as those during contraction (e.g. Alam & Smirk, 1938; Lind et al. 1964; Staunton et al. 1964). Presumably, neural signals other than muscle chemoreceptor activity must contribute to the increases in blood pressure and particularly heart rate during normal contractions. Centrally generated motor commands can increase heart rate and blood pressure. The cardiovascular responses due to motor command signals can be measured during attempts to contract muscles paralysed acutely (and completely) by a neuromuscular blocking agent or local anaesthesia. Both Freyschuss (1970) and Hobbs & Gandevia (1985) found that heart rate and blood pressure increased significantly during attempts to contract completely paralysed muscles at levels of effort (or command) associated with 70 and 50% of maximal voluntary contractile force, respectively. However, it is not known how the heart rate and pressor responses to central motor commands and muscle chemoreflexes compare in the same subject. Cardiovascular responses to static contraction of partially paralysed muscles increase when central motor commands are increased to sustain a particular force (Leonard et al. 1985; Mitchell et al. 1989b). Furthermore, the relationship between any command-induced increase in heart rate or blood pressure and the exact level of command used in the attempted contractions is unknown. This information is necessary to understand how these two signals may interact to produce the normal cardiovascular response to static exercise. The present studies were designed to measure the changes of heart rate and blood pressure to graded levels and durations of static handgrip contraction, and to measure, in isolation, both muscle chemoreflexes produced by these contractions,
CARDIOVASCULAR RESPONSES TO STATIC EXERCISE 107 and graded responses to command-related signals in the same subjects. These data are used to estimate the potential contribution of command-related signals and muscle chemoreflexes to the cardiovascular response to static contractions. A preliminary account of some findings has been published (Hobbs & Gandevia, 1987). METHODS
Six subjects (five male, one female; 21-32 years) were studied. Each subject participated in two sets of experiments. In one, the subject made static handgrip contractions for specific durations and, just before the end of each contraction, the blood supply to the contracting arm was occluded for 3 min. In the other, the muscles of the hand and forearm were acutely paralysed and anaesthetized, and the subject attempted to contract these muscles at three levels of effort. Informed consent was obtained in writing and the procedures were approved by the local institutional ethics committee. Apart from one author who was a subject in these experiments, the remaining subjects were unaware of the specific purpose of the study. In all experiments the subjects sat comfortably with both forearms and hands resting on a table. They were continuously observed to ensure that they made minimal movements of the limbs not involved in the handgrip contraction and did not hold their breath during any of the experimental procedures. The latter point was confirmed in some studies using an impedance pneumograph. In the first set of experiments each subject produced handgrip contractions with an isometric dynamometer for 45 and 75 s at 50 % of maximal voluntary contraction (MVC) on one day and 45, 75 and 120 s at 33 % MVC on another day at least 1 week later. Maximal voluntary contraction on each side was taken as the largest of the peak forces produced by three brief maximal handgrip contractions. The dynamometer was modified to produce an electrical signal proportional to force and this was displayed on an oscilloscope in front of the subjects to help them maintain the designated force. Each combination of % MVC and duration of contraction was produced 2-4 times, with a total of six to twelve contractions on a given day. Contractions alternated between the left and right sides, and the order in which the different durations were performed was randomized. Subjects rested at least 10 min between contractions and at least 25 min between contractions with the same muscle group. Five seconds before the end of each contraction, a wide sphygmomanometer cuff wrapped around the upper part of the arm was rapidly inflated to 250 mmHg. Once the cuff was inflated contraction ceased. After 3-4 min the cuff was deflated. The cuff was carefully positioned prior to the experiment so that inflation of the cuff to high pressures did not cause pain. Systolic and diastolic blood pressure were measured by auscultation using an electronic sphygmomanometer, the accuracy of which had been previously established (Hobbs & Gandevia, 1985) and was checked with a normal sphygmomanometer on the other arm in each subject. Heart rate and blood pressure were measured three or more times during rest immediately before the contraction began, during the last 15-20 s of contraction, the three times after the first 1-5 min of occlusion (Fig. 1, top panel). Measurements were not recorded before 1-5 min of occlusion to allow the response to occlusion to stabilize. In the second series of experiments the muscles of the hand and forearm on one side were paralysed and anaesthetized by the combined effects of anoxia and local anaesthetic. The arm initially wrapped in a compression bandage and then a wide sphygmomanometer cuff around the upper arm was inflated to 200-250 mmHg. The cuff remained inflated at this level until the end of the experiment, and care was again taken to ensure