Middle cerebral artery blood velocity, arterial diameter and muscle sympathetic nerve activity during post-exercise muscle ischaemia.

During exercise the transcranial Doppler determined mean blood velocity (Vmean) increases in the middle cerebral artery (MCA) and reflects cerebral flood flow when the diameter at the site of investigation remains constant. Sympathetic activation could induce MCA vasoconstriction and in turn elevate Vmean at an unchanged cerebral blood flow. In 12 volunteers we evaluated whether Vmean relates to muscle sympathetic nerve activity (MSNA) in the peroneal nerve during rhythmic handgrip and post-exercise muscle ischaemia (PEMI). The luminal diameter of the dorsalis pedis artery (AD) was taken to reflect the MSNA influence on a peripheral artery. Rhythmic handgrip increased heart rate (HR) from 74 +/- 20 to 92 +/- 21 beats min-1 and mean arterial pressure (MAP) from 87 +/- 7 to 105 +/- 9 mmHg (mean +/- SD; P < 0.05). During PEMI, HR returned to pre-exercise levels while MAP remained elevated (101 +/- 9 mmHg). During handgrip contralateral MCA Vmean increased from 65 +/- 10 to 75 +/- 13 cm s-1 and this was more than on the ipsilateral side (from 63 +/- 10 to 68 +/- 10 cm s-1; P < 0.05). On both sides of the brain Vmean returned to baseline during PEMI. MSNA did not increase significantly during handgrip (from 56 +/- 24 to 116 +/- 39 units) but the elevation became statistically significant during PEMI (135 +/- 86 units, P < 0.05), while AD did not change. Taken together, during exercise and PEMI, Vmean changed independent of an elevation of MSNA by more than 140% and the dorsalis pedis artery diameter was stable. The results provide no evidence for a vasoconstrictive influence of sympathetic nerve activity on medium size arteries of the limbs and the brain during rhythmic handgrip and post-exercise muscle ischaemia.

Influence of Naloxone on the cellular immune response to head-up tilt in humans.

To evaluate a possible role for beta-endorphin in the stress-induced modulation of natural killer (NK) cells, immunologically competent blood cells were followed in eight male volunteers administered either Naloxone or saline (control) during head-up tilt maintained until the appearance of presyncopal symptoms (PS). The PS appeared more rapidly with Naloxone compared to control [5.7 (SEM 1.1) vs 22.3 (SEM 5.1) min; P = 0.01]. The NK cell activity increased threefold during PS partly due to an increase in CD16+ and CD56+ NK cells in blood. In support, NK cell activity boosted with interferon-alpha and interleukin 2 rose in parallel with unboosted NK cell activity and NK cell concentration and activities returned to the baseline level after 105 min. The total lymphocyte count and the concentrations of CD3+, CD4+, CD8+, CD16+, and CD56+ cells increased during PS. Head-up tilt also induced an increase in plasma adrenaline concentration during control PS and a rise in plasma cortisol and adrenocorticotropic hormone concentrations up to 30 min thereafter, whereas no significant changes were found in plasma concentrations of noradrenaline, growth hormone, or beta-endorphin. The results would indicate an influence of endorphin on the increase in plasma adrenaline concentration during head-up tilt and at the same time contra-indicate a significant role for adrenaline in the provocation of PS. The influence of head-up tilt on plasma beta-endorphin was too small to influence the modulation of the cellular immune system.

Central command increases cardiac output during static exercise in humans.

Neural control of the circulation during static two-leg exercise was evaluated in 10 subjects. External compression of the legs was employed to assess muscle mechano-receptor influence by achieving the same intramuscular pressure (80 mmHg) as developed during exercise. The muscle metabo-reflex contribution was assessed by post-exercise muscle ischaemia, and the influence from higher centres in the central nervous system ('central command') was taken as the part of the response that could not be accounted for by the two reflex contributions. During static exercise, mean arterial pressure was higher (26 +/- 3 mmHg; P < 0.01) as compared with leg compression (10 +/- 2 mmHg) and with post-exercise muscle ischaemia (11 +/- 2 mmHg). Heart rate (25 +/- 4 b.p.m.) and cardiac output (0.8 +/- 0.3 L min-1) were increased only during static exercise (P < 0.05). Increase in total peripheral resistance were similar during static exercise, post-exercise muscle ischaemia and leg compression. The pressor response to static exercise with a large muscle group was equally attributable to mechanical and metabolic stimulation of afferent nerves; and the two influences were redundant in their effect on total peripheral resistance. In contrast, the influence from central command was directed to the heart with elevation of its rate and minute volume.

