Biomedical subjects

A C Shore

Publications and source records attributed to A C Shore.

At least 19 recordsLinked to original sources

PubMed1999

The biological zero signal in laser Doppler fluximetry - origins and practical implications.

This study seeks to identify the origin of the signal, known as biological zero, that is obtained using laser Doppler fluximetry when flow is arrested. It makes specific recommendations on how this signal should be measured and handled when undertaking flow studies. The experiments undertaken using flow models, animal and human tissue, organ preparations and human subjects showed that, although there may be contributions to the no-flow laser Doppler signal from vasomotion, Brownian motion from within the vascular compartment and the effects of cuff compression, the predominant contribution is from Brownian motion arising from the interstitial compartment. The biological zero signal is additive to the flow signal providing conditions within the interstitium remain constant with changes in blood flow. It is thus concluded that the biological zero signal arises from Brownian motion of the macro molecules within the interstitium. This signal should be obtained following 3-5 min of cuff occlusion with inflation applied rapidly with the smallest cuff that is compatible with flow arrest. Biological zero should be measured under each experimental condition and subtracted from the flow signal.

Adipose Tissue↗

PubMed1998

Peripheral microvascular parameters in the nephrotic syndrome.

BACKGROUND: Peripheral edema, in combination with severe proteinuria and low serum albumin levels, is pathognomonic of the nephrotic syndrome, yet the exact mechanism of its formation is unknown. Two of the most important of the factors in Starling's forces controlling fluid filtration across the capillary have hitherto not been studied in nephrotic subjects. METHODS: The hydrostatic capillary pressure at the finger nail-fold in actively nephrotic subjects and age and sex matched controls was studied, using direct puncture of the apex of the capillary under video microscopy, and a servonulling apparatus to give a direct measurement of capillary pressure. Capillary filtration capacity (CFC) at the calf was measured noninvasively by a modern derivative of the technique of mercury strain gauge plethysmography. Fifteen nephrotic subjects with a variety of underlying pathological lesions, and age matched controls were studied. RESULTS: Contrary to the assumption of the "overflow" hypothesis of edema formation, there was no evidence of capillary hypertension. The capillary pressure showed no difference between nephrotic subjects and controls: median (range) of 17.6 (12.0 to 24.2) compared with 17.3 (9.0 to 21.6) mm Hg, P = NS. CFC was significantly higher in nephrotic subjects than controls [5.23 (3.28 to 8.52) x 10(-3) versus 3.55 (2.43 to 5.28) x 10(-3) ml/min/100 g/mm Hg, P < 0.01]. CONCLUSIONS: An increase in CFC provides a potentially novel mechanism contributing at least in part to the formation of peripheral edema in the nephrotic syndrome.

Adult↗

PubMed1998

Pressure-permeability relationships in basement membrane: effects of static and dynamic pressures.

The glomerular basement membrane (GBM) is an important component of the filtration barrier that is the glomerular capillary wall. Previously GBM permeability has been investigated only under static pressures and often within a supraphysiological range. We used Matrigel as a model of GBM and formed membranes at the base of filtration chamber. We measured membrane permeability under static and dynamic pressures. Matrigel membranes were size and charge selective toward neutrally and negatively charged dextrans. Their permeability (as measured by hydraulic conductivity) was found to decrease from 1.61 +/- 0.06 to 0.75 +/- 0.07 x 10(-6) cm.s-1.cmH2O-1 as static pressure increased from 6 to 78 cmH2O, an effect attributed to membrane compression. In comparison to static pressure, sinusoidal pressure waves with a mean pressure of 50 cmH2O decreased membrane permeability, e.g., fluid flux was reduced by a maximum of 2% to a value of 5.47 +/- 0.38 x 10(-5) cm/s; albumin clearance was reduced by a maximum of 5.2% to a value of 9.63 +/- 1.06 x 10(-6) ml.cm-2.s-1. Such changes were affected by the frequency of pressure wave application and could be attributed to a switching on and off of the membrane compression effect.

Animals↗

PubMed1998

Ambulatory blood pressure monitoring for hypertension in general practice.

