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Biomedical subjects

J E Tooke

Publications and source records attributed to J E Tooke.

At least 109 records · Page 6Linked to original sources

Dynamic measurement of human capillary blood pressure.

1. Capillary blood pressure was measured in man using a dynamic servo-nulling system and direct micropuncture. This enabled assessments of the normal variations in pressure which influence fluid filtration and reabsorption. 2. Seventy-eight capillaries in 19 subjects were punctured in one of three positions around the capillary loop with the hand at the level of the sternal angle. Mean pressure around the loop fell from 37.7 +/- 3.7 mmHg (arteriolar limb, mean +/- SEM, n = 12) to 19.4 +/- 1.0 mmHg (apex, n = 25) to 14.6 +/- 0.5 mmHg (venular limb, n = 41) at skin temperatures of 18.7-33.1 degrees C. These values agree closely with Landis' original studies in 1930 [E. Landis (1930) Heart, 15, 209-228]. 3. The mean filtration/reabsorption state of any particular capillary limb was not static because of cardiac, vasomotor and respiratory fluctuations in capillary pressure. From a total of 38 capillaries in which recordings were analysed for 30 s, the fluctuations in pressure were such that 27 capillaries probably had periods of both filtration and reabsorption. 4. Computerized superimposition and coherent averaging of trains of capillary pulses enabled an accurate description of the pulse waveform to be made in three capillaries. This was remarkably similar to waveforms from the radial artery, albeit at reduced amplitude (average 3.6 +/- 3.4 mmHg, mean +/- SD overall). The time for the pulse to travel between the radial artery and the finger capillary was approximately 10 ms, which implies a propagation velocity of several metres per second.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mechanism of the postural vasoconstrictor response in the human foot.

1. The mechanism of postural vasoconstriction in the skin of the foot was examined in 102 healthy subjects by using laser Doppler flowmetry. 2. In 45 subjects, when one foot was lowered 50 cm below heart level and the other foot kept horizontal, blood flow was progressively reduced in the dependent foot (by 79%) with a concomitant, but less pronounced, reduction in flow in the horizontal foot (by 18%), indicating that a central mechanism is involved. After lumbar sympathetic blockade (in 10 patients with epidural anaesthesia), the flow in the horizontal foot remained virtually constant, indicating that the central component is mainly mediated via efferent sympathetic nerves, whereas the postural fall in flow in the dependent foot, though partially attenuated, was preserved, indicating that a local mechanism is mainly involved. 3. On lowering one foot below heart level in 12 subjects, there was a small but significant reduction in systolic and mean arterial pressures during the first minute of dependency. During the fourth minute, systolic pressure decreased, diastolic pressure and heart rate increased, but the mean arterial pressure was maintained. 4. In 19 subjects postural vasoconstriction was nearly abolished during local nervous blockade (lignocaine 3.7 x 10(-4)-7.4 x 10(-2) mol/l), indicating that the local mechanism mediating the vasoconstriction is mainly neurogenic in nature. However, there was still a small fall (19%) in flow in the dependent foot during blockade, probably indicating a minor contribution of a local myogenic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The effect of continuous subcutaneous insulin infusion (CSII) on microvascular blood flow in diabetes mellitus.

The effects of strict blood glucose control on total skin blood flow and capillary blood flow velocity in finger nailfold capillaries were assessed in nine diabetics. Measurements were made before (blood glucose: 11.2 +/- 0.8 mmol/l) and after nine days of continuous subcutaneous insulin infusion (CSII) (blood glucose 6.2 +/- 0.8 mmol/l, p less than 0.001). Resting finger skin blood flow, measured by venous occlusion plethysmography, was 18.6 +/- 2.7 ml/100 ml tissue/min before and 12.6 +/- 2.7 ml/100 ml/min (ns) after CSII. Nailfold capillary red cell velocity, measured by television video microscopy, rose significantly from 0.36 +/- 0.09 mm/s before to 0.71 +/- 0.14 mm/s (p less than 0.01) after CSII. Venous oxygen tension, measured in samples of blood taken from an antecubital vein, tended to fall after CSII (from 6.1 +/- 0.4 kPa to 4.6 +/- 0.5 kPa/ns). No change was seen in whole blood viscosity, plasma viscosity or red cell filtration rate during the study although heart rate fell from 81.3 +/- 2.0 to 75.2 +/- 1.7 beats/min (p less than 0.02). The results suggest that there is a redistribution of skin blood flow following improved diabetic control which favours the nutritive microcirculation.

