Postexercise Ischemia Research Articles

Point: The muscle metaboreflex does restore blood flow to contracting muscles

Imposed reductions in oxygen delivery to active skeletal muscle during dynamic exercise in conscious dogs evoke a powerful pressor response, termed the muscle metaboreflex. During submaximal work rates, the major mechanism used by this reflex is to increase cardiac output (CO), which generates a

Central command and the cutaneous vascular response to isometric exercise in heated humans

Cutaneous vascular conductance (CVC) decreases during isometric handgrip exercise in heat stressed individuals, and we hypothesized that central command is involved in this response. Seven subjects performed 2 min of isometric handgrip exercise (35% of maximal voluntary contraction) followed by postexercise ischaemia in normothermia and during heat stress (increase in internal temperature approximately 1 degrees C). To augment the contribution of central command independent of force generation, on a separate day the protocol was repeated following partial neuromuscular blockade (PNB; i.v. cisatracurium). Forearm skin blood flow was measured by laser-Doppler flowmetry, and CVC was the ratio of skin blood flow to mean arterial pressure. The PNB attenuated force production despite encouragement to attain the same workload. During the heat stress trials, isometric exercise decreased CVC by approximately 12% for both conditions, but did not change CVC in either of the normothermic trials. During isometric exercise in the heat, the increase in mean arterial pressure (MAP) was greater during the control trial relative to the PNB trial (31.0+/-9.8 versus 18.6+/-6.4 mmHg, P<0.01), while the elevation of heart rate tended to be lower (19.4+/-10.4 versus 27.4+/-8.1 b.p.m., P=0.15). During postexercise ischaemia, CVC and MAP returned to pre-exercise levels in the PNB trial but remained reduced in the control trial. These findings suggest that central command, as well as muscle metabo-sensitive afferent stimulation, contributes to forearm cutaneous vascular responses in heat stressed humans.

The Chemoreflex in Young Boys and Girls

In order to determine the influence of the chemoreflex on the cardiovascular system of young children, 35 boys and 35 girls (all 7 - 9 years old) performed three minutes of 30 % maximal voluntary contraction (MVC) static handgrip (SHG) exercise followed by four minutes of blood flow occlusion in the previously exercised arm, and then six minutes of passive recovery. Heart rate (HR) and blood pressure (BP) were measured each minute. Twenty girls performed a second occlusion trial to determine reliability. Reliability coefficients for HR (R = 0.51 - 0.78), diastolic (R = 0.46 - 0.81) and systolic (R = 0.57 - 0.78) BP throughout the occlusion trial were moderately high. There was a similar increase in HR (19 +/- 8 vs. 16 +/- 10 %), diastolic (34 +/- 12 vs. 34 +/- 16 %) and systolic (18 +/- 9 vs. 15 +/- 7 %) BP in boys and girls, respectively, during three minutes 30 % MVC exercise. During the occlusion period, diastolic (43 +/- 31 vs. 47 +/- 26 %) and systolic (51 +/- 25 vs. 54 +/- 32 %) BP dropped similarly during minute one but remained elevated significantly above baseline in both boys and girls the entire four-minute period. During the recovery period, minute one SBP and DBP dropped similarly in boys (23 +/- 37, 20 +/- 37 %) and girls (20 +/- 38, 12 +/- 38 %), respectively. In boys and girls DBP remained significantly above baseline the entire recovery period. HR in boys and girls returned to baseline immediately following SHG exercise and remained there through recovery. In conclusion, as reported in adults, the drop in HR to baseline during post-exercise ischemia with a concomitant maintenance of BP significantly above baseline indicates that at least two separate mechanisms, with varying influence, are responsible for HR and BP control in young children. Further, the chemoreflex operates similarly in young boys and girls.

Sweating responses during activation of the muscle metaboreflex in humans is altered by time of day

The aim of the present study was to test for a time-of-day effect on sweating responses to activation of the muscle metaboreflex. Eight male subjects each participated in two exercise sessions, one in the morning and one in the evening. Within each session there were two 60-s bouts of isometric handgrip (IHG) exercise at 50% maximal voluntary contraction. Prior to IHG, whole body warming by a water-perfused suit initiated mild sweating. The first bout of IHG exercise began at 06.00 hours (am) and 18.00 hours (pm). Blood circulation to the forearm was occluded for 120 s, beginning 5 s before the end of the second bout of IHG to activate the muscle metaboreflex. During both bouts of exercise, sweating rate (SR) on both the chest and right forearm significantly increased from the pre-exercise period in both am and pm sessions. SR rapidly decreased during first minute of recovery after the first bout of IHG exercise. However, during post-exercise ischaemia (PEI) after the second bout of IHG exercise, SR was maintained significantly above the pre-exercise level only in the pm session. The increases in SR on the chest and right forearm during PEI were significantly greater in the pm, than in the am, session. However, SR of the palm was not maintained during PEI. We conclude that under mild hyperthermic conditions, the sweating response in non-glabrous skin to activation of the muscle metaboreflex exhibits a time-of-day effect.

