Venoarteriolar Reflex Research Articles

Impaired venoarteriolar reflex as a possible cause for nifedipine-induced ankle oedema

Ankle oedema is not an uncommon side effect of treatment with nifedipine. To evaluate the possible effect of nifedipine on the microcirculation of the skin, 18 patients with systemic hypertension who were known to develop ankle oedema after nifedipine and 19 patients with systemic hypertension who did not develop ankle oedema after nifedipine were studied. Following four weeks of nifedipine therapy (10 mg, three times daily), the microcirculation on the dorsum of the foot was measured using laser-Doppler flowmetry. Estimation of the microcapillary flow was made both after supine resting and on standing upright. The venoarteriolar reflex was expressed as the standing flow in percentage of the resting flow. There was no significant difference between the two groups of patients in the resting flow, supine flow, or the venoarteriolar reflex before nifedipine therapy ( P > 0.4). Before nifedipine, the blood blow in the skin of both groups of patients was reduced from the supine level upon standing, thus indicating a normal response to dependency. After nifedipine administration, no significant difference was observed between the two groups of patients in the resting flow ( P > 0.5). The flow on standing, however, was 96.2% of that measured during resting supine in patients who developed ankle oedema and 79.8% of the resting flow in the patients who did not develop ankle oedema, suggesting a weaker venoarteriolar reflex in patients who developed ankle oedema following administration of nifedipine ( P < 0.0001). Thus, the microcapillary flow did not decrease upon standing in patients who developed ankle oedema following nifedipine therapy, indicating an abnormal venoarteriolar reflex. This may explain why ankle oedema develops in such patients following nifedipine.

Does combined kidney and pancreas transplantation reverse functional diabetic microangiopathy?

Using videophotometric capillaroscopy and laser Doppler fluxmetry, we have investigated skin microvascular reactivity in the fingers of 14 diabetic patients with severe, late complications 20 months after combined kidney and pancreas transplantation. The results were compared with those obtained in 20 diabetic patients awaiting pancreas transplantation and in 19 healthy subjects. The capillary blood cell velocity at rest (P less than 0.01) and during postocclusive reactive hyperemia (P less than 0.05) was significantly lower in both patient groups than in the healthy controls. However, the time to peak capillary blood cell velocity during hyperemia was normal in the post-transplantation group (NS) but significantly prolonged in the pretransplantation group (P less than 0.01). The ability to decrease flow during venous stasis-the so called venoarte-riolar reflex--was strongly impaired in the pretransplantation group (P less than 0.001) but less so in the post-transplantation group (P less than 0.05) as compared to healthy controls. It may be concluded that diabetic patients, after combined kidney and pancreas transplantation, show a tendency towards better microvascular reactivity than those awaiting transplantation.

Local sympathetic reflex control of blood flow in human skin following topical corticosteroid treatment

Local positional vasomotor activity, or the veno-arteriolar reflex, was studied in normal human skin over 3 days of treatment with a potent corticosteroid under occlusion. Eight healthy subjects participated in the study. Using the atraumatic epicutaneous 133-Xe washout technique on the outer 2 mm of the skin fold between the first and the second finger, and covering the rest of the hand with a lead shield, blood flow in cutaneous tissue only was monitored. The veno-arteriolar reflex was elicited by inducing venous stasis.Before treatment, 40 mmHg venous stasis reduced cutaneous blood flow by 37.1% (95 percentile, 24.5-56.0). Following 24 h and 48 h of treatment, the reflex became weaker and at day 3, the blood flow reduction was 17.8% (7.6-42.6). The diminution was significant (p<0.05).

Cutaneous blood flow rates during orthostatic manoeuvres measured by laser Doppler flowmetry.

The validity of Laser Doppler Flowmetry for measurements of changes in skin blood flow rates during orthostatic manoeuvres was evaluated. Fifteen healthy subjects were investigated. Relative skin blood flow rates on the dorsum of the hand were measured during stepwise raising and lowering of the arm in 10 cm increments to an extreme position of 40 cm below respectively above heart level. All measurements at test levels were preceded and followed by measurements at reference level, i.e. heart level. At all levels of arm elevation, relative blood flow rates were significantly increased compared with the corresponding reference level (p = 0.0005). This was unexpected in view of the auto-regulatory mechanism. Highly significant blood flow rate reductions were found at all levels of arm lowering. This is in contrast to previous findings of unchanged skin blood flow rate to a point of approximately 35 cm below heart level, where the veno-arteriolar reflex is elicited.

