Subcutaneous Blood Flow Research Articles

The reflex sympathetic dystrophy syndrome. An experimental study of sympathetic reflex control of subcutaneous blood flow in the hand.

Adrenergic sympathetic vasoconstrictor activity in subcutaneous tissue on the back of the hand was studied in 13 patients suffering from reflex sympathetic dystrophy syndrome. Subcutaneous blood flow was measured by the local 133Xe wash-out technique with simultaneous measurements on the healthy side as a control. The results indicated an increased subcutaneous blood flow in the affected hand compared with the control side. Proximal nervous blockade caused only a slight, 35% increase in subcutaneous blood flow on the affected side, whereas an increase of 122% was registered on the control side. Augmented sympathetic vasoconstrictor activity elicited by the local veno-arteriolar axon reflex mechanism or centrally elicited by head-up tilt caused an equal degree of arteriolar vasoconstriction in both hands. The results suggest that sympathetic vasomotor tone during resting conditions is reduced in the affected hand in patients with the reflex sympathetic dystrophy syndrome.

手部皮下組織の循環動態に関する研究 ＩＩ し位による血流量の変動と交感神経系について

In an earlier work in normal subjects, We demonstrated that the subcutaneous tissue blood flow in the hand region was found to be significantly reduced by the postural change from the supine to the upright position. In order to investigate the possible role of central mechanisms in the observed changes in blood flow rate during the postural change, the acute effects of the postural change from the supine to the upright position on the subcutaneous tissue blood flow in the hand region were studied in seven subjects with shoulder-arm-neck syndrome after an acute sympathetic denervation using the hydrogen washout technique.Acute sympathetic denervation was achieved by stellate ganglion block induced by lidocaine, 1 per cent, without adrenaline. Horner's syndrome was taken as evidence of effective sympathetic denervation.During the postural change from the sppine to the upright position after sympathetic denervation, the blood flow rate decreased to the mean value of 62.5 per cent of the initial value in the denervated hand and to the mean value of 63.6 per cent of the initial value in the non-denervated hand. The difference was not significant.These findings suggest that the vascular adjustments to postural changes may not be altered by the sympathetic denervation. This interpretation is consistent with Henriksen's evidence which suggests that vascular reactions to postural changes in vascular transmural pressure are not mediated via sympathetic ganglia.

Augmented vasoconstrictor response to head-up tilt in peripheral tissues during beta-receptor blockade

Subcutaneous and skeletal muscle blood flow in the forearm during 30 degrees head-up tilt was studied in 15 healthy subjects before and during treatment with propranolol. Relative blood flow was estimated by the local 133Xe washout technique. Head-up tilt elicited greater vasoconstriction in both tissues during beta-receptor blockade as compared to the pretreatment period. Proximal nerve blockade with lidocaine prevented the vasoconstrictor response in subcutaneous tissue to the tilt. In skeletal muscle injection of a low dose of propranolol had no effect on the vasoconstrictor response to tilt. Therefore, the augmented vasoconstrictor response to head-up tilt during beta-receptor blockade is most probably due to centrally elicited (baroreceptor) and neurogenically mediated impulses to resistance vessels in peripheral tissues and not to "unmasking" of peripheral alpha-receptors.

Sympatho-adrenal regulation of adipose tissue blood flow in dog and man

1. 1. A comparison is made between the sympatho-adrenal regulation of subcutaneous adipose tissue blood flow in the dog and in man. 2. 2. In the dog neuronally released noradrenaline causes vasoconstriction in subcutaneous adipose tissue by preferential activation of α-adrenoceptors located close to the sympathetic nerve terminals. 3. 3. In man sympathetic reflex activation also causes vasoconstriction in subcutaneous adipose tissue, presumably via activation of α-adrenoceptors. 4. 4. The adipose tissue vascular β-adrenoceptors are of the β 1-subtype in the dog and the β 2-subtype in man. 5. 5. Because of this adrenaline causes vasoconstriction in dog adipose tissue and vasodilation in human adipose tissue.

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 degrees, 45 degrees and 70 degrees) 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.

Effects of externally applied compression on blood flow in subcutaneous and muscle tissue in the human supine leg.