Central command is capable of modulating sweating from non-glabrous human skin.

Isometric handgrip exercise (IHG) increases sweating rate without changing core or skin temperatures. The contribution of central command resulting in increases in sweating rate during IHG is unknown. To investigate this question, seven subjects performed IHG (35 % maximum voluntary contraction (MVC) for 2 min) followed by 2-min of post-exercise ischaemia (PEI), with and without partial neuromuscular blockade (PNB). PNB was performed to augment central command during the IHG bout. These trials were conducted while the subject was normothermic, mildly heated, and moderately heated. On the non-exercising arm, forearm sweating rate was monitored over a microdialysis membrane perfused with neostigmine (acetylcholinesterase inhibitor), and at an adjacent untreated site. In normothermia with PNB, despite reduced force production during IHG (17 +/- 9 versus 157 +/- 13 N; P < 0.001), the elevation in sweating rate at the neostigmine-treated site was greater relative to the control IHG bout (P < 0.05). During subsequent PEI, for the PNB trial mean arterial blood pressure (MAP) and sweating rate returned towards pre-IHG levels, while during the control trial these variables remained elevated. During IHG while mildly heated, the elevation in sweating rate was greater during the PNB trial relative to the control trial. In contrast, during moderate heating sweating increased during IHG for both trials, however the elevation in sweating rate during the PNB trial was not greater than during the control trial. These results suggest that central command is capable of modulating sweating rate in all thermal conditions, however its effect is reduced when body temperatures and/or sweating rate are substantially elevated.

THE CHEMOREFLEX IN 7???9 YEAR OLD BOYS AND GIRLS

Differences in cardiovascular responses to static exercise have been reported between boys and girls (Verhaaren et al, J. Appl. Physiol., 1994). PURPOSE: Investigate possible mechanisms responsible for these differences. METHODS Heart rate (HR) and blood pressure (BP) were measured in 35 boys and 35 girls (7–9 yrs old) during 3 min of static handgrip exercise (SHG) at 30% maximal voluntary contraction, followed by 4 min of blood flow occlusion (OCL) in the previously exercised arm, and then 6 min of recovery (REC). RESULTS Maximal SHG was significantly (p ≤ 0.05) higher in boys than girls (19.7 vs 16.5 kg). Maximal SHG reliability was high for both boys (reported elsewhere) and girls (R=0.95). During the 3-min SHG HR (19.4 vs 16.1%), systolic (18.0 vs 15.1%), and diastolic (34.1 vs 32.8%) BP increased the same for boys and girls, respectively. During OCL systolic (51.4 vs 55.3%) and diastolic (42.5 vs 47.0%) BP dropped similarly during minute one in both boys and girls, respectively, yet remained above baseline the entire period. In both boys and girls DBP remained significantly (p ≤ 0.05) above baseline during OCL. SBP also remained significantly above baseline all four minutes of OCL in boys while in girls SBP significance above baseline was only reached during minute one. During minute one of REC systolic (22.5 vs 20.4%) and diastolic (20.4 vs 15.4%) BP decreased in both boys and girls, respectively. In girls DBP remained significantly above baseline for the first minute of REC while in boys it remained significantly above baseline for four minutes. HR in both boys and girls fell to baseline during OCL and remained there throughout REC. CONCLUSION The drop in HR to baseline during post-exercise ischemia with a concomitant maintenance of BP significantly above baseline indicates differential control of the cardiovsacular system in children as has been reported in adults. There is no difference in chemoreflex between young boys and girls since BP responded similarly during OCL and REC.

The exercise metaboreflex is maintained in the absence of muscle acidosis: insights from muscle microdialysis in humans with McArdle's disease.

