1 Department of Cardiology, Gentofte Hospital, DK-2900 Hellerup, Denmark ... of Neurophysiology, Gentofte Hospital, University of Copenhagen, Denmark.
Eur J Appl Physiol (1994) 69:147-153
Applied Physiology Journal of
and Occupational Physiology © Sprmger-Verlag 1994
Skeletal muscle vascular responses in human limbs to isometric handgrip Tage N. Jacobsen 1, Jim Hansen 1, Henrik V. Nielsen a, Gordon Wildschiodtz 2, Eli Kassis ~, Bjorn Larsen 1, Ole Amtorp ~ 1 Department of Cardiology, Gentofte Hospital, DK-2900 Hellerup, Denmark
2 Department of Neurophysiology, Gentofte Hospital, University of Copenhagen, Denmark Accepted: 8 April 1994
Abstract. Studies of whole limb blood flow have shown that static handgrip elicits a vasodilatation in the resting forearm and vasoconstriction in the resting leg. We asked if these responses occur in the skeletal muscle vascular bed, and if so, what is the relative contribution of local metabolic versus other mechanisms to these vascular responses. Blood flow recordings were made simultaneously in the skeletal muscle of the resting arm and leg using the Xenon-washout method in ten subjects during 3 min of isometric handgrip at 30% of maximal voluntary contraction. In the arm, skeletal muscle vascular resistance (SMVR) decreased transiently at the onset of exercise followed by a return to baseline levels at the end of exercise. In the leg SMVR remained unchanged during the 1st min of handgrip, but had increased to exceed baseline levels by the end of exercise. During exercise electromyography (EMG) recordings from nonexercising limbs demonstrated a progressive 20-fold increase in activity in the arm, but remained at baseline in the leg. During EMG-signal modelled exercise performed to mimic the inadvertent muscle activity, decreases in forearm SMVR amounted to 57% of the decrease seen with controlateral handgrip. The present study would seem to indicate that vascular tone in nonexercising skeletal muscle in the arm and leg are controlled differently during the early stages of static handgrip. Metabolic vasodilatation due to involuntary contraction could significantly modulate forearm skeletal muscle vascular responses, but other factors, most likely neural vasodilator mechanisms, must make major contributions. During the later stages of contralateral sustained handgrip, vascular adjustments in resting forearm skeletal muscle would seem to be the final result of reflex sympathetic vasoconstrictor drive, local metabolic vasodilator forces and possibly neurogenic vasodilator mechanisms. Key words: Isometric exercise - 133Xenon washout Skeletal muscle blood flow - Local metabolic vasodilatation - Neurogenic vasodilatation Correspondence to: O. Amtorp
Introduction It is well known that static exercise evokes large increases in arterial blood pressure. This pressor response is believed to be caused mainly by an increase in cardiac output, because total vascular resistance has not generally been found to increase with static exercise (Martin et al. 1974; Asmussen 1981; Shepherd et al. 1981; Gaffney et al. 1990). However, there is substantial evidence that little, if any, of this increment in cardiac output increases the perfusion pressure in the statically contracting muscles, even at low to moderate exercise intensities (Sjcgaard et al. 1988; Gaffney et al. 1990; Bystr6m and Kilbom 1990; Bertocci et al. 1990; Hansen et al. 1993). Thus, two unresolved issues are (a) to which regions the increased cardiac output is directed, and (b) the mechanisms by which redistribution of blood flow is accomplished during static exercise. Plethysmographic measurements of blood flow in the whole limb have demonstrated that circulatory adjustments to sustained handgrip (SHG) occur in the non-exercising limbs, producing vasodilatation in the resting forearm (Eklund et al. 1974; Lind et al. 1981; Rusch et al. 1981; Sanders et al. 1989), and vasoconstriction in the resting leg (Eklund et al. 1974; Rusch et al. 1981; Seals 1989). The peak vasodilator response in the resting arm occurs within the 1st min of contralateral SHG, whereas the vasoconstrictor response in the leg is progressive throughout the exercise period. Studies using direct recordings