Plasma endothelin-1 during central hypovolaemia in man.

Endothelin-1 (ET-1) is a potent vasoconstricting peptide with effect on resistance as well as capacitance vessels. We followed ET-1 in arterial plasma together with heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and thoracic electrical impedance (TI) in seven men during central hypovolaemia induced by 50 degrees head-up tilt. During tilting plasma ET-1 increased from 1.1 +/- 0.2 to 1.4 +/- 0.3 pmol l-1 (mean +/- SE) concomitant with an increase in total peripheral resistance (TPR) (from 15 +/- 2 to 25 +/- 3 mmHg min l-1) (P < 0.01), and HR (from 67 +/- 2 to 94 +/- 5 beats min-1) (P < 0.01) while MAP remained unchanged. CVP decreased (from 1.8 +/- 0.9 to -1.6 +/- 1.0 mmHg) (P < 0.01) during tilting and remained unchanged during sustained tilt despite further reduction of central blood volume as recorded by TI. Presyncopal symptoms occurred after 28 +/- 6 min associated with decreases in HR (to 70 +/- 6 beats min-1), MAP (from 90 +/- 3 to 52 +/- 4 mmHg) and TPR (to 11 +/- 2 mmHg min l-1) (P < 0.01). At this time plasma ET-1 reached its highest level of 1.6 +/- 0.3 pmol l-1 (P < 0.01). Data show that head-up tilt is associated with increased plasma concentrations of ET-1 which may play a role in maintaining vascular tone in situations with a reduced central blood volume.     

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° 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) ; 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 · mint, 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. The episode of hypotensive-bradycardia appeared as mean control HR decreased to 77 (SEM 7)beats · min^–1, TPR to 31.4(SEM 7.7)mmHg · min · 1^–1 and MAP to 60 (SEM 5)mmHg (P < 0.01), and the volunteers were tilted supine. Cardiovascular effects of naloxone on central hypovolaemia included a reduced elevation of HR and blood pressures and provocation of the episode of hypotensive-bradycardia.     

Arterial diameter during central volume depletion in humans

The luminal diameter of the radial artery was followed by high frequency ultrasound during 50° head-up tilt-induced central volume depletion in ten healthy subjects of whom six were tilted twice and pretreated with the serotonin receptor antagonist methysergide or placebo following a double-blind randomized design. Eight subjects without active treatment experienced presyncopal symptoms after 16–45 (mean 32 min). Central volume depletion was indicated by an increase in mean thoracic electrical impedance [from 31.5 (SEM 1.6) to 33.4 (SEM 1.7) P < 0.05]. Cardiac output decreased [from 4.1 (SEM 0.3) to 2.2 (SEM 0.3) l · min^–1] and heart rate [HR, from 64 (SEM 3) to 100 (SEM 7) beats · min^–1], mean arterial pressure {MAP, from 77 (SEM 4) to 89 (SEM 2) mmHg [10.3 (SEM 0.53 to 11.9 (SEM 0.27) kPa]} and total peripheral resistance {TPR, from 19 (SEM 2) to 34 (SEM 4) mmHg · min · l^–] [2.5 (SEM 0.27) to 4.5 (SEM 0.53) kPa · min^–1]} increased; but with the appearance of presyncopal symptoms, HR, MAP and TPR were reduced to 65 (SEM 8) beats · min^–1, 46 (SEM 4) mmHg [6.1(SEM 0.53) kPa] and 18 (SEM 3) mmHg · min · l^–1 [2.4 (SEM 0.4) kPa · min^–1 · l^–], respectively (P < 0.05). Vascular resistance was reflected in the arterial diameter which decreased from 2.42 (SEM 0.17) to 2.27 (SEM 0.14) mm during head-up tilt and increased to 2.71 (SEM 0.14) mm with the appearance of presyncopal symptoms (P < 0.05). Methysergide reduced the resting radial (15 ± 2%) and temporal artery diameters (10 ± 3%) (P < 0.05); however, it affected neither tilt-tolerance nor the central cardiovascular response to tilt. The results suggested a serotonergic influence on arterial tone at rest, and demonstrated that vessels as large as the radial artery participated in vascular control during central volume depletion independent of such a serotonergic influence.     

