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Biomedical subjects

T J Stallard

Publications and source records attributed to T J Stallard.

At least 19 recordsLinked to original sources

Cardiac hypertrophy as a result of long-term thyroxine therapy and thyrotoxicosis.

OBJECTIVES: To define the effects of long-term thyroxine treatment upon heart rate, blood pressure, left ventricular systolic function, and left ventricular size, as well as indices of autonomic function, and to compare findings with those in patients with thyrotoxicosis before and during treatment. DESIGN: Cross sectional study of patients prescribed thyroxine long term (n = 11), patients with thyrotoxicosis studied at presentation (n = 23), compared with controls (n = 25); longitudinal study of patients with thyrotoxicosis studied at presentation and serially after beginning antithyroid drug treatment (n = 23). METHODS: 24 h ambulatory monitoring of pulse and blood pressure, echocardiography, forearm plethysmography, and autonomic function tests. RESULTS: Long-term thyroxine treatment in doses that reduced serum thyrotrophin to below normal had no effect on blood pressure, heart rate, left ventricular systolic function or stroke volume index, but was associated with an 18.4% increase in left ventricular mass index (mean (SEM) 101.9 (3.09) g/m2 v controls 86.1 (4.61), P < 0.01). Thryoxine treatment, like thyrotoxicosis, had no effect on tests of autonomic function. Untreated thyrotoxicosis resulted in pronounced changes in systolic and diastolic blood pressure and an increase in heart rate during waking and sleep. Patients with thyrotoxicosis at presentation had an increase in left ventricular systolic function (ejection fraction 70.5 (1.66)% v 65.4 (1.79), P < 0.01; fractional shortening 40.4 (1.54)% v 35.6 (1.46), P < 0.01), increased stroke volume index (45.9 (2.4) ml/m2 v 36.6 (1.7), P < 0.001), and an increase in forearm blood flow, and decrease in vascular resistance. They had a similar degree of left ventricular hypertrophy to that associated with thyroxine treatment (99.3 (4.03) g/m2); all changes were corrected within 2 months by antithyroid drugs. CONCLUSIONS: The development of left ventricular hypertrophy in patients receiving thyroxine in the absence of significant changes in heart rate, blood pressure, and left ventricular systolic function is consistent with a direct trophic effect of thyroid hormone on the myocardium. The presence of left ventricular hypertrophy determines that further studies are essential to assess cardiovascular risk in patients taking thyroxine long term.

Adult

Effects of the angiotensin converting enzyme inhibitor, benazepril, on the sino-aortic baroreceptor heart rate reflex.

The effects of monotherapy with the angiotensin converting enzyme inhibitor benazepril (10 mg once daily) on cardiovascular baroreceptor reflexes were determined in 10 patients with essential hypertension using a randomized, double-blind, placebo-controlled, cross-over protocol. Early sino-aortic baroreceptor/heart rate reflex resetting was apparent with acute treatment; this effect persisted throughout the active treatment period. Changes in baroreflex sensitivity did not appear to mediate the hypotensive effect of benazepril.

Angiotensin-Converting Enzyme Inhibitors

Effect of unrestricted activity on accuracy of ambulatory blood pressure measurement.

A validation study of the Takeda TM-2420 ambulatory blood pressure recorder was performed on 10 subjects using the Oxford ambulatory intra-arterial recording apparatus during unrestricted activity. Electronic linkage of the two recorders ensured simultaneous blood pressure readings, taken from opposite arms. Although there was close approximation of intra-arterial and automated sphygmomanometric recordings over the range of blood pressure encountered in this study, there was a wide scatter of points and a tendency for the machine to underestimate systolic pressure by more than 15 mm Hg in the hypertensive range (systolic blood pressure more than 160 mm Hg) was detected. These findings suggest that automated recording of blood pressure during unrestricted activity may have a proportion of artifactual readings. Although simultaneous intra-arterial blood pressure recording may not be appropriate for widespread use in device validation, this study illustrated some potential disadvantages of the current validation recommendations, namely, the absence of assessment of device accuracy during unrestricted and ambulatory activity.

Adult

Xamoterol in the treatment of orthostatic hypotension associated with multiple system atrophy (Shy-Drager syndrome).

The effect of xamoterol on the orthostatic hypotension associated with Shy-Drager syndrome was investigated in three patients. Intra-arterial blood pressure was measured during a control period and during treatment with xamoterol, both in a cardiovascular investigation laboratory and for 24 h of unrestricted activity using portable apparatus. Xamoterol lessened the total number of symptomatic episodes of orthostatic hypotension by 67 per cent. Average untreated 24-h intra-arterial blood pressure was 132/78 mmHg; during treatment with xamoterol it rose to 138/90 mmHg. However episodes of severe hypertension (defined as a systolic intra-arterial blood pressure above 200 mmHg) were more frequent with xamoterol. Although xamoterol attenuated orthostatic hypotension, careful monitoring of ambulatory blood pressure may be necessary, particularly at the start of treatment, because of the development of severe supine hypertension. Intravenous test doses of xamoterol did not predict either the attenuation of orthostatic hypotension or the development of supine hypertension in all patients.

