Acta Physiol Scand 1988, 133, 233-237

Arterial blood pressure at the onset of dynamic exercise in partially curarized man

N . H. S E C H E R , M. K J E R and H. G A L B O Departments of Anaesthesia and Exercise Physiology Unit, Rigshospitalet, and Department of Medical Physiology B, Panum Institute, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen 0, Denmark.

SECHER, N. H., KJER, M. & GALBO, H., 1988. Arterial blood pressure at the onset of dynamic exercise in partially curarized man. Acta Physiol Scand 133,233-237. Received 16 June 1987, accepted 4 January 1988. ISSN 00014772. Department of Anaesthesia and Exercise Physiology Unit, Rigshospitalet, University of Copenhagen, and Department of Medical Physiology B. Panum Institute, University of Copenhagen, DK-2100 Copenhagen 0, Denmark.

In six young men, heart rate and arterial mean blood pressure responses to the onset of light dynamic exercise 99 W (range 59-138) on a stationary bicycle were followed during partial neuromuscular blockade with tubocurarine. Tubocurarine was used in order to accentuate the central nervous (central command) influence on the cardiovascular variables and reduced hand-grip strength to 42% (36-47) of control. At the onset of exercise heart rate increased immediately and similarly with and without neuromuscular blockade. Mean arterial blood pressure remained constant during the first 6 s of control exercise and then increased. With tubocurarine a decrease of 9 mmHg (3-12) was seen during the first 6 s (P < 0.01) before blood pressure increased. The similar heart rate responses seen with and without neuromuscular blockade indicate that central command has little influence on this variable at the onset of dynamic exercise. The constant blood pressure at the onset of control exercise suggests that the immediate changes in cardiac output and peripheral vascular resistance, respectively, are accurately matched. The decrease in blood pressure at the onset of exercise with tubocurarine suggests that central command stimulates vasodilatating nerves to arterioles in the working muscles.

Key words : arterial blood pressure, dynamic exercise, tubocurarine.

Dynamic exercise is always accompanied by an immediate cardiac acceleration (Krogh & Lind- hard 1913, 1917, Neukirch 1938, Asmussen & Nielsen 1951, Fragaeus & Linnarsson 1976) whereas the blood pressure response may be more variable. Apart from one study measuring proximal aortic pressure (Marx et al. 1967) all studies agree that eventually blood pressure increases during dynamic exercise in man. Neukirch (1938) and Eskildsen et al. (1949) have reported the increase in blood pressure to occur from the onset of exercise while others have seen an increase in blood pressure ‘after a short delay’ (Asmussen & Nielsen 1951) or oscillations in pressure during the first seconds of exercise

Correspondence: N. H. Secher, Department of Anaesthesia, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, 0, Denmark.

before blood pressure increases systematically (Holmgren 1965). Obviously, in particular onset of intense dynamic exercise on mechanically braked ergometers may involve a static com- ponent which could explain an immediate increase in blood pressure (Freyschuss 1970, Iwamoto et al. 1987). Conversely, a delayed pressure response may reflect that the static component is negligible.

Blood pressure is determined by cardiac output and peripheral vascular resistance. I t has been suggested that the vasodilatation in working muscles a t the onset of exercise is caused by nervous factors and that local vascular control becomes dominant only after the first min (Honig 1979). This concept is in accordance with the finding that muscle blood flow during the first min of exercise is as large in partially curarized

233

234 N . H . Secher et al.

red muscles of rat as in red muscles of control rats despite a markedly lower activity in the former as indicated by a smaller decrease in muscle glycogen staining intensity (Armstrong et af 1985). Thus, a t the onset of exercise the central nervous system may influence not only the heart (Krogh & Lindhard 1917, Freyschuss 1970, Secher 1985, Iwamoto et al. 1 9 8 7 ) ~ but also peripheral vascular resistance. In this context it is of interest that Mathur et al. (1986) have demonstrated an increase in forearm muscle blood flow with the anticipation of exercise.

We have followed heart rate and arterial blood pressure at the onset of light dynamic bicycle exercise on an electrically braked ergometer performed under control conditions and, using the same work load, in partially curarized man. This condition presumably allowed the static component involved in the onset of exercise to be minimal and the peripheral (muscle) influence to be held identical in the two experiments while central command had to be higher during curare than in control experiments in order to com- pensate for the reduction in muscle strength.

