Biomedical subjects
Publications and source records attributed to S Thom.
Hypertensive changes in the vasculature occur at all levels of the circulation--from the large arteries through to the microcirculation. Detection of these changes may offer useful predictive information in assessing cardiovascular risk and the need for treatment. Recent evidence shows that at least some of these changes are reversible with anti-hypertensive treatment.
BACKGROUND: Low birth weight is associated with hypertension and increased cardiovascular mortality, but the mechanism of this association is not known. Hypertension is accompanied by abnormalities of the microvasculature including rarefaction. OBJECTIVE: To test the hypothesis that low birth weight is associated with an alteration in microvascular architecture. DESIGN: A stratified random sample of 100 men aged 64-74 years was selected from a cohort of men whose birth weights were known. They were of relatively high or low birth weight ('high' > or = 3700 g, 'low' < or = 3200 g) and high or low systolic blood pressure (high > or = 160 mmHg, low < or = 140 mmHg). METHODS: Retinal arteriolar geometry was defined in terms of arteriolar bifurcation angles and junction exponents (a measure of the relative diameters of parent and daughter vessels), measured from photographic diapositives using operator-directed image analysis. RESULTS: Members of low-birth-weight groups had significantly narrower bifurcation angles than did members of high-birth-weight groups (74 +/- 1 degree versus 78 +/- 1 degree, P= 0.017 by analysis of variance). There was no significant difference between angles in members of groups with high and low blood pressures. Neither birth weight nor blood pressure grouping affected junction exponents. CONCLUSIONS: Narrower bifurcation angles are associated with increased circulatory energy costs and may be related to a lower than normal microvascular density. Our finding of differences in retinal microvascular architecture might reflect a persistent alteration in vascular architecture as a result of an impairment of foetal development and could provide a mechanistic link between low birth weight and subsequently increased cardiovascular risk.
Arterial hypertension is associated with structural changes in the cardiovascular system. This study has examined the effect of hypertension on the carotid artery wall and examined the relation between changes in the structure of carotid artery wall and left ventricle in untreated hypertensives. The carotid artery wall was visualized using a high resolution ultrasound technique in 37 untreated hypertensive patients (25 males, 12 females) and 37 age and sex matched normotensive individuals and carotid intima-media thickness (IMT) and carotid artery diameter measured. IMT and intima-media cross sectional area was significantly greater in the hypertensive group compared with the normotensive group, though the carotid artery diameter did not differ significantly. There was a significant association between age and IMT in both groups. In the hypertensive group there was also a significant association between left ventricular mass index, ventricular septal or posterior wall thickness and IMT. This study indicates that there is an association between cardiac and carotid arterial structure in hypertension. Such a relationship may be important in understanding the associated risks of high blood pressure.
Water-soluble fiber has been reported to reduce serum cholesterol and consequently, oat bran, which has a high soluble-fiber content, has been recommended as part of a lipid-lowering diet. However, a recent small study of 20 volunteers with low mean serum cholesterol concentrations (4.8 mmol/L) demonstrated no lipid-lowering effect of oat bran. The present study investigated 64 volunteers with cholesterol concentrations much more typical of the UK population (6 mmol/L). Subjects were randomly allocated to receive either a normal-sized helping of an oat-based cereal or a cereal containing no oats for 4 wk and then crossed over to the alternative regimen for a further 4 wk. Small (2.23% and 4.55%) but significant (P < 0.04 and P < 0.05) reductions in total and low-density-lipoprotein cholesterol, respectively, were observed in association with the consumption of oat-based cereal. These data support the view that consumption of oat-based cereals may well contribute usefully to a lipid-lowering diet.
Seven years' experience in teaching communication skills to first year clinical students at St Mary's Hospital School of Medicine is described. The first component consists of a day during the introductory clinical course; this is divided into a lecture and small seminar groups and involves behavioural scientists and clinicians from many departments. The second component uses simulated patients and video feedback and takes place in small groups later in the year. Participation of the students through active critical discussion, role play, and interactive video feedback are important aspects in the success of the course. The methods have been refined through evaluation by students and tutors. This article aims to allow others, already running or considering such a course, to develop effective courses within the practical constraints of their own institutions.
