Myocardial dysfunction in ankylosing spondylitis.

Echocardiographic evidence has suggested abnormalities of the myocardial function in patients with ankylosing spondylitis. In this work the cardiac function in patients with ankylosing spondylitis and in normal volunteers was evaluated. Twenty four normal volunteers and 21 patients with ankylosing spondylitis aged 18-45 were studied. None had overt cardiac disease. Cardiac function was assessed at rest with echocardiography, at rest and during supine bicycle exercise using radionuclide angiography in the left anterior oblique position following equilibration with 740 MBq of technetium-99. The subjects undertook supine bicycle exercise with 30 W increments every three minutes to the point of fatigue. Comparison of data from normal volunteers and patients with ankylosing spondylitis were made using Student's t test for independent samples or the Mann-Whitney non-parametric technique, as appropriate. Subjects were matched for age, sex, height, and weight. There were no echocardiographic differences; however, global nuclide left ventricular function showed several differences between normal volunteers and patients with ankylosing spondylitis. The peak filling rate during exercise was significantly lower in patients with ankylosing spondylitis: normal volunteers 6.5 (SD 1.2); patients with ankylosing spondylitis 5.7 (1.2). The time to reach peak filling during exercise was significantly lower in patients with ankylosing spondylitis: normal volunteers 102 (22); patients with ankylosing spondylitis 120 (23). Regional analysis also showed differences between patients with ankylosing spondylitis and normal volunteers both at rest and during exercise. In the anteroseptal region the filling fraction and peak filling rate were significantly lower in patients with ankylosing spondylitis. Most of the differences (although not all) were in the variables of diastolic function. This study shows that there are subtle abnormalities in cardiac function in patients with ankylosing spondylitis. The major abnormalities are in the diastolic function, suggesting a decrease in left ventricular compliance.

Twenty-four-hour blood pressure control: an intraarterial review.

Intraarterial blood pressure monitoring has shown the circadian rhythm of blood pressure control. Blood pressures tend to be highest in the morning before falling gradually during the day to a nadir at 3:00 a.m. There is a slight rise in the late afternoon that may correspond to patients' attendance at hospital for calibration of the equipment. There is a small rise in the blood pressure before awakening, and after arousal there is a rise in blood pressure to the peak level of the morning. In this article, we examine the effect of a variety of antihypertensive agents on this rhythm. In general, beta-adrenoceptor blockers appear to have less effect on nocturnal blood pressure and surge in pressure after arousal, while vasodilators, particularly alpha-adrenoceptor blockers, have a pronounced effect. These findings indicate that the rise in blood pressure before awakening and the rapid rise upon arousal appear to be due to increased alpha-adrenoceptor activity.

The effect of placebo on indirect and direct blood pressure measurements.

We have conducted a series of experiments which clearly show that intra-arterial ambulatory blood pressure is not altered by the administration of placebo. This finding is in contrast to the apparent fall in pressure that appears when the indirect (Korotkoff) method is used. The evidence suggests that the apparent fall in indirect pressure is due to abolition of the orienting reflex with time. Therefore, clinical trials of antihypertensive drugs using the intra-arterial method do not need a placebo control, whereas a placebo control is essential in all trials using the indirect technique for measuring blood pressure.

Noninvasive temporary pacemakers.

Temporary transcutaneous pacing involves passing a variable current across the chest wall synchronized to sensed electrical signals. We evaluated two systems, the Cardio-Aid and Pace-Aid both in routine, and emergency use. The Cardio-Aid was tested on 12 patients (9 routine and 3 emergency) and the Pace-Aid was tested alone in 4 patients (2 emergency and 2 routine). Both systems were tested on a further 7 patients (2 emergency and 5 routine). Overall, successful pacing was achieved in 3 out of 19 patients with the Cardio-Aid (1 emergency) and in 4 out of 11 patients with the Pace-Aid (3 emergency). The maximum current used was limited by the degree of pain experienced. These data suggest that the benefit derived from transcutaneous pacing is limited. The pain experienced by patients may be diminished by appropriate analgesics and sedation, thereby allowing a greater pacemaker output particularly in an emergency situation.