M E 'T H 0 D S

The experiments were carried out in six overnight fasted male volunteers who were acquainted with experimental protocols from previous studies. Their mean age was 24 years (range 23-27), height 177 cm (165-186), weight 69 kg (60-80), and maximal oxygen uptake 3.59 1 min ' (2.60-4.08). The investigation was part of a larger study approved by the Municipal Ethical Committee of Copenhagen (Galbo et al . 1987, Kjzr et al . 1987). Exercise was carried out on a Krogh bicycle ergometer at about 60 rev min-'. The actual number of revolutions performed was registered and from this and the load on the bicycle the work intensity was calculated. The subjects were placed in a semisupine position behind the ergometer in order to be as little hampered as possible by the effect of tubocurarine on eye and head muscles. The feet were placed in shoes fastened to the pedals in order to keep tight contact.

Heart rate was monitored by a continuous ECG recording and arterial blood pressure by a Bentley transducer positioned at the papillary level and connected to a 1.0 mm internal diameter cannula in the left radial artery. Mean blood pressure was calculated as one-third of the systolic blood pressure plus two-thirds of the diastolic blood pressure. One to three weeks elapsed between the control experiment and the one involving partial neuromuscular blockade. Before start of exercise neuromuscular blockade

was induced with tubocurarine (0.075 mg kg body weight-' (Nordisk Droge) supplemented by doses of 0.3 mg to obtain the appropriate reduction in strength. Each dose was given through a 1.4 mm Venflon catheter in a vein on the left hand and followed by 10 ml of saline. A constant level of curarization was maintained by adjusting drug administration accord- ing to hand-grip strength. In this way hand-grip strength was kept at 42% (range 3G47) of control strength. An Ambu-E resuscitator apparatus, neo- stigmine and atropine were available, but never needed. Tubocurarine has less effect on the diaphragm than on other skeletal muscles (Johansen et al. 1964, Gal & Goldberg 1980, De Troyer et a/. 1980). Values are presented as mean with range and compared using Student's t-test. A significance level of P < 0.05 for two-tailed testing was chosen.

RESULTS

I n the control experiments the work load was 102 W (range 59-138) versus 97 W (68-114) with tubocurarine (not significant). At the onset of both control exercise and exercise with neuromuscular blockade an immediate increase in heart rate was seen (Figs I & 2). There was no significant difference between the heart rate responses to exercise with and without neuro- muscular blockade.

At the onset of control exercise an unchanged mean blood pressure was seen during the first 6 s of exercise before a systematic increase appeared (Fig. I ) . I n contrast onset of exercise with tubocurarine involved a decrease of 9 mmHg (3-12) (P < 0.01) during the first 6 s followed by an increase similar to the one seen during control exercise (Fig. 2 ) . T h e decrease in mean arterial blood pressure at the onset of exercise with tubocurarine was due to a decrease in diastolic pressure of 12 mmHg (3-18) (P < 0.005) while the systolic pressure remained constant (Fig. 2) .

DISCUSSION

T h e immediate increase in heart rate at the onset of dynamic exercise confirms the findings of Krogh & Lindhard (1913, 1917), Neukirch (1938), and Asmussen & Nielsen (1951). T h e increase in heart rate was similar with and without neuromuscular blockade in accordance with the conclusion that central command has but little influence on this variable during dynamic exercise (Ochwadt et al. 1959, Asmus-

Blood pressure at onset of dynamic exercise 235

200

- ul I

150 -

I I I I

0 30 60 Time (s)

- -

- .

Fig. I. Heart rate and arterial (systolic, mean and diastolic) blood pressure followed at rest and during the first minute of dynamic exercise. Values are means and S.E. of mean, n = 6. In comparison with rest: * P < 0.05; ** P < 0.01.

sen et al. 1965, Bonde-Petersen et al. 1975, Galbo et al. 1987). However, in acceleration of the very first heart beat at the onset of dynamic exercise central command may play a role. Using electrical stimulation of the muscles Krogh & Lindhard (1917) found a delay in the heart-rate response of approximately one beat as compared with voluntary dynamic exercise.