Aged↗

Capillary blood pressure.

Human capillary blood pressure may be measured directly in nailfold capillaries of the fingers and toes. By applying servonulling pressure measuring techniques rapid fluctuations in capillary pressure may be recorded, opening the way to a greater understanding of capillary pressure control in health and disease. The estimation of mean pressure which may be accomplished manometrically is of value in determining the mechanism of oedema, identifying the site of raised peripheral resistance in disease states, evaluating the effects of vasoactive drugs on peripheral resistance, and investigating haemodynamic abnormalities associated with microangiopathies. Capillary pulse waveform analysis, made possible by servonulling techniques and computer analysis has already revealed important changes in hypertension.

Blood Pressure Determination↗

Skin microvascular blood flow control in long duration diabetics with and without complications.

The integrity of the regulation of skin microvascular blood flow has been studied in Type 1 diabetic patients with and without clinical evidence of microvascular complications after a long duration of diabetes. 13 uncomplicated patients with a mean duration of diabetes of 38 +/- 6 (SD) yr were compared with 10 patients with proliferative retinopathy and a group of healthy control subjects. Using laser Doppler flowmetry 2 distinct microvascular responses were examined in the skin of the finger: (a) reactive hyperaemia following the release of one minute's digital arterial occlusion, a response that is independent of neural mechanisms, and (b) the fall in skin blood flow on venous occlusion that occurs due to the veno-arteriolar reflex, a response that depends upon intact local sympathetic nervous function. The duration of reactive hyperaemia was longer in the complicated patients than either the group without complications (69 +/- 38: 23 +/- 17 s, p less than 0.01) or the healthy controls (27 +/- 20 s, p less than 0.05). In contrast the percentage fall in laser Doppler blood flow on venous occlusion was significantly less (p less than 0.01) in both diabetic groups than that achieved in healthy controls, (50 +/- 14% controls; 26 +/- 12% uncomplicated group; 28 +/- 12% patients with retinopathy). There was no difference in current or recent diabetic control in the 2 diabetic groups. These results suggest that some degree of sympathetic neuropathy is almost inevitable after a long duration of Type 1 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Impaired microvascular hyperaemic response to minor skin trauma in type I diabetes.

The microvascular response of foot skin to minor thermal injury and the skin of the anterior abdominal wall to injury from a needle was assessed by laser Doppler flowmetry in 23 patients with type I diabetes and 21 healthy control subjects. After minor thermal injury mean (SD) maximum skin blood flow was significantly lower in the diabetic group than the control group (0.53 (0.11) v 0.72 (0.10) V, in arbitrary units of flow, respectively, p less than 0.001) and was negatively correlated with the duration of diabetes (r = -0.60; p less than 0.01). After needle injury a similar pattern of impairment was seen, the peak flow value recorded being significantly lower in the diabetic group than the control group (0.28 (0.10) v 0.41 (0.09) V, respectively; p less than 0.001) and also negatively correlated with the duration of diabetes (r = -0.61; p less than 0.01). There was a significant relation between the response obtained at the two sites of injury in the diabetic group (r = +0.72, p less than 0.001) but not in the control group. The impairment in response was not related to diabetic control and was not explicable in terms of a reduction in superficial skin capillary density. The inability of the diabetic skin microvasculature to respond normally to injury may be an important factor in the development of foot ulceration that often follows minor trauma.

Adolescent↗

Blood flow in the skin of the foot related to posture in diabetes mellitus.

