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Biomedical subjects

A C Shore

Publications and source records attributed to A C Shore.

87 records · Page 5Linked to original sources

Changes in plasma immunoreactive atrial natriuretic peptide in response to saline infusion or to alterations in dietary sodium intake in normal subjects.

Plasma levels of immunoreactive atrial natriuretic peptide (irANP) have been measured in normal subjects in response to changes in sodium balance induced by either saline infusion or alterations in dietary sodium intake. In eight normotensive subjects, plasma levels of irANP (means +/- s.e.m.) increased from 5.8 +/- 0.9 to 15.8 +/- 4.4 pg/ml plasma after an infusion of isotonic saline (2 litres over a 60-min period). In seven subjects, plasma levels of irANP were measured on the 5th day of a low-sodium diet (10 mmol/day), a normal-sodium diet (150 mmol/day) and a high-sodium diet (350 mmol/day). Plasma levels of irANP increased with increasing sodium intake, with values of 4.0 +/- 0.9 (low-sodium diet), 6.9 +/- 1.3 (normal-sodium intake) and 12.1 +/- 1.8 pg/ml (high-sodium intake). These observations suggest that the atrial natriuretic peptides could be an important hormone system in the control of sodium excretion by the kidney, and thereby of sodium balance in normal man.

Adult↗

Effects of changes in dietary sodium intake and saline infusion on immunoreactive atrial natriuretic peptide in human plasma.

Plasma levels of immunoreactive atrial natriuretic peptide (IrANP) were measured in healthy normotensive subjects before and after saline infusion and changes in dietary salt intakes. When 2 litres of 0.9% saline (308 mmol Na+) were infused over 1 h, plasma levels (mean +/- SD) of IrANP increased from 5.8 +/- 2.8 pg/ml to 15.8 +/- 12.5 pg/ml. Plasma levels on the fifth day of a low sodium diet (10 mmol/day) were 3.8 +/- 2.4 pg/ml, a normal sodium intake (150 mmol/day) 6.4 +/- 2.9 pg/ml, and a high salt intake (350 mmol/day) 12.7 +/- 6 pg/ml. These results suggest that atrial natriuretic peptides could be important hormones in the control of sodium balance in normal man.

Adult↗

Lack of effect of oral magnesium on high blood pressure: a double blind study.

Seventeen unselected patients with mild to moderate essential hypertension and whose average supine blood pressure after two months' observation with no treatment was 154/100 mm Hg were entered into a double blind randomised crossover study of one month's treatment with magnesium aspartate (15 mmol magnesium/day) and treatment with placebo for a further month. This preparation of magnesium was well tolerated and did not cause diarrhoea. Despite a significant increase in plasma magnesium concentration and a significant increase in urinary excretion of magnesium while taking magnesium aspartate there was no fall in blood pressure compared with either treatment with placebo or values before treatment. The results provide no evidence for a role of dietary magnesium in the regulation of high blood pressure and are contrary to recent speculations.

Adult↗

Effects of synthetic atrial natriuretic peptides on sodium-potassium transport in human erythrocytes.

The effects of synthetic human and rat atrial peptides on sodium and potassium ion transport has been investigated in intact human erythrocytes. The effects of these peptides have been tested on the active, sodium pump-dependent (ouabain-sensitive) and on the sodium-potassium cotransport system (bumetanide-sensitive) with 86Rb used as a tracer. Human (alpha-ANP, 28 amino acids) or rat (atriopeptin III) atrial peptides, over a wide range of concentrations, did not influence the uptake of 86Rb in either the ouabain-sensitive or the bumetanide-sensitive transport system. These results suggest that the natriuretic effect of the atrial peptides is not mediated through inhibition of the sodium pump or the loop-diuretic-sensitive Na-K cotransport.

Animals↗

Renal vein renin studies in renovascular hypertension--do they really help?

