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.     

A comparison between 133Xenon washout technique and Laser Doppler flowmetry in the measurement of local vasoconstrictor effects on the microcirculation in subcutaneous tissue and skin

Changes in skin blood flow measured by Laser Doppler flowmetry and changes in subcutaneous blood flow measured by 133Xenon washout technique were compared during activation of the local sympathetic mediated veno-arteriolar vasoconstrictor reflex by lowering the area of investigation below heart level. The measurements were performed in tissue with and without sympathetic innervation. In five subjects, who all had been cervically sympathectomized for manual hyperhidrosis, the Laser Doppler and 133Xenon blood flow measurements were performed simultaneously on the sympathetically denervated forearm, and on the calf with preserved sympathetic nerve supply. The Laser Doppler method registered a 23% reduction in skin blood flow during lowering of the extremities independently of the sympathetic nerve supply to the skin. The 133Xenon method recorded a 44% decrease in blood flow in innervated and unchanged blood flow in denervated subcutaneous tissue during lowering of the extremities. Our results indicate that the Laser Doppler method and 133Xenon method are not comparable, and that the Laser Doppler method is not useful in measuring local sympathetic mediated blood flow changes.     

Contribution of local blood flow regulation mechanisms to the maintenance of arterial pressure in upright position during epidural blockade

The contribution of local blood flow regulation mechanisms to the maintenance of arterial pressure in upright position was studied in 5 normal subjects. Central sympathetic blockade was induced by epidural anesthesia. Blood flow in anterior tibial muscle in both legs and in brachioradial muscle in one arm was measured by the local 133Xe washout technique. Arterial blood pressure was recorded directly from the radial artery. Slow head-up tilt (about 30 degrees) caused a decrease in blood flow of about 36% in the dependent legs and in arm remaining at heart level. Arterial pressure decreased by about 10%. Blockade of the local sympathetic veno-arteriolar "axon reflex" in one leg by injection of phentolamine into the common femoral artery caused a vasodilatation in the ipsilateral muscle, while muscle blood flow did not change in the other leg or arm. Within 20 s after the injection of phentolamine arterial pressure decreased by about 7%. This cannot be explained by a "systemic" effect because injection of phentolamine into the femoral vein did not effect arterial pressure within the first 40 s. Vasoconstriction due to blood-borne factors is ruled out since preventing the increase in vascular transmural pressure in the leg by inducing counterpressure locally, abolished the vasoconstriction. Thus, the results suggest that the local veno-arteriolar "axon reflex" together with myogenic mechanisms contribute to the maintenance of arterial pressure in the upright position.     

Lack of effect of moderate hypoxaemia on human postural reflexes to skeletal muscle

The effect of moderate hypoxemia upon postural sympathetic vasoconstrictor reflexes in skeletal muscle was studied in five healthy young students, aged 20-30 years. The vasoconstrictor response to head-up tilt was studied in brachio radial muscle kept at heart level and in the anterior tibial muscle. The local sympathetic veno-arteriolar axon reflex was studied in the anterior tibial muscle placed at heart level and lowered 30-50 cm below heart level. Muscle blood flow was measured by the local 133Xe wash-out technique. The measurements were carried out with the subject breathing atmospheric air and with the subject breathing 10-11% oxygen. No sign of orthostatic intolerance was seen during hypoxaemia as arterial blood pressure remained constant in the tilted position. Hypoxaemia did not alter the head-up tilt induced vasoconstriction in brachio-radial and anterior tibial muscles. The vasoconstriction elicited by the local veno-arteriolar reflex was slightly reduced during hypoxaemia. The results suggest that central orthostatic vasoconstrictor reflexes to muscle are essentially normal during moderate hypoxaemia, but local veno-arteriolar reflexes are slightly attenuated. This does not, however, significantly alter blood pressure control during head-up tilt.     

