Cholinergic induced mesenteric vasorelaxation in response to head-up tilt.

Central hypovolaemia induced by head-up tilt evokes a reduction in superior mesenteric artery resistance resulting in maintenance of regional blood flow. Mechanisms of importance for this response are not known, but a parasympathetic contribution could be expected. To evaluate this hypothesis, superior mesenteric artery blood flow and resistance were evaluated by duplex ultrasound in eight healthy volunteers during postprandial head-up tilt with and without cholinergic blockade. During supine rest, cholinergic blockade did not influence the postprandial reduction in peripheral mesenteric artery resistance as expressed by analogous elevations in the diastolic blood velocity (to 62 +/- 9 vs. 56 +/- 7 cm s-1 with placebo). Throughout the normotensive and hypotensive phases of head-up tilt, cholinergic blockade reduced mesenteric artery mean blood velocity by 39 and 42%, respectively, corresponding to volume flow reductions by 35 and 41% (0.62 +/- 0.10 vs. 0.96 +/- 0.13 L min-1 and 0.52 +/- 0.07 vs. 0.88 +/- 0.16 L min-1; P < 0.05). Also, during both phases of head-up tilt, cholinergic blockade increased mesenteric artery resistance as reflected in a reduction in the diastolic blood velocity by 41 and 56%, respectively (44 +/- 4 vs. 74 +/- 13 cm s-1 and 24 +/- 6 vs. 54 +/- 8 cm s-1). These results support a cholinergic contribution to the mesenteric artery vasorelaxing response to central hypovolaemia induced by head-up tilt.     

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.     

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.     

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.     

Intensity-dependent effect of body tilt angle on calf muscle fatigue in humans

Body tilt angle affects the fatigue of human calf muscle at a high contractile force (i.e. 70 %MVC); but the range of forces across which this effect occurs is not known and we sought to determine this in the present study. Fourteen men performed intermittent calf muscle contractions at either 30, 40, 50 and 60 %MVC (Group 1 n = 7) or at 80 and 90 %MVC (Group 2 n = 7). Two tests were performed at each intensity in the supine (tilt angle = 0°) and inclined head-up position (tilt angle = 67°). MVC was measured prior to and during each calf exercise test, and the linear rate of decline in MVC during each test was used to estimate muscle fatigue. MVC prior to each test was unaffected by body tilt angle in Groups 1 and 2. In Group 1 muscle fatigue was significantly lower in the inclined than supine position at 50 %MVC (0.10 ± 0.05 vs. 0.19 ± 0.10 N s⁻¹) and 60 %MVC (0.22 ± 0.20 vs. 0.36 ± 0.33 N s⁻¹); but there was no significant difference in fatigue at 30 %MVC (0.07 ± 0.06 vs. 0.07 ± 0.07 N s⁻¹) and 40 %MVC (0.12 ± 0.07 vs. 0.18 ± 0.08 N s⁻¹). In Group 2, muscle fatigue was significantly lower in the inclined compared with the supine position at 80 %MVC (0.90 ± 0.50 vs. 1.49 ± 0.87 N s⁻¹) and 90 %MVC (1.19 ± 0.47 vs. 1.79 ± 0.78 N s⁻¹). These data demonstrate that the postural effect on calf muscle fatigue during intermittent contractions is manifest at moderate to very high forces, but that it does not occur at low forces.     

Effect of spinal sympathetic blockade upon postural changes of blood flow in human peripheral tissues

The effect of head-up tilt upon subcutaneous and skeletal muscle blood flow in the crus was studied before and during epidural blockade in 10 subjects. Relative changes in blood flow were estimated by the local ¹³³Xe washout technique. In subcutaneous tissue head-up tilt induced a decrease in blood flow of about 40% and there was no difference in the vascular response to head-up tilt before and during epidural blockade. In skeletal muscle tissue essentially the same was found as head-up tilt decreased blood flow by about 26% the response being uninfluenced by epidural blockade. In 3 patients local nervous blockade was induced by Lidocaine in ¹³³Xe labelled subcutaneous tissue on one side. During epidural blockade and tilt blood flow increased by 12% whereas blood flow decreased by 30% on the control side. Thus epidural blockade had no influence on the vasoconstrictor response in subcutaneous tissue and skeletal muscle to head-up tilt whereas local blockade was able to prevent the response. Local mechanisms including the local veno-arteriolar reflex appear to play an important role for the observed maintenance of arterial blood pressure in the tilted position during central sympathetic blockade.     