Sympathetic influence on cardiovascular responses to sustained head-up tilt in humans.

Sympathetic beta-adrenergic influences on cardiovascular responses to 50 degrees head-up tilt were evaluated with metoprolol (beta 1-blockade; 0.29 mg kg-1) and propranolol (beta 1 and beta 2-blockade; 0.28 mg kg-1) in eight males. A normotensive-tachycardic phase was followed by a hypotensive-bradycardic episode associated with presyncopal symptoms after 23 +/- 3 min (control, mean +/- SE). Head-up tilt made thoracic electrical impedance (3.0 +/- 1.0 omega), mean arterial pressure (MAP, 86 +/- 4-93 +/- 4 mmHg), heart rate (HR, 63 +/- 3-99 +/- 10 beats min-1) and total peripheral resistance (TPR, 15 +/- 1-28 +/- 4 mmHg min L-1) increase, while central venous oxygen saturation (74 +/- 2-58 +/- 4%), cardiac output (5.7 +/- 0.1-3.1 +/- 0.3 L min-1), stroke volume (95 +/- 6-41 +/- 5 mL) and pulse pressure (55 +/- 4-49 +/- 4 mmHg) decreased (P < 0.05). Central venous pressure decreased during head-up tilt (7 +/- 2-0 +/- 1 mmHg), but it remained stable during the sustained tilt. At the appearance of presyncopal symptoms MAP (49 +/- 3 mmHg), HR (66 +/- 4 beats min-1) and TPR (15 +/- 3 mmHg min L-1) decreased (P < 0.05). Neither metoprolol or propranolol changed tilt tolerance or cardiovascular variables, except for HR that remained at 57 +/- 2 (metoprolol) and 55 +/- 3 beats min-1 (propranolol), and MAP that remained at 87 +/- 5 mmHg during the first phase with metoprolol. In conclusion, sympathetic activation was crucial for the heart rate elevation during normotensive head-up tilt, but not for tilt tolerance or for the associated hypotension and bradycardia.

Brain and muscle oxygen saturation during head-up-tilt-induced central hypovolaemia in humans.

Near-infrared spectrophotometry-determined cerebral (ScO2) and muscle oxygen saturations (SmO2) were followed in 15 volunteers during passive 50 degrees head-up-tilt-induced central hypovolaemia, and in nine volunteers during ventilatory manoeuvres affecting arterial carbon dioxide tension. During head-up tilt, mean arterial pressure [MAP, 88 (77-118) to 97 (80-136) mmHg, median and range] and heart rate [HR; 66 (49-77) to 87 (42-132) beats min-1 P < 0.01] increased, but after 22 (1-45) min they declined [to 61 (40-91) mmHg and 69 (38-109) beats min-1, respectively, P = 0.001] and pre-syncopal symptoms developed. Central hypovolaemia was indicated by an increased thoracic electrical impedance, and a decreased cardiac output and central venous oxygen saturation. The arterial oxygen saturation, pulmonal oxygen uptake and skin temperatures remained constant. The ScO2 remained stable at 72 (62-77)% until the pre-syncopal incidence, when it decreased to 62 (31-73)% (P = 0.001), and tilt down made it increase to 75 (36-87)% (P < 0.05) before the recovery value was established. In contrast, SmO2 decreased during tilting [75(70-87) to 65 (53-70)%], and recovered to 70 (53-83)%, P < 0.01) during the hypotensive episode. The end-tidal CO2 tension decreased only during tilt-up. The ScO2 decreased, and SmO2 increased during hyperventilation, and ScO2 increased during breathing of 5% carbon dioxide. Rebreathing from a bag made SmO2 decrease and resulted in a biphasic ScO2 response: it first increased and subsequently decreased. Cardiovascular changes during tilt were not reflected in skin temperature. The ScO2 reflected the maintained autoregulation of cerebral blood flow until the perfusion pressure decreased markedly. In contrast, SmO2 mirrored muscle vasoconstriction early during tilt, and vasodilatation when pre-syncopal symptoms appeared.

Digoxin affects potassium homeostasis during exercise in patients with heart failure.

