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Biomedical subjects

P Sleight

Publications and source records attributed to P Sleight.

At least 127 records · Page 7Linked to original sources
PubMed1992

Ascending aortic Doppler velocity and the prediction of exercise capacity in post-infarction left ventricular dysfunction.

A system to improve analysis of the aortic pulsed Doppler velocity signal has been developed and used to study cardiac performance during a 4 min, 25 W incremental stage supine bicycle exercise to exhaustion. Twenty-two male subjects with stable chronic ischaemic heart disease were studied (15 with NYHA class II/III heart failure, and seven age-matched class I subjects). None had evidence of reversible ischaemia. Peak velocity (PV) from the intensity weighted mean velocity profile, early acceleration (eA) and stroke distance (SD) were all significantly lower at rest in class II/III compared to class I. For the change from rest to 50 W, PV did not alter, eAC increased significantly (P less than 0.05) and to a similar extent in both groups (18.6% class II/III vs 16.4% class I) and SD was reduced from 7.8 to 5.9 in class II/III (P less than 0.01) but did not change in class I (12.4 vs 11.8, ns). There was also a greater increase in heart rate (HR) in class II/III subjects (P less than 0.05). The duration of exercise was correlated with resting PV (r = 0.48, P less than 0.025) but was correlated best with the change in blood momentum (PV x Stroke volume x HR) between rest and peak exercise (r = 0.80, P less than 0.001). Thus Doppler velocimetry can give quantitative information on the response to exercise which discriminates between grades of ventricular dysfunction and is predictive of exercise capacity.

Adult↗
PubMed1992

The influence of ambulatory blood pressure monitoring on the design and interpretation of trials in hypertension.

OBJECTIVE: To describe the reproducibility of diastolic blood pressure (DBP) measurement by clinic and ambulatory monitoring and to evaluate the effects of this reproducibility on the design and interpretation of clinical trials in hypertension research. DESIGN: Prospective single-blind study of repeat measurement reproducibility of blood pressure recording. SETTING: Tertiary referral hospital hypertension clinic. PATIENTS: One hundred untreated mild-to-moderate hypertensive subjects taking 1 month of single-blind placebo. MAIN OUTCOME MEASURES: A single clinic measurement of DBP was poorly reproducible and the results for single DBP estimates taken out of a daytime ambulatory recording were similar. Average ambulatory DBP was much more reproducible, although this improvement depended upon the averaging of many measurements taken throughout the day. CONCLUSIONS: Ambulatory monitoring would decrease antihypertensive trial size by a factor of four or halve the size of detectable DBP difference between treatments. The use of poorly reproducible DBP measurements such as single clinic readings may have led to an underestimation of the risks of minor degrees of blood pressure elevation because of a 'regression dilution' bias. For single clinic DBP readings, we calculate this underestimation to be as much as 69%, and for average ambulatory DBP approximately 20%.

Adult↗
PubMed1992

Cholesterol and coronary heart disease mortality.

The epidemiological relation between increased levels of blood cholesterol and increased risk of future heart disease is clear, both within and between countries. These strong relationships have led to the adoption of consensus statements in most countries which recommend measures such as the reduction of dietary saturated fat/an increase in the polyunsaturated/saturated ratio and other dietary and sometimes drug methods to reduce serum cholesterol. There is controversy as to whether these measures should be targeted at individuals with high levels of cholesterol or whether there should be a public health approach to the whole population. The public and medical debate has become more heated since the data from intervention trials are conflicting. Taken overall the trials do appear to show reduction in risk of coronary which is stronger for non fatal, compared with fatal coronary events. Meta analysis suggests that increasing benefit accrues from larger reductions and also longer reductions in cholesterol by intervention. However, individual trials frequently show variable results and some, especially the recent 15 year follow up of a Finnish five year intervention (by diet, cholesterol lowering and blood pressure lowering drugs) was strikingly adverse-although the total number of events was not large. Total mortality is much harder to influence and the sum of the available trials is hopelessly inadequate in size to address these questions. As a result confusion abounds and is unlikely to be clarified by the present on going trials. The need for more data is clear. The pilot study for the Oxford Cholesterol Study will be presented as a prelude for a proposed main study in about 20,000 high risk individuals.