Effects of triglycyl-lysine-vasopressin on cardiovascular responses to orthostatic stress

The influence of triglycyl-lysine-vasopressin (TGLVP) on cardiovascular responses to orthostatic stress was studied. Arterial pressures, heart rate (HR) and stroke volume (SV) were measured in eight healthy males subjected to 20 min 70 degrees head-up tilt. On different days they received either 0.01 mg/kg b.w. of TGLVP or a corresponding volume of 0.9% saline i.v. after 15 min supine rest. After the drug injection, in supine subjects, HR had decreased from 58 to 50 beats min-1, total peripheral resistance (TPR) was elevated by 29%, systolic (SAP) and diastolic pressure (DAP) had increased by 7 and 8 mmHg, respectively. During tilt, values for HR and SAP were similar with and without TGLVP whereas DAP and MAP were elevated 8 and 7 mmHg, respectively, by the drug. 4-8 min into the tilt, TGLVP caused an 8% sustained curtailment of SV. Both with and without the drug TPR increased by about 30% in response to head-up tilt. Thus, the marked peripheral arteriolar constriction after vasopressin in the supine position was not affected by head-up tilt. Tilting also abolished the drug-induced elevation in SAP, most likely explained by the reduction in SV. Although TPR was markedly increased by TGLVP during head-up tilt, reflected in the behaviour of DAP, the response of SV speaks against any beneficial effect of this drug on orthostatic tolerance in healthy subjects.     

Near-infrared spectrophotometry determined brain oxygenation during fainting

During orthostatic hypotension we evaluated whether presyncopal symptoms relate to a reduced brain oxygenation. Nine subjects performed 50° head-up tilt for 1 h and eight subjects were followed during 2 h of supine rest and during 1 h of 10° head-down tilt. Cerebral perfusion was assessed by transcranial Doppler determined middle cerebral artery blood velocity (MCA v_mean), while brain blood oxygenation was assessed by near-infrared spectrophotometry determined concentration changes for oxygenated (ΔHbO₂) and deoxygenated haemoglobin and brain cell oxygenation by the oxidized cytochrome c concentration (ΔCytO₂). During head-up tilt, six volunteers developed presyncopal symptoms and mean arterial pressure (88 (78–103) to 68 (57–79) mmHg; median and range), heart rate (96 (72–111) to 65 (50–107) beats min^?1), MCA v_mean (59 (51–82) to 41 (29–56) cm s^?1), ΔHbO₂ (by ?5.3 (?3.0 to ?14.8) μmol l^?1) and ΔCytO₂ were reduced (by ?0.2 (?0.1 to ?0.4) μmol l^?1; P < 0.05). During tilt down the cardiovascular variables recovered immediately and ΔHbO₂ increased to 2.2 (?0.9–12.0) mmol L^?1 above the resting value and also ΔCytO₂ recovered. In the nonsyncopal head-up tilted subjects as in the controls, blood pressure, heart rate, MCA v_mean and brain oxygenation indices remained stable. The results suggest that during orthostasis, presyncopal symptoms relate not only to cerebral hypoperfusion but also to reduced brain oxygenation.     

Diabetes affects blood pressure and heart rate responses during acute hypothermia

Many diabetics are cold-intolerant and experience dramatic changes in normal systemic function during hypothermia. Little is known of the cardiovascular adjustments in diabetics exposed to an acute cold stress. In an effort to identify the alterations in mean arterial blood pressure (MAP) and heart rate (HR) in the diabetic during environmental cooling (10 ± 2 °C), we compared the in vivo MAP and HR responses of urethane-anaesthetized (1.5 g kg^?1), streptozotocin-diabetic (STZ, 65 mg kg^?1, n = 12) and control (CON, n = 10) rats during acute hypothermia. MAP was measured directly via an indwelling carotid artery cannula and HR was calculated from the peak systolic pressure waves. Overall, the STZ rats were more cold-intolerant than CON as evidenced by the greater rate of decline in colonic temperature (T_c) from 36 to 28 °C (STZ, 0.16 °C min^?1 vs. CON, 0.06 °C min^?1; P < 0.05). Prior to cooling, HR was significantly lower (P < 0.05) in STZ (282 ± 9 beats min^?1) than in CON rats (399 ± 24 beats min^?1); however, during the acute hypothermic period, HR displayed a similar rate of decline in both groups. With respect to MAP, both groups demonstrated similar pre-experimental pressor responses (CON, 81.7 ± 5.4 vs. STZ, 83.2 ± 5.1 mmHg, P > 0.05). During progressive hypothermia, MAP gradually increased (P < 0.05) in the CON group from baseline (T_c = 36 °C) and reached peak values (118.4 ± 2.5 mmHg) at T_c = 30 °C, while the STZ group failed to exhibit any cold pressor response. At the conclusion of the experiment (T_c = 28 °C), the STZ group pressor response to hypothermia was not different from baseline (T_c = 36 °C, 83.2 ± 5.1 vs. T_c = 28 °C, 77.4 ± 3.4 mmHg; P > 0.05). The absence of any pressor response in the diabetic group during progressive hypothermia reflects the poor overall vasoconstrictive capacity to cooling and could partially explain the rapid decline of core temperature in this group.     