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Hypertension is associated with structural changes in the vascular system and in the heart. This study has examined the relationships between carotid artery intima-media thickness and other risk factors in 52 untreated patients (20 hypertensive). Carotid intima-media thickness was measured bilaterally using a Duplex doppler ultrasonic scanner. In the hypertensive individuals the left ventricle was examined by echo-cardiography and the left ventricular mass index determined. There was a significant association between age and IMT, and both SBP and DBP and IMT. The IMT in the hypertensive group was significantly larger than in the normotensive group and in the hypertensive subjects there was a positive association between left ventricular mass index and IMT. There was no significant difference in calculated media stress between the normotensive and hypertensive groups, probably due to a small increase in carotid intima-media area combined with a small reduction in carotid lumen diameter. Hypertension is associated with a thickening of the intima-media of the carotid artery and an increase in left ventricular mass. Whether these changes in cardiac and arterial structure are in response to similar influences remains to be established.
An investigation was undertaken to determine whether Acanthamoeba polyphaga SHI and Naegleria gruberi 1518/1e could affect the survival of various strains of Vibrio cholerae in laboratory microcosms. In microcosms pre-inoculated with trophozoites of amoebae, all six strains of V. cholerae tested survived and multiplied during 24 h. In control microcosms without trophozoites of amoebae, survival of the V. cholerae strains was much decreased. Two strains of V. cholerae were used to determine whether V. cholerae might survive ingestion within amoebae and subsequent encystment. Strain 152 was re-isolated from encysting N. gruberi 1518/1e but not from A. polyphaga SHI. Strain 9112 could not be isolated from cysts of either species of amoebae.
To investigate whether reduction in blood pressure has a beneficial effect on left ventricular diastolic function, we investigated 20 hypertensive patients with evidence of diastolic dysfunction at baseline and at 3 and 6 months after initiation of captopril therapy. Two-dimensional echocardiography was used to determine left ventricular mass index and Doppler ultrasound to assess diastolic function. Fifteen of the 20 patients had a significant reduction in blood pressure at 3 and 6 months and left ventricular mass index remained unchanged during the study period. Despite reduction in blood pressure, no difference in isovolumic relaxation time, early and atrial filling velocities or their ratio was observed. Our results suggest that a direct relationship between blood pressure and left ventricular diastolic function does not exist and that other factors such as alterations in muscle or collagen composition of the left ventricle may be more important in determining abnormal diastolic function in hypertension.
The relationship of left ventricular (LV) filling to the clinical and echocardiographic characteristics of 51 patients with untreated hypertension (borderline hypertension n = 17, essential hypertension n = 34) was investigated using two-dimensional echocardiography and Doppler ultrasound. Twenty-five patients had evidence of abnormal LV filling. Linear regression analysis revealed weak but significant correlations of LV filling with age (r = -0.53; P less than 0.0001), systolic blood pressure (r = -0.38; P less than 0.006), LV septal wall thickness (r = -0.44; P less than 0.0001) and LV mass index (r = -0.33; P less than 0.02). There was no association between LV filling and sex, race, heart rate or LV posterior wall thickness or cavity dimension. After stepwise regression analysis, age was found to be the only independent variable associated with LV filling, indicating that the other variables were dependent on age. This study suggests that a) abnormal LV filling is a frequent observation in hypertension b) LV filling is more dependent on age than blood pressure or LV size and c) other pathophysiological factors, so far undetermined, must contribute to the development of these abnormalities.
The effect of antihypertensive therapy on regression of left ventricular hypertrophy and left ventricular diastolic function was investigated in 25 hypertensive patients for up to 18 months after initiation of treatment. Left ventricular mass index was calculated by two-dimensional echocardiography and left ventricular diastolic function assessed by transmitral pulsed doppler ultrasound. Significant reduction in left ventricular mass index was observed after 9 months of treatment. Only 13 patients had a reduction in mass greater than the intraobserver variability of the technique. There was no change in doppler indices of left ventricular diastolic function. In 7 patients who were studied for a further 9 months after regression had occurred there was still no appreciable difference in left ventricular diastolic function. These findings indicate that there is no direct relation between left ventricular mass and abnormal left ventricular diastolic function.
Hypertension is associated with abnormal lipoprotein metabolism, which may be exacerbated by some groups of antihypertensive drugs and represents an additional powerful coronary heart disease risk factor. Of our Hypertension Clinic population, 75% had a total fasting serum cholesterol greater than 5.2 mmol/l. Dietary advice and adjustment of antihypertensive therapy has achieved significant reductions in total cholesterol, serum triglycerides and body weight (14%, 18% and 4.3%, respectively) in a cohort of 65 patients reassessed over a period of 3-21 months. The reduction in cholesterol is likely to represent at least a 28% reduction in the risk of a major coronary heart disease event, even before taking account of any improvement in other coronary heart disease risk factors.
