Michael J. White

Sarcoplasmic reticulum function and muscle contractile character following fatiguing exercise in humans

1 This study examined the alterations in calcium release, calcium uptake and calcium ATPase activity of skeletal muscle sarcoplasmic reticulum in response to a bout of intense dynamic knee extensor exercise, and the relationship between these changes and alterations in muscle contractile characteristics in the human quadriceps. 2 In biopsy samples taken from the vastus lateralis, sarcoplasmic reticulum calcium release and calcium uptake were significantly depressed (P < 0.01 and 0.05, respectively) immediately following the exercise with no alteration in the sarcoplasmic reticulum Ca2+‐ATPase activity. 3 A 33 % reduction in the maximum voluntary isometric torque was found following the exercise, with reduced torques from electrically evoked isometric contractions at low frequencies of stimulation (10 and 20 Hz) but not at higher frequencies (50 and 100 Hz). 4 The depressed calcium release was correlated (P < 0.05) with a decreased ratio of torques generated at 20:50 Hz, indicating an involvement in low frequency fatigue; however, no correlations between the muscle relaxation times or rates of change of torque and calcium uptake were observed.

Autonomic nervous system influence on arterial baroreflex control of heart rate during exercise in humans

A combination of sympathoexcitation and vagal withdrawal increases heart rate (HR) during exercise, however, their specific contribution to arterial baroreflex sensitivity remains unclear. Eight subjects performed 25 min bouts of exercise at a HR of 90, 120, and 150 beats min−1, respectively, with and without metoprolol (0.16 ± 0.01 mg kg−1; mean ±s.e.m.) or glycopyrrolate (12.6 ± 1.6 μg kg−1). Carotid baroreflex (CBR) function was determined using 5 s pulses of neck pressure (NP) and neck suction (NS) from +40 to −80 Torr, while transfer function gain (GTF) was calculated to assess the linear dynamic relationship between mean arterial pressure and HR. Spontaneous baroreflex sensitivity (SBR) was evaluated as the slope of sequences of three consecutive beats in which systolic blood pressure and the R–R interval of the ECG either increased or decreased, in a linear fashion. The β‐1 adrenergic blockade decreased and vagal cardiac blockade increased HR both at rest and during exercise (P < 0.05). The gain at the operating point of the modelled reflex function curve (GOP) obtained using NP and NS decreased with workload independent of β‐1 adrenergic blockade. In contrast, vagal blockade decreased GOP from −0.40 ± 0.04 to −0.06 ± 0.01 beats min−1 mmHg−1 at rest (P < 0.05). Furthermore, as workload increased both GOP and SBR, and GOP and GTF were correlated (P < 0.001), suggesting that the two dynamic methods applied to evaluate arterial baroreflex (ABR) function provide the same information as the modelled GOP. These findings suggest that during exercise the reduction of arterial baroreceptor reflex sensitivity at the operating point was a result of vagal withdrawal rather than an increase in sympathetic activity.

Muscle afferent contributions to the cardiovascular response to isometric exercise

The cardiovascular response to isometric exercise is governed by both central and peripheral mechanisms. Both metabolic and mechanical stresses on the exercising skeletal muscle produce cardiovascular change, yet it is often overlooked that the afferent signal arising from the muscle can be modified by factors other than exercise intensity. This review discusses research revealing that muscle fibre type, muscle mass and training status are important factors in modifying this peripheral feedback from the active muscles. Studies in both animals and humans have shown that the pressor response resulting from exercise of muscle with a faster contractile character and isomyosin content is greater than that from a muscle of slower contractile character. Athletic groups participating in training programmes that place a high anaerobic load on skeletal muscle groups show attenuated muscle afferent feedback. Similarly, longitudinal studies have shown that specific local muscle training also blunts the pressor response to isometric exercise. Thus it appears that training may decrease the metabolic stimulation of muscle afferents and in some instances chronic exposure to the products of anaerobic metabolism may blunt the sensitivity of the muscle metaboreflex. There may be surprising parallels between the local muscle conditions induced in athletes training for longer sprint events (e.g. 400 m) and by the low‐flow conditions in, for example, the muscles of chronic heart failure patients. Whether their similar attenuations in muscle afferent feedback during exercise are due to decreased metabolite accumulation or to a desensitization of the muscle afferents is not yet known.