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.     

High afterload during 10 min of regional ischaemia affects diastolic creep but not systolic function in reperfused (stunned) myocardium

The effect of afterload during regional ischaemia on myocardial stunning was studied in 15 pentobarbital anaesthetized cats. 10 min occlusion of the left anterior descending artery (LAD) was followed by 60 min of reperfusion. Afterload was decreased by intravenous infusion of nitroglycerine 3–8 μg kg^-1 min^-1 in group I (n=8); left ventricular peak systolic pressure (LVSP) 84±4 mmHg (mean±SEM) during coronary artery occlusion. In group II (n=7) LVSP was increased to 188±10 mmHg by inflating an intraaortic balloon during coronary artery occlusion. Regional function in the LAD perfused region was evaluated by cross-oriented sonomicrometry. Myocardial tissue blood flow was evaluated by radio-labelled microspheres. Afterload alterations did not affect regional systolic shortening (10.8±2.0% vs. 11.0±1.5% in group I and II, respectively, after 60 min of reperfusion). However, increased end-diastolic dimensions (diastolic creep) in both the circumferential and longitudinal segments were markedly more pronounced in the high afterload group (group II). Also important, the markedly increased myocardial tissue blood flow during reperfusion in group II as compared with group I (2.30±0.18 vs.  1.34±0.08 mL min^-1 g^-1 and 2.58±0.23 vs. 1.49±0.07 mL min^-1 g^-1 in subepicardial and subendocardial layers in the LAD perfused region) suggests that increased diastolic creep increased metabolic demands. This study indicates that passive stretching of the ischaemic area during coronary artery occlusion is an important mechanism behind diastolic creep.     

Regulation of subcutaneous blood flow during head-up tilt (45°) in normals

Local and remote regulation of subcutaneous blood flow in the forearm and leg was studied during head-up tilt (45°) in 6 young healthy male subjects. Relative blood flow was estimated by the local ¹³³Xe washout technique. Lowering of a leg lead to a 51 % decrease in its subcutaneous blood flow due to a veno-arteriolar reflex elicited by the increase in venous transmural pressure. During head-up tilt subcutaneous blood flow in the arm remaining at heart level decreased by 27%, in the leg blood flow decreased by 50%. Following proximal nervous blockade, head-up tilt did not induce vasoconstriction in forearm at heart level, but blood flow in distal leg decreased by 45%. Thus there was no difference in the vasoconstrictor response in the leg to head-up tilt or lowering of the labelled area by 40 crn. Since head-up tilt caused neurogenically mediated vasoconstriction in subcutaneous tissue, subcutaneous blood flow in the extremities seems to be regulated by remote (baroreceptor) as well as local sympathetic reflex mechanisms (veno-arteriolar reflex).     

Middle cerebral artery blood velocity during rowing

Dynamic exercise increases the transcranial Doppler determined mean blood velocity in basal cerebral arteries corresponding to the cortical representation of the active limb(s) and independent of the concomitant rise in the mean arterial pressure. In 12 rowers we evaluated the middle cerebral artery blood velocity response to ergometer rowing when regulation of the cerebral perfusion is challenged by stroke synchronous fluctuation in arterial pressure. Rowing increased mean cerebral blood velocity (57 ± 3 to 67 ± 5 cm s^?1; mean ± SE) and mean arterial (86 ± 6 to 97 ± 6 mmHg) and central venous pressures (0 ± 2 to 8 ± 2 mmHg; P < 0.05). The force on the oar triggered an averaging procedure that demonstrated stroke synchronous sinusoidal oscillations in the cerebral velocity with a 12 ± 2% amplitude upon the average exercise value. During the catch phase of the stroke, the mean velocity increased to a peak of 88 ± 7 cm s^?1 and it was in phase with the highest mean arterial pressure (125 ± 14 mmHg), while the central venous pressure was highest after the stroke (20 ± 3 mmHg). The results suggest that during rowing cerebral perfusion is influenced significantly by the rapid fluctuations in the perfusion pressure.     