Bedside nuclear probe for detection and quantification of left to right intracardiac shunts.

A cadmium telluride nuclear probe with an Elscint gamma camera was used to detect and measure left to right intracardiac shunts at the bedside in 34 patients. Fifteen also had right heart catheterisation and oximetric measurement of the shunt. For the nuclear technique 740 MBq (20 mCi) of technetium-99m pertechnetate was injected into the right antecubital vein and the pulmonary to systemic flow ratio (QP:QS) was measured by the gamma variate technique. Data were not obtained in four patients because the nuclear probe failed in three patients and one storage disc was corrupted. Data from the gamma camera were lost in another patient. When the size of the shunt measured by the nuclear probe was compared with that measured by the oximetric technique the mean difference (SD of mean difference) was 0.36 (SD 0.78) and when it was compared with the gamma camera it was 0.08 (SD 0.67). Analysis of scatter plots showed that the larger the shunt, the larger the discrepancy. Twenty four of 29 data sets showed complete agreement between the nuclear probe and gamma camera on the size of the shunt. Any differences were small. These data indicate that left to right intracardiac shunts may be measured accurately by a nuclear probe at the bedside in either the coronary care unit or outpatient department.

An evaluation of the Avionics Pressurometer III 1978 at home and in hospital.

The Avionics Pressurometer III is the only noninvasive indirect ambulatory blood pressure system which provides 24-h blood pressure measurements, but it has been subjected to limited evaluation. We report a critical evaluation comparing it to simultaneous intra-arterial blood pressures both at home and at hospital as well as during standardized exercise. Comparisons with simultaneous indirect methods were also made. Twenty-two hypertensives undergoing intra-arterial ambulatory blood pressure monitoring wore the two recorders for one day. The mean difference (standard deviation SD) for intra-arterial blood pressure--Avionics blood pressure was 2 (SD 8.6)/-14 (SD 10.3) mmHg at home and -3 (SD 15.4)/-11 (SD 12.3) mmHg at hospital. At the end of exercise the figures for the same comparison were -7 (SD 16)/0 (SD 15.6) mmHg. In general the agreement between intra-arterial and Avionics pressurometer recordings was closer for systolic than for diastolic blood pressures but there was wide variation for individuals as shown by the standard deviations about the mean difference. We did not use the recorder at night as patients complained that the noise kept them awake and so night-time blood pressures were not attainable. We do not think the recorder performed satisfactorily during physical exertion, and in view of its expense, this recorder is of limited potential value in supplying accurate information.

An evaluation of self-recorded blood pressure during drug trials.

To our knowledge, there have been no published comparisons of different techniques for measuring blood pressure during clinical trials. We undertook a comparison during clinical trials with verapamil and prazosin. During an open trial of verapamil we compared the treatment-induced blood pressure reductions as measured by clinic, intra-arterial, and self-recorded methods. The mean reduction in blood pressure was 38 +/- 13.6/20 +/- 10.1 mm Hg for clinic blood pressure, 24 +/- 17.9/16 +/- 7.3 mm Hg for self-recorded blood pressure, and 23 +/- 12.3/19 +/- 10.1 mm Hg for mean daytime intra-arterial blood pressure. During prazosin treatment the mean reduction in blood pressure was 28 +/- 21.5/18 +/- 8.5 mm Hg for clinic blood pressure, 21 +/- 20.5/6 +/- 13.7 mm Hg for self-recorded blood pressure, and 18 +/- 19.2/5 +/- 9.6 mm Hg for mean daytime intra-arterial blood pressure. There was little agreement between methods within individual patients and for group comparisons of intra-arterial or clinic methods. There was, however, good agreement between intra-arterial and self-recorded methods. This study suggests that self-recorded blood pressure recording is suitable for monitoring efficacy of antihypertensive agents in a group of patients, although caution must be exercised when interpreting the effects of therapy when measured by indirect methods in an individual patient.

Twice-daily verapamil for hypertension: a comparison with propranolol.