Cardiovascular and endocrine responses to haemorrhage in the pig

Heart rate (HR), mean arterial pressure (MAP), indices of sympathetic and parasympathetic activity (plasma concentrations of adrenaline, noradrenaline and pancreatic polypeptide, PP), vasopressin (VP) and aldosterone (ALDO) were measured in six pigs during continuous bleeding resulting in hypovolaemic shock, from which five survived. Three stages of haemorrhage could be defined. Stage I. Resting MAP was 85 ± 6 mmHg and increased to 96 ± 5 mmHg with a blood loss of 275 (range 250–300) (10 (9–12)% of the estimated blood volume) concomitant with an increase in HR from 105 ± 5 to 113 ± 6 beats min^-1 (P < 0.05). Stage II. After a blood loss of 375 (300–500) ml (15 (13–16)%) MAP fell to 62 ± 9 mmHg and HR to 95 ± 5 beats min^-1 (P < 0.05). Stage III. A blood loss of 1113 (825–1450) ml (44 (30–52)%) resulted in a MAP of 50 ± 4 mmHg and an increase in HR to 206 ± 3 beats min^-1 (P < 0.05). Adrenaline increased from 0.3 ± 0.1 to 0.8 ± 0.3 (stage II) and 3.6 ± 1.1 nmol l^-1 (stage III) (P < 0.05); noradrenaline from 0.4 ± 0.1 to 1.5 ± 0.4 (stage II) and 5.9 ± 1.7 nmol l^-1 (stage III) (P < 0.05); PP from 6.2 ± 1.6 to 13.3 ± 2.3 (stage II) and 20.9 ± 7.8 pmol l^-1 (stage III) (P < 0.05). VP changed only marginally, but ALDO increased from 496 ± 54 to 623 ± 76 pmol l^-1 (stage III) (P < 0.05). The results suggest that a high HR and intense sympathetic activity is seen during severe haemorrhage in the pig while vagal slowing of the heart and moderate hypotension are prominent when bleeding amounts to approximately 15% of the estimated blood volume.     

Middle cerebral artery blood velocity during exercise with β‐1 adrenergic and unilateral stellate ganglion blockade in humans

A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA V_mean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA V_mean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V_mean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA V_mean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s^?1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min^?1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min^?1) and ΔMCA V_mean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s^?1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA V_mean (10.2 ± 2.5 cm s^?1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system.     

Cardiovascular and ventilatory responses to electrically induced cycling with complete epidural anaesthesia in humans

Cardiovascular and ventilatory responses to electrically induced dynamic exercise were investigated in eight healthy young males with afferent neural influence from the legs blocked by epidural anaesthesia (25 ml 2% lidocaine) at L3-L4. This caused cutaneous sensory anaesthesia below T8-T9 and complete paralysis of the legs. Cycling was performed for 22.7 ± 2.7 min (mean, SE) (fatigue) and oxygen uptake (Vo₂) increased to 1.90 ± 0.13 1 min^-1. Compared with voluntary exercise at the same Vo₂, increases in heart rate (HR) (135 ± 7 vs. 130 ± 9 beats min^-1) and cardiac output (16.9 ± 1.1 vs. 17.3 ± 0.9 1 min^-1) were similar, and ventilation (54 ± 5 vs. 45 ± 4 1 min^-1) was higher (P < 0.05). In contrast, the rise in mean arterial blood pressure during voluntary exercise (93 ± 4 (rest) to 119 ± 4 mmHg (exercise)) was not manifest during electrically induced exercise with epidural anaesthesia [93 ± 3 (rest) to 95 ± 5 mmHg (exercise)]. As there is ample evidence for similar cardiovascular and ventilatory responses to electrically induced and voluntary exercise (Strange et al. 1993), the present results support the fact that the neural input from working muscle is crucial for the normal blood pressure response to exercise. Other haemodynamic and/or humoral mechanisms must operate in a decisive manner in the control of HR, CO and VE during dynamic exercise with large muscle groups.     