Normal healthy subjects show a reflex rise in precapillary resistance in the skin of the foot when they rise from lying to standing. To investigate the integrity of this reflex in patients with diabetes mellitus blood flow in the plantar region of the big toe was measured, using a laser Doppler flowmeter. The responses of diabetic patients with and without peripheral sensory neuropathy and healthy control subjects matched for age and sex were studied, with the foot at heart level and the foot passively lowered to 50 cm below the heart. In normal subjects mean blood flow recorded during the third to fourth minute of dependency fell to 18.1 (SD 11.9)% of the preceding resting flow determined with the foot at heart level. In the diabetic patients without neuropathy blood flow fell to 28.9 (18.6)% of the preceding resting flow. In the diabetic patients with neuropathy blood flow fell to 53.5 (23.7)% of the preceding resting flow, which was significantly different from the value achieved by the diabetics without neuropathy (p less than 0.02) and the healthy controls (p less than 0.002). Six normal subjects were indirectly heated to release sympathetic tone and achieve the same mean skin temperature of the foot as the diabetic patients with neuropathy, and blood flow fell to 38.7 (24.3)% of the preceding resting flow, a value not significantly different from the response seen in the patients with neuropathy. These findings suggest that the postural control of blood flow in the foot is disturbed in patients with diabetic neuropathy, and this disturbance is compatible with a loss of sympathetic vascular tone. The resultant hyperperfusion on dependency may account for the oedema seen in some patients with neuropathy and may also act as a stimulus for the thickening of capillary basement membranes.

Adolescent↗

Effect of indirect heating on the postural control of skin blood flow in the human foot.

It has been shown in previous studies that skin blood flow in the human foot falls when the extremity is placed below heart level, owing to an increase in precapillary resistance that is probably mediated by a local sympathetic axon reflex or a myogenic response. In order to clarify the influence of the central thermoregulatory mechanisms on this local postural vasoconstrictor response, 12 normal male subjects were studied under standardized conditions, at rest and during heating of the trunk with an electric blanket. Skin blood flow was measured before and during body heating using laser Doppler flowmetry with the foot maintained at heart level and placed passively 50 cm below the heart. Skin blood flow and skin temperature were determined at two sites: the plantar surface of the big toe, an area with a relatively large number of arteriovenous anastomoses, and the dorsum of the same foot, where these anastomoses are few or absent. When the foot was placed in the dependent position, skin blood flow recorded in the dorsum of the foot during indirect heating fell to a level similar to that achieved before heating. In contrast, indirect heating greatly diminished the postural fall in skin blood flow recorded in the plantar surface of the big toe. In conclusion, the partial release of sympathetic vasoconstrictor tone associated with indirect heating appears to over-ride the local postural control of cutaneous vascular tone in areas where arteriovenous anastomoses are relatively numerous.

Body Temperature Regulation↗

Effect of dazoxiben, a thromboxane synthetase inhibitor on skin-blood flow following cold challenge in patients with Raynaud's phenomenon.

The effects of dazoxiben on finger-blood flow in response to cold challenge were studied in normal subjects and patients with Raynaud's phenomenon. In normal subjects concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in blood taken from dorsal hand veins following cold challenge. In a parallel multicentre study we examined the effects of dazoxiben on finger temperature and capillary blood cell velocity in patients with Raynaud's phenomenon. Dazoxiben did not affect finger arterial inflow at rest or during cold challenge in patients or controls. However in both groups, recovery was quicker after cold challenge on dazoxiben treatment. In patients median flow was 5 ml (100(-1) ml) min-1 (range 1-10) v. 2 (0.5-15), P less than 0.05 dazoxiben v. placebo at 15 min after cold challenge. However, in normal subjects this did not prove to be statistically significant. In normal subjects there was a fall in TXB2 concentrations and relative rise in 6-oxo-PGF1 alpha following dazoxiben treatment indicating redirection of prostaglandin endoperoxides towards synthesis of PGI2. Comparison of the sum-total output of each eicosanoid following treatment with dazoxiben revealed a 65% reduction in TXB2 concentrations (P less than 0.025 compared with placebo) and a 40% increase in 6-oxo-PGF1 alpha concentrations (P less than 0.05 compared with placebo). However a simultaneous increase in concentrations of FPA indicated generation of thrombin, probably at the needle tip. Long-term treatment with dazoxiben resulted in no significant change in finger-skin temperature or capillary blood cell velocity, duration, or severity of attacks of Raynaud's phenomenon.