Training‐induced adaptations in the central command and peripheral reflex components of the pressor response to isometric exercise of the human triceps surae

1 The effect of calf raise training of the dominant limb on the pressor response to isometric exercise of the triceps surae was examined in the trained dominant limb and the contralateral untrained limb. Blood pressure and heart rate responses to electrically evoked and voluntary exercise at 30% maximum voluntary contraction (MVC), followed by post‐exercise circulatory occlusion (PECO), were compared before and after a 6 week training period. 2 In the trained limb the diastolic blood pressure rise seen during electrically evoked exercise was reduced by 27% after training. However, the response during PECO was not significantly affected. 3 During voluntary exercise of the trained limb, diastolic blood pressure rise was reduced by 28%, and heart rate rise was significantly attenuated after training. During PECO no significant effects of training were observed. 4 Voluntary exercise of the untrained limb resulted in a 24% reduction in diastolic blood pressure rise after the training period, and a significant attenuation of the heart rate increase during exercise. Responses to electrically evoked exercise and PECO of the untrained limb remained unaltered after training. 5 Attenuation of blood pressure and heart rate responses, in the contralateral untrained limb, during voluntary but not electrically evoked exercise, indicates a training‐induced alteration in central command.

Cardiovascular responses to human calf muscle stretch during varying levels of muscle metaboreflex activation.

The purpose of the present study was to investigate the cardiovascular responses to muscle metaboreflex‐ and concurrent muscle stretch‐induced mechanoreflex activation. Eight subjects (7 males, 1 female) performed 90 s of isometric calf plantarflexion at 0, 30, 50 and 70% of maximum voluntary contraction. During exercise and for 3.5 min postexercise, circulatory occlusion (PECO) was ensured by inflation of a thigh cuff. After 90 s of PECO the calf muscle was stretched for 60 s (Stretch). Heart rate (HR; assessed from ECG), blood pressure (BP; Finapres) and phase of respiratory cycle were recorded. Exercise increased diastolic BP (DBP) from rest by 1 ± 0.8, 14 ± 2.5, 29 ± 3.9 and 35 ± 3.6 mmHg, during the 0, 30, 50 and 70% conditions, respectively (ANOVA rest versus exercise, P < 0.05). During PECO DBP remained elevated, by 2 ± 0.4, 8 ± 0.3, 12 ± 0.3 and 13 ± 0.9 mmHg, respectively. Stretch produced a further increase in DBP that was not different between conditions (3 ± 1.4, 2 ± 0.8, 3 ± 1.0 and 3 ± 0.9 mmHg, for the 0, 30, 50 and 70%, respectively). HR increased during exercise but returned to baseline during PECO. HR increased at Stretch onset in all conditions. No EMG was detected from the gastrocnemius and soleus during Stretch. Our data show that the cardiovascular responses to human calf Stretch are independent of the level of concurrent muscle metaboreflex activation.

The human pressor response during and following voluntary and evoked isometric contraction with occluded local blood supply.

1. Changes in heart rate and blood pressure were observed, in nine healthy subjects, during and after voluntary and electrically evoked isometric contractions of the triceps surae under conditions of local circulatory arrest. 2. The progressive increases in heart rate and blood pressure seen during 2 min voluntary and evoked contractions at 30% of maximal voluntary contraction were not significantly different in the two conditions. On cessation of contraction but with circulatory arrest maintained, heart rate fell to control levels while blood pressure fell to a similar though still significantly elevated level in both conditions. Elevated blood pressure was maintained for 2 min until the circulatory occlusion was removed; however it was maintained at a significantly higher level for the last 60‐90 s of occlusion following electrically evoked contractions compared to voluntary contraction. 3. Comparison of the responses to voluntary and involuntary electrically evoked contractions suggest that ‘central command’ is not necessary for the initial increases in heart rate and blood pressure to occur. In addition the removal of central command on cessation of contraction need not account for the return of heart rate to control levels or the drop in blood pressure at that time. Maintained blood pressure elevation during circulatory occlusion would seem to be due to the trapping of chemical substances within the muscle interstitium.

Cardiovascular responses to external compression of human calf muscle vary during graded metaboreflex stimulation

This study investigated the cardiovascular response to a standard external muscle compression during concomitant muscle metaboreflex stimulation of varying intensity in human calf muscle. Eleven healthy male subjects (mean (s.d.) age, 26 (5.6) years; height, 177 (5) cm; weight, 74.3 (6.8) kg) were seated in an isometric dynamometer with the angle of the knee at 90 deg, and the angle of the ankle at 85 deg. After a 150‐s rest period, subjects were asked to either perform isometric plantar flexion at 20, 30, 40, 50, 60, 70 or 80% of previously determined maximum isometric contractile force (MVC) for 90 s, or to sit at rest for this period. A thigh cuff maintained circulatory occlusion throughout the exercise period and for 180 s post exercise. After 60 s of post‐exercise circulatory occlusion (PECO), a calf cuff was inflated to 300 mmHg for 60 s followed by a further 60 s of PECO alone after which the thigh cuff was deflated. During PECO the mean arterial pressure (MAP) increase from rest was dependent upon the preceding exercise intensity (P < 0.001). Compression elicited a further significant change in MAP, and the magnitude of this change from the PECO baseline was also dependent upon the preceding exercise intensity (P < 0.01). These results are compatible with activation of a metabolically sensitised population of mechanoreceptive afferents in human muscle during external compression.

