Understanding central fatigue: where to go?
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Electromyography↗
Biomedical subjects
Niels H Secher
Publications and source records attributed to Niels H Secher.
[The muscles work, but the brain gets tired].
Central fatigue is the term used to describe when muscle contractions become limited by the ability of the central nervous system to recruit motor neurones. Central fatigue becomes manifest when the effort is intense and is associated not only with reduced strength but also with an inability to maintain the contraction. The contractions thereby resemble those developed during partial neuromuscular blockade that mainly affect slow twitch muscle fibres. We suggest that central fatigue also manifests as a reduction in the ratio between the brain's uptake of oxygen relative to that of carbohydrate from 6 to less than 3. This imbalance between oxygen and glucose plus lactate uptake remains unsolved, but glycogen and accumulation of intermediates of metabolism are likely to play a key role.
Brain↗
[Patients with kidney disease].
For patients with kidney disease it is particularly important to secure normovolaemia before anaesthesia. By providing the volume that secures a maximal venous oxygen saturation or a maximal cardiac output, such a volume can be defined with an accuracy of 100-200 ml. Surgical procedures for the kidney patient are dominated by providing an i.v. access. The internal jugular vein is preferred after identification of its lumen by ultrasound.
Anesthesia↗
High glycogen levels in the hippocampus of patients with epilepsy.
During intense cerebral activation approximately half of the glucose plus lactate taken up by the human brain is not oxidized and could replenish glycogen deposits, but the human brain glycogen concentration is unknown. In patients with temporal lobe epilepsy, undergoing curative surgery, brain biopsies were obtained from pathologic hippocampus (n=19) and from apparently 'normal' cortical grey and white matter. We determined the in vivo brain glycogen level and the activity of glycogen phosphorylase and synthase. Regional differences in glycogen concentration were examined similarly in healthy pigs (n=5). In the patients, the glycogen concentration in 'normal' grey and white matter was 5 to 6 mmol/L, but much higher in the hippocampus, 13.1+/-4.3 mmol/L (mean+/-s.d.; P<0.001); the activities of glycogen phosphorylase and synthase displayed the same pattern. In normal hippocampus from pigs, glycogen was similarly higher than in grey and white matter. Consequently, in human grey and white matter and, particularly, in the hippocampus of patients with temporal lope epilepsy, glycogen constitutes a large, active energy reserve, which may be of importance for energy provision during sustained synaptic activity as epileptic seizures.
Adult↗
Central command and the onset of exercise.
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Animals↗
Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans.
Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78%+/-4%; mean+/-s.d.) was halfway between the arterial (98%+/-1%) and jugular venous oxygenation (SvO2; 61%+/-6%). Both NIRS devices monitored SCap (P<0.001) within approximately 5% as SvO2 increased from 39%+/-5% to 79%+/-7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29+/-8 to 65+/-15 cm/sec. When SCap fell below approximately 70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P<0.001) and brain lactate release increased concomitantly (P<0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r>0.74; P<0.05). These results show that NIRS is an adequate cerebral capillary-oxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.
Adult↗
Regulation of middle cerebral artery blood velocity during recovery from dynamic exercise in humans.
We sought to examine the regulation of cerebral blood flow during 10 min of recovery from mild, moderate, and heavy cycling exercise by measuring middle cerebral artery blood velocity (MCA V). Transfer function analyses between changes in arterial blood pressure and MCA V were used to assess the frequency components of dynamic cerebral autoregulation (CA). After mild and moderate exercise, the decreases in mean arterial pressure (MAP) and mean MCA V (MCA Vm) were small. However, following heavy exercise, MAP was rapidly and markedly reduced, whereas MCA Vm decreased slowly (-23 +/- 4 mmHg and -4 +/- 1 cm/s after 1 min for MAP and MCA Vm, respectively; means +/- SE). Importantly, for each workload, the normalized low-frequency transfer function gain between MAP and MCA Vm remained unchanged from rest to exercise and during recovery, indicating a maintained dynamic CA. Similar results were found for the systolic blood pressure and systolic MCA V relationship. In contrast, the normalized low-frequency transfer function gain between diastolic blood pressure and diastolic MCA V (MCA Vd) increased from rest to exercise and remained elevated in the recovery period (P < 0.05). However, MCA Vd was quite stable on the cessation of exercise. These findings suggest that MCA V is well maintained following mild to heavy dynamic exercise. However, the increased transfer function gain between diastolic blood pressure and MCA Vd suggests that dynamic CA becomes less effective in response to rapid decreases in blood pressure during the initial 10 min of recovery from dynamic exercise.