1. In McArdle's disease, muscle glycogenolysis is blocked, which results in absent lactate and enhanced ammonia production in working muscle. Using McArdle patients as an experimental model, we studied whether lactate and ammonia could be mediators of the exercise pressor reflex. 2. Changes in muscle interstitial ammonia and lactate were compared with changes in blood pressure and muscle sympathetic nerve activity (MSNA) during static arm flexor exercise at 30% of maximal contraction force. Muscle interstitial changes in lactate and ammonia were assessed by microdialysis of the biceps muscle, and MSNA by peroneal nerve microneurography, in six McArdle patients and 11 healthy, matched controls. One McArdle patient also had myoadenylate deaminase deficiency, a condition associated with abolished ammonia production in exercise. 3. Exercise-induced increases were higher in McArdle patients vs. controls for MSNA (change of 164 +/- 71 vs. 59 +/- 19%) and blood pressure (change of 47 +/- 7 vs. 38 +/- 4 mmHg). Interstitial lactate increased in controls (peak change 1.3 +/- 0.2 mmol x l(-1)) and decreased in McArdle patients (peak change -0.5 +/- 0.1 mmol x l(-1)) during and after exercise. Interstitial ammonia did not change during exercise in either group, but was higher post-exercise in McArdle patients, except in the patient with myoadenylate deaminase deficiency who had a flat ammonia response. This patient had an increase in MSNA and blood pressure comparable to other patients. MSNA and blood pressure responses were maintained during post-exercise ischaemia in both groups, indicating that sympathetic activation was caused, at least partly, by a metaboreflex. 4. In conclusion, changes in muscle interstitial lactate and ammonia concentrations during and after exercise are temporally dissociated from changes in MSNA and blood pressure in both patients with McArdle's disease and healthy control subjects. This suggests that muscle acidification and changes in interstitial ammonia concentration are not mediators of sympathetic activation during exercise.

Evidence for metaboreceptor stimulation of sweating in normothermic and heat‐stressed humans

1. Isometric handgrip (IHG) exercise increases sweat rate and arterial blood pressure, and both remain elevated during post-exercise ischaemia. The purpose of this study was to identify whether the elevation in arterial blood pressure during post-exercise ischaemia contributes to the increase in sweating. 2. In normothermia and during whole-body heating, 2 min IHG exercise at 40% maximal voluntary contraction, followed by 2 min post-exercise ischaemia, was performed with and without bolus intravenous administration of sodium nitroprusside during the ischaemic period. Sodium nitroprusside was administered to reduce blood pressure during post-exercise ischaemia to pre-exercise levels. Sweat rate was monitored over two microdialysis membranes placed in the dermal space of forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine, while the other was perfused with the vehicle. 3. In normothermia, IHG exercise increased sweat rate at the neostigmine-treated site but not at the control site. Sweat rate remained elevated during post-exercise ischaemia even after mean arterial blood pressure returned to the pre-IHG exercise baseline. Subsequent removal of the ischaemia stimulus returned sweat rate to pre-IHG exercise levels. Sweat rate during post-exercise ischaemia without sodium nitroprusside administration followed a similar pattern. 4. During whole-body heating, IHG exercise increased sweat rate at both neostigmine-treated and untreated sites. Similarly, regardless of whether mean arterial blood pressure remained elevated or was reduced during post-exercise ischaemia, sweat rate remained elevated during the ischaemic period. 5. These results suggest that sweating in non-glabrous skin during post-IHG exercise ischaemia is activated by metaboreflex stimulation and not via baroreceptor loading.

Postexercise ischemia is associated with increased neuropeptide Y in patients with coronary artery disease.

Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease. Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223+/-20.2 microV (P:<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49+/-8.9 microV, P:<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0+/-0.77 microV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r=-0.61, P:= 0.0005), the ST deficit at the corresponding time point (r=-0.66, P:= 0.0001), and the duration of ST-segment depression after exercise (r= 0.42, P:=0.02). In contrast, no such correlations were found for NE. The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.

Human carotid baroreflex during isometric lower arm contraction and ischemia.

Our aim was to determine the roles of somatomotor activation and muscle ischemia for the tachycardia and hypertension of isometric arm contraction. Carotid-cardiac and carotid-mean arterial pressure (MAP) baroreflex response curves were determined in 10 men during rest, during isometric arm contraction at 30% of maximum, and during postcontraction ischemia. Carotid distending pressure (CDP) was changed by applying pressure and suction in a neck chamber. Pressures ranged from +40 to -80 mmHg and were applied repeatedly for 15 s during the three conditions. Maximum slopes and ranges of the response curves did not differ among conditions. The heart rate (HR) curve was shifted to a 14 +/- 1.8 (mean +/- SE) beats/min higher HR and a 9 +/- 5.7 mmHg higher CDP during contraction and to a 14 +/- 5.9 mmHg higher CDP during postcontraction ischemia with no change of HR compared with rest. The MAP curve was shifted to a 20 +/- 2.8 mmHg higher MAP and to a 18 +/- 5.4 mmHg higher CDP during contraction, and the same shifts were recorded during postcontraction ischemia. We conclude that neither somatomotor activation nor muscle ischemia changes the sensitivity of arterial baroreflexes. The upward shift of the MAP response curve, with no shift of the HR response curve during postexercise ischemia, supports the notion of parallel pathways for MAP and HR regulation in which HR responses are entirely caused by somatomotor activation and the pressor response is mainly caused by muscle ischemia.