In previous studies on humans no effect of tubocurarine in a dose of approximately 0.1 mg kg-' has been found on blood pressure at rest or during exercise (Asmussen et al. 1965, Galbo et al. 1987). Correspondingly, using a similar dose in the present study the drug did not significantly affect blood pressure. In animal studies larger doses of tubocurarine have been

150r I

c

I $ 1 1 , I ,

30 60 50L

I I

I -------f

; 9 I / I

1::

3 m m I-+, /I 2: 100 - 0

m 1 -?-!? /! I * I I I I I I

0 30 60 Time (s )

Fig. 2. Heart rate and arterial blood pressure followed at rest and during the 1st min of dynamic exercise with partial neuromuscular blockade by tubocurarine. See Fig. I for signatures.

' I* I *

I I I I

30 60 t I 0

Time (s )

Fig. 2. Heart rate and arterial blood pressure followed at rest and during the 1st min of dynamic exercise with partial neuromuscular blockade by tubocurarine. See Fig. I for signatures.

shown to induce a blockade of sympathetic nerves. (Hughes & Chapple, 1976). However, direct recordings of sympathetic nervous activity in human experiments involving the cold pres- sure test and the Valsalva manoeuvre have shown that the dose of tubocurarine we used (0.075 mg kg-') does not affect sympathetic nervous activity (Pryor et al. 1987). In accordance with this neither at rest nor during exercise are plasma catecholamine levels lower during tubo- curarine administration than in control experi- ments (Galbo et af. 1987, Kjier et al. 1987).

The constant blood pressure seen during the first seconds of control exercise indicates that peripheral vasodilatation is accurately matched by a rapidly increasing cardiac output (Adams et al. 1987). It could be speculated that the increase in

236 N . H. Secher et al.

blood pressure becomes manifest with a delay corresponding to the activation of sympathetic nervous activity from muscle metaboreceptors (Mark et ai. 1986). In addition, some time may be necessary to increase the venous return to the heart as stroke volume decreases temporarily a t the onset of exercise (Adams et al. 1987). Concomitant recordings of blood pressure, stroke volume, heart rate and venous return from the working legs are needed to clarify this point. With partial neuromuscular blockade the increased central command through e.g., the periventricular region of hypothalamus (AV3V) which may cause release of adrenalin in muscles (Berecek & Brody 1982) and in turn dilatation of arterioles (Proctor & Bealer 1986) could give rise to a decrease in vascular resistance and thereby to an initial decrease in arterial blood pressure. Later, blood pressure increases similarly whether tubocurarine is administered or not (Ochwadt et al. 1959, Asmussen et al. 1965, Galbo et al. 1987) as local metabolic blood flow regulation gradually takes over and the importance of neurogenic vascular control diminishes. Our data are compatible with the hypothesis that at onset of dynamic exercise in man, central command stimulates vasodilatating nerves to arterioles in the working muscles.

This study was supported by the Danish Medical Research Council ( I 2-5903).

REFERENCES ADAMS, L., Guz, A,, INNES, J.A. & MURPHY, K.

1987. The early circulatory and ventilatory responses to voluntary and electrically induced exercise in man. 3 Physiol (Lond) 383, 19-30,

ARMSTRONG, R.B., VANDENAKKER, C.B. & LAUGHLIN, M.H. 1985. Muscle blood flow patterns during exercise in partially curarized rats. 3 Appl Physiol (Lond) 58, 698-701.

NIELSEN, M. 1965. On the nervous factors con- trolling respiration and circulation during exercise. Acta Physiol Scand 63, 343-350.

ASMUSSEN, E. & NIELSEN, M. 19 j I . The arterial blood pressure on transition from rest to work. Acta Physiol Scand 25 (Suppl. 89), 5-7.

BERECEK, K.H. & BRODY, 1M.J. 1982. Evidence for a neurotransmitter role for epinephrine derived from the adrenal medulla. Am 3 Physiol242, H593-601.

BONDE-PETERSEN, F., GOLLNICK, P.D., HANSEN, T.I., H U L T ~ N , N., KRISTENSEN, J.H., SECHER, N. & SECHER, 0. 1975. Glycogen depletion pattern in

ASMUSSEN, E., JOHANSEN, S.H., JBRGENSEN, M. &

human muscle fiber during work under curarization (d-Tubocurarine). In: H. Howald & J. R. Poo- rtmans (eds) Metabolic Adaptation to Prolonged Physical Exercise pp. 422-430. Birkhauser Verlag, Basel.

DE TROYER, A,, BASTENIER, J. & DELHEZ, L. 1980. Function of respiratory muscles during partial curarization in humans. 3 Appl Physiol 49,

ESKILDSEN, P., GOTSCHE, H. & HANSEN, A. T. 1949. Measuring intra-arterial blood pressure during exercise. Acta Cardiol 4, 199-204.