Anticholesteremic Agents↗
PubMed1992

Trials and tribulations: the ISIS experience.

The ISIS trials group has grown slowly over the last ten years and now includes about 1000 collaborating hospitals worldwide. The original stimulus came from the thesis of a research student, Salim Yusuf, a newly qualified Rhodes Scholar from India. Yusuf's thesis (begun in 1976) examined methods of measuring infarct size quantitatively and paved the way to a preliminary trial of i.v. atenolol in 477 patients in Manchester and Oxford. Richard Peto was consulted about the statistical aspects of a trial design and pointed out that most clinical trials at that time were hopelessly inadequate in size to have the power reliably to ascertain the value of moderate but medically worthwhile treatments in many common conditions. We thus developed much larger collaboration, which still continues to grow. Dr Rory Collins joined the Oxford Cardiac Department and the CTSU in 1981 and now is the coordinator of the ISIS trials, and co-director with Richard Peto of the CTSU. Simple trials answer the questions rapidly and effectively. The mechanics of the trial do not hinder patient entry by participating doctors and nurses. The trials are mainly funded by industry, with 'priming' grants from the British Heart Foundation. Once the protocol is agreed the funding companies have no further input. The trials are planned and supervised by an international steering committee. Sir Richard Doll chairs the data monitoring committees. A brief overview of the three completed trials will be given, together with some peeps behind the scenes.

Clinical Trials as Topic↗
PubMed1992

Baroreflex control of stroke volume in man: an effect mediated by the vagus.

1. Beat-by-beat changes in cardiac performance in response to arterial baroreceptor stimulation induced by phenylephrine were evaluated by pulsed-wave aortic Doppler ultrasound in eighteen subjects. Stroke distance was used as an index of stroke volume and minute distance as an index of cardiac output; peak velocity was also measured. 2. The sensitivity of the baroreceptor-cardiac reflex was assessed by calculating the slope of the regression lines relating the changes in heart period (R-R interval), peak velocity and stroke distance in response to the rise in systolic blood pressure (SBP) induced by phenylephrine. In ten subjects the experiment was repeated after vagal blockade by atropine. Since the tachycardia induced by vagal blockade could alter the sensitivity of the baroreflex, we compared the results obtained after atropine with those obtained during pacing at similar rates in six subjects with cardiac pacemakers. 3. As R-R interval lengthened in response to the rise in SBP, stroke distance and peak velocity fell sharply. The subjects with a highly sensitive baroreceptor-heart rate reflex showed the greatest fall in peak velocity and stroke distance. The slope of the relationship between R-R interval and SBP for each subject correlated closely with that of peak velocity/SBP (correlation coefficient, r = 0.88) and stroke distance/SBP (r = 0.93) relationships. 4. Atropine virtually abolished all the cardiac reflex changes, despite a considerable increase in SBP induced by phenylephrine. At comparable heart rates achieved by pacing the sensitivity of the baroreceptor-cardiac reflex (calculated from the slopes of the regression lines relating changes in stroke distance and in peak velocity to the rise in SBP) was maintained and was significantly greater when compared to that obtained after vagal blockade. 5. These results show that the stimulation of arterial baroreceptors is accompanied by a fall in the Doppler-derived indices of stroke volume and cardiac output. This response is neural and is abolished by atropine, which indicates that it is mediated through the efferent vagus.

Adult↗
PubMed1992

Ventilation in chronic heart failure: effects of physical training.