Adult↗
Beta-adrenergic receptor desensitization in man: insight into post-exercise attenuation of cardiac function.
Desensitization of the beta-adrenoreceptors (beta-AR) may contribute to a post-exercise reduction in left ventricular (LV) function. However, attenuation of the chronotropic and inotropic responses to a beta-AR agonist may depend upon alterations in parasympathetic tone. Furthermore, changes in cardiac output and LV diastolic function in response to a beta-AR agonist, pre- to post-prolonged exercise, remain unclear. Seven trained males (mean+/-s.d., age 27+/-6 years) performed 4 h of ergometer rowing. Peak heart rate (HR) and LV systolic and diastolic functional responses to incremental isoproterenol (isoprenaline) infusion (2, 4 and 6 microg kg min-1) were assessed after vagal blockade (glycopyrrolate, 1.2 mg). LV systolic function was assessed by the pressure/volume ratio (systolic blood pressure/end systolic volume) and , whilst diastolic function was evaluated as peak early and late transmitral filling velocities. Following exercise, the pressure/volume ratio decreased by 25% (P<0.05), whereas was unchanged (P>0.05). The early/late filling ratio was reduced by 36% after exercise, due to an elevation in late LV filling (P<0.01). The increase in HR response to isoproterenol infusion was blunted post-exercise at both 4 and 6 microg kg min-1 (127+/-7 and 132+/-6 beats min-1) compared with pre-exercise (138+/-8 and 141+/-12 beats min-1, P<0.05). Additionally, the pressure/volume ratio and were blunted post-exercise in response to isoproterenol (P<0.05). In contrast, diastolic function was similar before and after exercise during isoproterenol infusion (P>0.05). Desensitization of the beta-AR contributes to an attenuated left ventricular systolic but not diastolic function following prolonged exercise.
Adrenergic beta-Agonists↗
Time course analysis of baroreflex sensitivity during postural stress.
Postural stress requires immediate autonomic nervous action to maintain blood pressure. We determined time-domain cardiac baroreflex sensitivity (BRS) and time delay (tau) between systolic blood pressure and interbeat interval variations during stepwise changes in the angle of vertical body axis (alpha). The assumption was that with increasing postural stress, BRS becomes attenuated, accompanied by a shift in tau toward higher values. In 10 healthy young volunteers, alpha included 20 degrees head-down tilt (-20 degrees), supine (0 degree), 30 and 70 degrees head-up tilt (30 degrees, 70 degrees), and free standing (90 degrees). Noninvasive blood pressures were analyzed over 6-min periods before and after each change in alpha. The BRS was determined by frequency-domain analysis and with xBRS, a cross-correlation time-domain method. On average, between 28 (-20 degrees) to 45 (90 degrees) xBRS estimates per minute became available. Following a change in alpha, xBRS reached a different mean level in the first minute in 78% of the cases and in 93% after 6 min. With increasing alpha, BRS decreased: BRS = -10.1.sin(alpha) + 18.7 (r(2) = 0.99) with tight correlation between xBRS and cross-spectral gain (r(2) approximately 0.97). Delay tau shifted toward higher values. In conclusion, in healthy subjects the sensitivity of the cardiac baroreflex obtained from time domain decreases linearly with sin(alpha), and the start of baroreflex adaptation to a physiological perturbation like postural stress occurs rapidly. The decreases of BRS and reduction of short tau may be the result of reduced vagal activity with increasing alpha.
Adaptation, Physiological↗
MCA Vmean and the arterial lactate-to-pyruvate ratio correlate during rhythmic handgrip.