Ambulatory blood pressure monitoring (ABPM) is being increasingly used in general practice. There is at present little published evidence regarding the clinical utility of ABPM in the care of patients with established hypertension in this setting. We examined this issue by undertaking ABPM in a group of patients with established hypertension. 40 patients (aged 33-60 years) currently being treated for hypertension were randomly selected from a general practice list and underwent a single 24-hour ABPM study. ABPM values were compared with clinic blood pressure (CBP) values obtained on the day of monitoring together with previous readings taken by the general practitioner (GP). In the case of mean arterial pressure, 24-hour, awake and asleep ABPM values were found to underestimate CBP values by 14 mmHg (95% confidence interval 11-16 mmHg), 9 mmHg (95% C16-12 mmHg) and 24 mmHg (95% CI 21-27 mmHg), respectively. When used to classify blood pressure control, ABPM values produced equivalent results to CBP except by the criterion of BP load, for which 24-hour ABPM showed a higher rate of unsatisfactory control. 5 patients classified by CBP to have satisfactory BP control according to current international guidelines were found to have unsatisfactory BP control by ABPM. This study demonstrates the potential value of ABPM in patients with essential hypertension in a general practice setting. ABPM provided information over and above that obtained by CBP in a substantial proportion of patients.

Adult↗

PubMed1997

Does change in skin perfusion provide a good index to monitor the sympathetic response to a noxious stimulus in preterm newborns?

Skin perfusion was measured using laser Doppler fluximetry (LDF) in 16 preterm babies undergoing a standardised heel prick procedure. Although there was a significant reduction in skin blood flow following the heel prick, this was variable and dependent on basal skin blood flow. This, together with loss of data due to movement artefact, makes this technique unreliable in quantifying the sympathetic response to a noxious stimulus in preterm infants.

Artifacts↗

PubMed1997

Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure.

Increased vascular resistance in essential hypertension occurs mainly in microvessels with luminal diameters < 100 microm. It is not known whether abnormalities in these vessels are a cause or consequence of high blood pressure (BP). We studied 105 men (aged 23-33 yr) in whom predisposition to high blood pressure has been characterized by both their own BP and those of their parents. Factors that are secondary to high BP correlate with offspring BP irrespective of parental BP, but factors that are components of the familial predisposition to high BP are more closely associated with higher BP in offspring whose parents also have high BP. Offspring with high BP whose parents also have high BP had impaired dermal vasodilatation in the forearm following ischemia and heating (289+/-27 [n = 25] versus 529+/-40 [n = 26], 476+/-38 [n = 30], and 539+/-41 flux units [n = 24] in other groups; P < 0.0001) and fewer capillaries on the dorsum of the finger (23+/-0.8 capillaries/0.25 mm2 versus 26+/-0.8 in all other groups; P < 0.003). Except for BP, other hemodynamic indices (including cardiac output and forearm vascular resistance) were not different. The dermal vessels of men who express a familial predisposition to high BP exhibit increased minimum resistance and capillary rarefaction. Defective angiogenesis may be an etiological component in the inheritance of high BP.

Adult↗

PubMed1997

Relationship of insulin resistance to microvascular dysfunction in subjects with fasting hyperglycaemia.

Microvascular hyperaemia is decreased in subjects at risk of developing non-insulin-dependent diabetes mellitus (NIDDM) who have fasting hyperglycaemia. Such microvascular abnormalities may be involved in the pathogenesis of diabetic microangiopathy. To investigate the relationship of reduced microvascular hyperaemia to metabolic and blood pressure abnormalities associated with the prediabetic state, we studied 24 subjects with fasting hyperglycaemia and 24 age- and sex-matched control subjects. The microvascular hyperaemic response to local heating of the skin on the dorsum of the foot measured by laser Doppler fluximetry was reduced in the subjects with fasting hyperglycaemia (1.18 [0.87-1.83] volts vs 1.51 [1.30-2.14] volts normal subjects; p = 0.0002) and was negatively correlated with fasting plasma insulin concentration (Rs = 0.70; p = 0.001) and positively related to insulin sensitivity determined by continuous infusion of glucose with model assessment (CIGMA) (Rs = 0.52; p = 0.01), but showed no association with fasting plasma glucose, beta-cell function 24 h ambulatory blood pressure profiles or serum lipid concentrations. These results suggests that hyperinsulinaemia, as a result of insulin resistance, may have a detrimental effect on microvascular function in the prediabetic state.