6-Ketoprostaglandin F1 alpha↗

Skin microvascular autoregulatory responses in type I diabetes: the influence of duration and control.

We have studied skin microvascular autoregulatory responses in healthy control subjects (n = 11) and three subgroups of uncomplicated Type 1 diabetics. Group 1 (n = 10) had a duration of diabetes of less than one year. Group 2 (n = 10) had a mean duration of diabetes of 11 years. Group 3 (n = 9), of similar duration to group 2, were selected on the basis of having HbAl values persistently below 9%. To assess autoregulatory capacity we determined time to peak capillary flow velocity (CBV) in single nailfold capillaries following release of 60 s arterial occlusion by videophotometric capillaroscopy, and the percentage fall in finger skin rest flow measured by laser Doppler flowmetry when 50 mm Hg venous occlusion was applied. Time to peak CBV was prolonged in groups 1 and 2 compared to controls, (controls 7.7 +/- 1.4 s, mean +/- ISD, group 1 10.7 +/- 2.9 s, p less than 0.01; group 2 11.6 +/- 3.0 s, p less than 0.002) but not in group 3 (9.3 +/- 3.0 s, NS). The percentage fall in resting microcirculatory flow in response to venous occlusion was reduced in groups 1 and 2 compared to controls (controls 57 +/- 16%, group 1 40 +/- 19%, p less than 0.05; group 2 22 +/- 16%, p less than 0.002). In group 3 the response was significantly different from the control value (group 33.7 +/- 20%, controls 57 +/- 16%, p less than 0.05). Thus skin microvascular autoregulatory responses are disturbed within the first year of diabetic life and after 10 years disease duration the impairment is more marked.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of intravenous insulin infusion on skin microcirculatory flow in Type 1 diabetes.

The effects of insulin infusion (1.5 u/h and 15 u/h) on finger nailfold capillary diameter, microcirculatory resting flow and microvascular reactivity were studied in eleven Type 1 diabetics. Blood glucose was maintained at pre-infusion values by intravenous glucose infusion as necessary. Venous limb capillary diameter was significantly wider on 15 u/h compared with pre-infusion values (14.3 +/- 4.5 micron pre, 16.9 +/- 5.1 micron 15 u/h, p less than 0.01. Resting blood flow measured by laser doppler flowmetry increased on the low dose infusion compared with pre-infusion values (2.6 +/- 1.7 V pre, 3.3 +/- 1.9 V 1.5 mu/h, p less than 0.05) but fell on high dose infusion (2.5 +/- 1.9 V, p less than 0.02). Dynamic measurement of capillary blood flow velocity in single capillaries suggested that insulin infusion increased the circulatory debt repayment following 60 s arterial occlusion. The high dose infusion caused a significant impairment of the reflex rise in precapillary resistance that normally accompanies venous congestion. It is concluded that insulin has effects on skin microvascular haemodynamics that are independent of the hormone's hypoglycaemic action.

Adult↗

Synchronous assessment of human skin microcirculation by laser Doppler flowmetry and dynamic capillaroscopy.