Effect of diazepam on endocrine and cardiovascular responses to head-up tilt in humans

Effects of the GABAergic drug diazepam (0.15 mg kg^-1, i.v.) on cardiovascular and endocrine responses to 50± head-up tilt were evaluated in seven men. During the initial phase of tilt (normotensive phase), increases in heart rate (HR) and total peripheral resistance (TPR) and decreases in cardiac output were unaffected by diazepam. Also the associated increase in plasma noradrenaline did not change, while response in plasma ACTH was diminished and in plasma cortisol abolished by diazepam (F(1, 10) = 6.45; P < 0.03). After 42 ± 4 min of sustained tilt with saline (control) and 47 ± 6 min (n.s.) after diazepam, presyncopal symptoms appeared (hypotensive phase) associated with decreases in HR, MAP, and TPR (P < 0.01). This episode induced a 2–3-fold increase in plasma ACTH, β-endorphin, prolactin, cortisol (< 0.01), and a moderate increase in plasma adrenaline (P < 0.05). Diazepam did not significantly change cardiovascular and endocrine responses to the hypotensive phase of tilt. Results indicate that diazepam attenuates the cortisol part of pituitary-adrenal responses to moderate, but not to severe, central hypovolaemia in humans with no effect on cardiovascular tolerance.     

Leg vascular resistance increases during head-up tilt in paraplegics

Despite loss of centrally mediated sympathetic vasoconstriction to the legs, spinal cord-injured individuals cope surprisingly well with an orthostatic challenge. This study assessed changes in leg vascular resistance following head-up tilt in healthy (C) and in paraplegic (P) individuals. After 10 min of supine rest, subjects were tilted 30° head-up. Mean arterial pressure (MAP) and total peripheral resistance (TPR) increased in C (MAP from 76.7±6.6 mmHg to 80.6±8.2 mmHg; TPR from 1.12±0.26 AU to 1.19±0.31 AU) while both remained unchanged in P. Echo Doppler ultrasound determined red blood cell velocity in the femoral artery, which decreased (P from 18.9±6.2 cm/s to 12.5±4.5 cm/s, P=0.001; C from 16.3±6.2 cm/s to 10.8±5.0 cm/s, P=0.001) and leg vascular resistance, which increased (P from 402±137 AU to 643±274 AU, P=0.001; C from 238±68 AU to 400±122 AU, P=0.003) from supine to upright. The present study shows that independent of supraspinal sympathetic control, humans are able to increase leg vascular resistance and maintain blood pressure during head-up tilt.     

Left ventricular responses to experimental aortic coarctation in growing puppies

The haemodynamic status of 8 coarctated and 7 sham-operated beagle puppies was studied by a catheterization technique at rest and during isoproterenol and volume loading at the ages of 7 (I) and 9 (II) months (5 and 7 months after the experimental coarctation). Proximal aortic systolic and pulse pressures were constantly higher in the coarctation group than in the control group (P < 0.05), and the systolic pressure gradient across the coarctation was always significantly higher in the coarctation group [I at rest mean 45 pL 5 (SD) vs 5 pL 4 mmHg, P < 0.001, and after I isoproterenol infusion 56 pL 9 vs 10 pL 6 mmHg, P < 0.001, and after I dextran infusion 58 pL 10 vs 8 pL 7 mmHg, P < 0.001]. The time constant of exponential isovolumic left ventricular pressure fall after the isoproterenol tests was longer in the coarctation group (I 28 pL 8 ms and II, 30 pL 4 ms) than in the control group (I, 21 pL 2, P < 0.05 and II, 19 pL 3 ms, P < 0.005), indicating impaired relaxation. The tension time index during the volume loading tests increased in the coarctation dogs (I, 4150 pL 660 and II, 4080 pL 810 mmHg s min^-1) to higher levels than in the control group (I, 3550 pL 220, II, 2540 pL 1140 mmHg s min^-1, P < 0.05 both). Cardiac output, left ventricular end diastolic pressure, inotropic parameters and heart rate were similar in both groups during the infusions. The results show that the hearts of the young animals exposed to chronic pressure load by aortic coarctation maintained their pump performance well. The changes in left ventricular relaxation may be an early sign of impaired diastolic function.     