Adrenergic beta-Agonists

Effects of perindopril on ambulatory intra-arterial blood pressure, cardiovascular reflexes and forearm blood flow in essential hypertension.

The effects of monotherapy with the angiotensin converting enzyme (ACE) inhibitor perindopril (8 mg once daily) on 24-h ambulatory intra-arterial blood pressure, forearm blood flow, left ventricular mass, vasoactive hormones and cardiovascular reflexes were determined in eight hypertensive patients using a randomized, double blind, placebo-controlled, cross-over protocol. Six weeks of perindopril treatment was associated with a significant reduction of ambulatory blood pressure and a significant increase in forearm blood flow. Whilst the haemodynamic responses to Valsalva's manoeuvre, tilt, isometric forearm exercise and cold pressor testing were unaffected by perindopril, significant augmentation of the bradycardia during facial immersion was seen after chronic therapy. Sino-aortic baroreceptor-heart rate reflex resetting was apparent within 2 h of the first dose; this effect persisted throughout the active treatment period. Withdrawal of treatment was associated with a persisting hypotensive effect and an increase in heart rate which was not accompanied by an increase in plasma catecholamines. We conclude that perindopril, in a dose of 8 mg once daily, was an effective antihypertensive agent. We postulate that chronic therapy was associated with a sustained increase in parasympathetic tone.

Adult

Forearm haemodynamics and blood pressure variability in hypertensive patients.

Ambulatory blood pressure variability and forearm haemodynamics were measured in 23 untreated hypertensive patients with a mean casual blood pressure of 162/102(11/9) mmHg (without target organ damage). There was a good inverse correlation between blood pressure variability and the ability of the forearm resistance vessels to dilate after a period of venous occlusion. Previous work has shown that this vasodilatory component of the response to forearm venous occlusion is significantly reduced in hypertensive patients compared with normotensive controls and is probably an indicator of the compliance properties of these vessels. The present results suggest that blood pressure variability is greater when resistance vessels are stiffer and emphasise the need to account for this vascular factor in studies of blood pressure behaviour.

Adult

Can sinoaortic baroreceptor heart rate reflex sensitivity be determined from phase IV of the Valsalva manoeuvre?

A new time related method of analysing the sinoaortic baroreceptor heart rate reflex, which determines reflex latency as well as sensitivity, was used to compare the results obtained with a phenylephrine ramp method (P) with those obtained using the whole of phase IV of Valsalva (V1) and using the phase IV systolic blood pressure overshoot alone (V2). Twenty five subjects with large ranges of age and resting blood pressures were studied. Each performed two standardised Valsalva manoeuvres and received three bolus injections of phenylephrine sufficient to cause transient pressor responses of 20-30 mmHg. Mean sensitivity values with P (6.2(3.5) ms.mmHg-1) were greater than those with V1 (4.6(2.3) ms.mmHg-1, p less than 0.001) and less than V2 (7.8(4.0) ms.mmHg-1, p less than 0.001). However, linear regression analysis showed a correlation of P with V1 (r = 0.76, p less than 0.0001) and with V2 (r = 0.80, p less than 0.0001). Reflex latency with P (1084(427) ms) was less than V1 (2416(423) ms, p less than 0.0001) and V2 (1504(441) ms, p less than 0.0005). Reflex sensitivity results obtained using phase IV of Valsalva's manoeuvre are proportionately related to phenylephrine results, but large errors were introduced into the absolute values obtained when relatively small changes were made to the method of analysis.

Adult

Variation in cuff blood pressure in untreated outpatients with mild hypertension--implications for initiating antihypertensive treatment.

Thirty-two patients with mildly elevated blood pressure (BP), but without target organ damage, attended a BP measuring clinic where duplicate BP measurements were made on 12 visits. During visits 1-3, BP showed a systematic decrease which varied from patient to patient. During visits 4-12, no further systematic changes in BP were observed. During the latter period, between-visit variation in BP was substantial, the standard deviation of the difference in BP from one visit to another being 10.4 mmHg for systolic, 6.8 mmHg for diastolic (phase IV) and 7.0 mmHg for diastolic (phase V). These values were used to determine the chance that the BP estimated after a number of visits differed from the average stable BP. After visit 4, the chance of a difference of 5 mmHg or more was 0.50 systolic blood pressure (SBP) and 0.32 diastolic blood pressure (DBP; phase V). Increasing the number of visits to six or more reduced the chance of error. Before initiating lifelong treatment in mild hypertensives free of target organ damage, BP should be recorded in duplicate on a minimum of six visits.