Defective venoarteriolar reflex as a possible cause for ankle oedema following nifedipine therapy

Defective venoarteriolar reflex as a possible cause for ankle oedema following nifedipine therapy

Local sympathetic reflex control of blood flow in human skin following topical corticosteroid treatment

Local positional vasomotor activity, or the veno-arteriolar reflex, was studied in normal human skin over 3 days of treatment with a potent corticosteroid under occlusion. Eight healthy subjects participated in the study. Using the atraumatic epicutaneous 133-Xe washout technique on the outer 2 mm of the skin fold between the first and the second finger, and covering the rest of the hand with a lead shield, blood flow in cutaneous tissue only was monitored. The veno-arteriolar reflex was elicited by inducing venous stasis. Before treatment, 40 mmHg venous stasis reduced cutaneous blood flow by 37.1% (95 percentile, 24.5-56.0). Following 24 h and 48 h of treatment, the reflex became weaker and at day 3, the blood flow reduction was 17.8% (7.6-42.6). The diminution was significant (p less than 0.05).

Cutaneous blood flow rates during orthostatic manoeuvres measured by laser Doppler flowmetry.

The validity of Laser Doppler Flowmetry for measurements of changes in skin blood flow rates during orthostatic manoeuvres was evaluated. Fifteen healthy subjects were investigated. Relative skin blood flow rates on the dorsum of the hand were measured during stepwise raising and lowering of the arm in 10 cm increments to an extreme position of 40 cm below respectively above heart level. All measurements at test levels were preceded and followed by measurements at reference level, i.e. heart level. At all levels of arm elevation, relative blood flow rates were significantly increased compared with the corresponding reference level (p = 0.0005). This was unexpected in view of the auto-regulatory mechanism. Highly significant blood flow rate reductions were found at all levels of arm lowering. This is in contrast to previous findings of unchanged skin blood flow rate to a point of approximately 35 cm below heart level, where the veno-arteriolar reflex is elicited.

Development of gangrene during sleep

A method for continuous measurement of subcutaneous adipose tissue blood flow in the forefoot over 24 h (SBF) is described. The method is based on the radioisotope wash-out principle using 133-Xenon (133Xe). A portable semiconductor detector is placed just above a local depot of 37-74 kBq 133Xe in 0.1 ml isotonic saline, injected into the subcutaneous adipose tissue in the forefoot. The detector is connected to a memory unit allowing for storage of data. Because of the short distance, the recorded elimination rate constant must be corrected for combined convection and diffusion of the radioactive indicator. Characteristic 24-h blood flow patterns were unveiled in patients with normal peripheral circulation and in patients having ischaemic nocturnal rest pain. In normal subjects, SBF doubled from day to night. This is ascribed to the local veno-arteriolar sympathetic axon reflex, which induces vasoconstriction when the transmural pressure of the veins exceeds approximately 25 mmHg. In patients having ischaemic rest pains SBF was reduced by 37% on the average from day to night. This was caused by nocturnal hypotension, which is reflected proportionally in the foot. As the resistance vessels most probably are fully dilatated in feet with rest pain, the blood pressure drop during sleep causes the perfusion pressure and, therefore, blood flow to drop below a certain critical limit. There was a pronounced correlation between the reduction systemic mean arterial blood pressure and SBF. The patients complaining of intermittent claudication, but no rest pains, demonstrated a variety of changes in SBF compatible with the continuous spectrum of peripheral arteriosclerotic disease. The reduced blood flow during sleep in patients having ischaemic rest pains give rise to the concept of the development of gangrene during sleep.

The venoarteriolar reflex in diabetic and other neuropathies.

Limb dependency activates the venoarteriolar reflex (VAR), resulting in reflex vasoconstriction (RV). Since others have reported the VAR to fail in diabetic neuropathy, we examined the reliability of this test in detecting sympathetic failure in diabetic and other neuropathies. We studied 40 controls, 49 diabetic subjects, and 29 patients with other neuropathies. The mean RV was greater in controls than in diabetics or other neuropathies, but there were marked overlaps among groups. We conclude that the VAR, while impaired in the neuropathies, is of little value as a clinical test and is a poorer test of autonomic function than the quantitative sudomotor axon reflex test or heart rate responses to deep breathing or the Valsalva maneuver.

Microvascular evaluation of the effects of nifedipine in vascular patients by laser-Doppler flowmetry.

Skin blood flow in the microcirculation of the distal foot was evaluated in patients with vascular disease and diabetes and compared with that in normal volunteers by use of laser-Doppler flowmetry. Resting flow (RF) and the flow on standing (SF) were measured in a room at constant temperature (20-22 degrees C). RF was significantly different in the five groups, being increased in patients with diabetes (in comparison with normal volunteers) and decreased in patients with intermittent claudication, rest pain, and ischemic limbs. The venoarteriolar reflex (in response to standing) was also decreased or abolished in diabetic and in all vascular patients. After treatment of all vascular patients with nifedipine (10 mg tid) for one week, there was a significant increase in RF in all patients. The venoarteriolar reflex was improved but still remained below the normal limit. In conclusion laser-Doppler flowmetry is useful both for differentiating classes of different vascular patients and for evaluating the microcirculatory changes induced by nifedepine.