Thoracic impedance and pulmonary atrial natriuretic peptide during head-up tilt induced hypovolaemic shock in humans

Head up and down tilts were used for manipulating the central blood volume in eight volunteers. During head-up tilt thoracic electrical impedance (TI) increased from 36.7 (33.9–52.1) ohm (mean and range) to 41.9 (36.9–59.2) ohm, heart rate from 60 (49–72) to 80 (65–90) beats min^-1 (P < 0.05) and decreased again to 57 (48–67) beats min^-1 accompanying a fall in mean arterial pressure from 86 (76–97) to 54 (41–79) mmHg and in cardiac output from 9.2 (5.9–12.1) to 6.9 (3.4–8.8) 1 min-¹ (n= 7, P < 0.07). Central venous pressure did not change significantly. Pulmonary arterial mean, 6 (3–12) mmHg, and wedge pressures, 4 (1–9) mmHg, decreased to 4 (1–11) and 1 (0–7) mmHg, respectively, and mixed, 78 (77–79%), and central venous oxygen saturations, 72 (71–73)%, fell to 62 (46–75) and 54 (44–58)%, respectively (P < 0.05). Atrial natriuretic peptide (ANP) was determined from blood of the superior vena cava and pulmonary and brachial arteries. Pulmonary artery ANP, 18.4 (7.5–30.7) pmol l^-1, was higher than in vena cava, 13.3 (5.2–20.9) pmol 1^_1 (P < 0.05). At the time of presyncope, pulmonary artery ANP decreased from 20.8 (37.4–10.1) to 13.7 (19.7-5.7) pmol l^-1, in vena cava from 13.8 (23.1–7.1) to 10.2 (17.9-6.7) pmol l^-‘ and in the brachial artery from 16.9 (34.1–5.2) to 11.3 (18.5-5.1) pmol l“¹ (P < 0.05). Head-down tilt did not affect the recorded variables significantly. Thoracic electrical impedance, pulmonary artery pressure and venous oxygen saturations were sensitive indices of the central blood volume as reflected in the release of atrial natriuretic peptide from the right side of the heart.     

Chronic inhibition of standing behaviour alters baroreceptor reflex function in rats

Aim: To investigate whether daily orthostatic stress during development is an important factor affecting arterial baroreceptor reflex function, we examined the effect of chronic inhibition of upright standing behaviour on the baroreceptor reflex function in rats. Methods: Upright standing behaviour was chronically inhibited during the developmental period between 3 and 8 weeks of age in Sprague–Dawley rats and heart rate (HR) and aortic nerve activity in response to increased and decreased mean arterial pressure (MAP) was measured after the treatment period. Results: The baroreceptor cardiac gain in the rats grown without standing behaviour was significantly lower than the control rats grown in a normal commercial cage (1.0 ± 0.1 beats min^?1 mmHg^?1 vs. 1.6 ± 0.2 beatsmin^?1 mmHg^?1, P < 0.05). The range of HR change in the MAP–HR functional curve was also lowered by chronic inhibition of orthostatic behaviour (56.2 ± 5.9 beats min^?1) compared with that of the control rats (76.8 ± 6.9 beats min^?1, P < 0.05). However the aortic afferent function remained normal after the treatment period, indicating that the attenuated baroreceptor reflex function may be due to other mechanisms involving functional alterations in the cardiovascular centres, efferents and/or peripheral organs. Body weight and adrenal weight were not affected by the inhibition of orthostatic behaviour, suggesting that the animals were not exposed to specific stress by this treatment. Conclusion: These results indicate that active haemodynamic changes induced by orthostatic behaviour are an important factor for setting the basal level of reflex function during development. Moreover, our experimental model may be useful for studying mechanisms of attenuated baroreceptor reflex observed after exposure to a chronic inactive condition.     