Effects of dynamic leg exercise on subcutaneous blood flow rate in the lower limb of man

Subcutaneous blood flow (SBF) was studied simultaneously in the upper arm at heart level and in the lower limb during positional changes and during leg exercise in seven healthy males. SBF was estimated by local clearance of ‘“Xenon registered by portable cadmium telluride detectors. Venous pressure was recorded directly on dorsum on the foot. Changinr the position from supine to head-up tilt, SBF decreased by 43 % (P < 0.01) at the arm level, 40% at the thigh (P < 0.01), 47% at the calf (P < 0.01) and decreased by 51 % at the ankle level (P < 0.01). Performing 20 heel-raisings per min in nearly erect posture, SBF increased by 96% at the thigh (P < 0.01), 25% at the calf (P > 0.1) and increased by 18% at the ankle level (P > 0.1). At 40 heel-raisings per min SBF increased by 99% at the thigh (P < 0.0 1), 121 % at the calf (P < 0.0 1), but only 44% at the ankle level (P > 0.1). During leg exercise subcutaneous vascular resistance was significantly increased at arm and ankle levels. In contrast, a vasodilatory response was noticed at the thigh and calf levels and seemed associated with a decrease in local venous pressure to below the trigger level of the sympathetic veno-arteriolar reflex mechanism. In conclusion, SBF in the lower limb of man was increased during exercise. The increase in SBF could only partly be ascribed to the concomitant increase in perfusion pressure. The local blood flow response seemed modified by changes in sympathetic nervous activity and metabolic rate.     

Effects of dynamic leg exercise on subcutaneous blood flow rate in the lower limb of man

Subcutaneous blood flow (SBF) was studied simultaneously in the upper arm at heart level and in the lower limb during positional changes and during leg exercise in seven healthy males. SBF was estimated by local clearance of ¹³³Xenon registered by portable cadmium telluride detectors. Venous pressure was recorded directly on dorsum on the foot. Changing the position from supine to head-up tilt, SBF decreased by 43% (P < 0.01) at the arm level, 40% at the thigh (P < 0.01), 47% at the calf (P < 0.01) and decreased by 51 % at the ankle level (P < 0.01). Performing 20 heel-raisings per min in nearly erect posture, SBF increased by 96% at the thigh (P < 0.01), 25% at the calf (P > 0.1) and increased by 18% at the ankle level (P > 0.1). At 40 heel-raisings per min SBF increased by 99% at the thigh (P < 0.01), 121% at the calf (P < 0.01), but only 44% at the ankle level (P > 0.1). During leg exercise subcutaneous vascular resistance was significantly increased at arm and ankle levels. In contrast, a vasodilatory response was noticed at the thigh and calf levels and seemed associated with a decrease in local venous pressure to below the trigger level of the sympathetic veno-arteriolar reflex mechanism. In conclusion, SBF in the lower limb of man was increased during exercise. The increase in SBF could only partly be ascribed to the concomitant increase in perfusion pressure. The local blood flow response seemed modified by changes in sympathetic nervous activity and metabolic rate.     

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).     

Effect of lower body negative pressure upon local regulation of blood flow in human subcutaneous tissue

Local regulation of subcutaneous blood flow in the forearm was studied during lower body negative pressure (LBNP) in 7 young healthy male subjects in supine position. Blood flow was measured on the forearm by the local ¹³³Xe washout technique. LBNP of -40 and -60 mmHg induced a decrease in the ¹³³Xe washout rate of 34 and 50% respectively. This response to LBNP could be blocked by proximal nervous blockade indicating that the vasoconstriction observed was due to a central sympathetic reflex mechanism. The vasoconstrictor response to increase in venous transmural pressure induced by lowering the arm (veno-arteriolar reflex mechanism) could not be demonstrated during 40 mmHg LBNP. The abolishment of this reflex is most likely due to centrally elicited increase in sympathetic activity as a normal veno-arteriolar reflex was elicited following proximal nervous blockade.     

Local regulation of subcutaneous blood flow in normal subjects and in migraine patients before and after single-dose ergotamine tartrate

Local blood flow regulation of the foot was studied in 15 normal subjects and in nine migraine patients. Changes in arterial and venous pressures were induced by lowering and elevation of the limb. Changes in blood flow were estimated from the changes in the wash-out rate of a subcutaneous 133-Xenon depot. The local vasoconstrictor response to increased venous pressure elicited during lowering was identical in the normal subjects and in the migraine patients. During elevation, however, an abnormality in the autoregulation of blood flow could be demonstrated, as a decrease in blood flow during elevation to +40 cm was more pronounced in the patients than in the normal subjects (P = 0.04). About 3 h after 0.5 mg ergotamine tartrate/70 kg body weight i.v. the local regulation of blood flow had markedly changed in normal subjects as well as in migraine patients. During elevation to +20 and to +40 cm, blood flow increased significantly (P = 0.01 and P = 0.02). In two subjects the isotope depot was infiltrated with lidocaine and the ergotamine-induced increase in blood flow during elevation was blocked. The results may indicate that the veno-receptor of the veno-arteriolar reflex underlying the local vasoconstrictor response is a tension receptor, which due to the veno-constrictor effect of ergotamine is triggered even at heart level.     