The veno-arteriolar reflex in free skin flaps.

The veno-arteriolar reflex was measured in 10 subjects in whom an area of denervated skin was present in the lower limb following free flap transfer of skin and subcutaneous tissue 3 weeks to 2 years previously. The vasoconstrictor response to dependency was measured in the skin of the flap, in adjacent innervated skin and after chemical dilatation of cutaneous vessels in the skin of the flap. This veno-arteriolar reflex resulting in a reduction of blood flow of 30-40% was present and equal in both normal and denervated skin. The response was abolished by chemical vasodilatation. The results indicate that sympathetic innervation is not essential for the veno-arteriolar reflex, and suggest that myogenic mechanisms may be more important than previously believed.

Evaluation of the Microcirculatory Effects of Venoruton (H.R.) in Patients with Chronic Venous Hypertension by Laser-Doppler Flowmetry, Transcutaneous PO2 and PCO2 Measurements, Leg Volumetry and Ambulatory Venous Pressure Measurements

The effect of Venoruton on the symptoms and microcirculation was investigated in an open randomised placebo controlled study involving 35 patients with chronic venous hypertension. Treatment was for 6 weeks. There was a significant symptomatic relief (ache, cramps, skin irritation and swelling) according to an analogue scale line score in the active treatment group, but not in the placebo group. The symptomatic relief in this group was associated with a reduction in leg volume ( p &lt; 0.5), resting and standing skin blood flow ( p &lt; 0.05), restoration of the venoarteriolar reflex, a decrease in transcutaneous PO2 ( p &lt; 0.01) an increase in PO2 ( p &lt; 0.05). These parameters did not change in the placebo group. The results of this study demonstrate that Venoruton therapy has a marked effect on the microcirculation and indicate possible mechanisms of the relief of symptoms.

Blood Flow in the Perimalleolar Skin in Relation to Posture in Patients with Venous Hypertension

The resting and standing perimalleolar skin blood flow and venoarteriolar response have been studied in 20 patients with postphlebitic limbs and 25 normal volunteers using laser-Doppler flowmetry. In postphlebitic limbs the venoarteriolar reflex was impaired and both the resting and standing skin blood flow were increased, suggesting the presence of local vasoparalysis similar to that previously observed in diabetics with peripheral neuropathy.

Microvascular circulatory changes in the lower extremities after reconstructive vascular surgery for intermittent claudication

We have studied the circulatory changes in the lower extremities after reconstructive vascular surgery in ten patients with intermittent claudication. The following examinations were carried out 3 days before, 3 days, and 28 days after the operation: measurement of ankle systolic blood pressure, calf plethysmography, resting calf muscle blood flow and resting subcutaneous foot blood flow. The vasoconstrictor response (veno-arteriolar reflex) was also assessed. On the night before the operation and on the 28th night after aorto-bifemoral bypass surgery, subcutaneous adipose tissue blood flow in the forefoot was measured during sleep. The ankle systolic blood pressure and the ankle index rose significantly. The former increased from 57 +/- 16.4 mmHg to 93 +/- 24.0 mmHg (mean +/- S.E.M.) and was still elevated on the 28th postoperative day. The total limb blood flow, the muscle blood flow and the blood flow in the subcutaneous tissue of the forefoot during daytime were unchanged. In contrast, the blood flow in the forefoot during sleep increased significantly from 3.5 +/- 1.63 ml x (min x 100 g)-1 to 5.2 +/- 2.14 ml x (min x 100 g)-1 (mean +/- S.E.M.) on the 28th night. The vasoconstrictor response was potentiated, and increased from 27% before the operation to 45% on the third postoperative day. This change was maintained 28 days postoperatively. In conclusion the increase in arterial blood pressure was only reflected in the vasoconstrictor response which had returned to normal by the third postoperative day and nocturnal blood flow in the subcutaneous adipose tissue which did likewise.

Arteriolar hyalinosis does not interfere with the local veno-arteriolar reflex regulation of subcutaneous blood flow in insulin-dependent diabetic patients

The function of the local nervous veno-arteriolar reflex regulation of blood flow in subcutaneous tissue of the lower leg was studied in diabetic patients. The material comprised 11 long-term insulin-dependent diabetic (IDDM) patients with retinopathy and nephropathy and eight short-term IDDM patients without retinopathy or nephropathy and 11 non-diabetic subjects. The diabetic patients had no or a slight to moderate degree of peripheral autonomic and sensoric neuropathy. Blood flow was measured by the local 133Xe wash-out technique. Blood flow was determined before, during and after an approximately 40 mmHg increase in venous transmural pressure, induced by lowering the lower leg 50 cm below heart level. During lowering of the leg, the subcutaneous blood flow decreased to the same level in long-term IDDM patients (mean: 46%), short-term IDDM patients (53%) and control subjects (53%). There was no association between the relative local blood flow during lowering and the degree of terminal arteriolar hyalinosis studied in skin biopsies from the same tissue area. Our results suggest that terminal arteriolar hyalinosis does not interfere with the local sympathetic-mediated veno-arteriolar reflex regulation of blood flow. Moreover, the vasoconstriction mediated by the veno-arteriolar reflex probably occurs in the larger arterioles (greater than 50-100 micron) or small arteries.