Muscle metaboreceptor modulation of cutaneous active vasodilation.

Isometric handgrip exercise in hyperthermia has been shown to reduce cutaneous vascular conductance (CVC) by inhibiting the cutaneous active vasodilator system. To identify whether this response was initiated by muscle metaboreceptors, in seven subjects two 3-min bouts of isometric handgrip exercise in hyperthermia were performed, followed by 2 min of postexercise ischemia (PEI). An index of forearm skin blood flow (laser-Doppler flowmetry) was measured on the contralateral arm at an unblocked site and at a site at which adrenergic vasoconstrictor function was blocked via bretylium iontophoresis to reveal active cutaneous vasodilator function unambiguously. Sweat rate was measured via capacitance hygrometry, CVC was indexed from the ratio of skin blood flow to mean arterial pressure and was expressed as a percentage of maximal CVC at that site. In normothermia, neither isometric exercise nor PEI affected CVC (P > 0.05). The first bout of isometric handgrip exercise in hyperthermia reduced CVC at control sites and this reduction persisted through PEI (pre-exercise: 59.8 +/- 5.4, exercise: 49.8 +/- 4.9, PEI: 49.7 +/- 5.3% of maximum; both P < 0.05), whereas there were no significant changes in CVC at the bretylium treated sites. The succeeding bout of isometric exercise in hyperthermia significantly reduced CVC at both untreated (pre-exercise: 59.0 +/- 4.8, exercise: 47.3 +/- 4.0, PEI: 50.1 +/- 4.1% of maximum; both P < 0.05) and bretylium treated sites (pre-exercise: 61.4 +/- 7.3, exercise: 50.6 +/- 5.1, PEI: 53.9 +/- 6.0% of maximum, both P < 0.05). At both sites, CVC during PEI was lower than during the pre-exercise period (P < 0.05). Sweat rate rose significantly during both bouts of isometric exercise and remained elevated during PEI. These data suggest that the reduction in CVC during isometric exercise in hyperthermia, including the inhibition of the active vasodilator system, is primarily mediated by muscle metaboreceptors, whereas central command or muscle mechanoreceptors have less influence.

Noninvasive measures of oxidative metabolism on working human muscles by near-infrared spectroscopy.

The purpose of this study was to determine whether the initial rate of hemoglobin and myoglobin deoxygenation during immediate postexercise ischemia, a reflection of muscle O2 consumption (VO2mus), can be a quantitative measure of muscle oxidative metabolism. The finger flexor muscles of five healthy men (aged 25-31 yr) were monitored by 31P-magnetic resonance spectroscopy for changes in phosphocreatine (PCr), Pi, and pH. Tests were conducted during 15 min of cuff ischemia and during 5 min of submaximal isotonic grip exercise at 10, 20, 30, and 40% of maximal voluntary contraction, one contraction every 4 s. The VO2mus changes were also monitored by near-infrared spectroscopy with continuous wave. The VO2mus during exercise was expressed relative to the resting value. The resting metabolic rate, calculated from the PCr breakdown rate after complete O2 depletion, was 0.0010 (SD) mM ATP/s. During submaximal exercise (pH > 6.9), the VO2mus increased with a rise in intensity (0.036 +/- 0.011, 0.054 +/- 0.016, 0.062 +/- 0.012, and 0.067 +/- 0.020 mM ATP/s during 10, 20, 30, and 40% maximal voluntary contraction, respectively) and showed significant correlation with changes in both calculated ADP and PCr values (r2 = 0.98 and r2 = 0.99, respectively). In conclusion, because of the significant correlation with regulatory metabolites (ADP and PCr) of oxidative phosphorylation, O2 decline rate in immediate postexercise ischemia determined by near-infrared spectroscopy with continuous wave can be utilized for the quantitative evaluation of localized muscle oxidative metabolism.