FAGRAEUS, L. & LINNARSSON, D. 1976. Autonomic origin of heart rate fluctuations at the onset of muscular exercise. 3 Appl Physiol 40, 679-682.

FREYSCHUSS, U. 1970. Cardiovascular adjustment to somatomotor activation. Acta Physiol Scand (Suppl. 342).

GAL, T.J . & GOLDBERG, S.K. 1980. Diaphragmatic function in healthy subjects during partial curari- zation. 3 Appl Physiol 48, 921-926.

GALBO, H., KJIER, M. & SECHER, N.H. 1987. Cardiovascular, ventilatory and catecholamine re- sponses to maximal dynamic exercise in partially curarized man. 3 Physiol (Lond) 389, 5 57-568.

HOLMGREN, A. 1956. Circulatory changes during muscular work in man. Scand 3 Clin Lab Invest 8 ,

HONIG, C.R. 1979. Contributions of nerves and metabolites to exercise vasodilation : a unifying hypothesis. Am 3 Physiol236, H705-719.

HUGHES, R. & CHAPPLE, D.J. 1976. Effect of non- depolarizing neuromuscular blocking agents on peripheral autonomic mechanisms in cats. Br 3 Anaesth 48, 5947.

IWAMOTO, G.A., MITCHELL, J.H., MIZUNO, M. & SECHER, N.H. 1987. Cardiovascular responses at the onset of exercise with partial neuromuscular blockade in cat and man. 3 Physiol (Lond) 384, 39-47.

JOHANSEN, S.H., JBRGENSEN, M. & MOLBECH, s. 1964. Effect of tubocurarine on respiratory and non- respiratory muscle power in man. 3 Appl Physiol ' 9 . 99-94,

KJER, M., SECHER, N.H., BACH, F.W. & GALBO, H. 1987. Role of motor center activity for hormonal changes and substrate mobilization in exercising man. Am 3 Physiol253, R687495.

KROGH, A. & LINDHARD, J. 1913. The regulation of respiration and circulation during the initial stages of muscular work. 3 Physiol (Lond) 47, 112-136.

KROGH, A. & LINDHARD, J. 1917. A comparison between voluntary and electrically induced muscu- lar work in man. JPhysiol (Lond) 51, ISz-zoI.

MARK, A.L., VICTOR, R.G., NERHED, C., SEALS, D.R. & WALLIN, B.G. 1986. Mechanisms of sympathetic nerve responses to static and rhythmic exercise : new insight from direct intraneural recordings in

I 049-1 056.

(SUPPI. 24).

Blood pressure at olzset of dynamic exercise 237

humans. In: N. J. Christensen, 0. Henriksen & N. A, Lassen. (eds), The Sympathoadrenal System pp. 221-229. Munksgaard, Copenhagen.

MARX, H.J., ROWELL, L.B., CONN, R.D., BRUCE, R.A. & KUSUMI, F. 1967. Maintenance of aortic pressure and total peripheral resistance during exercise in heat. 3 Appl Physiol22, 519-525.

MATHUR, V.D., ZBROZYNA, A.W. & WESTWOOD, D. 1986. Forearm muscle blood flow increases in anticipation of exercise. Proc Int U Physiol Sci 16, 171.

NEUKIRCH, F. 1938. Eksperimentelle kredslobsvndersr- gelser [in Danish]. Nyt Nordisk Forlag, Kjebenhavn.

OCHWADT, B., BUCHERL, E., KREUZER, H. & LOE- SCHCKE, H. 1959. Beeinfussung der Atemsteigerung bei Muskelarbeit durch partiellen neuromuskularen Block (Tubocurarine). Pjugers Arch 269, 613-621.

PROCTOR, K.G. & BEALER, S.L. 1986. Skeletal muscle vasodilation during electrical stimulation of the preoptic recess. Am 3 Physiol 19, HZZI-ZZ~.

PRYOR, S.L., MITCHELL, J.H., SECHER, N. & VICTOR, R.G. 1987. Does central command increase sympa- thetic nerve activity in humans! (abstract) Fed Proc

SECHER, N.H. 1985. Heart rate at the onset of static exercise in man with partial neuromuscular block- ade. 3 Physiol (Lond) 368, 481-490.

46, 495.