Synchronous assessments of microcirculatory flow in human skin have been made by the techniques of laser Doppler flowmetry and dynamic capillaroscopy in adjacent areas of the same nailfold. Microvascular flow was studied at rest, following release of arterial occlusion and during application of venous occlusion in seven normal subjects. Despite broad comparability in the pattern of responses recorded by the two techniques certain significant differences were observed. Vasomotor activity of a similar frequency (4 to 9 cycles per min) was recorded by both techniques, but the activity was asynchronous. The amplitude of the cyclical change in the mean resting flow value recorded by dynamic capillaroscopy was considerably greater than that recorded by laser Doppler (X +/- SD, 25.3 +/- 7.0% mean rest flow; 11.4 +/- 4.9% mean rest flow, p less than 0.01). The time to peak flow following release of a 60 s arterial occlusion was significantly longer as assessed by dynamic capillaroscopy (5.7 +/- 1.6 s: 3.3 +/- 1.0 s. p less than 0.02). In response to a venous congestion pressure of 50 mm Hg, capillary flow rate fell to 24 +/- 6% of the resting flow value as assessed by dynamic capillaroscopy over the first 30 s of occlusion. Laser Doppler flowmetry also recorded a fall in microcirculatory flow to 59 +/- 21% of resting flow value during this period, but this reduction was significantly less than that recorded by dynamic capillaroscopy (p less than 0.05). These discrepancies are interpreted as evidence that laser Doppler flowmetry records blood flow in vessels in addition to the superficial, nutritional capillaries.

Adult↗

Effects of prostaglandin E1 on microvascular haemodynamics in progressive systemic sclerosis.

The effects of prostaglandin E1 infusion on nailfold capillary haemodynamics were studied in eight patients with Raynaud's phenomenon secondary to progressive systemic sclerosis. Using a modified Landis microinjection technique the mean (+/- SEM) transcapillary pressure gradient was increased during and six weeks after infusion by 13.9 +/- 3.2 cm H2O (p less than 0.05) and 5.5 +/- 2.5 cm H2O (p less than 0.05) respectively. Capillary red cell velocity measured in two patients by video television microscopy also increased during and after infusion with prostaglandin E1. Six patients claimed subjective benefit and in three their ulcers healed. These findings support the observed beneficial effect of prostaglandin E1 and suggest that it improves the nutritive capillary circulation by lowering precapillary resistance.

Adult↗

Effect of venesection on calf blood flow in polycythaemia.

Calf blood flow at rest and during postocclusive reactive hyperaemia was measured using an electrocardiogram-triggered plethysmograph in 14 patients with polycythaemia (nine with primary disease and five with polycythaemia secondary to cyanotic heart disease) before and after a course of venesection. The mean packed cell volume was reduced from 0.57 to 0.47, and whole-blood viscosity fell by 50% at low shear rates. Venesection did not affect rest flow, but peak flow was increased by 18%. The increase in peak flow failed to compensate for the reduced haemoglobin content of the blood, calculated haemoglobin delivery being reduced by 23% at rest and 10% during reactive hyperaemia. These results indicate that while venesection improves blood viscosity, this does not necessarily lead to improved delivery of oxygen to the tissues.

Adult↗

Aspirin, prostacyclin and post-occlusive reactive hyperaemia in man.

We studied post-occlusive reactive hyperaemia using ecg-triggered mercury strain-gauge plethysmography in eight normal subjects treated with incremental doses of aspirin (27.5-1200 mg). The reactive hyperaemic response was measured in the finger (predominantly skin blood flow) and the calf (predominantly muscle). Concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in venous effluent blood from the hand by RIA, following arterial occlusion. Levels of TXB2 were significantly higher at 0-10 and 60-70 seconds (p less than 0.01), and 90-100 seconds (p less than 0.05) following release of occlusion compared to pre-occlusion values. However there was no significant change in concentrations of 6-oxo-PGF1 alpha and therefore by this method release of prostacyclin during reactive hyperaemia in the hand. Aspirin had no influence on finger or calf reactive hyperaemia 90 minutes after dosing, despite marked inhibition of platelet MDA production (75% after 110 mg, maximal inhibition after 1200 mg). These data provide no support for the hypothesis that prostacyclin is involved in the determination of the post-occlusive reactive hyperaemic response in the finger and calf in man.

6-Ketoprostaglandin F1 alpha↗