Measurement of the renal vein renin ratio (RVRR) is commonly used to predict the response of blood pressure to surgery in hypertensive patients with unilateral renovascular disease. We have reviewed our experience in 37 such patients in whom renal vein renin levels were measured basally and after stimulation of renin secretion with intravenous diazoxide or tilting. Twenty-four patients were cured or improved. When a basal ratio of greater than or equal to 1.5 (diseased: normal kidney) was taken as a positive test the false positive rate was 39% and the false negative rate 71%, there being little difference in outcome between those with ratios above or below 1.5. No other threshold value of RVRR identified those responding to surgery, and acute stimulation of renin secretion did not increase the value of the test. We conclude that the RVRR is of no prognostic value in the surgical treatment of hypertension due to unilateral renovascular disease.

Adult↗

Mononuclear leucocyte intracellular free calcium--does it correlate with blood pressure?

Abnormalities of calcium binding and calcium transport in cells from hypertensive subjects or animals have been previously described. Total cell sodium is reported to be increased in white blood cells from hypertensive subjects; thus by analogy with Blaustein's proposal for the vascular smooth muscle cell, mononuclear leucocyte cytosolic calcium might be increased via a reduction of the Na-Ca exchange. Using the fluorescent calcium indicator, quin 2, cytosolic calcium was measured in mononuclear leucocytes from 22 hypertensive and 19 normotensive subjects. There was no significant difference between the mononuclear leucocyte cytosolic calcium level in the two groups. Incubation of the cells with 10(-4) M ouabain reduced 86 rubidium (86Rb) uptake by 80% of the control value but failed to alter cytosolic calcium. These findings are consistent with a minimal role of the Na-Ca exchange in the mononuclear leucocyte and may explain why the cytosolic calcium was not increased in hypertension despite the previous reports of increased total cell sodium in white blood cells.

Adult↗

The renin-angiotensin-aldosterone system in decompensated cirrhosis: its activity in relation to sodium balance.

Plasma renin activity (PRA), plasma renin concentration (PRC), plasma angiotensin II concentration (AII), plasma and urinary aldosterone (PA, UA) and urinary sodium excretion (UNaV) were measured in 51 normal controls, 16 patients with decompensated cirrhosis (i.e. ascites and/or oedema present) in sodium equilibrium (Group 1) and 13 patients with decompensated cirrhosis in a phase of active sodium retention (Group 2). In Group 1 the mean supine and erect values, although lower, were not significantly different from controls. In Group 2 the mean values were significantly elevated, but several individual values were within the normal range; there were significant direct relationships between plasma renin activity and plasma renin concentration (r = 0.85, p less than 0.001 erect), plasma renin concentration and plasma angiotensin II concentration (r = 0.86, p less than 0.001 erect), and plasma angiotensin II concentration and plasma aldosterone (r = 0.70, p less than 0.01 erect). In Group 2 there was an inverse correlation between urinary sodium excretion and both urinary aldosterone (r = -0.50) and erect plasma aldosterone (r = -0.36) but, perhaps because of the narrow range of sodium excretion rates, significance was not reached. The normal values in Group 1 indicate that hyperaldosteronism is not essential for the maintenance of established ascites, but do not exclude a role for aldosterone in the control of sodium excretion if it is accepted that renal tubular sensitivity to aldosterone is increased in these patients. In Group 2, the raised mean plasma and urinary aldosterone levels and the trend towards an inverse relationship with urinary sodium excretion suggests a role for aldosterone in the active retention of sodium. It appears that stimulation of the renin-angiotensin system is the major factor in the elevation of plasma aldosterone; there was no relationship between plasma aldosterone and either plasma sodium or potassium levels. The mechanism of renin hypersecretion is unclear but this may represent part of a sympathetically mediated response in order to maintain blood pressure. The close relationship between plasma renin activity and plasma renin concentration indicates that the former is a valid measure of circulating renin levels in cirrhosis, despite low renin-substrate levels.

Aldosterone↗

Sodium status and the renin-angiotensin-aldosterone system in compensated liver disease.