OBJECTIVE: To assess the effects of exercise training on ventilatory function in chronic heart failure. DESIGN: Observer blinded random allocation crossover training and detraining trial. SETTING: Assessment in hospital based clinical laboratory; training home based. PATIENTS: 22 patients with chronic heart failure (New York Heart Association (NYHA) class II or III) recruited from a tertiary referral centre. All finished the study. INTERVENTION: Bicycle ergometer exercise for 20 minutes a day, five days a week for eight weeks at 70%-80% of maximum heart rate. MAIN OUTCOME MEASURES: Exercise capacity on graded incremental exercise test, minute ventilation, oxygen consumption and carbon dioxide output. RESULTS: Peak work load increased from 96 W to 112 W and peak oxygen consumption from 14.1 ml/kg/min to 15.4 ml/kg/min (p < 0.01). At submaximal workloads carbon dioxide excretion (VCO2) and minute ventilation (Vi) decreased significantly (p < 0.05) though oxygen consumption was unchanged. The relation between Vi and carbon dioxide excretion changed: the slope of the Vi to VCO2 plot decreased from 38.6 to 35.3, indicating an improvement in overall ventilary efficiency. The instantaneous carbon dioxide ventilatory equivalent (Vi/VCO2) decreased at submaximal workloads, and reached a lower minimum value after training, indicating that optimum ventilatory performance improved. The exercise capacity of patients was related to the optimum ventilatory performance. It is suggested that this may in part be mediated through changes in skeletal muscles. CONCLUSION: Exercise training reduces the ventilatory abnormalities in chronic heart failure; thus some of these changes may be due to physical deconditioning.

Aged↗
PubMed1992

Validation of the beat to beat measurement of blood velocity in the human ascending aorta by a new high temporal resolution Doppler ultrasound spectral analyser.

OBJECTIVE: To develop and validate a high temporal resolution spectral analysis system for Doppler measurements of blood velocity in the ascending aorta. DESIGN: An observational laboratory and clinical study comparing Doppler velocity-based measurements with fluid collection, electromagnetic flow catheters and probes, and thermodilution. SETTING: Tertiary referral cardiology unit and cardiac catheter laboratory. PATIENTS: Patients undergoing routine cardiac catheterisation for ischaemic heart disease, cardiac failure, and primary pulmonary hypertension. RESULTS: There was good agreement between Doppler-derived and electromagnetic cuff or catheter measurements of velocity in an experimental flow rig (SD of differences 4.75% for velocity integral) and in the patients (SD of differences 4% for velocity integral). There was also reasonably good agreement between simultaneous Doppler-derived and thermodilution-estimated cardiac output measurements in patients undergoing cardiac catheterisation (SD of differences 12.6%). CONCLUSIONS: This new method of high temporal resolution spectral analysis improves the resolution of rapidly changing blood velocities and may improve the ability to describe blood velocity patterns in the ascending aorta.

Adolescent↗
PubMed1992

The secondary prevention of myocardial infarction by drug treatment; excluding lipid lowering agents.

About 10% of survivors of an acute myocardial infarction will die in the following year. Thereafter the risk declines but reinfarction is still an important cause of mortality and morbidity. The post infarction trials have clearly shown that the best proven agents to mitigate this toll are aspirin, beta adrenoceptor blockers, and verapamil (but not other calcium blockers, except diltiazem for non Q wave infarction). In the context of hypertension treatment these post infarction trials may have important lessons for drug selection and ancillary treatment since the majority of subjects will ultimately die of ischaemic heart disease. Although the newer agents such as ACE and renin inhibitors, newer calcium channel blockers and alpha blockers have many promising properties in terms of risk factor reduction, no convincing mortality data exists; it is needed. This review will deal with the known effects (both good and bad) of antihypertensive agents and will also review other drug strategies relevant to the hypertensive patient. It will also point out large areas of ignorance.

Adrenergic beta-Antagonists↗
PubMed1992

Methodology of baroreflex testing.