The effect of positive tissue pressure on blood flow in subcutaneous adipose tissue and skeletal muscle tissue was studied in eight healthy humans resting in the supine position. Blood flow was measured by the local 133Xe clearance technique in the mid-calf region. Tissue pressure was increased by inflating a whole leg cuff to pressure levels between 10 and 60 mmHg. In subcutaneous tissue as well as in skeletal muscle tissue, blood flow and local vascular resistance was not significantly changed at compression with 10 mmHg (P greater than 0.1). The pressure-flow curve obtained from subcutaneous tissue was curvilinear with the convexity towards the pressure axis, as blood flow was significantly reduced, while local vascular resistance was significantly increased by further increase in cuff pressure. Compression with 60 mmHg reduced subcutaneous blood flow to 21% of the reference value (P less than 0.01), while local vascular resistance was increased 91% above the reference value (P less than 0.01). In skeletal muscle tissue the pressure-flow curve was curvilinear with the convexity towards the flow axis, as local vascular resistance was reduced to 93% of the reference value at compression with 20 mmHg (P less than 0.05). Compression with 60 mmHg reduced muscle blood flow to 41% of the reference value (P less than 0.01), while local vascular resistance was increased 32% above the reference value (P less than 0.05). Venous distension in compressed subcutaneous tissue increased blood flow with 46% (P less than 0.02), while regional vascular resistance was reduced with 53% (P less than 0.01). In skeletal muscle tissue the same procedure was not followed by significant changes in blood flow or vascular resistance (P less than 0.01). It is concluded that the observed difference between the two tissues could be caused by a difference in vessel collapsibility. Another mechanism responsible could be a difference in autoregulatory capacity.

Determination of the subcutaneous tissue to blood partition coefficient in patients with severe leg ischaemia by a double isotope washout technique.

Knowledge of the tissue to blood partition coefficient (lambda) is essential for calculation of the perfusion coefficient in a single tissue based on measurements of the washout of locally injected isotopes. No measurements of lambda for Xenon in subcutaneous tissue in the leg have been done in patients with occlusive arterial disease. In 12 patients with occlusive arterial disease in the legs lambda for Xenon was determined in subcutaneous tissue in the calf region and foot as the ratio between the washout rate constant of 131I-Antipyrine and 133Xe. A mixture of the two indicators was injected subcutaneously laterally on the calf and in the first interosseous space on the foot. The time until the curves followed a monoexponential course varied between 15 and 45 min in the calf and 5 and 45 min in the foot. The calculated lambda for Xe showed a great variance between individuals in calf as well as foot. Mean value was 3.7 ml X g-1 (range: 1 X 7-10 X 7) in the calf and 2 X 7 ml X g-1 (range: 1 X 2-4 X 9) in the foot. It is concluded that lambda measurements are necessary for determination of subcutaneous blood flow from 133Xe washout curves in these patients. Determination of lambda is especially important when comparisons are made between individuals.

Subcutaneous blood flow over 24-hour periods in patients with severe leg ischaemia.

This paper describes a method for studying the clearance of 133Xenon from the subcutaneous tissue of the calf and foot over 24-h periods. The average blood flow over this period can be estimated from the clearance constant obtained. Two series of measurement of the radioactivity are made, the first 2 h after the injection of 1-2 mCi 133Xenon in saline and the second 18-24 h later. The distance between the detector and the depot is reproduced using a cylinder 20 cm long. The median washout rate of the isotope (k) in 25 patients was 2.57 X 10(-3) min-1 for the calf and 2.39 X 10(-9) min-1 for the foot. The median difference between repeated measurements in the same patient ws 0.24 X 10(-3) min-1 in the calf and 0.43 X 10(-3) min-1 in the foot. This method, which can be used to estimate the average blood flow over 24 h while the patient undertakes his normal activities, should be useful in assessing the effect of therapy on the blood flow to the limb.

Subcutaneous blood flow during insulin-induced hypoglycaemia: studies in juvenile diabetics with and without autonomic neuropathy and in normal subjects.

Subcutaneous blood flow was measured preceding insulin-induced hypoglycaemia, at the onset of hypoglycaemic symptoms and 2 h later in juvenile diabetics with and without autonomic neuropathy and in normal males. In all groups subcutaneous blood flow decreased at the onset of hypoglycaemic symptoms compared with pre-hypoglycaemic flow. Two hours after onset of hypoglycaemic symptoms, subcutaneous blood flow was still significantly decreased compared with pre-hypoglycaemic flow. In normal subjects local nerve blockade had no effect on blood flow changes during hypoglycaemia, whereas local alpha-receptor blockade abolished the vasoconstrictor response. We suggest that circulating catecholamines stimulating vascular alpha-receptors are probably responsible for flow reduction in the subcutaneous tissue during hypoglycaemia.