OBJECTIVE: The aim was to evaluate whether digitalisation of heart failure patients affects extrarenal potassium handling during and following exercise, and to assess digoxin receptor occupancy in human skeletal muscle in vivo. METHODS: In a paired study of before versus after digitalisation, 10 patients with congestive heart failure underwent identical exercise sessions consisting of three bouts of increasing work rates, 41-93 W, on a cycle ergometer. The final bouts were followed by exercise to exhaustion. The femoral vessels and brachial artery were catheterised. Arterial blood pressure, heart rate, leg blood flow, cardiac output, plasma potassium, haemoglobin, pH, and skeletal muscle receptor occupancy with digoxin in biopsies were determined. RESULTS: Occupancy of skeletal muscle Na/K-ATPase with digoxin was 9% (P < 0.05). Following digitalisation femoral venous plasma potassium increased by 0.2-0.3 mmol.litre-1 (P < 0.05) at work rates of 69 W, 93 W, and at exhaustion, as well as during the first 3 min of recovery. Following digitalisation the femoral venoarterial difference in plasma potassium increased by 50-100% (P < 0.05) during exercise, and decreased by 66-75% (P < 0.05) during early recovery. Total loss of potassium from the leg increased by 138%. The effects of digitalisation on plasma potassium were not the outcome of changes in haemodynamics, because cardiac output and leg blood flow increased by up to 13% and 19% (P < 0.05), nor was it the outcome of changes in haemoconcentration or pH. CONCLUSIONS: Extrarenal potassium handling is altered as a result of digoxin treatment. This is likely to reflect a reduced capacity of skeletal muscle Na/K-ATPase for active potassium uptake because of inhibition by digoxin, adding to the reduction of skeletal muscle Na/K-ATPase concentration induced by heart failure per se. In heart failure patients, improved haemodynamics induced by digoxin may, however, increase the capacity for physical conditioning. Thus the impairment of extrarenal potassium homeostasis by heart failure and digoxin treatment may be counterbalanced by training.

Reduced arterial diameter during static exercise in humans.

In eight subjects luminal diameter of the resting limb radial and dorsalis pedis arteries was determined by high-resolution ultrasound (20 MHz). This measurement was followed during rest and during 2 min of static handgrip or of one-leg knee extension at 30% of maximal voluntary contraction of another limb. Static exercise increased heart rate and mean arterial pressure, which were largest during one-leg knee extension. After exercise heart rate and mean arterial pressure returned to the resting level. No changes were recorded in arterial carbon dioxide tension, and the rate of perceived exertion was approximately 15 units after both types of exercise. The dorsalis pedis arterial diameter was 1.50 +/- 0.20 mm (mean and SE) and the radial AD 2.45 +/- 0.12 mm. During both types of contractions the luminal diameters decreased approximately 3.5% within the first 30 s (P < 0.05), and during one-leg knee extension they continued to decrease to a final exercise value 7.6 +/- 1.1% lower than at rest (P < 0.05). Thus, they became smaller than during the handgrip. After exercise resting values were reestablished. When the arterial diameter was expressed in relation to mean arterial pressure for the radial and dorsalis pedis artery was 22 +/- 3 and 28 +/- 3% lower during handgrip than the relation during rest, respectively. After one-leg knee extension both arteries reached 30 +/- 4% lower values. This study demonstrated arterial constriction in the resting limbs within the first 30 s of static exercise, and continued constriction during one-leg knee extension.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of epidural anaesthesia on dorsal pedis arterial diameter and blood flow.

In nine subjects the influence of low (LE: blockade at or below the umbilicus; Th. 10) and high epidural anaesthesia (HE: block above the umbilicus) on vascular tone was evaluated by high frequency ultrasound (20 mHz) determined luminal diameter and a Doppler (8 mHz) assessment of mean blood flow velocity (Vmean) in the dorsalis pedis artery. The LE was induced by 0.5% bupivacain through a catheter at L3-L4, and HE was established by further infusion. Resting blood pressure and heart rate were not affected by LE or HE. One subject developed selective thoracic anaesthesia, and another was blocked on the contralateral side only. In the seven adequately blocked subjects, the luminal diameter of the dorsalis pedis artery increased from 1.70 (1.25-1.93) to 1.90 (1.75-2.23) mm during LE (+12%) and further to 2.08 (1.83-2.96) mm during HE (22%; P < 0.05). The Vmean was similar during control (7[4-26] cm s-1) and LE (12[4-55] cm s-1), but increased during HE to 35(12-78 cm s-1 (+500%; P < 0.05). Thus, arterial blood flow was higher during LE (21[7-98] ml min-1; +263%) and HE (94[21-177] ml min-1; +1175%) than at rest (8[7-36] ml min-1; P < 0.05). This study quantified the importance of sympathetic nerve activity for vascular tone and in turn blood flow in an artery of a resting human limb, as the diameter and Vmean increased with progressive epidural anaesthesia.

Dynamic exercise enhances regional cerebral artery mean flow velocity.