of sympathetic vasomotor discharge have shown parallel and progressive increases in sympathetic outflow targeted to skeletal muscle in the resting arm and leg during later stages of SHG (Mark et al. 1984; Wallin et al. 1989; Seals and Victor 1990). This would be expected to produce vasoconstriction in the skeletal muscle bed, not only as demonstrated in the leg (Seals 1989; Saito et al. 1990), but also in the resting arm. Several different mechanisms have been proposed to explain the vasodilator response in the resting arm. Firstly, Lind et al. (1981) have attributed the forearm vasodilatation to local metabolic factors due to involuntary contraction. They
148 h a v e r e p o r t e d t h a t e l e c t r o m y o g r a p h i c ( E M G ) activity in t h e r e s t i n g f o r e a r m i n c r e a s e d g r a d u a l l y d u r i n g c o n t r a l a t e r a l S H G , w h e r e a s o t h e r s h a v e f o u n d t h a t little o r n o activity o c c u r r e d d u r i n g t h e 1st m i n o f c o n t r a c t i o n ( E k l u n d et al. 1974; R u s c h et al. 1981). S e c o n d l y , autonomic blocking studies have suggested that a neur o g e n i c v a s o d i l a t a t i o n is r e s p o n s i b l e for t h e d e c r e a s e in r e s t i n g f o r e a r m v a s c u l a r r e s i s t a n c e d u r i n g c o n t r a l a t e r a l S H G ( E k l u n d a n d K a i j s e r 1976; S a n d e r s et al. 1989). A t h i r d e x p l a n a t i o n c o u l d b e t h a t t h e o b s e r v e d differences between arm-leg vascular responses reflect a d i f f e r e n t i a l c o n t r o l of v a s c u l a r r e s i s t a n c e in s k e l e t a l m u s c l e tissue c o m p a r e d to skin d u r i n g S H G ( K i l b o m a n d B r u n d i n 1976; T a y l o r et al. 1989b; Vissing et al. 1991), w i t h a g r e a t e r c o n t r i b u t i o n f r o m skin d o m i n a t ing t h e r e s p o n s e in t h e arm. A c c o r d i n g l y , t h e a i m of t h e p r e s e n t s t u d y was t w o fold: firstly to c o n f i r m t h e e x i s t e n c e o f a d i f f e r e n t i a l c o n t r o l o f v a s o m o t o r t o n e in h u m a n l i m b s d u r i n g S H G , b y m e a s u r i n g b l o o d flow c h a n g e s s e l e c t i v e l y in t h e s k e l e t a l m u s c l e b e d o f t h e r e s t i n g a r m a n d leg, t h e r e b y e l i m i n a t i n g a n y c o n f o u n d i n g effects o f differences in p r o p o r t i o n s o f t h e two tissues in t h e two limbs, a n d s e c o n d l y , to d e t e r m i n e t h e r e l a t i v e i m p o r t a n c e o f m e t a b o l i c c o m p a r e d to o t h e r f a c t o r s (such as n e u r a l , h u m o r a l o r m y o g e n i c ) in c a u s i n g v a s o d i l a t a t i o n in t h e r e s t i n g f o r e a r m . T o a c h i e v e this aim, w e a p p l i e d a local 133Xenon w a s h o u t t e c h n i q u e ( L a s s e n et al. 1983) to m e a s u r e r e l a t i v e c h a n g e s in s k e l e t a l m u s c l e b l o o d flow in t h e i n a c t i v e m u s c l e o f t h e r e s t i n g f o r e a r m a n d t h e r e s t i n g l o w e r leg d u r i n g S H G at 30% o f maximal voluntary contraction (MVC), while simultan e o u s l y m e a s u r i n g E M G a c t i v i t y o f t h e s a m e muscles, to o b t a i n a m e a s u r e o f i n a d v e r t e n t m u s c l e activity. T o q u a n t i f y t h e m a g n i t u d e o f b l o o d flow c h a n g e s t h a t c o u l d b e a s c r i b e d to i n a d v e r t e n t m u s c l e activity, w e repeated the measurements during voluntary, EMGm o d e l l e d s i m u l a t i o n of t h e m u s c l e activity in t h e s a m e subj eets.
Methods Subjects. Ten healthy young men mean age 25 (SEM 1) years participated in this study. The protocol was carefully explained and informed consent was obtained from each subject. The protocol was approved by the Ethics Committee in Copenhagen. All experiments were carried out at least 2 h postprandially. All subjects were studied in the supine position. The forearm and leg were horizontal at the midaxillary line. Room temperature was 22°C and remained constant during the investigation. No coffee, tea. alcohol or tobacco consumption was allowed from the day before the study.