Arteriolar hyalinosis does not interfere with the local veno-arteriolar reflex regulation of subcutaneous blood flow in insulin-dependent diabetic patients

Arteriolar hyalinosis does not interfere with the local veno-arteriolar reflex regulation of subcutaneous blood flow in insulin-dependent diabetic patients

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.

Blood flow in skeletal muscle of tetraplegic man during postural changes.

Relative changes in blood flow and vascular resistance in arm and leg muscle during head-up tilt at 45 degrees were studied in eight patients with complete cervical spinal cord transection and in 13 healthy volunteers. Muscle blood flow was measured by the local 133Xe washout method. In forearm muscle kept at heart level blood flow remained constant in the tetraplegic patients during head-up tilt, in contrast to that seen in the normal subjects, where blood flow decreased by 30%. In the dependent leg muscle, head-up tilt caused a decrease in blood flow of 46% and 40% in the patients and normals, respectively. Abolition of the local veno-arteriolar axon reflex, by inducing local counter-pressure to prevent venous distension in the dependent leg muscle, reduced the decrease in blood flow to 24% and 23%, respectively. Thus, the vascular response to head-up tilt differed significantly in forearm muscle between the two groups, whereas no difference was seen in the leg muscle. The absence of the vasoconstrictor response in forearm muscle indicates that postural sympathetic reflexes to this region depend on sympathetic reflexes integrated in centres located rostrally to the spinal cord. The results further suggest that local veno-arteriolar axon reflexes as well as spinal reflexes contribute to the observed vasoconstriction in the leg muscle.

Local Regulation of Cutaneous Blood Flow in Psoriasis

Local regulation of cutaneous blood flow (CBF), i.e., the venoarteriolar reflex mechanism and the autoregulation response, was studied in 27 patients with psoriasis using atraumatic epicutaneous 133Xe-labeling tracer washout technique. Venous stasis of 40 mm Hg induced a significant reduction in CBF--as in normal subjects (i.e., a vasoconstrictor response)-in both involved psoriatic skin (0.47 +/- SEM 0.04, p less than 0.0001) and uninvolved psoriatic skin (0.38 +/- SEM 0.03, p less than 0.0001). The vasoconstrictor response to neural blockade with lidocaine was investigated in two control experiments in psoriatic skin. It was found to be normal: neural blockade with lidocaine 2 cm outside the measured field did not affect the vasoconstrictor response, whereas local infiltration with lidocaine did block the vasoconstrictor reflex. Limb elevation of 40 cm above heart level induced a 2-fold significant increase in the CBF of involved psoriatic skin in 10 patients. This response is a paradoxical deviation from normal local autoregulation of the CBF (p less than 0.002). Limb elevation had no significant influence on CBF of uninvolved psoriatic skin, indicating a normal autoregulation of the CBF. The paradoxical increase in CBF during limb elevation in involved psoriatic skin was not influenced by local neural blockade with lidocaine, or by local neural and vascular, smooth muscle blockade obtained by injection of lidocaine and papaverine. The results indicate that the reason for this paradoxical phenomenon might be due to the special morphology of the capillaries of involved psoriatic skin.

Sympathetic vasoconstrictor nerve function in alcoholic neuropathy.

The peripheral sympathetic vasomotor nerve function was investigated in 18 male chronic alcoholics admitted for intellectual impairment or polyneuropathy. By means of the local 133Xenon washout technique, the sympathetic veno-arteriolar axon-reflex was studied. This normally is responsible for a 50% decrease in tissue blood flow, when the ankle is lowered 40 cm below heart level in the supine individual. The patients with moderate to severe polyneuropathy, taken as a group, did not differ significantly from the group of patients with no or only mild polyneuropathy, although a lesser response was seen (18% and 48% decrease respectively). However, in three patients with moderate neuropathy, and in one patient with no signs of neuropathy, this veno-arteriolar reflex was absent, indicating dysfunction of the peripheral sympathetic adrenergic nerve fibres. The three patients also showed a lesser degree of arteriolar constriction during 45 degrees passive head-up tilt, although none developed symptoms of orthostatic hypotension. Anhidrosis of the feet was found in only three patients. This study lends support to the view that individual differences in the susceptibility to the deleterious effect of alcohol comprise not only the peripheral sensory and motor nerve fibres, but also the thin pseudomotor and vasomotor nerves.