Increased muscle perfusion reduces muscle sympathetic nerve activity during handgripping

This study sought to determine whether increasing blood flow to active muscles can blunt the normal rise in muscle sympathetic nerve activity (MSNA) during heavy rhythmic forearm exercise in humans. Subjects performed 5- to 6-min exercise bouts of handgripping (30/min) at 40-50% of maximum voluntary contraction (MVC). Blood flow was increased by application of suction (50 mmHg) around the forearm. Suction increased deep venous oxygen saturation in blood draining the forearm from 34 +/- 4 to 45 +/- 4%, indicating that muscle blood flow had risen by approximately 20%. Suction had no impact on the heart rate, perceived exertion, or electromyographic responses to the handgripping. During 6 min of exercise at 50% of MVC, MSNA rose from 376 +/- 67 to 970 +/- 125 units during the control trial vs. 396 +/- 69 to 729 +/- 94 units during the suction trial, and the difference was maintained during 2 min of postexercise ischemia (P < 0.05; suction < control). Mean arterial pressure (MAP) rose from 99 +/- 4 to 129 +/- 6 mmHg during control vs. 99 +/- 4 to 126 +/- 6 mmHg during the suction trial, and these responses were only different (P < 0.05; suction < control) during the final minute of the exercise bouts. During postexercise ichemia, MAP was 122 +/- 6 mmHg after the control trial but was only 112 +/- 4 mmHg after the suction trial. These results indicate that forearm suction augmented muscle blood flow, limited the activation of chemosensitive muscle afferents, and blunted the rise in MSNA during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of epidural anaesthesia with 1% lidocaine on the pressor response to dynamic exercise in man.

1. In order to examine the sensitivity to local anaesthetics of afferent neural feedback from working muscle during dynamic exercise, sixteen subjects cycled for 12 min before and after epidural anaesthesia using 1% lidocaine. The presence of afferent neural blockade was verified by elimination of the blood pressure response to a cold pressor test, laser-induced evoked potentials and increases in pain detection and tolerance thresholds of the foot. Conversely, epidural anaesthesia had no effect on these variables in the unblocked skin areas or on electrically evoked potentials in blocked or unblocked skin. 2. During dynamic exercise, heart rate increased as did mean arterial pressure and cardiac output. Mean arterial pressure remained at the exercise level during post-exercise ischaemia, but heart rate and cardiac output decreased while total peripheral resistance increased. Epidural anaesthesia did not significantly affect these variables during rest, dynamic exercise, post-exercise ischaemia or recovery. 3. The results of this study show that, in order to affect blood pressure during dynamic exercise, epidural anaesthesia must block the pressor response to post-exercise ischaemia. The implication of these data is that complete or almost complete block of group III and/or group IV muscle afferents is necessary to inhibit the pressor response to dynamic exercise in man.

Autonomic mechanisms of muscle metaboreflex control of heart rate.

Ischemia in active skeletal muscle induces reflex increases in systemic arterial pressure (SAP) and heart rate (HR), termed the muscle metaboreflex. When metaboreflex activation is maintained during postexercise muscle ischemia, SAP remains elevated; however, HR decreases. Why the HR responses differ with metaboreflex activation during exercise vs. during postexercise ischemia while the SAP responses are similar in each setting remains unclear. Two hypotheses were tested: 1) the increase in HR with muscle ischemia occurs predominantly via an increase in sympathetic activity, and 2) sympathetic activity to the heart remains elevated during post-exercise ischemia; however, HR decreases because of an increase in parasympathetic outflow. The muscle metaboreflex was activated in conscious dogs during treadmill exercise (3.2 kph, 0% grade) by progressively decreasing perfusion to the hindlimbs. Experiments were performed before and after muscarinic (atropine) or beta- (atenolol or propranolol) receptor blockade. In control experiments, once beyond the threshold for the reflex, the HR sensitivity of the muscle metaboreflex averaged -2.4 +/- 0.3 beats.min-1.mmHg-1 and the reflex open-loop gain averaged -3.2 +/- 0.3 (calculated as the ratio of the increase in HR or SAP to the decrease in hindlimb perfusion pressure beyond threshold). Atropine had no effect on either HR sensitivity (-2.7 +/- 0.4 beats.min-1.mmHg-1) or open-loop gain (-3.3 +/- 0.5, both P > 0.05 vs. control). However, pretreatment with beta-receptor antagonist significantly decreased both HR sensitivity (-0.7 +/- 0.1 beats.min-1.mmHg-1, P < 0.001) and open-loop gain (-1.9 +/- 0.3, P < 0.01). During postexercise ischemia, HR decreased while SAP remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)