Exchangeable sodium, plasma renin activity, plasma angiotensin II and plasma aldosterone were measured in forty-six control subjects, nineteen patients with chronic non-cirrhotic liver disease and twenty patients with compensated cirrhosis (i.e. without ascites or oedema). In the three groups respectively, mean exchangeable sodium (mmol/kg lean body mass) was 53 (SD = 3), 50 (SD = 5) and 52 (SD = 8). Mean plasma renin activity (pmol l(-1) min(-1)) was 3.2, 3.1 and 3.0 supine and 6.2, 6.2 and 5.1 erect. Mean plasma angiotensin II (pmol l(-1) was 7.3, 5.8 and 6.6 supine and 10.6, 7.9 and 9.0 erect. Mean plasma aldosterone (pmol l(-1)) was 82, 64 and 77 supine and 188, 133 and 121 erect. There were no significant differences among the mean values of any of these variables. These findings indicate that, on the basis of exchangeable sodium measurements, sodium retention is not present in compensated liver disease and that the renin--angiotensin--aldosterone system is essentially normal.

Adult↗

Capillary filtration coefficient in type II (non-insulin-dependent) diabetes.

Changes in microvascular permeability may be important in the pathogenesis of diabetic microangiopathy. In order to assess microvascular fluid permeability, the capillary filtration coefficient was determined in the forearm of 24 normotensive type II diabetic patients with minimal evidence of microangiopathy and satisfactory glycemic control, and 24 age- and sex-matched control subjects, using a sensitive strain gauge plethysmographic system. The median capillary filtration coefficient was not significantly different in the type II diabetic patients and control subjects [5.3 (3.2 - 9.1) x 10(-3) mL.min-1.100 g tissue-1.mm Hg-1 versus 5.4 (3.5 - 8.0) x 10(-3) mL.min-1.100 g tissue-1.mm Hg-1, p = 0.98)]. There were no correlations between capillary filtration coefficient and age, blood pressure, body mass index, duration of diabetes, glycemic control, or the presence of microvascular complications. These findings contrast with type I diabetes, where capillary filtration coefficient is elevated at an early stage in the disease, and lend support to the theory that there are differences in early microvascular functional abnormalities between type I and type II diabetes.

Adult↗

Impaired microvascular hyperaemic response in children with diabetes mellitus.

Clinically detectable microvascular complications of diabetes are uncommon in children with diabetes especially in the prepubertal group. It is unclear whether subtle functional abnormalities of the microcirculation occur in children without evidence of clinical microangiopathy and in particular whether abnormalities can be demonstrated in children before puberty. The maximum hyperaemic response to direct local heating (44 degrees C) of the foot skin was measured by laser Doppler fluximetry in 50 diabetic and 50 non-diabetic children. An impaired hyperaemic response occurred in the diabetic children compared with control children (diabetic 1.25 (95% CI 1.13-1.37) V; control 1.74 (1.60-1.88) V; p less than 0.001) and was significantly related to duration of diabetes but not to long-term blood glucose control. The impaired response was also present in prepubertal diabetic children (diabetic 1.37 (1.16-1.58) V; control 1.89 (1.67-2.12) V; p less than 0.001). Systolic and diastolic blood pressure were significantly raised in the prepubertal diabetic children. These data suggest that a functional abnormality of the microcirculation occurs in children with diabetes in the absence of clinically detectable microangiopathy, and even before puberty.

Adolescent↗

Capillary pulse waveform in aortic stenosis.

The importance of the dynamic nature of perfusion pressure within the peripheral microcirculation is increasingly recognised. Capillary pressure is determined not only by arterial inflow pressure, but is also subject to a variety of local and systemic influences which have been shown to affect both mean pressure and the capillary pulse waveform. To what extent changes in central pulse waveform influence capillary pressure has yet to be determined. By using a dynamic technique of capillary pressure measurement in human subjects with aortic stenosis, we have been able to show that the characteristics of the pulse waveform typically associated with large vessels in this condition are also readily detectable at a capillary level despite local influences. However, changes in the rate of pulse wave transmission described in large arteries were not apparent at a microvascular level. Unlike mean capillary pressure and capillary pulse pressure, pulse waveform in the capillary mimics central haemodynamics.