Dynamic exercise enhances regional cerebral artery mean flow velocity. J. Appl. Physiol. 78(1): 12-16, 1995.--Anterior (ACA) and middle (MCA) cerebral artery mean flow velocities (Vmean) and pulsatility indexes were determined using transcranial Doppler in 14 subjects during dynamic exercise after assessment of the carbon dioxide reactivity for both arteries. Right hand contractions provoked an elevation in left MCA Vmean [19% (12-28); P < 0.01], whereas the pulsatility decreased in all four arteries (P < 0.05). During right foot movement, left ACA Vmean increased by 23% (11-37; P < 0.01) with lesser (approximately 10%; P < 0.05) increases in the other arteries, and pulsatility index decreased (P < 0.05). During cycling, ACA and MCA Vmean increased bilaterally by 23% (10-49) and 18% (5-32), respectively (P < 0.01), and the pulsatility was also elevated (P < 0.05). Cerebral artery pulsatility did not demonstrate a focal response but depended did not demonstrate a focal response but depended on the muscle mass involved during exercise. The data demonstrate a significant increase in Vmean for the artery supplying the cortical projection of the exercising limb. Insignificant and marginally significant increases in Vmean may be related to sympathetically mediated vasoconstriction and/or coactivation of untargeted muscle groups.

Naloxone-provoked vaso-vagal response to head-up tilt in men.

A double-blind paired protocol was used to evaluate, in eight male volunteers, the effects of the endogenous opiate antagonist naloxone (NAL; 0.05 mg.kg-1) on cardiovascular responses to 50 degrees head-up tilt-induced central hypovolaemia. Progressive central hypovolaemia was characterized by a phase of normotensive-tachycardia followed by an episode of hypotensive-bradycardia. The NAL shortened the former from 20 (8-40) to 5 (3-10) min (median and range; P < 0.02). Control head-up tilt increased the means of thoracic electrical impedance [from 35.8 (SEM 2.1) to 40.0 (SEM 1.8) omega; P < 0.01] of heart rate [HR; from 67 (SEM 5) to 96 (SEM 8) beats.min-1, P < 0.02], of total peripheral resistance [TPR; from 25.5 (SEM 3.2) to 50.4 (SEM 10.5)mmHg.min.1-1, P < 0.05] and of mean arterial pressure [MAP; from 96 (SEM 2) to 101 (SEM 2)mmHg, P < 0.02]. Decreases were observed in stroke volume [from 65 (SEM 12) to 38 (SEM 9) ml, P < 0.01], in cardiac output [from 3.7 (SEM 0.7) to 2.5 (SEM 0.5) 1.min-1, P < 0.01], in pulse pressure [from 55 (SEM 4) to 37 (SEM 3)mmHg, P < 0.01] and in central venous oxygen saturation [from 73 (SEM 2) to 59 (SEM 4)%, P < 0.01]. During NAL, mean HR increased from 70 (SEM 3); n.s. compared to control) to only 86 (SEM 9) beats.min-1 (P < 0.02 compared to control) and MAP remained stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Reflex increase in blood pressure induced by leg compression in man.

1. We tested the hypotheses that the increase in mean arterial pressure with the application of external leg compression in man is (i) blocked with epidural anaesthesia, and (ii) dependent upon the level of external pressure applied, the quantity of leg muscle mass compressed and the vascular volume of the leg. Fourteen healthy subjects were fitted with an anti-shock trouser garment to provide three levels (30, 60 and 90 mmHg) of leg compression, while cephalad translocation of fluid was prevented by upper-thigh cuffs inflated to a supra-systolic pressure. Cardiovascular responses were recorded during leg compression before and after the administration of epidural anaesthesia in eight subjects, while blood pressure responses from six subjects were compared with their single leg pressor response. 2. Both mean arterial and diastolic pressures were elevated with increasing leg compression, with no changes in heart rate, cardiac output, thoracic impedance, and central venous pressure. The leg compression-induced blood pressure increases were abolished by epidural anaesthesia. Furthermore, when only one leg was compressed at 90 mmHg, the pressor response was less than that elicited from compression of both legs at the same external pressure. Changes in vascular volume of the leg did not influence the pressor response to leg compression. 3. The results indicate that the mean arterial pressure increases in response to external compression of the legs and that a reflex mechanism, mediated by muscle afferent nerves, is involved. The response is dependent upon both the changes in intramuscular pressure and the quantity of muscle mass compressed.

Maximal oxygen deficit of sprint and middle distance runners.