Intra- and extracranial artery blood velocity during a sudden blood pressure decrease in humans

The intra- and extracerebral Doppler artery blood velocity responses to a 10-mmHg abrupt blood pressure (BP) decrease in ten healthy men were studied. This decrease was obtained using two cuffs placed over both thighs. First, cuffs were inflated to pressures greater than the arterial BP for 5 min. Next, they were deflated to 60 mmHg in order to prevent venous return from the legs. We obtained a decrease in mean arterial BP of from 101 (10) to 90 (10) mmHg [mean (SD), P < 0.01] without modifications in the heart rate [HR, 88 (14) beats min⁻¹]. Middle cerebral artery mean blood velocity (MCAmv) decreased immediately from 50 (10) to 42 (12) cm s⁻¹ (P < 0.05). Simultaneously, temporal superficial artery mean blood velocity (TSAmv) decreased from 11 (3) to 7 (2) cm s⁻¹ (P < 0.05) and common carotid artery blood flow (CCAbf ) decreased from 305 (23) to 233 (33) ml min⁻¹ (P < 0.05). After 5 s, MCAmv and CCAbf returned to baseline values, whereas TSAmv [8 (2) cm s⁻¹], mean arterial BP [86 (10) mmHg] remained low and HR increased [92 (12) beats min⁻¹]. TSAmv, BP and HR returned to baseline values in 1 min. These data confirm that cerebral blood flow (CBF) is very rapidly regulated but that blood flow in extracranial territories is not and that it follows the arterial BP changes. Accepted: 8 April 1997     

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 (V_mean) increases in the middle cerebral artery (MCA) and reflects cerebral blood flow when the diameter at the site of investigation remains constant. Sympathetic activation could induce MCA vasoconstriction and in turn elevate V_mean at an unchanged cerebral blood flow. In 12 volunteers we evaluated whether V_mean 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 V_mean 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 V_mean 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, V_mean 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.     

A comparative assessment of two techniques for investigating initial cardiovascular reflexes under acute orthostatic stress

The physiological differences between active and passive changes in posture have been previously established. This study determined the extent of the differences in the initial cardiovascular responses to the passive head-up tilt (HUT) and the active squat-stand test (SST). Eleven females and 13 males underwent one +75° HUT and one SST. Beat-to-beat diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were determined non-invasively. Data were recorded 10 s prior to (control) and 30 s after tilt or stand (event). Blood pressure and HR responses were analysed by calculating the deviation from control at 10 s (T10), 20 s (T20) and 30 s (T30) after the onset of each test. The DBP response (reflecting changes in systemic vascular resistance) at T10 was –10 (2) mmHg [mean (SEM)] for the HUT and –25 (2) mmHg for the SST (P<0.01). DBP returned to control levels by T30 for the HUT, but remained depressed for the SST. MAP responses directly reflected these changes in DBP. HR significantly increased from control values (P<0.001) for the HUT [+14 (1) bpm] and the SST [+16 (1) bpm], and remained elevated for the entire 30-s period for both tests. This study demonstrates that although the magnitude of the initial blood pressure decrease is greater for the active SST compared with the passive HUT, the reflex compensatory response is no different, making the SST a greater challenge for the cardiovascular reflexes.     

Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass

We tested the hypothesis that pharmacological reduction of the increase in cardiac output during dynamic exercise with a large muscle mass would influence the cerebral blood velocity/perfusion. We studied the relationship between changes in cerebral blood velocity (transcranial Doppler), rectus femoris blood oxygenation (near-infrared spectroscopy) and systemic blood flow (cardiac output from model flow analysis of the arterial pressure wave) as induced by dynamic exercise of large (cycling) vs. small muscle groups (rhythmic handgrip) before and after cardioselective β₁ adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.). During rhythmic handgrip, the increments in systemic haemodynamic variables as in middle cerebral artery mean blood velocity were not influenced significantly by metoprolol. In contrast, during cycling (e.g. 113 W), metoprolol reduced the increase in cardiac output (222 ± 13 vs. 260 ± 16%), heart rate (114 ± 3 vs. 135 ± 7 beats min^?1) and mean arterial pressure (103 ± 3 vs.112 ± 4 mmHg), and the increase in cerebral artery mean blood velocity also became lower (from 59 ± 3 to 66 ± 3 vs. 60 ± 2 to 72 ± 3 cm s^?1; P < 0.05). Likewise, during cycling with metoprolol, oxyhaemoglobin in the rectus femoris muscle became reduced (compared to rest; ?4.8 ± 1.8 vs. 1.2 ± 1.7 μmol L^?1, P < 0.05). Neither during rhythmic handgrip nor during cycling was the arterial carbon dioxide tension affected significantly by metoprolol. The results suggest that as for the muscle blood flow, the cerebral circulation is also affected by a reduced cardiac output during exercise with a large muscle mass.     