Regulation of cerebral blood flow during physiological activation including exercise remains unknown but may be related to the arterial lactate-to-pyruvate (L/P) ratio. We evaluated whether an exercise-induced increase in middle cerebral artery mean velocity (MCA Vmean) relates to the arterial L/P ratio at two plasma lactate levels. MCA Vmean was determined by ultrasound Doppler sonography at rest, during 10 min of rhythmic handgrip exercise at approximately 65% of maximal voluntary contraction force, and during 20 min of recovery in seven healthy male volunteers during control and a approximately 15 mmol/l hyperglycemic clamp. Cerebral arteriovenous differences for metabolites were obtained by brachial artery and retrograde jugular venous catheterization. Control resting arterial lactate was 0.78 +/- 0.09 mmol/l (mean +/- SE) and pyruvate 55.7 +/- 12.0 micromol/l (L/P ratio 16.4 +/- 1.0) with a corresponding MCA Vmean of 46.7 +/- 4.5 cm/s. During rhythmic handgrip the increase in MCA Vmean to 51.2 +/- 4.6 cm/s was related to the increased L/P ratio (23.8 +/- 2.5; r2 = 0.79; P < 0.01). Hyperglycemia increased arterial lactate and pyruvate to 1.9 +/- 0.2 mmol/l and 115 +/- 4 micromol/l, respectively, but it did not significantly influence the L/P ratio or MCA Vmean at rest or during exercise. Conversely, MCA Vmean did not correlate significantly, neither to the arterial lactate nor to the pyruvate concentrations. These results support that the arterial plasma L/P ratio modulates cerebral blood flow during cerebral activation independently from the plasma glucose concentration.
Adult↗
Carotid-cardiac baroreflex function does not influence blood pressure regulation during head-up tilt in humans.
The influence of the carotid-cardiac baroreflex on blood pressure regulation was evaluated during supine rest and 40 degrees head-up tilt (HUT) in 9 healthy young subjects with and without full cardiac vagal blockade. The carotid baroreflex responsiveness, or maximal gain (G(MAX)), was assessed from the beat-to-beat changes in heart rate (HR) and mean arterial pressure (MAP) by the variable neck pressure and suction technique ranging in pressure from +40 to -80 Torr, with and without glycopyrrolate (12.0 +/- 1.0 microg/kg body weight; mean +/- SE). In the supine position, glycopyrrolate increased the HR to 91 +/- 3 bpm, from 54 +/- 3; MAP to 89 +/- 2 mmHg, from 76 +/- 2; and cardiac output to 6.8 +/- 0.3 l.min(-1), from 4.9 +/- 0.3 (P < 0.05). The G(MAX) of the carotid baroreflex control of HR was reduced to -0.06 +/- 0.01 bpm.mmHg(-1), from -0.30 +/- 0.02 (P < 0.05) with no significant effect on the G(MAX) of the carotid baroreflex control of MAP. During HUT the carotid baroreflex control of MAP was unchanged, though the G(MAX) of the carotid baroreflex control of HR was increased (P < 0.05). During HUT, central blood volume, assessed by electrical thoracic admittance, and total vascular conductance were decreased with and without glycopyrrolate. Furthermore, glycopyrrolate reduced G(MAX) of the carotid baroreflex control of HR during HUT (P < 0.05) with no significant effect on G(MAX) of the carotid baroreflex control of MAP. These data suggest that during supine rest and HUT-induced decreases in central blood volume, the carotid baroreflex control of HR is mediated primarily via parasympathetic activity. Furthermore, the maintenance of arterial blood pressure during postural stress is primarily mediated by arterial and cardiopulmonary reflex regulation of sympathetic activity and its effects on the systemic vasculature.
Adult↗
Metabolism of perfused pig intercostal muscles evaluated by 31P-magnetic resonance spectroscopy.