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.     

The effect of acute aerobic exercise on pulse wave velocity and oxidative stress following postprandial hypertriglyceridemia in healthy men

Oxidative stress is postulated to be responsible for the postprandial impairments in vascular function. The purpose of this study was to measure pulse wave velocity (PWV) and markers of postprandial oxidative stress before and after an acute bout of moderate exercise. Ten trained male subjects (age 21.5 ± 2.5 years, VO₂ max 58.5 ± 7.1 ml kg⁻¹ min⁻¹) participated in a randomised crossover design: (1) high-fat meal alone (2) high-fat meal followed 2 h later by a bout of 1 h moderate (60% max HR) exercise. PWV was examined at baseline, 1, 2, 3, and 4 h postprandially. Blood Lipid hydroperoxides (LOOHs), Superoxide dismutase (SOD) and other biochemical markers were measured. PWV increased at 1 h (6.49 ± 2.1 m s⁻¹), 2 h (6.94 ± 2.4 m s⁻¹), 3 h (7.25 ± 2.1 m s⁻¹) and 4 h (7.41 ± 2.5 m s⁻¹) respectively, in the control trial (P < 0.05). There was no change in PWV at 3 h (5.36 ± 1.1 m s⁻¹) or 4 h (5.95 ± 2.3 m s⁻¹) post ingestion in the exercise trial (P > 0.05). LOOH levels decreased at 3 h post ingestion in the exercise trial compared to levels at 3 h (P < 0.05) in the control trial. SOD levels were lower at 3 h post ingestion in the control trial compared to 3 h in the exercise trial (0.52 ± 0.05 vs. 0.41 ± 0.1 units μl⁻¹; P < 0.05). These findings suggest that a single session of aerobic exercise can ameliorate the postprandial impairments in arterial function by possibly reducing oxidative stress levels.     

Leg blood flow during slow head-down tilt with and without leg venous congestion

The effects of slow changes in body position on leg blood flow (LBF) were studied in nine healthy male subjects. Using a tilt table, sitting volunteers were tilted about 60° backwards to a supine position within 40?s. To modify the venous filling in the legs, the tilt manoeuvre was repeated with congestion of the leg veins induced by two thigh cuffs inflated to a subdiastolic pressure of 60?mmHg. Doppler measurements in the femoral artery were used to estimate LBF. Additional Doppler measurements at the aortic root in five of the subjects were taken for the determination of cardiac output. The LBF was influenced by body position. In the control experiment it increased from 500 ml?·?min^?1 in the upright to 780 ml?·?min^–1 after 15?min in the supine position. A mean maximal value of 950 ml?·?min^?1 was observed 20?s after the tilt. Heart rate remained almost constant during the tilt phase, whereas stroke volume increased from 90?ml to 120?ml and it remained at that level after the cessation of the tilt. Congestion of the leg veins had no significant effect on heart rate, stroke volume and mean blood pressure. However, it increased vascular resistance of the leg during and after the tilt. After 15?min in the tilted position LBF amounted to 600 ml?·?min^?1. The results suggest that the filling of the leg veins is inversely related to leg blood flow. The most likely mechanism underlying this observation is a local effect of venous filling on vasomotor tone.     

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.     

Adaptations of aortic and pulmonary artery flow parameters measured by phase-contrast magnetic resonance angiography during supine aerobic exercise

Purpose

Increased oxygen uptake and utilisation during exercise depend on adequate adaptations of systemic and pulmonary vasculature. Recent advances in magnetic resonance imaging techniques allow for direct quantification of aortic and pulmonary blood flow using phase-contrast magnetic resonance angiography (PCMRA). This pilot study tested quantification of aortic and pulmonary haemodynamic adaptations to moderate aerobic supine leg exercise using PCMRA.