Motor control and cardiovascular responses during isoelectric contractions of the upper trapezius muscle: evidence for individual adaptation strategies

Ten females (25–50 years of age) performed isometric shoulder flexions, holding the right arm straight and in a horizontal position. The subjects were able to see the rectified surface electromyogram (EMG) from either one of two electrode pairs above the upper trapezius muscle and were instructed to keep its amplitude constant for 15 min while gradually unloading the arm against a support. The EMG electrodes were placed at positions representing a “cranial” and a “caudal” region of the muscle suggested previously to possess different functional properties. During the two contractions, recordings were made of: (1) EMG root mean square-amplitude and zero crossing (ZC) frequency from both electrode pairs on the trapezius as well as from the anterior part of the deltoideus, (2) supportive force, (3) heart rate (HR) and mean arterial blood pressure (MAP), and (4) perceived fatigue. The median responses during the cranial isoelectric contraction were small as compared to those reported previously in the literature: changes in exerted glenohumeral torque and ZC rate of the isoelectric EMG signal of ?2.81%?·?min^?1 (P = 0.003) and 0.03%?·?min^?1 (P= 0.54), respectively, and increases in HR and MAP of 0.14 beats?·?min^?2 (P= 0.10) and 0.06?mmHg?·?min^?1 (P= 0.33), respectively. During the contraction with constant caudal EMG amplitude, the corresponding median responses were ?2.51%?·?min^?1 (torque), 0.01%?·?min^?1 (ZC rate), 0.31 beats?·?min^?2 (HR), and 0.93 mmHg ·?min^?1 (MAP); P=0.001, 0.69, 0.005, and 0.003, respectively. Considerable deviations from the “isoelectric” target amplitude were common for both contractions. Individuals differed markedly in response, and three distinct subgroups of subjects were identified using cluster analysis. These groups are suggested to represent different motor control scenarios, including differential engagement of subdivisions of the upper trapezius, alternating motor unit recruitment and, in one group, a gradual transition towards a greater involvement of type II motor units. The results indicate that prolonged low-level contractions of the shoulder muscles may in general be accomplished with a moderate metabolic stress, but also that neuromuscular adaptation strategies differ significantly between individuals. These results may help to explain why occupational shoulder-neck loads of long duration cause musculoskeletal disorders in some subjects but not in others.     

Skeletal muscle glycolysis during submaximal exercise following acute β-adrenergic blockade in man

The present study describes the influence of β-adrenergic blockade on glycogen utilization and lactate accumulation in skeletal muscle of exercising man. Twelve physically active men were examined during 25 min of continuous cycle exercise equivalent to 65% of their maximal oxygen uptake both with and without oral administration of 80 mg of propranolol (Inderal®). Heart rate, oxygen uptake, rate of perceived exertion (RPE) and blood lactate concentration were measured during exercise. Muscle biopsies were obtained from m. vastus lateralis after 5 and 25 min of exercise, β-adrenergic blockade decreased steady state exercise heart rate by (mean + SD) 35 ± 10 beats min^-1 (P < 0.001) and oxygen uptake from 2.47 to 2.39 1-min^-1 (P < 0.01). Muscle glycogen decreased from the 5th to the 25th min of exercise, and β-blockade had no significant effect on this decrease. In contrast to without drug, β-blockade resulted in a decrease (P < 0.05) in muscle lactate concentration from the 5th (6.9 mmolkg^-1 w./w.) to the 25th min (4.8 mmolkg^-1 w./w.). Similarly blood lactate levels were lower (P < 0.05) with than without β-blockade in the last but not the first 10 min of exercise. The alteration in muscle lactate concentration pattern following β-blockade, may imply that adrenergic effects per se contribute to the stimulation of glycolysis during submaximal exercise, except in its earliest phase. Nevertheless, the effect is not great enough to produce substantial differences in glycogen utilization.