that the inflated cuff caused as little discomfort as possible. Lignocaine (3 mg/kg up to a maximal dose of 200 mg) in 40 ml of saline was injected retrogradely into the forearm and hand through a catheter in a superficial vein. The arm and hand were massaged to disperse the local anaesthetic. Paralysis was considered complete when the subject could no longer contract intrinsic hands muscles and the flexors and extensors of the fingers and wrist. Sensory blockade was considered complete when there was clinically complete anaesthesia below the elbow as judged by loss of pain, temperature and tactile sensation. Complete paralysis and sensory blockade occurred 25-45 min after the cuff was inflated. Subjects attempted to perform handgrip contractions with the paralysed, anaesthetized arm. Subjects made one or two attempted contractions at levels of effort associated with 33, 50 and 75 %
S. C. GANDEVIA AND S. F. HOBBS
108
MVC. The order in which different levels of effort were attempted was varied. No level of effort was repeated until each level had been performed once. Before each attempted contraction the effort required was indicated to the subject by having him produce a brief 'control' contraction for less than 5 s with the normal arm at the nominated % MVC (Fig. 1, lower panel; see Results). Visual
+
+ Rest
+
ontraction
Attempt
Rest C
,4 +_
+
+
+ l
Occlusion
.X B
60s-
Fig. 1. Protocol used to measure the cardiovascular responses to contraction and to occlusion at the end of contraction (top panel) and to attempted contraction of paralysed muscles (bottom panel). The arrows indicate when both heart rate and blood pressure were measured. In the top panel the dashed line and the arrows indicate that contractions lasted for 45, 75 or 120 s and that heart rate and blood pressure were measured at the end of the contraction. In the bottom panel, 'C' shows when the brief 'control' contraction was made with the normal arm (and visual feedback) to indicate to the subject the level of effort to be used during the following attempted contraction, and 'B' indicates when the 'blind' contraction was made with the normal arm (without visual feedback) to indicate the level of effort actually used during the attempt.
feedback was provided for this contraction. Once heart rate and blood pressure had returned to the control values measured, prior to the 'control' contraction the attempted contraction began. Each attempted contraction lasted 1-15 min and blood pressure and heart rate were measured twice during each attempted contraction. Throughout each attempted contraction the subject was continuously encouraged to maintain the desired level of effort. To asses the actual level of effort used during an attempted contraction, the subject used the same effort that accompanied the attempted contraction to produce a 'blind' contraction with the normal arm (Fig. 1). The % MVC produced during this 'blind' contraction indicated the level of effort used during the previous attempted contraction. During 'blind' contractions the subject received no visual or auditory feedback about the force of contraction. Control experiments in three subjects showed that the % MVC elicited by a given level of effort was not significantly different for the two arms. Similar results have been observed in other studies (McCloskey, Ebeling & Goodwin, 1974). Thus the % MVC produced during 'blind' contractions was taken as an indicator of effort during the attempted contractions. In both sets of experiments mean arterial pressure (calculated as the diastolic pressure plus onethird of the pulse pressure) was used as the indicator of blood pressure. Statistical significance (P < 0 05) was assessed by Student's paired t tests (two-tailed), analysis of variance and Newman-Keuls tests. Averages are reported as mean + S.E.M. RESULTS
Control responses In the six subjects, the maximal voluntary force (MVC) with the handgrip dynamometer was 44 + 5 and 42+5 kg on the right and left sides, respectively. Resting heart rate and blood pressure averaged 65 + 2 beats/min and 85 + 3 mmHg during the studies involving the responses to contraction and occlusion. During anaesthetic paralysis of the lower arm, resting blood pressure steadily increased (over
109 CARDIOVASCULAR RESPONSES TO STATIC EXERCISE 1-2 h) so that at the time of attempted contractions heart rate and blood pressure averaged 71 + 6 beats/min and 98 + 5 mmHg. Blood pressure but not heart rate was significantly higher (P < 0-05) before attempted contractions compared to real contractions. However, in subjects who made two attempted contractions at the B
A
Occ
50- Con E E
40
MVC
U
EQ50 %
*
0
Con
Occ
MVC
50 % U * 0 0 33%
33%
25-
-5 7 ~ ~ ~~~~~0 ~~~~~~~~~~~0 C~~~~~~~~~ C) ~ onrcto duain()Cnrcindrtots
0
45
75
120
2
c
120 0 4575 Contraction duration (s)
0
75 ~~~~45 Contraction duration (s)
120
Fig. 2. The relationships between the increment (mean+ S.E.M.) in mean arterial pressure (A) and heart rate (B) to handgrip contractions (Con) held for 45, 75 or 120 s at 33 and 50 % of maximal voluntary contraction (MVC) and to occlusion (Occ) at the end of these contractions. The pressor and heart rate responses to occlusion were significantly smaller (P < 0 01 and P < 0 05, respectively) than those to the corresponding contractions. The pressor responses to contraction and to occlusion increased in parallel as the duration of contraction increased. Heart rate increased with increasing durations of contraction. For the group of subjects heart rate did not increase with the duration of contraction. See also Fig. 4.