Effect of Spinal Sympathetic Blockade upon Local Regulation of Blood Flow in Subcutaneous Tissue

The influence of spinal sympathetic blockade upon local regulation of blood flow in subcutaneous adipose tissue was investigated in six subjects. The effect of changes in orthostatic pressure on blood flow in subcutaneous tissue in the crus and distal forearm was measured before and after sympathetic blockade obtained by epidural anesthesia in 4 subjects and by a bilateral sympathectomy in 2 patients suffering from manual hyperhidrosis. Blood flow in subcutaneous tissue measured by ¹³³Xe washout technique decreased by about 40 per cent when the limb was lowered, and remained constant during 30 cm elevation. This was found both before and after the blockade, though in one of the patients, the orthostatic decrease in blood flow was less pronounced 24 h after sympathectomy. Hence central sympathetic reflexes do not alter local orthostatic changes of blood flow in subcutaneous tissue. These changes therefore are most likely due to local mechanisms.     

Effect of chronic sympathetic denervation upon the transcapillary filtration rate induced by venous stasis

The effect of venous pressure elevation upon capillary filtration rate in the limb was studied in 6 chronically sympathectomized patients. Five healthy subjects served as controls. Volume changes of the forearm or calf were recorded by a strain-gauge plethysmograph. Relative blod flow in subcutaneous and muscle tissue during venous stasis was measured by the local ¹³³Xe washout technique. In the denervated limbs there was a linear relationship between net capillary filtration rate and venous pressure elevation. In the controls a non-linear relationship was seen as venous pressure elevation of 40 mmHg only caused an increase in net filtration rate of about 66% of that expected from a linear relationship. In the denervated limbs blood flow in muscle and subcutaneous tissue remained constant during venous pressure elevation of more than 30 mmHg whereas in the non-denervated limbs blood flow decreased by about 50% in both tissues. The results suggest that a local sympathetic veno-arteriolar (axon) reflex plays a dominant role for the reduced increase in net capillary filtration rate during large increases in venous pressure. The local axon reflex may therefore act as an edema protecting factor.     

Effect of spinal sympathetic blockade upon local regulation of blood flow in subcutaneous tissue.

The influence of spinal sympathetic blockade upon local regulation of blood flow in subcutaneous adipose tissue was investigated in six subjects. The effect of changes in orthostatic pressure on blood flow in subcutaneous tissue in the crus and distal forearm was measured before and after sympathetic blockade obtained by epidural anesthesia in 4 subjects and by a bilateral sympathectomy in 2 patients suffering from manual hyperhidrosis. Blood flow in subcutaneous tissue measured by 133Xe washout technique decreased by about 40 per cent when the limb was lowered, and remained constant during 30 cm elevation. This was found both before and after the blockade, though in one of the patients, the orthostatic decrease in blood flow was less pronounced 24 h after sympathectomy. Hence central sympathetic reflexes do not alter local orthostatic changes of blood flow in subcutaneous tissue. These changes therefore are most likely due to local mechanisms.     

Effect of vein pump activation upon muscle blood flow and venous pressure in the human leg

The effect of vein pump activation upon superficial venous pressure and blood flow in human skeletal muscle tissue was studied in 7 healthy subjects. Blood flow was measured in the anterior tibia muscle by the local ¹³³Xe washout technique. The subjects were placed on a steeply tilted couch in nearly erect position. The vein pump in gastroenemius-soleus muscles was activated by heel-raisings. and the anterior tibial muscle remained relaxed during this procedure. Blood flow in the resting anterior tibial muscle was constant before, during and after 20 heel-raisings per min. A more heavy exercise with 40 heel-raisings per min increased blood flow about 100%. This increase in blood flow was absent during venous stasis (40 mmHg), and in areas infiltrated with lidocaine. It is concluded, that intense dynamic exercise in gastrocnemius-soleus muscles, in erect humans, increased blood flow considerably in another crural muscle remaining in the resting state. The present study strongly suggests, that the observed increase in blood flow, was associated with a decrease in regional subfascial venous pressure to below the threshold level of the local sympathetic veno-arteriolar reflex.     