Anaerobic energy capacity was evaluated by maximal oxygen deficit (MOD) as well as by blood gas and muscle biopsy variables during short exhausting running in six recreational (RR) and eight competitive sprint and middle distance runners (SMDR). On 3 days runs to exhaustion were executed. Two runs were performed at a treadmill gradient of 15% at speeds which resulted in exhaustion after approximately 1 (R15%,1 min) and 2-3 min (R15%,2-3 min), respectively. On the 3rd day, the subjects ran with the treadmill at a gradient of 1% at a speed which caused exhaustion after 2-3 min (R1%,2-3 min). The runner performance was assessed from 400 m [RR, median 64.8 (range 62.2-69.6) s; SMDR, median 49.4 (range 48.5-52.0) s] and 800 m [RR, median 158.8 (range 153.3-170.2) s; SMDR, median 115.2 (range 113.3-123.3) s] track times. Muscle biopsies from gastrocnemius muscle were obtained before and immediately after R15%,2-3 min, from which muscle lactate and creatine phosphate (CP) concentrations, fibre type distribution, capillaries per fibre, total lactate dehydrogenase (LDH) activity and the LDH isoenzyme pattern were determined. The MOD increased with the treadmill gradient and duration. During both treadmill and track runs, SMDR performance was superior to that of RR, but no significant differences were observed with respect to MOD, muscle fibre type distribution, total LDH activity, its iso-enzyme pattern, changes in muscle lactate or CP concentrations. However, after treadmill runs, peak venous lactate concentration and partial pressures of carbon dioxide were higher, and pH lower in SMDR. Also the number of capillaries per muscle fibre and the maximal oxygen uptake were larger in SMDR. These findings would suggest that the superior performance of SMDR depended more on their aerobic than on their anaerobic capacity.

Peripheral venous oxygen saturation during head-up tilt induced hypovolaemic shock in humans.

We followed central, median cubital and dorsal metacarpal venous oxygen saturations (SvO2) during 50 degrees head-up tilt (anti-Trendelenburg's position) induced central hypovolaemia in eight males. Head-up tilt resulted in slight tachycardia of 101 (60-120) beats min-1 (median with range) and a stable mean arterial pressure (MAP) of 100 (88-114) mmHg. After 13 (6-23) min presyncopal symptoms appeared, accompanied by decreases in heart rate to 75 (51-97) beats min-1 and in MAP to 59 (49-76) mmHg (p < 0.01). Cardiac output decreased 0.9 (0.3-1.6) 1 min-1 while thoracic electrical impedance increased 3.4 (-1.2-5.9) Ohm (p < 0.01). Tilt-up decreased central venous pressure, but during sustained tilt it remained unchanged. Arterial oxygen saturation did not change. Head-up tilt decreased central SvO2 by 12 (5-24)% (p < 0.01). Median cubital SvO2 decreased 8 (-5-25)% (p < 0.02) during tilting, and it remained at this level during sustained tilt. Only five of eight samples from the dorsal metacarpal vein could be obtained. In these samples SvO2 was lowered by 15 (7-26)% (p = 0.01) at the onset of presyncopal symptoms. The results indicate that loss of central blood volume is reflected in central as well as peripheral SvO2. However, for reliable monitoring of blood volume changes, central SvO2 is the most useful variable, as this SvO2 changed consistently with the central blood volume, and blood samples could be obtained readily from the central venous catheter.

Accumulated oxygen deficit increases with inclination of uphill running.

This study examined whether accumulated oxygen deficit depends on treadmill grade during uphill running. Oxygen uptake was measured during steady-state submaximal running. By linear extrapolation at each grade, energy demand was estimated for short exhaustive runs. Oxygen deficit was the difference between this estimate and accumulated oxygen uptake. Six subjects ran at grades of 1, 15, and 20% (study I), and five males trained for anaerobic metabolism ran at 1, 10.5, and 15% (study II). Accumulated oxygen deficit was 40 +/- 11 (SD), 72 +/- 20, and 69 +/- 8 ml O2/kg, respectively (study I), and 57 +/- 8, 78 +/- 10, and 100 +/- 7 ml O2/kg (study II). The finding that accumulated oxygen deficit became larger with treadmill inclination could reflect involvement of an increasing muscle mass. However, variation in accumulated oxygen deficit was too large to make this possibility the only explanation. More likely at small treadmill inclinations energy demand for high-intensity running is underestimated by extrapolation from oxygen uptake during submaximal exercise. At high grades of uphill running, accumulated oxygen deficit reached a maximum that may reflect the subjects' anaerobic capacity for running. This hypothesis was substantiated by an enhanced accumulated oxygen deficit in the anaerobically trained subjects during 15%, but not during 1%, uphill running.