This study presents a perfused preparation for evaluation of metabolism in pig intercostal muscle in vitro. Preserved vessels and nerves to an intercostal segment including two adjacent ribs allowed for tissue perfusion and electrical stimulation with measurement of contraction force, oxygen consumption and 31P-magnetic resonance spectroscopy (31P-MRS). When perfused at rest with Krebs-Ringer buffer, the preparation maintained physiological levels of phosphocreatine (PCr), inorganic phosphate (Pi), ATP and pH at a stable oxygen consumption of 0.51 +/- 0.01 micromol min(-1) g(-1) for more than 2 h. Tonic stimulation of the nerve caused anaerobic energy consumption as PCr and pH decreased, and both variables recovered after the contraction with half-time values of approximately 7 min. Force increased to 0.040 N g(-1) (range, 0.031-0.103 N g(-1)) and it gradually decreased by about 70% during the subsequent 5 min of stimulation. The calculated free ADP concentration increased from 7.4 +/- 2.1 nmol g(-1) at rest to 28 +/- 12 nmol g(-1) (mean +/- s.d.) by the end of the stimulation. Thus anaerobic ATP turnover was zero at rest, 6.1 +/- 2 micromol min(-1) g(-1) during the first minute of stimulation and 3.5 +/- 0.5 micromol min(-1) g(-1) during the two last minutes, corresponding to the drop in force. When the preparation was left unperfused, anaerobic ATP turnover averaged 0.40 +/- 0.15 micromol min(-1) g(-1) for the first 10 min. The preparation can also be applied to human intercostal muscles, as demonstrated in one preliminary experiment. The results demonstrate a stable and functional in vitro preparation of intact perfused intercostal muscles in the pig.
Adenosine Diphosphate↗
Cerebrospinal fluid IL-6, HSP72, and TNF-alpha in exercising humans.
During exercise the concentration of interleukin (IL)-6 and of heat shock protein (HSP) 72 increases in plasma, especially in fasting subjects. Both IL-6 and HSP72 are involved in a variety of metabolic and immunological processes, including some within the central nervous system and, accordingly, they are present not only in plasma but also in the cerebrospinal fluid (CSF). To evaluate whether, the two pools equilibrate we determined the levels of IL-6 and HSP72 in CSF, at a time when their plasma levels were increased due to exercise. Measurements of TNF-alpha served as a control, as its plasma level remains stable during exercise. Two groups of healthy, fit males performed 2 h of strenuous exercise with either carbohydrate ingestion (n=8) or placebo (n=8). The concentration of IL-6, HSP72, and TNF-alpha was measured in arterial blood and in the CSF obtained by a lumbar puncture immediately after exercise. A third group of subjects served as resting controls (n=8). At rest, CSF levels of IL-6 and HSP72 were 2- and 3-fold higher than the plasma levels, respectively (P<.05). During exercise, with and without carbohydrate ingestion, plasma IL-6 increased 8- and 18-fold, respectively, and HSP72 increased 5-fold (P<.05). However, the concentrations of IL-6 and HSP72 in CSF did not change with exercise and were therefore below their corresponding plasma levels. The concentration of TNF-alpha in CSF was below that in plasma and both remained stable during exercise. The findings that resting CSF levels of IL-6 and HSP72 are higher than in plasma and that they remain stable despite exercise-induced, profound increases in their systemic levels, suggest that the CSF pool is segregated from that in blood.
Adult↗
Cardiac and vasomotor components of the carotid baroreflex control of arterial blood pressure during isometric exercise in humans.
We sought to examine the importance of the cardiac component of the carotid baroreflex (CBR) in control of blood pressure during isometric exercise. Nine subjects performed 4 min of ischaemic isometric calf exercise at 20% of maximum voluntary contraction. Trials were repeated with beta1-adrenergic blockade (metoprolol, 0.15 +/- 0.003 mg kg(-1)) or parasympathetic blockade (glycopyrrolate, 13.6 +/- 1.5 microg kg(-1)). CBR function was determined using rapid pulses of neck pressure and neck suction from +40 to -80 mmHg, while heart rate (HR), mean arterial pressure (MAP) and changes in stroke volume (SV, Modelflow method) were measured. Metoprolol decreased and glycopyrrolate increased HR and cardiac output both at rest and during exercise (P < 0.05), while resting and exercising blood pressure were unchanged. Glycopyrrolate reduced the maximal gain (G(max)) ofthe CBR-HR function curve (-0.58 +/- 0.10 to -0.06 +/- 0.01 beats min(-1) mmHg(-1), P < 0.05), but had no effect on the G(max) of the CBR-MAP function curve. During isometric exercise the CBR-HR curve was shifted upward and rightward in the metoprolol and no drug conditions, while the control of HR was significantly attenuated with glycopyrrolate (P < 0.05). Regardless of drug administration isometric exercise produced an upward and rightward resetting of the CBR control of MAP with no change in G(max). Thus, despite marked reductions in CBR control of HR following parasympathetic blockade, CBR control of blood pressure was well maintained. These data suggest that alterations in vasomotor tone are the primary mechanism by which the CBR modulates blood pressure during low intensity isometric exercise.