Recent clinical data have generated fresh interest in the assessment of baroreflex sensitivity, largely because of the relationship between this parameter and prognosis after a myocardial infarction. The present article reviews and discusses some of the methodologies currently used for the determination of baroreflex sensitivity. The Neck Chamber involves stimulation of the carotid baroreceptors by either augmenting or decreasing pressure at the level of the neck. The main advantage of this technique is to allow the simultaneous measurement of changes in heart rate and in the peripheral resistances. Another advantage is represented by the fact that no drugs are necessary for this type of study. On the other hand, this procedure modifies autonomic influences in several receptors areas while the stimulus is acting only at the carotid level; as a result of the baroreceptor activation or deactivation, this will produce complex and not uniform afferent information from receptors that are exposed to mechanical stimuli of opposite direction. In addition, it is difficult to quantify the pressure transmitted to the baroreceptors located in the carotid wall. The use of vasoactive substances, usually phenylephrine or nitroglycerin, produces a brisk change in pressure which is then linearly correlated with the attendant changes in the R-R interval to obtain a "baroreflex slope". The first concern with vasoactive drugs is that they act also on smooth muscle in the carotid sinus wall and might thereby interfere with the mechanical effects on the baroreceptors. The second is that peripheral resistance cannot be calculated at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1991

Effects of endurance training on baroreflex sensitivity and blood pressure in borderline hypertension.

Physical training offers a potential nonpharmacological strategy for control of mild and borderline hypertension, but its effect on blood pressure is controversial. We investigated the effects of endurance training on waking and sleeping blood pressure and on baroreflex sensitivity in 16 borderline hypertensive patients. First, 8 patients were assessed before and after a 6-month endurance training programme. Then, when it was clear that blood pressures were lower after training, a further 8 patients were studied not only at the end of the training programme but also after 4 months' abstention from exercise (detraining). Measurements were taken of baroreflex sensitivity (response to iv phenylephrine), blood pressure, R-R interval, and blood pressure and R-R variability. Ambulatory blood pressures were measured in 13 patients (7 trained, 6 detrained) and sleep blood pressures in 6 patients (3 trained, 3 detrained). Increased fitness was associated with a decline in resting arterial blood pressure of 9.7 (SE 2.0) mm Hg systolic and 6.8 (1.2) mm Hg diastolic, and with a decline in ambulatory blood pressure of 4.8 (1.4) mm Hg and 7.5 (2.1) mm Hg, respectively; both p less than 0.05. Baroreflex sensitivity was 14.0 (1.8) ms/mm Hg in the unfit and 17.5 (2.0) ms/mm Hg in the fit; p less than 0.05. Sleep blood pressures were not lower in the fit despite longer sleep R-R intervals. These findings indicate that, in some subjects with borderline or mild hypertension, a physical training programme is sufficient to bring the blood pressure within normal limits.

Adult↗
PubMed1991

Cardiovascular risk factors and the effects of intervention.

Cardiovascular risk factors can be substantially modified by changes in life-style such as diet, exercise, smoking cessation, and moderation of alcohol consumption. In turn, these can reduce blood pressure, heart rate at rest, and blood lipid concentrations. Epidemiologic evidence shows that for every 1% change in serum cholesterol levels, there is a 3% change in the likelihood of developing coronary heart disease. In addition, a long-term (5-year) change of 5 to 6 mm Hg in diastolic blood pressure can reduce the chances of stroke by 35 to 40% and of coronary heart disease by 20 to 25%. The full impact of this broad range of interventions on population health has still to be fully realized in many countries, including the United Kingdom, however it is likely to be considerable. Some of the recent evidence in support of such cardiovascular risk factor modification is selectively reviewed.

Alcohol Drinking↗
PubMed1991

Interdependence of blood pressure and heart period regulation in mild hypertension.

Blood pressure and heart period variability have been measured directly in 142 subjects with mild hypertension over 24 h. The variabilities have been expressed as the standard deviation of 2 min averages of all beats over 24 h. Baroreflex sensitivity was assessed in 102 subjects by the phenylephrine method. Blood pressure varies over a range of approximately 40% around the mean by day and by approximately 20% at night. The variability of blood pressure by day was inversely proportional to the sensitivity of the baroreflex (r = -0.33, P less than .001), while the variability of heart period was directly related to the sensitivity of the reflex (r = 0.27, P less than .01). Neither of these relationships was significant at night. An inverse relationship between heart period and blood pressure was shown by regression analysis of blood pressure and heart period averages over 24 h. The steepness of the slope of the heart period-systolic blood pressure relationship was strongly correlated with the baroreflex sensitivity (r = -0.55, P less than .001), suggesting that blood pressure variations are substantially buffered by changes in heart frequency. Thus, a more stable heart rate that results from an ineffective baroreflex is associated with a more variable systolic blood pressure.