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1. The effect of a alpha-human atrial natriuretic peptide (1-28) (ANP) on human vasculature was investigated in vivo and in vitro. Possible involvement of vascular dopamine receptors and the renin-angiotensin system in the response to ANP was also studied in vivo. 2. Forearm blood blow was measured by venous occlusion plethysmography. Isolated human blood vessels were studied using conventional organ bath techniques. 3. ANP (0.1-1 microgram/min, intra-arterially) produced a dose-dependent increase in forearm blood flow, corresponding to a 163% increase in net forearm blood flow in the study arm. This action of ANP was not antagonized by (R)-sulpiride (100 micrograms/min, intra-arterially), a selective vascular dopamine receptor antagonist, or 50 mg of oral captopril, an inhibitor of angiotensin-converting enzyme. 4. ANP (1 nmol/l-1 mumol/l) produced concentration-dependent relaxation of isolated human arteries, including brachial artery, but was without effect on isolated human saphenous vein. 5. ANP produces vasodilatation in vivo and relaxes isolated human arterial smooth muscle. This action of ANP may contribute to its reported hypotensive effects in vivo.
1. The role of the endothelium in mediating relaxation to acetylcholine, the calcium ionophore A23187, vasoactive intestinal peptide and peptide histidine methionine was studied using isolated human blood vessels. 2. Segments of renal, colic, pulmonary, uterine, transverse cervical, brachial, coronary and coeliac branch arteries, and saphenous veins, were obtained from surgical resection material for use in tissue bath studies. 3. Acetylcholine or A23187 produced endothelium-dependent relaxation in isolated vessels from all vascular beds studied. Coronary arteries, however, differed in their response to acetylcholine which produced predominantly a contractile response, either alone or after initial relaxation. 4. Vasoactive intestinal peptide and peptide histidine methionine produced endothelium-dependent relaxation in coeliac branch arteries. However, these peptides relaxed isolated pulmonary arteries independently of endothelium. 5. Endothelium-dependent relaxation in response to acetylcholine and A23187 was antagonized by nordihydroguaretic acid, a lipoxygenase inhibitor, and methylene blue and haemoglobin, inhibitors of soluble guanylate cyclase. In these respects the endothelium-dependent responses of human arteries to acetylcholine and A23187 resemble those described in other species.
Celiprolol is reported to be a new cardioselective beta blocker with novel ancillary properties including vasodilator effects. The purpose of this study was to investigate whether celiprolol possesses a direct vasodilatory effect on human vasculature in vivo and in vitro. We studied the in vivo effects of intra-arterial celiprolol (1-100 micrograms/min i.a.) on forearm blood flow (FBF). Forearm blood was measured by venous occlusion plethysmography. Possible vasorelaxant actions of celiprolol on human vascular smooth muscle were studied using segments of isolated human saphenous vein in vitro. The effect of celiprolol was investigated on resting tone or noradrenaline induced tone. Possible alpha 2-adrenoceptor antagonist effects of celiprolol were assessed using celiprolol as an antagonist of BHT933 induced constriction. Celiprolol was without significant effect on FBF and failed to relax isolated saphenous vein segments preconstricted with noradrenaline. The weak alpha 2-adrenoceptor antagonist action of celiprolol was demonstrable in human saphenous vein. This study does not provide evidence for a direct vasodilatory effect of celiprolol on human vasculature.
The mechanisms of the cardiovascular and renin responses to vasoactive intestinal polypeptide (VIP) are unclear. Rabbit studies suggest that VIP-induced tachycardia is largely beta-adrenoceptor mediated, but that the renin response may be partially prostaglandin-dependent. To examine the relative importance of prostaglandins and reflex sympathetic activation in the haemodynamic and renin responses to VIP infusion in man, we completed two randomised single-blind crossover studies in two groups of six healthy male volunteers (aged 24-35 years). We recorded the effects of indomethacin and propranolol pretreatment on VIP-related changes in heart rate (HR), blood pressure (BP), forearm vascular resistance (FVR), plasma renin activity (PRA), plasma noradrenaline (PNA) and plasma arginine vasopressin (AVP) concentrations. Intravenous VIP (calculated dose: 6 pmol kg-1 min-1) produced cutaneous flushing, increased HR and PRA, decreased FVR, but did not alter mean arterial BP or AVP levels. Indomethacin (375 mg over 3 days) lowered basal PRA and propranolol (circa 40 mg i.v. over 60 min) decreased resting HR and increased FVR. Although indomethacin and propranolol reduced the absolute rise in PRA and HR, respectively, during VIP infusion, the percentage changes were no different from control. Neither drug altered the flush response to VIP and propranolol did not affect the fall in FVR. We conclude that the measured cardiovascular responses to VIP infusion in man are probably direct and do not involve a significant contribution from reflex sympathetic stimulation, nor prostaglandin release.