Microvascular physiology and its clinical relevance with special reference to diabetes.
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Blood Pressure↗
Biomedical subjects
J E Tooke
Publications and source records attributed to J E Tooke.
Noninvasive estimation of increased structurally-based resistance to blood flow in the skin of subjects with essential hypertension.
A Laser-Doppler flowmeter was used to investigate the effect of essential hypertension on blood flow in maximally vasodilated skin, heated to 44 degrees C. Maximum Laser-Doppler flux (MLDF) was measured in 12 subjects with essential hypertension on no treatment and in 12 normotensive control subjects, and the resistance to flow was estimated by dividing pressure by flux. MLDF was not significantly different in the two groups: 3.69 +/- 0.87 V (arbitrary units, subjects with hypertension, mean +/- S.D.) vs 3.48 +/- 1.29 V (normotensive control subjects), despite the higher mean arterial pressure in the hypertensive group: 128.9 +/- 16.3 mmHg vs 91.8 +/- 9.1 mmHg (p less than 0.01). Resistance to flow was elevated in the subjects with hypertension: 37.2 +/- 12.8 mmHg/V vs. 29.6 +/- 10.4 (p = 0.05), and in the hypertensive group resistance was significantly correlated with mean arterial pressure (r = 0.69, n = 12, less than 0.025). Following two weeks vasodilator treatment in 6 of the hypertensive subjects, MLDF and mean arterial pressure fell, but the resistance remained elevated. These findings confirm the presence of a structurally-based increase in flow-resistance in the skin in subjects with hypertension, which prevents overperfusion of this tissue in the face of increased arterial pressure. The simple and noninvasive technique described herein could be used on a large scale to prospectively evaluate the reversibility (or otherwise) of structural resistance changes with pharmacological antihypertensive therapy.
Humans↗
Microvascular vasodilatation in feet of newly diagnosed non-insulin dependent diabetic patients.
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Adult↗
Cyclical hypothermia: successful treatment with ephedrine.
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Adolescent↗
Microvascular hemodynamics in hypertension and diabetes.
Microvascular damage occurs in both diabetes and hypertension and hypertension is a risk factor for diabetic microangiopathy. In both conditions, indirect evidence suggests that capillary pressure might be raised. A servonulling pressure measuring technique has been used in conjunction with direct micropuncture of finger nailfold capillaries to determine capillary pressure dynamically. In patients with essential hypertension, capillary pressure is raised compared to matched normotensive controls. In insulin-dependent diabetic patients, capillary pressure is also raised, to a degree that correlates with recent diabetic control. In a pilot study of hypertensive diabetic patients, elevated capillary pressure has been normalized using an angiotensin-converting enzyme inhibitor. Manipulation of microvascular hemodynamics in diabetes and hypertension may provide a means of protecting against the microvascular complications of these two conditions.
Adult↗
Capillary blood cell velocity is reduced in fever without hypotension.
Capillary blood cell velocity was measured in a group of normotensive febrile patients as a basis for further study into the microvascular physiology of febrile hypotensive patients with sepsis. Television videomicroscopy was used to record the capillary blood cell movement in the finger nailfold. Analysis of all moving gaps in the red cell column seen during a minimum of 2 minutes was done by the frame-by-frame technique and mean blood cell velocity derived. Core (external auditory meatus) and skin (finger) temperature were also measured. Subjects (n = 6) were sex and skin temperature matched to controls. Although the mean skin temperature of subjects [28.73 degrees C, SD = 0.28] was not significantly different to controls [30.63 degrees C, SD = 3.11; p less than 0.05] the mean velocity was significantly reduced in the febrile subject group [0.28 mm/sec, SD = 0.17] as compared with controls [0.56 mm/sec, SD = 0.22; p less than 0.05]. It is likely therefore that these skin vessels vasoconstrict as part of the integrated response to reduce heat loss.
Adolescent↗
Postural vasoconstriction in women during the normal menstrual cycle.