Methods

Nine adult healthy volunteers underwent pulse gated free breathing PCMRA while performing heart rate targeted aerobic lower limb exercise. Flow was assessed in mid ascending and mid descending thoracic aorta (AO) and main pulmonary artery (MPA) during exercise at 180 % of individual resting heart rate. Flow sequence analysis was performed by experienced operators using commercial offline software (Argus, Siemens Medical Systems).

Results

Exercise related increase in HR (rest: 69 ± 10 b min^?1, exercise: 120 ± 13 b min^?1) resulted in cardiac output increase (from 6.5 ± 1.4 to 12.5 ± 1.8 L min^?1). At exercise, ascending aorta systolic peak velocity increased from 89 ± 14 to 122 ± 34 cm s^?1 (p = 0.016), descending thoracic aorta systolic peak velocity increased from 104 ± 14 to 144 ± 33 cm s^?1 (p = 0.004), MPA systolic peak velocity from 86 ± 18 to 140 ± 48 cm s^?1 (p = 0.007), ascending aorta systolic peak flow rate from 415 ± 83 to 550 ± 135 mL s^?1 (p = 0.002), descending thoracic aorta systolic peak flow rate from 264 ± 70 to 351 ± 82 mL s^?1 (p = 0.004) and MPA systolic peak flow rate from 410 ± 80 to 577 ± 180 mL s^?1 (p = 0.006).

Conclusion

Quantitative blood flow and velocity analysis during exercise using PCMRA is feasible and detected a steep exercise flow and velocity increase in the aorta and MPA. Exercise PCMRA can serve as a research and clinical tool to help quantify exercise blood flow adaptations in health and disease and investigate patho-physiological mechanisms in cardio-pulmonary disease.     

Contribution of local blood flow regulation mechanisms during head-up tilt in human subcutaneous tissue

Local and remote regulation of subcutaneous blood flow in the forearm and leg was studied during head-up tilt (30°, 457deg; and 70°) in 7 young healthy subjects. Relative blood flow was estimated by the local ¹³³Xe washout technique. Incremental levels of head-up tilt elicited increasing vascular resistance on arm and leg, respectively. Positive pressure similar to a blood column of the same height was able to prevent a significant part of the vasoconstrictor response on the leg to head-up tilt. Thus if venous distension is prevented the local veno-arteriolar reflex is abolished, whereas arteriolar constriction due to centrally elicited reflexes remains unaffected. Subcutaneous blood flow in the extremities are regulated by remote (baroreceptor) as well as local sympathetic reflex mechanisms (veno-arteriolar reflex); but the relative influence of the local veno-arteriolar reflex on the increase in total peripheral resistance seems to decrease with increasing tilt angles.     

Thermogenic response to adrenaline during restricted blood flow in the forearm

To elucidate the underlying mechanism behind the thermogenic effect of adrenaline in human skeletal muscle, nine healthy subjects were studied during intravenous infusion of adrenaline. Restriction of blood flow to one forearm was obtained by external compression of the brachial artery, to separate a direct metabolic effect of adrenaline from an effect dependent on increased blood flow. The other arm served as the control arm. In the control arm, the forearm blood flow increased 4.7-fold (from 2.0 ± 0.3 to 9.3 ± 1.5 mL 100 g^–1 min^–1, P < 0.001) during the adrenaline infusion. Adrenaline significantly increased forearm oxygen consumption (from 4.7 ± 2.1 to 7.0 ± 3.6 μmol 100 g^–1 min^–1, P < 0.025). In the arm with restricted blood flow, the forearm blood flow increased 2.9-fold (from 1.6 ± 0.3 to 4.6 ± 0.8 mL 100 g^–1 min^–1, P < 0.002) but the forearm oxygen consumption did not increase (baseline period: 5.6 ± 2.3 μmol 100 g^–1 min^–1, adrenaline period: 6.1 ± 2.1 μmol 100 g^–1 min^–1, P = 0.54). The experimental design and the difficulties in interpretation of the result are discussed. The results give evidence for the hypothesis that the vascular system plays a key role in the thermogenic effect of adrenaline in skeletal muscle in vivo.     