Aged↗

Postural vasoconstrictor response in human heart failure.

In order to study whether posturally induced vasoconstriction is impaired in subjects with heart failure, laser Doppler fluximetry was used to measure blood flow in the cutaneous microvascular bed of the foot at rest and during passive lowering of the extremity below heart level, in subjects with idiopathic dilated cardiomyopathy and in healthy controls. Two sites were studied: the toe pulp where arteriovenous anastomoses are numerous and the dorsum of the foot where such anastomoses are absent. Despite demonstrating a marked reduction in cutaneous blood flow at rest at each site [dorsum 3.0 AU (1.8-4.5) [median (range)] in heart failure patients vs 4.5 AU (1.8-31.6) in controls; toe 8.7 AU (3.1-33.5) in heart failure vs. 44.7 AU (5.2-280.0) in controls, p < 0.01], the results suggest that in non-oedematous subjects with severe left ventricular dysfunction there is no major disturbance of the postural vasoconstrictor response, either at a site rich in highly innervated anastomoses [43.6% (14.5-89.4) vs. 43.7% (15.6-91.1)] or in a site with few such anastomoses [79.7% (39.6-92.3) vs 69.6% (10.1-94.9)].

Adult↗

Newly developed software for capillary blood pressure analysis in microcirculatory research.

The introduction of the servonulling technique by Wiederhielm in 1963 allowed for the first time continuous and dynamic recording of capillary blood pressure (CP). In 1979 Mahler used this technique for the first measurements in humans. Data analysis was limited to manual analysis of chart recordings. Nowadays fast analog-digital converters with ay high sampling frequency are used for data recordings, and consequently there is a need for an easy-to-use software for data analysis of CP data. The presented newly developed computer software allows analysis of mean CP, taking into account the zero pressure measured before and after capillary cannulation. The simultaneously recorded electrocardiogram R wave is used as a marker for the calculation of the mean capillary pulse pressure waves and of their characteristic data. This may help determine the significance of the capillary pulse waveform for microvascular function. Changes in the pulse waveform may be the only detectable difference between patients and healthy controls. Analysis of simultaneously recorded temperature, the display of markers for valid readings, and the possibility of excluding nonvalid data or artefacts from analysis are additional features.

Adult↗

Comparison of CapiFlow and frame by frame analysis for the assessment of capillary red blood cell velocity.

CapiFlow (CF), a new fully computerized system for the measurement of capillary blood velocity (CBV) was compared to manual frame by frame analysis (a) in a model system, and (b) in finger nailfold capillaries recorded on video tape. In the model the overall agreement between the two methods was very good (figure 1), with no significant differences being noted between the two sets of results and the calculated velocities. However, when comparing frame by frame and CapiFlow directly, CapiFlow read on average 4.50 +/- 5.21% higher than frame by frame analysis (figure 2). The in vivo results obtained by the two methods showed similar dynamic changes although some differences between the overall mean CBVs were noted (capillary 1, manual 0.13 +/- 0.59 mm s-1 versus CF 0.12 +/- 0.02 mm s-1, (mean +/- SD), p = 0.354; capillary 2, manual 0.66 +/- 0.23 mm s-1 versus CF 0.47 +/- 0.09 mm s-1, p < 0.001; capillary 3, manual 2.53 +/- 0.73 mm s-1 versus CF 2.35 +/- 0.34 mm s-1, p = 0.062). Further analyses established the optimum settings of delta limit and cross correlation. Investigations into the effects of changes in window size, window distance or video settings on CBV results obtained by CapiFlow, indicated that only settings radically different from the optimum had a significant effect on the results obtained.

Blood Flow Velocity↗