1. Postural vasoconstriction in the foot was examined in 15 women during the menstrual, follicular and luteal phases of the menstrual cycle, and in 13 age-matched men on two separate occasions, in a constant-temperature environment (22 degrees C). 2. Skin blood flow was measured using laser Doppler flowmetry with the subject lying down, first with the foot maintained at heart level, then with the foot lowered passively 50 cm below the heart. In six of the women, at the time of experiment, serum oestradiol and progesterone were determined by radioimmunoassay. In four women and three men, foot swelling rate was also measured in the dependent foot using a strain gauge plethysmograph in addition to the postural changes in flow. At each visit, in all subjects, arterial blood pressure, heart rate, body temperature, foot skin temperature and body weight were also recorded. 3. The men showed no significant changes in all the variables assessed. In contrast, in women during the luteal phase diastolic and mean arterial pressures were significantly reduced, whereas heart rate, body temperature, foot skin temperature and body weight were significantly increased, as compared with the follicular and menstrual phases of the cycle. 4. During the follicular phase, when oestradiol concentration was high, there were significant reductions in dependent flow and foot swelling rate associated with a significantly augmented postural fall in flow, whereas during the luteal phase, when both oestradiol and progesterone levels were high, there were significant increases in dependent flow and foot swelling rate associated with a significantly impaired postural fall in flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Capillary hypertension and abnormal pressure dynamics in patients with essential hypertension.
1. Pressure was measured within 28 capillaries of the nailfolds of nine patients with essential hypertension and in 33 capillaries of nine age- and sex-matched normotensive control subjects, using direct micropuncture, a dynamic servo-nulling system and computerized analysis. 2. Average pressure at the apex of the capillary was found to be elevated in the patients with hypertension (21.1 +/- 4.9 mmHg compared with 13.0 +/- 2.0 mmHg in the control subjects; mean +/- SD, P less than 0.01). If the two groups were combined, there was an overall correlation between average capillary pressure and mean blood pressure (r = 0.68, P less than 0.01, n = 18), but within each group separately there was no significant relation between these parameters. 3. There were also abnormalities in the waveforms of pulsations in capillary pressure in the group with hypertension, with an increased attenuation of high-frequency harmonics. Pulses appeared to be conducted more rapidly along the vascular tree in the patients with hypertension. 4. The elevation of capillary pressure in essential hypertension demonstrated in this study is in agreement with indirect evidence of capillary hyperfiltration provided by other studies which showed a reduced plasma volume and increased transcapillary escape rate of plasma proteins. 5. The finding of elevated capillary pressure demands the inclusion of the postcapillary segment (and possibly vascular density) in the resistance equation in essential hypertension.
Adult↗
The skin hyperaemic response to local injection of substance P and capsaicin in diabetes mellitus.
Recent studies have demonstrated impaired skin hyperaemia to local injury in diabetes mellitus. In order to gain insight into the mechanisms of impaired hyperaemia, dose-response curves to intradermal substance P (25, 50, 100 pmol) and capsaicin (1.0, 2.5, 5.0 nmol) were examined before and after histamine blockade with chlorpheniramine, in 6 patients with uncomplicated Type 1 diabetes and 9 matched control subjects. Skin hyperaemia was measured indirectly as the peak laser Doppler flow in proximity to the area of hyperaemia. The response to the three doses of substance P was significantly lower in diabetic patients (0.37 +/- 0.12 (+/- SD), 0.51 +/- 0.12, 0.67 +/- 0.09 V) than in control subjects (0.57 +/- 0.15, 0.70 +/- 0.19, 0.84 +/- 0.21 V; p less than 0.01). In contrast there was no significant difference in skin hyperaemia to capsaicin between diabetic patients (0.41 +/- 0.07, 0.50 +/- 0.09, 0.59 +/- 0.09 V) and control subjects (0.41 +/- 0.06, 0.52 +/- 0.08, 0.63 +/- 0.07 V). Following chlorpheniramine, the response to capsaicin remained unaltered (0.39 +/- 0.07, 0.51 +/- 0.05, 0.60 +/- 0.07 in diabetic patients and 0.43 +/- 0.08, 0.50 +/- 0.10, 0.63 +/- 0.07 V in control subjects), but there was a significant reduction in hyperaemia to substance P in both patients (20.4 +/- 12.3% reduction, p less than 0.05) and control subjects (20.6 +/- 14.1% reduction, p less than 0.05). It is suggested that impaired skin hyperaemia may represent decreased vascular reactivity to locally released substance P from peripheral nerve fibres.
Adult↗
European Consensus Document on Critical Limb Ischaemia: implications for diabetes.
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Diabetic Neuropathies↗
Ketanserin and capillary flow in Raynaud's phenomenon.