Adult↗

PubMed1997

Capillary filtration coefficient and urinary albumin leak at altitude.

Rapid ascent to altitude risks the development of acute mountain sickness. This study demonstrates changes in peripheral capillary filtration coefficient and renal protein loss in subjects suffering from various degrees of mountain sickness after passive ascent to 4559 m. Capillary filtration coefficient of the calf capillary bed, measured by computer-based multistep strain gauge plethysmography, increased significantly after 23.5 h at altitude when symptoms were most severe: 4.45 (2.76-6.03) to 6.31 (3.86-11.07) ml min(-1) per 100 g of tissue mmHg(-1), median (range) (P < 0.02). Urinary albumin excretion was increased after one night at altitude from 1.1 (0.6-1.5) to 2.45 (1.0-6-8) mg of albumin per mmol of creatinine (P < 0.05). These results demonstrate simultaneous leakage of a peripheral capillary bed to fluid measured by strain gauge plethysmography, and renal albumin leak, and suggest a systemic process of increased capillary leakage for different-sized molecules caused by rapid exposure to hypobaric hypoxia.

Adult↗

PubMed1996

Skin blood flow responses to the iontophoresis of acetylcholine and sodium nitroprusside in man: possible mechanisms.

1. The mechanisms involved in the human skin blood flow responses to iontophoretic application of acetylcholine (ACH; delivered using an anodal charge) or sodium nitroprusside (SNP; administered with a cathodal charge) are unclear. The aims of this study were to investigate possible contributions of prostaglandin production to the increase in skin blood flow induced following the iontophoresis of ACh and to investigate possible contributions from local sensory nerves to the perfusion responses induced by ACh, SNP and their vehicles. 2. The contribution of prostaglandins to the ACh response was determined in a randomized double-blind study of eight healthy subjects, who were studied on two occasions. Basal responses to ACh were measured before the oral administration of 600 mg soluble aspirin in diluted orange juice (1 occasion or orange juice (1 occasion) and again 30 min after the drink. The contribution of local sensory nerve activation to the responses to ACh and ACh vehicle (8 subjects) and to SNP and SNP vehicle (7 subjects) was assessed. EMLA (5%) (a eutectic mixture of lignocaine and prilocaine) and placebo cream were applied to two separate areas on the forearm in a double-blind randomized manner 2 h before drug responses were measured. In all studies the skin microcirculation responses to iontophoretically applied drug vehicle (1 site) and drug (2 sites) were recorded by laser Doppler perfusion imaging. 3. The increase in forearm skin perfusion (P < 0.001) in response to the iontophoresis of ACh minus the response to ACh vehicle was not significantly different following placebo or aspirin administration. The increase in forearm skin red blood cell flux (P < 0.001) in response to the iontophoresis of ACh minus the response to ACh vehicle was not significantly different at the placebo-compared with the EMLA-treated site. THe small increase in perfusion (P < 0.001) in response to the iontophoresis of ACh vehicle was significantly inhibited at the EMLA-compared with the placebo-treated site (P < 0.05). The marked increase in perfusion (P < 0.001) in response to the iontophoresis of SNP vehicle was significantly inhibited at the EMLA-compared with the placebo-treated site (P < 0.01). 4. These data suggest that in healthy volunteers: (1) mechanisms other than prostaglandin production and local sensory nerve activation may be involved in the increase in skin perfusion observed following the iontophoretic application of ACh; and (2) stimulation of local sensory nerves may be responsible for the increase in tissue perfusion observed following the iontophoretic application of either ACh vehicle or SNP vehicle.

Acetylcholine↗

PubMed1996

The effect of acetylcholine on finger capillary pressure and capillary flow in healthy volunteers.