Exercise‐induced muscle chemoreflex modulation of spontaneous baroreflex sensitivity in man

1 The goal of this study was to determine the effect of exercise‐induced muscle chemoreflex activation on baroreflex sensitivity (BRS). This is a retrospective study using data obtained during two prior studies. 2 Twenty‐three subjects with a mean (s.e.m.) age of 28 (1.5) years took part in the study. Sequence analysis was performed on the systolic blood pressure (SBP) responses, measured by a Finapres, and R‐R intervals, measured from the ECG. 3 Electrically evoked isometric exercise (Stim) of the triceps surae was performed for 2 min at 30 % maximum voluntary contraction force. During exercise and for a further 2 min thereafter, circulation to the lower leg was occluded by inflation of a thigh cuff to above 200 mmHg. 4 Prior to exercise mean (±s.e.m.) BRS was 10.92 ± 6.3 ms mmHg−1, and BRS remained at this level during evoked exercise (10.90 ± 7.1 ms mmHg−1). BRS increased to 12.34 ± 6.0 ms mmHg−1 during post‐exercise circulatory occlusion (PECO) (P < 0.05, MANOVA, post hoc Students paired t test vs. Stim) and fell to 9.27 ± 4.4 ms mmHg−1 during recovery (P < 0.01vs. PECO value, P= 0.059vs. resting value). 5 These data indicate that during PECO following electrically evoked plantar flexion, where only muscle chemosensitive afferents were likely to be stimulated, BRS was increased.

Human arterial responses to isometric exercise: the role of the muscle metaboreflex

The effects of exercise on the distensibility of large and medium-sized arteries are poorly understood, but can be attributed to a combination of local vasodilator effects of exercise opposed by sympathetic vasoconstrictor tone. We sought to examine this relationship at the conduit artery level, with particular reference to the role of the sympatho-excitatory muscle metaboreflex. The effect of maintained muscle metaboreflex activation on a previously passive or exercised limb femoral artery was investigated. A total of ten healthy volunteers performed 2 min of isometric ankle plantar-flexion at 40% MVC (maximal voluntary force), in conjunction with 2 min of either non-ischaemic isometric HG (handgrip; control condition) or IHG (ischaemic HG) at 40% MVC. IHG was followed by 2 min of PECO (post-exercise circulatory occlusion) to maintain muscle metaboreflex activation. FTPWV [femoral-tibial PWV (pulse wave velocity)] was measured in the exercised or contralateral limb at baseline and immediately following calf exercise. BP (blood pressure) and HR (heart rate) were measured continuously throughout. In the HG condition, BP and HR returned promptly to baseline post-exercise, whereas exercised leg FTPWV was decreased (less stiff) by 0.6 m/s (P<0.05) and the non-exercised leg PWV was not changed from baseline. PECO caused a sustained increase in BP, but not HR, in the IHG condition. Contralateral leg PWV increased (stiffened) during PECO by 0.9 m/s (P<0.05), whereas exercised limb FTPWV was not changed from baseline. In conclusion, muscle metaboreflex activation causes a systemic stiffening of the arterial tree, which can overcome local exercise-induced decreases in arterial PWV.

Local metabolite accumulation augments passive muscle stretch-induced modulation of carotid–cardiac but not carotid–vasomotor baroreflex sensitivity in man

We examined the effects of muscle mechanoreflex stimulation by passive calf muscle stretch, at rest and during concurrent muscle metaboreflex activation, on carotid baroreflex (CBR) sensitivity. Twelve subjects either performed 1.5 min one‐legged isometric plantarflexion at 50% maximal voluntary contraction with their right or left calf [two ischaemic exercise (IE) trials, IER and IEL] or rested for 1.5 min [two ischaemic control (IC) trials, ICR and ICL]. Following exercise, blood pressure elevation was partly maintained by local circulatory occlusion (CO). 3.5 min of CO was followed by 3 min of CO with passive stretch (STR‐CO) of the right calf in all trials. Carotid baroreflex function was assessed using rapid pulses of neck pressure from +40 to −80 mmHg. In all IC trials, stretch did not alter maximal gain of carotid–cardiac (CBR–HR) and carotid–vasomotor (CBR–MAP) baroreflex function curves. The CBR–HR curve was reset without change in maximal gain during STR‐CO in the IEL trial. However, during the IER trial maximal gain of the CBR–HR curve was smaller than in all other trials (−0.34 ± 0.04 beats min−1 mmHg−1 in IER versus−0.76 ± 0.20, −0.94 ± 0.14 and −0.66 ± 0.18 beats min−1 mmHg−1 in ICR, IEL and ICL, respectively), and significantly smaller than in IEL (P < 0.05). The CBR–MAP curves were reset from CO values by STR‐CO in the IEL and IER trials with no changes in maximal gain. These results suggest that metabolite sensitization of stretch‐sensitive muscle mechanoreceptive afferents modulates baroreflex control of heart rate but not blood pressure.