Influence of vasoactive drugs on local tumor blood flow

The influence of vasoactive drugs, including noradrenaline, isoprenaline and papaverine, on the local blood flow of a transplantable rat sarcoma and of normal subcutaneous tissue of the rat was studied by local [ 133 xenon] clearance technique. The microvascular bed of the tumour was studied by transmission electron microscopy (TEM). Vessels with one layer of contractile cells were found in the tumour vascular bed by TEM. A significant reduction of both tumour and normal subcutaneous tissue blood flow was found after administration of noradrenaline added to the injected xenon solution. In a dose—response experiment the tumour and subcutaneous vascular beds seemed to be equally sensitive to noradrenaline. Isoprenaline did not influence the blood flow in either subcutaneous tissue or tumour, while papaverine increased subcutaneous tissue blood flow significantly but did not influence tumour blood flow. The results of the present blood flow studies might suggest that the tumour vascular bed is normally in a state close to maximal dilatation.

Sympathetic reflex control of subcutaneous blood flow in tetraplegic man during postural changes.

1. The effect of head-up tilt upon subcutaneous blood flow in the distal arm and leg was studied in 12 patients with complete traumatic spinal cord transection at the cervical level. 2. Blood flow was measured by the local 133Xe washout technique. 3. Leg lowering induced a 47% decrease in blood flow in the distal leg. During head-up tilt (45 degrees) blood flow in the leg decreased by 48%. In the arm remaining at heart level blood flow decreased by 37% during tilt and this vasoconstriction could be prevented by nervous blockade with lignocaine injected subcutaneously 5 cm proximally to the labelled area. Leg blood flow was unaltered by proximal blockade but could be blocked by local infiltration in the labelled area with lignocaine in low doses. 4. Head-up tilt of tetraplegic patients induced vasoconstriction in the subcutaneous tissue of the forearm, which could be prevented by proximal blockade. Thus the vasoconstriction could be due to a spinal sympathetic reflex mechanism. This as well as local mechanisms including the venoarteriolar reflex may play a role in recovery of arterial blood pressure during head-up tilt in the tetraplegic patient.

Effect of locally applied subatmospheric pressure on subcutaneous blood flow during the course of acute myocardial infarction.

1. The effect of locally applied subatmospheric pressure on subcutaneous blood flow was studied in six patients with acute myocardial infarction. 2. Blood flow was measured by the local 133Xe washout technique. 3. Application of subatmospheric pressures of -80 and -150 mmHg to the labelled area induced no vasoconstriction on day 1. On day 7 pressures of -40, -80 and -150 mmHg induced a decrease in blood flow of about 40-50%. 4. The absence of a vasoconstrictor response to locally applied subatmospheric pressure on day 1 could not be due to decreased venous distensibility. The underlying mechanism may be neuronal inhibition, probably antidromic, in sympathetic fibres.

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.

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.

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

Local and remote regulation of subcutaneous blood flow in the forearm and leg was studied during head-up tilt (45 degrees) in 6 young healthy male subjects. Relative blood flow was estimated by the local 133Xe washout technique. Lowering of a leg 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 cm. 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).

Subcutaneous adipose tissue blood flow and triacylglycerol-mobilization during prolonged exercise in dogs

In 6 dogs concentration differences for glycerol and FFA were measured between the aorta and the external pudendal vein, a vein which mainly drains subcutaneous adipose tissue in dogs, during prolonged exercise. It was found that the a-v differences increased about 2-fold for both glycerol and FFA, however great interindividual differences were found. In 4 dogs adipose tissue blood flow, glycerol and FFA a-v differences were measured simultaneously, and the mobilizations of glycerol and FFA as well as the re-esterification of FFA were calculated. After 2 h of exercise the values were in the range of 1-7 umol/(100 g.min) for FFA and glycerol mobilizations while the FFA re-esterification was in the range of 2-14 umol/(100 g.min). It was found that the FFA/albumin ratio in adipose venous blood, on average 3.6 was at a level at which the FFA mobilization has been shown to depend on the adipose tissue blood flow in isolated fat pads. In 11 dogs subcutaneous adipose tissue blood flow rose 2-fold during exercise from about 5-10 ml/(100 g.min). It is concluded that the subcutaneous adipose tissue blood flow response to exercise is equal in man and dog, that lipolysis, FFA mobilization and FFA re-esterification are increased in subcutaneous adipose tissue during exercise, and that the increase in blood flows is of importance for the enhanced FFA mobilization during exercise.

Hemodynamics in diabetic orthostatic hypotension.