Changes in subcutaneous blood flow during locally applied negative pressure to the skin

The effect of locally applied subatmospheric pressure on subcutaneous blood flow was studied in 12 healthy subjects. Blood flow was measured on the forearm by the local ¹³³Xe wash-out technique. Air suction between 10 mmHg and 250 mmHg was applied to the skin. Subatmospheric pressure of 20 mmHg caused only a minor increase of estimated vascular resistance of 9 per cent. Increasing the suction to 40 mmHg caused a pronounced vasoconstriction corresponding to an increase in vascular resistance of about 90%. Further increase in local suction beyond 40 mmHg caused no additional increase in vascular resistance. The vasoconstriction induced by local suction was abolished by local nervous blockade induced by lidocaine in low doses which do not affect myogenic activity of the vascular smooth muscle cells. This finding confirms previous studies that the vasoconstriction mainly is due to a local sympathetic veno-arteriolar axon reflex mechanism. The results suggest that the dominant part of the vasoconstriction induced by the local axon reflex occurs when vascular transmural pressure increases from 20 mmHg to 40 mmHg.     

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.     

Blood eosinophil numbers and activity during 24 hours: effects of treatment with budesonide and bambuterol.

The effects of the inhaled corticosteroid budesonide and the oral long-acting beta-agonist bambuterol on circadian variation of blood eosinophil numbers, serum levels of eosinophil cationic protein (ECP), serum eosinophil chemotactic activity (ECA), and serum neutrophil chemotactic activity (NCA) were studied in two groups of patients with allergic asthma. Group 1 (n = 8) had a circadian variation of peak expiratory flow (PEF) 15% or greater, and group 2 (n = 9) had a circadian PEF variation less than 15%. Both groups were randomized and crossover treated for 4 weeks with (A) 0.4 mg budesonide at 8 AM and 8 PM, (B) 20 mg bambuterol at 8 PM, and (C) placebo. At the end of each period blood eosinophil numbers, ECP, ECA, and NCA were measured during 24 hours at 4-hour intervals. No significant differences in the inflammatory parameters could be observed between the groups, although eosinophil numbers tended to be higher in group 1 than in group 2. Highest eosinophil numbers were observed at night. Budesonide reduced both eosinophil numbers and ECP levels, especially at night; bambuterol had no effect on both variables. No circadian variation or treatment effects were observed for ECA and NCA. This study suggests a role for the eosinophil in the nocturnal worsening of asthma, and it demonstrates that budesonide produces, in contrast to bambuterol, a reduction of (nocturnal) eosinophil numbers and activity.     

24-Stunden-Blutdruckmessungen im Verlauf der normalen Schwangerschaft und bei hypertensiven Schwangeren

Summary Noninvasive 24-hour ambulatory blood pressure monitoring was performed in 17 normotensive and 19 preeclamptic pregnant women. The normotensive women showed a significant nightly decline in their systolic and diastolic blood pressure. In contrast, the preeclamptic women demonstrated either an attenuated circadian rhythm or no circadian rhythm at all. This result was even more pronounced in patients with severe hypertension, some of whom had a nocturnal increase in blood pressure in spite of being treated with antihypertensive drugs in an evening dose. The lack of nocturnal blood pressure decrease was also found 24 hours post partum.In summary, these results suggest that preeclamptic women are endangered by hypertensive emergencies mostly during the night. Therefore blood pressure controls should be extended into the night, and antihypertensive drugs should also be given in a sufficient evening dose.