Adult

Estimation of sinoaortic baroreceptor heart rate reflex sensitivity and latency in man: a new microcomputer assisted method of analysis.

A new method for analysing baroreflex sensitivity has been developed. It obviates the mathematical bias inherent in earlier methods and in addition provides a direct measurement of reflex latency. Sensitivity results obtained using this method in 25 patients with a wide range of ages and resting blood pressures were similar to, but consistently lower than, those achieved with the Oxford method. Baroreflex latency results ranged from 650 to 2900 ms (mean(SD) 1084(427) ms) and were reproducible within individuals. Sensitivity results were inversely related to age and resting systolic blood pressure. Reflex latency was not related to these variables or to resting heart rate or reflex sensitivity. This method was able to identify inadequate starting data and greatly reduced the analysis time.

Adult

Felodipine in hypertension.

Felodipine, a selective arteriolar dilator, was given to 13 hypertensive patients to assess its hypotensive effects and duration of action. Nine patients were treated with 5 mg three times a day and 4 with 10 mg three times a day. Mean blood pressures fell with both treatment regimens: 5 mg placebo 170/103 mmHg; 5 mg felodipine 148/91 mmHg; 10 mg placebo 154/93 mmHg; 10 mg felodipine 137/82 mmHg. Heart rates increased as blood pressures fell with both treatments. However, in the patients given 5 mg three times a day this effect was less noticeable after successive doses. Plasma concentrations of noradrenaline, both resting and tilted, increased after felodipine. There was a negative correlation between the fall in blood pressure and the increase in noradrenaline, suggesting that those patients with good baroreceptor reflexes were better able to counteract the effects of vasodilatation. Four of the nine patients treated with 5 mg felodipine three times a day experienced mild and transient adverse effects. Of the four patients treated with 10 mg three times a day, three experienced moderate to severe headache, and for this reason recruitment into this group was stopped. Felodipine at a divided daily dose of 15 mg effectively lowered blood pressure.

Adult

Regression of left ventricular hypertrophy in hypertension: comparative effects of three different drugs.

We examined the effect of three antihypertensive agents with differing modes of action on blood pressure, heart rate, plasma catecholamines, plasma renin activity, and echocardiographic left ventricular mass. Twenty-six patients were studied; nine were treated with nifedipine, a calcium antagonist, nine were treated with timolol, a nonselective beta-blocker, and eight were treated with indapamide, a diuretic with some probable calcium antagonist properties. All drugs reduced blood pressure satisfactorily; the reduction of systolic blood pressure was not significantly different among the three drugs, but timolol reduced diastolic blood pressure by a greater amount than did either indapamide or nifedipine. Left ventricular (LV) mass was reduced equally by all three drugs. However, there were markedly different effects on the other parameters measured. Heart rate was reduced to a greater extent by timolol than by the other two drugs. Plasma renin activity was reduced by timolol, unchanged by nifedipine, and increased by indapamide. There were no significant changes in either adrenaline or noradrenaline with any of the three drugs. We conclude that these data do not support the hypothesis that the sympathetic nervous system is primarily responsible for left ventricular hypertrophy, and suggest that reduction of left ventricular mass with antihypertensive agents is not the property of any one class of drug.

Adult

The effect of felodipine on forearm haemodynamics and the myogenic response of the forearm resistance vessels in normal man.

The effect of felodipine 10 mg oral solution or placebo on peripheral haemodynamics and the response of the forearm resistance vessels to venous occlusion was studied in seven normotensive individuals. Felodipine produced a significant fall in diastolic blood pressure (DBP max = -15 mm Hg), a rise in heart rate (heart rate max = +15 beats min-1) (both P less than 0.01), and an overall fall in calculated forearm vascular resistance (calculated forearm vascular resistance max = -19.6 units, P less than 0.001). Felodipine had no significant effect on the vasodilator response, but limited the vasoconstrictor response following venous occlusion. These observations suggest that felodipine is a potent vasodilator and interferes with the myogenic response of vascular smooth muscle of the forearm resistance vessels.

Adult

Calcium channel blockers--are they diuretics?

Seven untreated patients with essential hypertension but without target organ damage were admitted to hospital. Urine was collected the following day from 08.00 to 13.00 h, 13.00 to 18.00 h, and 18.00 to 08.00 h. The protocol was repeated the next day following 30 mg oral nicardipine. Intra-arterial blood pressure (IABP), plasma volume, and plasma renin activity (PRA) also were measured daily. Following the single-dose study, the patients were treated as outpatients and received oral nicardipine 20, 30, or 40 mg four times daily. They were readmitted 2 months later for further study, at which time the protocol was repeated. Urine output between 08.00 and 13.00 h significantly increased after the single- and multiple-dose studies. Following the single-dose study, this diuresis was associated with a natriuresis. Urine output increased over the 24 h following multiple-dose treatment, but this increase was not statistically significant. During the multiple-dose 24 h study, there was an increase in urinary potassium (P less than 0.05). Mean IABP was reduced significantly after the single- and multiple-dose studies (P less than 0.02 and less than 0.05, respectively). During the study, there were no significant changes in plasma volume, weight, or plasma renin activity.