same % MVC but at different resting blood pressures, the responses measured at the higher pressures were not different from those measured at the lower ones. Thus, the change in basal blood pressure was not considered to affect systematically the response to attempted contractions.
Responses to real contractions and circulatory occlusion At a particular contraction intensity, blood pressure increased progressively with the duration of handgrip contraction in all subjects. The average responses for the group of subjects are shown in Fig. 2. During circulatory occlusion blood pressure remained above resting values, but always below that during contractions (Fig. 2A). This pressor response during occlusion was directly related to the duration of contraction in all subjects. Furthermore, the pressor responses to contraction and to occlusion increased in parallel. The difference between the pressor response to contraction and to occlusion was highly significant (P < 0-01), and this difference averaged 7-9 + 1-9 and 11-9 + 1-3 mmHg at 33 and 50 % MVC, respectively. During handgrip contractions at 33 and 50 % MVC, heart rate increased consistently in five of six subjects. In one subject heart rate did not change or fell at 45 and 75 s of contraction at 33 % MVC and at 45 s of 50 % MVC. The mean changes
S. C. GANDEVIA AND S.
110
F.
HOBBS
in heart rate for the group of subjects are shown in Fig. 2B. The rise in heart rate was directly related to the duration of contraction. The increment in heart rate was also directly related to the rise in blood pressure. For example, contractions at 50 % MVC for 45 s and at 33 % MVC for 120 s produced similar increments in blood pressure and A
12
B
2
EE
16
-
~~~~~~~~E co
co
C
0)0
MV (%)
MVC ()
Fig. 3. The relationship between the fraction of the maximal voluntary handgrip contraction (% MVC) at which subjects indicated that attempted contractions were made and the changes in mean arterial pressure (A) and heart rate (B). The blood pressure and heart rate responses at all three levels of % MVC were significantly greater than zero (P < 0-01). The rise in heart rate was positively correlated (P < 005) to the % MVC attempted, but the pressor responses were not.
heart rate. This also indicates that the force of contraction did not increase heart rate independent of blood pressure. Compared to resting levels, the chemoreflexes increased heart rate in two subjects, did not changed heart rate in two subjects, and decreased it in the remaining two subjects. The average response for the six subjects was no change in heart rate from resting values regardless of the duration or the force of contraction (Fig. 2B). The average difference between the heart rat response to contraction and to occlusion was significant (P < 0 01) for every combination of force and duration.
Responses to attempted contractions of paralysed muwcles For attempted contraction of paralysed hand and forearm muscles, the subjects were instructed to use the levels of effort associated with the brief trial contraction at 33, 50 or 75 % MVC. After the attempted contractions 'blind' contractions were made with the normal arm, and in these the subjects produced forces equivalent to 29 + 2, 46 + 1, and 73 +1 % MVC. Thus subjects were able to sustain and grade their effort during complete paralysis, a finding supported by direct recording from motor axons (Gandevia, Macefield, Burke & McKenzie, 1990). Blood pressure increased in all subjects in response to attempted contractions. The first and second measurements of blood pressure during the attempted contractions were not different as
III CARDIOVASCULAR RESPONSES TO STATIC EXERCISE the pressor response was sustained throughout the attempted contraction. The rises in pressure were significant (P < 001) at each level of effort, but a dependence on the intensity of effort could not be demonstrated (Fig. 3A). Attempts to contract paralysed muscles increased heart rate throughout the attempted contraction in each subject at each intensity of effort. These increments
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