The serotonin (S2) antagonist ketanserin has been proposed as a useful therapy for Raynaud's phenomenon. The present study was designed to investigate the effects of 8 weeks therapy with oral Ketanserin (40 mg tds for the last 6 weeks) on finger nailfold capillary flow velocity at rest and following cold challenge and symptom score in 30 patients with Raynaud's in a double-blind, placebo-controlled, parallel design study. The ketanserin treated group reported a 16.7% improvement in symptom score (p less than 0.05) relative to the end of the run-in phase compared with a 2.4% (NS) improvement in the placebo group. Improvement in capillary flow was confined to a significant (p less than 0.02) rise in rest flow in the ketanserin treated group but no beneficial changes were observed following cold challenge. The disparity between the subjective and objective benefits demonstrated for this drug suggest the possibility of a central action rather than one that involves the correction of a local vascular fault.
Adult↗
Dependent oedema and attenuation of postural vasoconstriction associated with nifedipine therapy for hypertension in diabetic patients.
We studied the incidence of oedema 2 weeks following initiation of nifedipine therapy for hypertension in a group of 10 diabetic subjects, and also measured skin blood flow (SBF) with a laser Doppler flowmeter, before and after lowering the foot. SBF with the foot horizontal increased after nifedipine from 0.31 V (arbitrary units of flow) to 0.51 V (NS). The postural fall in blood flow in dependency was significantly attenuated by nifedipine from 64.4 to 24.0%. Five patients developed ankle oedema. Results were similar in a small group of non-diabetic subjects starting nifedipine. The attenuation of reflex postural vasoconstriction is therefore likely to contribute to development of the oedema associated with starting nifedipine therapy, which should be monitored carefully in diabetic patients.
Adult↗
Effect of postural change and thermoregulatory stress on the capillary microcirculation of the human toe.
1. We have applied the technique of television capillary microscopy to make direct measurements of nutritional capillary flow in the toe nailfold (i) at heart level and (ii) in a near standing position, with the foot 96 cm below heart level. By indirect heating we have examined the relationship between posture-related changes and thermoregulation in the capillary circulation of the toe. 2. Capillary blood flow in 14 male subjects with their feet at heart level showed a positive correlation with increasing skin temperature. 3. On quiet standing, capillary blood flow decreased to 11.3% of supine values, achieved both by a reduction in capillary blood velocity and the duration of flow. 4. Indirect heating of the trunk led to a partial release of sympathetic tone and induced a significant increase in capillary blood flow in both the supine and dependent positions. However during heating, the percentage fall in capillary blood flow associated with dependency remained unchanged. 5. In conclusion, it appears that in the dependent foot, compensatory mechanisms exist to limit nutritional capillary blood flow by regulating both erythrocyte velocity and the duration of flow. These mechanisms fulfil a physiological requirement to limit the rate of oedema formation. The preservation of this response during the partial sympathetic release induced by indirect heating suggests a mechanism independent of that controlling flow through arteriovenous shunts. Our results are compatible with the hypothesis that a local vasoconstrictor mechanism is operative in the vascular resistance elements in closest relation with the capillary bed, and distal to that regulating arteriovenous shunt flow.
Adult↗
Microcirculation and diabetes.
Many late complications of diabetes stem from damage to the microcirculation. Changes in the microvascular wall, haemodynamic control and circulating blood may all contribute to impairment of capillary transfer function although the relative importance of the various possible mechanisms is unclear. Early functional disturbance appears more responsive to optimal diabetic control than established disease, and as microangiopathy becomes clinically apparent organ tissue damage is compounded by secondary mechanisms. Until more is learnt of the biochemical and cellular basis of the component pathogenetic mechanisms optimal diabetic control early in the disease remains the sole available primary prevention strategy, although evidence is emerging that manipulation of microvascular haemodynamics may have therapeutic potential.
Blood Glucose↗
An evaluation of ketanserin therapy for the hypertensive diabetic patient.