1. Constitutive nitric oxide (NO) synthase has been demonstrated in human skin microvascular endothelial cells; however, the physiological significance of this finding is not known. The aim of this study was to investigate the effects of acetylcholine (ACh), which stimulates the release of NO from endothelial cells, on skin capillary pressure, capillary pulse pressure amplitude (CPPA) and capillary red blood cell velocity (CBV) in healthy volunteers. 2. Finger nailfold capillary pressure was measured in five healthy volunteers. CBV was measured in capillaries of the dorsal middle phalangeal area of the finger in six subjects using a recently developed capillary anemometer. In each case the responses to ionophoretically applied ACh and vehicle were measured on two separate fingers on the left hand. 3. Application of vehicle did not significantly change either capillary pressure, CPPA or CBV. ACh significantly increased capillary pressure (from 15.8 +/- 2.2 mmHg under basal conditions to 27.7 +/- 3.8 mmHg at the plateau of the ACh response; P < 0.008), CPPA (from 2.4 +/- 2.4 mmHg at baseline to 8.4 +/- 2.4 mmHg at the plateau of the drug response; P < 0.013) and CBV (from 0.54 +/- 0.22 mm s-1 at baseline to 2.46 +/- 1.12 mm s-1 after ACh; P < 0.008). 4. The increases in capillary pressure, CPPA and CBV following the application of ACh suggest that the overall effect of ACh was to induce a reduction in the pre- to postcapillary resistance ratio.

Acetylcholine↗

PubMed1996

Local inhibition of nitric oxide generation in man reduces blood flow in finger pulp but not in hand dorsum skin.

1. Nitric oxide generation is important in the regulation of resistance vessel tone. Until now, however, there has been no evidence of such a role for basal generation of nitric oxide in the skin microcirculation of humans. 2. To investigate this, L-NG-monomethylarginine (L-NMMA), a competitive inhibitor of nitric oxide synthase, was administered at 1, 2 and 4 mumol min-1 (each for 10 min), via the brachial artery, in six healthy male subjects. 3. At each dose, using laser Doppler fluximetry, red blood cell flux was measured as an index of blood flow in the pulp of the thumb, an area rich in arteriovenous anastomoses, and on the dorsal surface of the hand, where arteriovenous anastomoses are rare. Finger nailfold capillary blood velocity was monitored at each dose using videomicroscopy. Forearm blood flow was measured by venous occlusion plethysmography, before, and 8 min after, completing infusion of L-NMMA. All data were obtained from both the infused and control arms. 4. L-NMMA reduced blood flow in the infused forearm by 37% (P = 0.005). In contrast, dorsum red cell flux, capillary blood velocity, and skin temperature were unchanged. There was, however, a significant reduction in thumb red cell flux (ANOVA, P = 0.0001), reaching a maximum reduction of 33% with 4 mumol min-1 L-NMMA. There were no effects apparent in the opposite arm. 5. These results suggest that endogenous nitric oxide production may be more important in regulating microvascular skin blood flow in regions rich in arteriovenous anastomoses than in areas containing mainly nutritive vessels.

Adult↗

PubMed1996

Skin capillary density in subjects with impaired glucose tolerance and patients with type 2 diabetes.

In view of recent interest in the role of impaired early development and the pathogenesis of cardiovascular disease and carbohydrate intolerance in adults, this study examines whether reduced skin capillary density contributes to the limited microvascular hyperaemic responses observed in patients with Type 2 diabetes and subjects with impaired glucose tolerance (IGT). Fifteen patients with Type 2 diabetes, 15 subjects with IGT and 15 matched non-diabetic control subjects were studied. Capillary videomicroscopy was used to record images of the skin capillaries on the dorsum of the middle phalanx of the left middle finger before and after 10 min venous occlusion at 35 mmHg. There were no significant differences between the three groups in either basal capillary density (112 (71-144) caps mm-2 Type 2 patients (median and range) vs 107 (76-140) caps mm-2 IGT subjects vs 112 (76-138) caps mm-2 control subjects; p = 0.9, Kruskal Wallis), or following venous occlusion (122 (87-157) caps mm-2 vs 121 (90-143) caps mm-2 vs 123 (81-147) caps mm-1; p = 0.9). In addition there were no differences in blood pressure, BMI or skin temperature. These results do not support the concept of impaired early development of the skin microcirculation in patients with Type 2 diabetes or IGT and suggest that mechanisms other than reduced capillary density are involved in limiting microvascular vasodilation.