Experimental procedure. A handgrip dynamometer (Stoelting Co., Chicago, Ill., USA) was used and handgrip MVC (best of five) was determined before experiments. After i h of rest. SHG at 30% of MVC was performed. Care was taken that no Valsalva manoeuvres occurred during the protocol. Skeletal muscle blood flow was measured by a local 133Xe-washout technique (Lassen et al. 1983). Isotonic saline (0.1 ml) containing 300 IxCi (1.11"107 Bq) of 133Xe (Radiochemcial Centre, Amersham, England) was injected into the brachioradial muscle of the left forearm and the anterior tibial muscle of the left leg. To avoid influences due to
injection trauma, measurements began 30 rain after the injection (TCnnesen and Sejrsen 1970). Two Cd T1 (C1)-detectors (Novo Memolog System, Denmark) were placed above the radio-active depots and fixed to the skin. Each detector was connected to a standard one-channel impulse height analyser and count rates were recorded every 1 s. Arterial blood pressure was recorded from the right upper arm using a sphygmomanometer. Heart rate was continuously recorded on a Siemens Elema Mingograph. The EMG recordings were made with two surface disc-electrodes placed at a distance of 2 cm on each side of the Xenon depots in the belly of the brachioradial muscle of the left forearm and the belly of the tibial muscle of the left leg. An earth electrode was placed on the resting limb (wrist or ankle). The myo-electrical signal was recorded continuously at a sampling rate at 1,024 kHz (Nicolet, USA). To ensure that the sensitivity of the EMG recordings were approximately the same in all subjects, EMG was also recorded during maximal voluntary isometric extension (against resistance) of the hand and foot. To avoid external noise the experiments were carried out in a room with a Faraday cage.
Protocol During experiments measurements of blood flow in skeletal muscle together with EMG recordings from the nonexercising forearm and leg were obtained simultaneously during three consecutive periods each lasting 3 min: at rest (control), during SHG at 30% MVC and during recovery. At 10 min after SHG the subjects performed 3 min of voluntary contraction of the left arm, producing the same EMG activity as recorded from the same arm during contralateral SHG. Ipsilateral muscle blood flow was recorded before, during and after voluntary contraction.
Calculations. Mean arterial pressure (MAP) was calculated as diastolic pressure plus one-third pulse pressure. The peffusion coefficient, f, was calculated according to Kety (1951) as: f = h .k. 100 (ml. rain -1.100 g -1) where A denotes the tissue-to-blood partition coefficient (ml.g -1) and k the fractional washout rate constant (rain-l). In skeletal muscle the initial steep washout after the injection of 133Xe has been shown to give an overestimation of blood flow due to the local influence of the injection trauma lasting about 10 rain (TCnnesen and Sejrsen 1970). The later mono-exponential part of the washout curve has been shown to be influenced by recirculation of 133Xe due to veno-arteriolar shunting by diffusion (Sejrsen and TCnnesen 1972) and accumulation of the tracer in the fatty tissue lining of the veins (Lindberg et al. 1966). In the present study, the same radio-active depot was used throughout the entire period of the experiment. The relative changes in skeletal muscle blood flow were calculated by relating the washout rate during SHG to the mean value of those before and after exercise. By relating the washout rates obtained just before and after the exercise, the small spontaneous decrease in washout rate was thus taken into account, as the relative effect of shunting by diffusion and fat accumulation has been shown to remain constant within the measurement period (Lassen et al. 1983). Within the sequence of measurements from the same 133Xe depot, ,~ was assumed to remain constant and relative blood flow in skeletal muscle tissue was calculated as: ftestlfrest = k t e s t / k . . . .
where ktest denotes the washout rate constant obtained during SHG and krest the average washout rate obtained before and after SHG. The k value was calculated from regression analysis (least squares method) of count rates transformed logarithmically and corrected for background activity. Changes in local vascular resistance (R) were calculated by using the conventional method as MAP divided by mean blood flow. In this study, we used the relative changes of blood flow (Rtest/Rrest) instead of the actual numeric changes in blood flow, i.e. the relation MAPtest/ktest / MAPrest/krest expresses the changes in the relative local skeletal
149 muscle vascular resistance (SMVR). The Rtest is the SMVR during SHG and R .... is the average value of SMVR before and after SHG. Mean venous pressure was assumed to remain constant in nonexercising limbs.
%
Flow
300~'P