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

Sympathetic β-adrenergic influences on cardiovascular responses to 50d? head-up tilt were evaluated with metoprolol (β₁-blockade; 0.29 mg kg^-1) and propranolol (β₁ and β-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 23pL3 min (control, mean pLSE). Head-up tilt made thoracic electrical impedance (3.0pL10Ω), mean arterial pressure (MAP, 86pL4-93pL4 mmHg), heart rate (HR, 63pL3-99pL10 beats min^-1) and total peripheral resistance (TPR, 15pL1-28pL4 mmHg min L^-1) increase, while central venous oxygen saturation (74pL2-58pL4%), cardiac output (5.7pL0.1–3.1pL0.3 L min^-1), stroke volume (95pL6-41pL5 mL) and pulse pressure (55pL4-49pL4 mmHg) decreased (P < 0.05). Central venous pressure decreased during head-up tilt (7pL2-0pL1 mmHg), but it remained stable during the sustained tilt. At the appearance of preswyncopal symptoms MAP (49pL3 mmHg), HR (66pL4 beats min^-1) and TPR (15pL3 mmHg min L^-1) decreased (P < 0.05). Neither metoprolol or propranolo changed tilt tolerance or cardiovascular variables, except for HR that remained at 57pL2 (metoprolol) and 55pL3 beats min^-1 (propranolol), and MAP that remained at 87pL5 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.     

Effect of propranolol on the tone of collateral arteries in patients with occlusion of the superficial femoral artery

The effect of administration of 0.5 mg propranolol into the femoral artery in eight patients with lower limb ischaemia and superficial femoral artery occlusion on collateral arterial resistance was studied in supine and tilted head-up position. Mean blood pressures were recorded directly from the femoral and popliteal artery and femoral blood flow was measured by an indicator dilution technique. After beta-receptor blockade in the supine position the collateral arterial resistance increased by 7 +/- 2%, femoral blood flow decreased 10 +/- 4%, and popliteal artery pressure increased by 4 mmHg (8 +/- 3%). During head-up tilt there was no change in femoral blood flow and collateral arterial resistance after propranolol. The peripheral vasoconstrictor effect of propranolol, therefore, seems not to be harmful to patients with vascular disease.     

Noisy fluctuation of heart rate indicates cardiovascular system instability

Heart rate spontaneously fluctuates despite homeostatic regulatory mechanisms to stabilize it. Harmonic and fractal fluctuations have been described. Non-harmonic non-fractal fluctuation has not been studied because it is usually thought that it is caused by apparatus noise. We hypothesized that this fluctuation looking like apparatus noise (that we call “noisy fluctuation”) is linked to challenged blood pressure stabilization and not to apparatus noise. We assessed noisy fluctuation by quantifying the small and fastest beat-to-beat fluctuation of RR-interval by means of spectral analysis (Nyquist power of heart rate variability: nyHRV) after filtering out its fractal component. We observed nyHRV in healthy supine subjects and in patients with vasovagal symptoms. We challenged stabilization of blood pressure by upright posture (by means of a head-up tilt table test). Head-up position on the tilt table dramatically decreased nyHRV (0.128 ± 0.063 vs. 0.004 ± 0.002, p < 0.01) in healthy subjects (n = 12). Head-up position also decreased nyHRV in patients without vasovagal symptoms (n = 24; 0.220 ± 0.058 vs. 0.034 ± 0.015, p < 0.05), but not in patients with vasovagal symptoms during a head-up tilt table test (age and sex paired, 0.103 ± 0.041 vs. 0.122 ± 0.069, not significant). Heart rate variability includes a physiological non-harmonic non-fractal noisy fluctuation. This noisy fluctuation indicates low engagement of regulatory mechanisms because it disappears when the cardiovascular system is challenged (upright posture). It also indicates cardiovascular instability because it does not disappear in upright patients before vasovagal syncope, a transient failure of cardiovascular regulation.