Adult↗

PubMed1996

Microvascular functional abnormalities in diabetes: the role of the endothelium.

The development of techniques for measuring microvascular pressure, flow and permeability in man has allowed the construct of a pathophysiological framework for the development of diabetic microangiopathy. In insulin dependent disease the abnormalities observed conform to the haemodynamic hypothesis with early elevation of capillary pressure playing a primary role. In non insulin dependent diabetes differences are apparent, supporting the concept that changes in microvascular vasodilatory mechanisms may antedate the emergence of diabetes. Given the crucial role played by the endothelium in the regulation of local microvascular haemodynamics it is not surprising that disturbance of this tissue has been implicated in the pathogenetic process, an assertion supported by mounting experimental evidence suggesting that the nitric oxide pathway is crucially involved.

Diabetes Mellitus, Type 1↗

PubMed1996

Differences in microvascular fluid permeability between long-duration type I (insulin-dependent) diabetic patients with and without significant microangiopathy.

1. To further investigate the role of microvascular functional changes in the pathogenesis of diabetic microangiopathy in type 1 diabetes, microvascular fluid permeability was measured in nine patients with a long disease duration and no or minimal (background retinopathy alone) microangiopathy, nine age-, sex- and duration-matched patients with microalbuminuria and nine control subjects. Microvascular fluid permeability was assessed by determination of the forearm capillary filtration coefficient using a sensitive strain-gauge plethysmographic technique. 2. Microvascular fluid permeability was significantly higher in the patients with microalbuminuria [8.5 (6.8-15.2) x 10(-3)ml min-1 100g-1 of tissue mmHg-1; median (range)] than in the patients with no or minimal complications [5.2 (3.6-7.0) x 10(-3) ml min-1 100g-1 of tissue mmHg-1, P < 0.001]. There was, however, no significant difference in microvascular fluid permeability between the patients with no or minimal complications and control subjects [4.5 (3.2-5.7) x 10(-3) ml min-1 100g-1 of tissue mmHg-1, P = 0.31]. Blood pressure and glycaemic control were similar in the two groups of diabetic patients. 3. These results provide further evidence that changes in microvascular permeability are found in other vascular beds in patients with incipient nephropathy, whereas no such changes are found in patients with a long disease duration and little evidence of microangiopathy.

Adult↗

PubMed1996

Disturbance of peripheral microvascular fluid permeability by the onset of atrioventricular asynchrony in patients with programmable pacemakers.

BACKGROUND: In vitro and in vivo evidence suggests that atrial natriuretic peptide can enhance fluid flux from intravascular to extravascular compartments. The relevance of this to human pathophysiology remains unclear. OBJECTIVES: To determine whether a central haemodynamic change associated with increased plasma concentrations of atrial natriuretic peptide produces detectable change in the capillary filtration coefficient in a peripheral microvascular bed. PATIENTS: 12 patients with programmable dual chamber permanent pacemakers. METHODS: Calf capillary filtration coefficient (using a modified plethysmographic technique) and plasma atrial natriuretic peptide concentrations were measured during atrioventricular synchronous and ventricular pacing. RESULTS: Atrioventricular asynchrony was associated with higher mean (SD) concentrations of atrial natriuretic peptide (231.9 (123.1) v 53.5 (38.8) pg/ml) and an increased mean (SD) calf capillary filtration coefficient (4.2 (1.1) v 3.6 (1.1) ml/min.mm Hg.100 ml x 10(-3)), but there was no correlation between the magnitude of the change in these variables in individual patients. CONCLUSIONS: The peripheral capillary filtration coefficient may change in response to altered central haemodynamics. Atrial natriuretic peptide remains one potential candidate mechanism, but other factors are also likely to be involved.

Adult↗

PubMed1995

Capillary pressure during and after incremental venous pressure elevation in man.