Hemodynamic variables (blood pressure, cardiac output, heart rate, plasma volume, splanchnic blood flow, and peripheral subcutaneous blood flow) and plasma concentrations of norepinephrine, epinephrine, and renin were measured in the supine position and after 30 min of quiet standing. This was done in normal subjects (n = 7) and in juvenile-onset diabetic patients without neuropathy (n = 8), with slight neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation) (n = 8), and with severe neuropathy including orthostatic hypotension (n = 7). Blood pressure decreased precipitously in the standing position in the diabetics with orthostatic hypotension, whereas moderate decreases were found in the other three groups. Upon standing, heart rate rose and cardiac output and plasma volume decreased similarly in the four groups. The increases in total peripheral resistance, splanchnic vascular resistance and subcutaneous vascular resistance were all significantly lower (P less than 0.025) in the patients with orthostatic hypotension compared with the other three groups. The increase in plasma norepinephrine concentrations in the patients with orthostatic hypotension was significantly lower (P less than 0.025) than in the patients without neuropathy, whereas plasma renin responses to standing were similar in the four groups. We conclude that in diabetic hypoadrenergic orthostatic hypotension the basic pathophysiological defect is lack of ability to increase vascular resistance, probably due to impaired sympathetic activity in the autonomic nerves innervating resistance vessels; cardiac output and plasma volume responses to standing are similar to those found in normal subjects and in diabetics without neuropathy.

Augmented vasoconstrictor response to changes in vascular transmural pressure in patients with essential arterial hypertension.

The vasoconstrictor response to increase in venous transmural pressure in subcutaneous tissue was studied in 9 patients with essential arterial hypertension. Subcutaneous blood flow was measured on the distal part of the forearm and at the lateral malleolus by the local 133Xe washout technique. Increase in venous transmural pressure was obtained by lowering the area under study 40 cm below midaxillary line in the recumbent subject. Average mean arterial pressure +/- 1 S.E. was 133 +/- 6 mmHg. The fractional increase in vascular resistance induced by arteriolar constriction was more pronounced in the hypertensive patients that in a normotensive control group. "Minimal vascular resistance" in the papaverine relaxed vascular bed was higher in the hypertensive patients than in the controls. Distensibility of the papaverine relaxed resistance vessels was diminished in the patients. Follow-up studies after 6-18 months of anti-hypertensive treatment indicate that the vasoconstrictor response as well as "minimal vascular resistance" are normalized, whereas the distensibility of the papaverine relaxed arterioles remained unaltered in the hypertensive patients. The results indicate that the arteriolar smooth muscle cells of hypertensive patients are subjected to reversible hypertrophy whereas the reduced distensibility of the resistance vessels is due to irreversible structural changes.

Local regulation of blood flow in subcutaneous tissue in patients with acute myocardial infarction.

1. Local regulation of subcutaneous blood flow in the forearm was studied in the acute phase of myocardial infarction. Blood flow was measured by the local 133Xe-washout technique. 2. Plasma concentrations of noradrenaline and adrenaline were increased on day 1, suggesting an increase in sympathetic neuronal activity, but gradually returned to normal thereafter. 3. Subcutaneous blood flow on day 1 was far below normal (38%) and steadily increased to reach normal at day 7 after coronary occlusion. The sympathetic vasoconstrictor activity that caused the initial reduction in flow could be blocked by proximal nervous blockade, increasing the subcutaneous blood flow by 130, 63 and 14% on days 1, 3 and 7 respectively after coronary occlusion. A normal response to decrease in arterial perfusion pressure was observed, suggesting that intrinsic vascular reactions responsible for autoregulation of blood flow were not affected by the increase in sympathetic vasoconstrictor activity. The vasoconstrictor response to increase in venous transmural pressure could not be demonstrated on day 1 after coronary occlusion but gradually reappeared during the following days. 4. Abolition of the vasoconstrictor response is most likely to be due to a centrally elicited increase in sympathetic activity, as a normal vasoconstrictor response was obtained after proximal nervous blockade. Thus the local sympathetic reflex mechanism underlying the vasoconstrictor response appears to be suppressed by a centrally elicited increase in sympathetic discharge rate.

Effect of head-up tilt on subcutaneous blood flow during the course of acute myocardial infarction.

1. Central and local regulation of subcutaneous blood flow in the forearm was studied in the acute phase of myocardial infarction. 2. Blood flow was measured by the local 133Xe-washout technique. 3. The vasoconstrictor response to increase in venous transmural pressure was not present on day 1 after coronary occlusion but gradually recurred during days 2, 3 and 7. 4. Passive 30 degrees head-up tilt induced a vasoconstriction in subcutaneous tissue. There was no difference in this response at any time during the course of acute myocardial infarction. The vasoconstriction could be blocked by proximal nervous blockade. 5. Thus a decrease in baroreceptor activity induced by head-up tilt enabled a marked neurogenically mediated vasoconstriction in subcutaneous tissue, indicating that orthodromic impulse activity in sympathetic fibres can be further increased even on day 1 of acute myocardial infarction.