Adult↗
Cerebral autoregulation and CO2 responsiveness of the brain.
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Blood Pressure↗
Erythrocytes and the regulation of human skeletal muscle blood flow and oxygen delivery: role of erythrocyte count and oxygenation state of haemoglobin.
Blood flow to dynamically contracting myocytes is regulated to match O(2) delivery to metabolic demand. The red blood cell (RBC) itself functions as an O(2) sensor, contributing to the control of O(2) delivery by releasing the vasodilators ATP and S-nitrosohaemoglobin with the offloading of O(2) from the haemoglobin molecule. Whether RBC number is sensed remains unknown. To investigate the role of RBC number, in isolation and in combination with alterations in blood oxygenation, on muscle and systemic perfusion, we measured local and central haemodynamics during one-legged knee-extensor exercise ( approximately 50% peak power) in 10 healthy males under conditions of normocythaemia (control), anaemia, anaemia + plasma volume expansion (PVX), anaemia + PVX + hypoxia, polycythaemia, polycythaemia + hyperoxia and polycythaemia + hypoxia, which changed either RBC count alone or both RBC count and oxyhaemoglobin. Leg blood flow (LBF), cardiac output (Q) and vascular conductance did not change with either anaemia or polycythaemia alone. However, LBF increased with anaemia + PVX (28 +/- 4%) and anaemia + PVX + hypoxia (46 +/- 6%) and decreased with polycythaemia + hyperoxia (18 +/- 5%). LBF and Q with anaemia + PVX + hypoxia (8.0 +/- 0.5 and 15.8 +/- 0.7 l min(-1), respectively) equalled those during maximal knee-extensor exercise. Collectively, LBF and vascular conductance were intimately related to leg arterial-venous (a-v) O(2) difference (r(2)= 0.89-0.93; P < 0.001), suggesting a pivotal role of blood O(2) gradients in muscle microcirculatory control. The systemic circulation accommodated to the changes in muscle perfusion. Our results indicate that, when coping with severe haematological challenges, local regulation of skeletal muscle blood flow and O(2) delivery primarily senses alterations in the oxygenation state of haemoglobin and, to a lesser extent, alterations in the number of RBCs and haemoglobin molecules.
Adaptation, Physiological↗
Supraorbital cutaneous blood flow rate during carotid endarterectomy.
BACKGROUND: The supraorbital skin region is supplied by the supraorbital artery, which is a branch of the internal carotid artery. The supraorbital cutaneous blood flow rate may therefore be influenced by changes in the internal carotid artery flow during carotid endarterectomy. METHODS: The supraorbital cutaneous blood flow rate was measured by the application of heat to the skin and following the subsequent dissipation of the heat in seven patients undergoing carotid endarterectomy. At the same time, the oxygenation in the right and left frontal region was monitored by near-infrared spectroscopy (NIRS). RESULTS: During cross-clamping of the carotid artery, the ipsilateral NIRS-determined frontal oxygenation tended to decrease [67 +/- 13% to 61 +/- 11% (P = 0.06); contralateral 68 +/- 11% to 66 +/- 8%] as did the supraorbital cutaneous blood flow rate from 56 +/- 23 to 44 +/- 7 ml 100 g(-1) min(-1). With the opening of the external carotid artery, the NIRS-determined frontal oxygenation reversed to 66 +/- 8% (P<0.05) on the ipsilateral side, with no significant change on the contralateral side and the supraorbital cutaneous blood flow rate increased to 53 +/- 11 (P<0.05). Opening of the internal carotid artery did not significantly affect the NIRS (67 +/- 8% and 69 +/- 9%; ipsilateral, contralateral), but the supraorbital cutaneous blood flow rate increased to 88 +/- 10 ml 100 g(-1) min(-1) (P<0.001). CONCLUSION: Cross-clamping of the internal carotid artery affects the supraorbital cutaneous blood flow rate as well as the frontal lobe oxygenation.
Blood Pressure↗