1. The relationship between capillary pressure and venous pressure was investigated during incremental venous pressure elevation in seven healthy volunteers. Pressure was measured simultaneously at the apex of finger nailfold capillaries and in the dorsal vein of the ipsilateral hand. Elevation of venous pressure was accomplished by inflation of a sphygmomanometer cuff around the upper arm. 2. As venous pressure rose, apical capillary pressure (Pc) approached venous pressure (Pv). For changes in Pv greater than 20 mmHg, the increment in Pc was invariably less than the increment in Pv. 3. Above a cuff pressure of 20 mmHg, capillary pulse pressure amplitude (CPPA) tended to decline. At 50 mmHg cuff pressure, CPPA was lower than at baseline for all subjects. At baseline, CPPA was 4.2 +/- 2.0 mmHg (mean +/- S.D.) and at 50 mmHg it was 2.3 +/- 1.1 mmHg (P = 0.02). 4. In the period between 1 and 6 min following cuff release, both Pc and CPPA were lower than at baseline. (At baseline, Pc was 16.1 +/- 2.3 mmHg and following cuff release it was 11.2 +/- 1.5 mmHg (P = 0.02). At baseline, CPPA was 4.2 +/- 2.0 mmHg and following cuff release it was 1.8 +/- 1.1 mmHg (P = 0.03).) 5. Estimated changes in the ratio of pre- to postcapillary resistance (Ra/Rv), using arterial blood pressure (Pa) measured in the contralateral arm, and taking (Pa-Pc)/(Pc-Pv) to approximate to Ra/Rv, closely mirrored changes in CPPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients with NIDDM.

The mechanisms involved in the pathogenesis of microangiopathy occurring in non-insulin-dependent diabetes mellitus (NIDDM) are unclear. In the present study, blood flow responses to the vasodilators acetylcholine (which acts via the endothelium) and sodium nitroprusside (a smooth muscle relaxant) were evaluated in this patient group. In 14 male patients with NIDDM, treated with either diet alone (n = 6) or diet plus insulin, (mean age 59 years) and 14 age-pair-matched control subjects, forearm skin perfusion following multiple doses of iontophoretically applied 1% acetylcholine and 0.01% sodium nitroprusside was recorded by laser Doppler perfusion imaging. Basal skin blood flow was not significantly different in the diabetic group compared with the control group. The following results are expressed as drug-minus-vehicle response. Acetylcholine significantly increased forearm skin perfusion (p < 0.001, analysis of variance) in all subjects, but the vasodilatation was attenuated in the patient group compared with control subjects (0.86 +/- 0.09 vs 1.36 +/- 0.14 arbitrary units of volts (V) respectively, at the fifth measurement point, mean +/- SEM, p < 0.01). Skin perfusion significantly increased following sodium nitroprusside (p < 0.001) but was lower in patients than control subjects (0.12 +/- 0.05 vs 0.45 +/- 0.11 V, respectively, at the fifth measurement point, p < 0.01). These data suggest that endothelial and/or smooth muscle function may be impaired in the skin microcirculation of patients with NIDDM.

Acetylcholine↗

PubMed1995

Microvascular function in type 2 (non-insulin-dependent) diabetes: improved vasodilation after one year of good glycaemic control.

Abnormalities of microvascular function may be important in the development of diabetic microangiopathy. The major functional abnormality identified in patients with Type 2 diabetes has been a marked limitation of microvascular vasodilation, which is present from the time of diagnosis. The effects of sustained improvements in glycaemic control on vasodilator capacity in Type 2 diabetes are unknown. Twelve Type 2 diabetic patients were studied prospectively for 1 year after diagnosis. The reduced maximum hyperaemic response to local heating of the foot skin present at the time of diagnosis remained unchanged after 3 months of improved glycaemic control (1.12 +/- 0.56 V at diagnosis vs 1.21 +/- 0.69 V at 3 months, mean +/- SD; p = 0.25), but was improved after 1 year (1.42 +/- 0.91 V; p = 0.04 vs 3 months). The percentage increase in maximum hyperaemia correlated with the percentage decrease in HbA1c (rs = 0.53, p = 0.04). These results suggest that the early microvascular abnormalities demonstrated in Type 2 diabetes are potentially reversible and provide a further reason for striving for optimal glycaemic control in this patient group.

Adult↗