Adult

Once daily indapamide in the treatment of the elderly and young hypertensive.

Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly.

Adolescent

Ambulatory blood pressure and its response to exercise in the elderly.

Thirty-three elderly subjects--9 hypertensives, 15 with a history of unexplained falls and 9 asymptomatic volunteers, underwent 24 h continuous intra-arterial ambulatory blood pressure (BP) monitoring under controlled conditions. During this time their response to standardized exercise and baroreflex activity were assessed. The casual BP of the hypertensives was significantly higher than that of the other groups, but during ambulatory BP monitoring, the BP of all 3 groups fell and indeed diastolic BP (DBP) of the hypertensives and fallers was similar during the awake period of monitoring whilst all 3 groups had similar DBP during sleep. Variability of awake and sleep BP was similar. During exercise all 3 groups sustained similar increases in systolic BP (SBP) but the increase in DBP was lower in the volunteers. Baroreflex activity was similar in all groups. The results show little difference between the groups other than those pre-selected by casual BP measurement, and the parameters recorded reflect the process of ageing rather than specific abnormalities associated with the elderly hypertensives or fallers.

Aged

Continuous ambulatory monitoring of blood pressure and assessment of cardiovascular reflexes in the elderly hypertensive.

Thirteen elderly hypertensives underwent continuous ambulatory blood pressure (BP) monitoring and measurement of cardiovascular reflexes. The results were compared with elderly normotensives and young hypertensives studied using the same protocol. There was a greater disparity between casual systolic BP (SBP) and ambulatory awake SBP in the elderly hypertensives than either the elderly normotensives or young hypertensives. Variability of SBP was greater in the elderly than the young, whilst baroreflex activity was reduced in the elderly, and more markedly so in the elderly hypertensives. Response to tilt and pressor tests was similar for the elderly. The elderly hypertensives showed a greater fall of SBP in response to tilt and a greater rise of SBP during dynamic exercise than the young hypertensives. Stimulation of plasma renin activity (PRA) in response to upright tilt was less in the elderly hypertensives than the young hypertensives. Resting plasma noradrenaline (PNA) increased with age.

Adolescent

Effect of environment on blood pressure: home versus hospital.

The effect of environment on blood pressure was studied by recording intra-arterial pressure continuously in nine patients with essential hypertension during controlled periods of activity and rest at home and in hospital. Mean systolic pressure was higher at home (152 +/- 16 mm Hg) than in hospital (138 +/- 11 mm Hg, p less than 0.01), the difference being greatest during the period of activity (165 +/- 21 v 142 +/- 13 mm Hg, p less than 0.001); heart rates and diastolic pressures did not differ significantly at these times. Systolic pressure recorded by conventional sphygmomanometry was also higher at home (173 +/- 23 v 159 +/- 23 mm Hg, p less than 0.01), as was diastolic pressure (98 +/- 10 v 89 +/- 11 mm Hg, p less than 0.02). Systolic pressure was consistently higher at home, and this effect was independent of the pressure of an observer. This must be taken into consideration when assessing blood pressure and efficacy of treatment in hospital.

Adult

The effect of nifedipine on arterial pressure and reflex cardiac control.

Nine patients with untreated essential hypertension (mean casual blood pressure 173/109 +/- 14/7 mm Hg) (+/- SD) were studied in the control state and after 16 weeks of treatment with nifedipine, 10 mg orally every 8 hours. Direct arterial blood pressure monitored continuously over 24 hours showed that nifedipine significantly reduced systolic and diastolic blood pressure throughout the day and the night. The variability of blood pressure was not altered by nifedipine therapy. There was no significant change in heart rate after nifedipine therapy. Chronic nifedipine therapy increased forearm blood flow and decreased forearm vascular resistance, consistent with its action as a vasodilator. The absolute blood pressure responses to tilt, handgrip and cold were reduced, but the percent increase in pressure was not altered by therapy. Plasma renin activity was not altered by chronic nifedipine therapy. At each study, the sensitivity and setting of the baroreflex response to i.v. phenylephrine was measured. After chronic nifedipine therapy there was resetting of the sinoaortic baroreflex and an increase in its sensitivity. Successful control of blood pressure with nifedipine led to a significant reduction in the left ventricular mass index.

Adult