---

Abkürzungsverzeichnis H haemolysis - el elevated liver enzymes - lp low platelets - SSW Schwangerschaftswoche - RR Blutdruck Herrn Prof. Dr. med. F. Scheler zum 65. Geburtstag gewidmet. Diese Arbeit enthält Teilergebnisse einer noch nicht eingereichten Inaugural-Dissertation von U. Guhlke     

Effect of Chronic Sympathetic Denervation upon Local Regulation of Blood Flow in Human Subcutaneous Tissue

The effect of chronic sympathetic denervation upon the vasoconstrictor response to an increase of vascular transmural pressure in human subcutaneous adipose tissue was investigated in 6 patients suffering from manual hyperhidrosis. Changes in transmural pressure were obtained either by postural changes of a forearm or by venous stasis of 30 mmHg. Blood flow was measured in the distal part of the forearm or crus by means of the local ¹³³Xenon washout technique. 2 patients were studied before and after sympathectomy. When the area under study was lowered about 40 cm below the jugular notch, blood flow decreased about 50 per cent preoperatively, about 30 per cent 24 h after the operation, but remained constant 4 days after or later. Similar results were obtained during venous stasis. Hence about 4 days after sympathectomy, the vasoconstrictor response to an increase in vascular transmural pressure was abolished. In 3 chronically sympathectomized patients blood flow remained constant in the denervated limb, but decreased significantly in the control limb. In another patient studied 580 days after surgery blood flow remained constant during lowering of the denervated forearm as well as during venous stasis. These findings might indicate that the vasoconstrictor response to an increase in vascular transmural pressure in human subcutaneous adipose tissue is due to a local nervous mechanism involving symphathetic adrenergic nerves, but a myogenic mechanism cannot be definitively excluded.     

Effect of “Vein Pump” Activation upon Venous Pressure and Blood Flow in Human Subcutaneous Tissue

The effect of “vein pump” activation upon superficial venous pressure and blood flow in human subcutaneous adipose tissue was studied in 6 normals and 2 patients with venous insufficiency. Blood flow in subcutaneous tissue was measured at the lateral malleolus by the local ¹³³Xenon washout technique. with the subject placed in a supine position. During passive lowering of the leg blood flow decreased 50 per cent and total vascular resistance increased 136 per cent. Activation of the vein pump by continuously tipping the foot up and down caused a decrease in venous pressure of 5 mmHg in horizontal position. Venous pressure increased only by 8 mmHg when the leg was lowered during exercise. In this situation blood flow remained constant corresponding to an increase in vascular resistance of 42 per cent. However increasing venous pressure to 28 mmHg by venous stasis in the lowered leg during exercise caused an additional increase in vascular resistance of 82 per cent. In the patients with venous insufficiency exercise did not prevent the decrease in blood flow during lowering of the leg. Hence venous pressure elevation of 25 mmHg or more caused an additional increase in vascular resistance in subcutaneous tissue, “vasoconstrictor response”. It is concluded that this “vasoconstrictor response” depends on a vasoconstrictor impulse transmission from veins to arterioles, veno-arteriolar reflex.     

Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism

Sympathetic reflex regulation of subcutaneous blood flow (SBF) in the forearm was studied in eight patients with primary hypothyroidism. Diastolic arterial pressure was greater than or equal to 95 mmHg in five patients. SBF was determined by local clearance of Na99mTcO4. Sympathetic vasoconstriction normally seen after lowering the forearm 40 cm below heart level was absent since SBF only decreased by 4% (+/- 7%, P greater than 0.1) during these conditions. In head-up vertical position we noticed a diminished baroreceptor response as SBF at heart level was reduced by 11% (+/- 7%, P greater than 0.1) compared to supine position. After proximal local anaesthesia SBF increased by 351% (+/- 81%, P less than 0.01) and disclosed a normal vasoconstrictor response as SBF was reduced by 53% (+/- 5%, P less than 0.01) during arm lowering. Five of the treated patients were restudied in the euthyroid state. Mean arterial pressure was reduced in mean by 20 mmHg (+/- 6 mmHg, P less than 0.02) during treatment and a significant vasoconstriction was observed both during arm lowering (SBF = -52% (+/- 6%, P less than 0.02)) and in head-up vertical position (SBF = -45% (+/- 11%, P less than 0.02)). In conclusion sympathetic vasoconstrictor activity in adipose tissue is markedly increased in primary hypothyroidism. Sympathetic tone and arterial pressure are reduced during treatment.