Hypertension may accelerate the development of the vascular complications of diabetes but many conventional antihypertensive agents have adverse effects on glucose tolerance or peripheral perfusion. To investigate the potential of ketanserin as an antihypertensive agent for hypertensive diabetics we performed a randomly allocated, double-blind, placebo-controlled trial in 17 patients. A range of peripheral blood flow responses was determined using laser Doppler flowmetry, and diabetic control was assessed at the time of allocation to groups and after 8 weeks' therapy (20 mg twice a day for 2 weeks; 40 mg twice a day for 6 weeks). The mean decrease in standing blood pressure was 14.1/9.3 mmHg (ketanserin treatment) versus 7.1/5.9 mmHg (placebo). The maximum skin blood flow and a posturally induced vasoconstriction of the foot skin were unaffected by the therapy, and glycaemic control was unchanged. Ketanserin was well tolerated. These studies suggest that ketanserin may be a useful agent for the treatment of hypertension in the diabetic patient.
Blood Flow Velocity↗
Studies on the circulation in normotensive febrile patients.
Normotensive febrile patients were studied in a constant-temperature room during stable fever, They were restudied later while afebrile and after heating the trunk. Finger and forearm blood flow were measured by venous occlusion plethysmography. The ability of cutaneous vessels to constrict on dependence of the limb was measured by laser Doppler flowmetry. The volume, velocity and acceleration of the blood in the ascending aorta were determined using pulsed Doppler ultrasound with a probe in the supra-sternal notch; measurements of systolic time intervals were made. While febrile, patients had a tachycardia and shortened systolic ejection times; cardiac output and total peripheral resistance were unchanged on average as compared to when afebrile. There was no evidence of any change in left ventricular contractility during fever from measurements of the peak velocity, maximum acceleration of blood or from the systolic time intervals. As compared to when heated, febrile patients had a skin blood flow that was relatively reduced for their skin temperature and had preservation of postural vasoconstriction.
Adult↗
Direct measurement of capillary blood flow in the diabetic neuropathic foot.
The two major components of the microcirculation in the diabetic neuropathic foot have been examined in detail. Nutritive capillary blood flow was measured directly using the non-invasive technique of television microscopy, applied to the toe nailfold. Arteriovenous shunt flow was assessed using the technique of laser Doppler flowmetry, applied to the toe pulp. Fourteen diabetic patients with peripheral and autonomic neuropathy, 11 with no clinical evidence of neuropathy and 14 normal subjects were studied. Laser Doppler flowmetry (predominantly arteriovenous shunt flow) was increased more than three-fold (p less than 0.01) in the diabetic patients with neuropathy compared to control subjects, (median 3.57, interquartile range 2.00-5.32 volts vs median 0.93, interquartile range 0.47-2.36 volts, respectively). There was no evidence of skin capillary closure. The calculated capillary blood flow (erythrocyte flux) was significantly increased in the diabetic neuropathic patients compared to control subjects (median 76.4, interquartile range 34.4-109.8 picolitres/s vs median 23.2, range 8.0-44.8 picolitres/s, p less than 0.01). This study demonstrates that foot skin capillary blood flow is increased in diabetic patients with neuropathy. There is, therefore, no evidence to support the supposition that capillary ischaemia, either secondary to a "capillary steal phenomenon" or "advanced microangiopathy", is a feature of diabetic neuropathy under resting conditions.
Adult↗
Effect of changes in local skin temperature on postural vasoconstriction in man.
1. The effects of locally induced alterations in skin temperature on the postural changes in skin blood flow of the foot were assessed in 38 healthy subjects in a constant-temperature environment (22 +/- 0.5 degrees C, mean +/- SD). 2. Moderate local cooling and warming of the foot (26-36 degrees C) was induced by blowing cold or hot air. Higher ranges of temperature (38-44 degrees C) were achieved by a thermostatically controlled disc heater. 3. Skin blood flow was measured before and during each change in local skin temperature using a laser Doppler flowmeter with the foot maintained at heart level, and placed passively 50 cm below the heart. Blood flow was measured in two skin areas: (i) the dorsum on the foot, where arteriovenous anastomoses are absent, and (ii) the pulp of the big toe, where these anastomoses are relatively numerous. 4. It was found that within the physiological temperature range of 26-36 degrees C the normal postural fall in foot skin blood flow was preserved, whereas it was markedly attenuated or totally abolished at higher temperatures (38-44 degrees C). The pattern of response was quite similar in areas having or lacking arteriovenous anastomoses. 5. It is suggested that the failure of postural vasoconstriction observed at the higher skin temperatures might contribute to some of the problems of cardiovascular adaptations seen in a hot environment.
Adult↗