Adolescent↗
PubMed1991

Holter monitoring of ventricular arrhythmias in a randomised, controlled study of intravenous streptokinase in acute myocardial infarction.

The occurrence of ventricular arrhythmias attributed to streptokinase treatment in acute myocardial infarction is not well defined. Holter monitoring was performed for 24 hours in 81 patients with suspected acute myocardial infarction randomised in a ratio of 2:1 to intravenous streptokinase 1.5 x 10(6) IU (n = 55) or placebo infusion (n = 26) 6.7 hours (mean) after the onset of symptoms. No episodes of ventricular fibrillation were recorded. For the whole 24 hour period and during the first three hours after the start of treatment the incidence and frequency of ventricular arrhythmias were similar in the patients randomised to streptokinase and to placebo. But when the results in patients randomised "early" after the onset of symptoms of suspected acute myocardial infarction were analysed separately the frequency of abnormal complexes, pairs, runs, and repetitive arrhythmias seemed to be higher in patients allocated to streptokinase. This may reflect arrhythmias associated with reperfusion.

Arrhythmias, Cardiac↗
PubMed1991

Postexercise hypotension is not sustained in normal and hypertensive humans.

Blood pressure falls after a single session of exercise. The duration for which this fall in blood pressure persists is not known. Sustained hypotension after a single session of exercise may have important implications in the treatment of patients with mild hypertension. We studied 24 subjects (12 normotensive subjects and 12 patients with mild or borderline hypertension). Blood pressure was measured in the laboratory for 30 minutes before and for an hour after graded bicycle exercise to maximal voluntary capacity. Subjects then left the hospital and measured their blood pressures at home (three measurements every 2 hours) following a strict measurement protocol for the rest of the day (usually between 8 and 12 hours). These home blood pressure measurements were compared with home blood pressure measurements recorded at the same times on a nonexercise control day. At 30 minutes after the graded maximal exercise test, the hypertensive patients experienced a fall in blood pressure from 142 +/- 3.5/93 +/- 6.5 mm Hg (mean +/- SEM) to 124 +/- 4.5/79 +/- 2.8 mm Hg (p less than 0.01). For the normotensive subjects, blood pressure after exercise fell from 117 +/- 3.1/70 +/- 2.1 mm Hg to 109 +/- 3.1/62 +/- 2.8 mm Hg (p less than 0.01). Despite these striking blood pressure reductions for the second half hour after exercise, blood pressure measurements recorded at home were not significantly different on the exercise and control days in either group. We conclude that although a single bout of exercise lowers blood pressure for a short (1-hour) period, this hypotension is not sustained.

Blood Pressure↗
PubMed1991

Cardiac and blood pressure responses to mental stress in reactive hypertensives.

To study the haemodynamic response to a standardized mental stress, we measured ascending aorta velocity using Doppler ultrasonography in 20 reactive ("white-coat") hypertensives and 20 age and sex matched normal controls (NC) familiar with the hospital setting. Reactive hypertensives (RH) had 3 office diastolic BP recordings between 90-110 mmHg and ambulatory BP less than 140/90 mmHg. The cardiac response to mental arithmetic was greater in RH than NC (minute distance, RH: +36.7 +/- 40.2% vs NC: +10.3 +/- 19%, p less than 0.05; peak velocity, RH: +8.4 +/- 16.5% vs NC: -1.4 +/- 11.9%, p less than 0.05), and there was a different peripheral resistance response (RH: -12.2 +/- 24.2% vs NC: +6.5 +/- 22%, p less than 0.05). We suggest that subjects with reactive hypertension have a strong cardiac response to mental stress and this could be a characteristic of this condition.

Adult↗