Recent reports have confirmed that some slow calcium channel inhibitors have useful antihypertensive properties because they produce dilatation of the peripheral arterioles without reflex tachycardia. Verapamil is such a drug, but its clinical role in the management of hypertension is not clear. An open crossover trial was performed to compare the 24-hour profiles of blood pressure reduction after long-term therapy with a standard beta-adrenoceptor blocker, propranolol, and verapamil. Nineteen patients were studied by continuous ambulatory intraarterial recording and the order of drug administration was determined by random allocation. The drugs were administered 2 times a day and titrated according to casual clinic pressures (propranolol, 40 to 240 mg 2 times a day; verapamil, 120 to 240 mg 2 times a day). Mean hourly blood pressure and heart rate values were obtained over a 24-hour cycle and the responses to isometric and dynamic exercise were also examined. The drugs produced a uniform and comparable reduction in blood pressure throughout the day, together with a reduction in heart rate, which was greater with propranolol. Comparable effects were also seen on the pressor responses to exercise. Both drugs were equally well tolerated and caused no patient withdrawals. Thus, oral verapamil given 2 times a day shows a degree of efficacy similar to that of propranolol and provides 24-hour blood pressure control. This slow calcium channel inhibitor was well tolerated and may be used as initial therapy for hypertension.

Is the blood pressure the same in both arms?

It is generally believed that there are blood pressure differences between the right and left arms, but most of the validation studies have used nonsimultaneous measurements. It is important to know whether there is a difference, as methodological comparisons are often made using a different technique on each arm. We have measured the blood pressure simultaneously in both arms in 91 patients, using two observers and two cuffs to provide eight measurements in a fully balanced design. The mean difference in blood pressure between the arms (left/right) was -1.3 (SE 0.4)/1.1 (SE 0.3) mmHg. Mean differences of the same magnitude were found between the two observers, and between the cuffs. Thus, no systematic difference of any consequence was found, although individual patients had mean between-arm differences in blood pressure of up to 10 mmHg. These results suggest that no significant bias is introduced in methodological comparisons that use both arms.

Indirect measurement of blood pressure during exercise testing can be misleading.

Indirect blood pressures recorded with a random zero sphygmomanometer were compared with simultaneous intra-arterial blood pressures recorded with the Oxford system. Twenty five patients undertook a graded bicycle exercise test, cycling at workloads increasing from 41, 65, 114, and 163 W (250 to 400, 700, and 1000 kpm per min) with each grade being maintained for three minutes unless the exercise test was terminated earlier at the point of fatigue. Intra-arterial pressures were recorded continuously and indirect measurements made at steady state levels in the 30 seconds before each change in grade and immediately after the termination of the exercise protocol. The mean difference in systolic blood pressure at 5.5 minutes of exercise showed that the indirect measurement underestimated the direct measurement. Immediately after the termination of exercise the blood pressure fell precipitiously to a highly significant degree. For both systolic and diastolic pressures there was considerably individual variability. These data confirm that indirect methods of blood pressure measurement during dynamic exercise testing are inaccurate and may provide misleading information.

Propranolol versus verapamil for the treatment of essential hypertension.

Recent reports have confirmed that slow calcium channel inhibitors have useful antihypertensive properties because they produce dilatation of the peripheral arterioles without reflex tachycardia. Their clinical place in the management of hypertension has yet to be clearly defined, and thus we have performed an open crossover trial to compare the 24-hour profiles of blood pressure reduction after chronic therapy with propranolol and verapamil. Nineteen patients were studied by continuous ambulatory intraarterial recording and the order of drug administration was decided by random allocation. Drug dosage was twice daily and titrated according to casual clinic pressures (propranolol, 40 to 240 mg twice a day; verapamil, 120 to 240 mg twice a day). Mean hourly blood pressure and heart rate values were obtained over a 24-hour cycle, and the responses to isometric and dynamic exercise were also examined. Both drugs were shown to produce a uniform and comparable reduction in blood pressure throughout the whole day, together with a reduction in heart rate, which was greater with propranolol. Comparable effects were also seen on the pressor responses to exercise. Both drugs were equally well tolerated and caused no patient withdrawals. We conclude that oral verapamil given twice daily showed a similar degree of efficacy to propranolol and provided 24-hour blood pressure control. This slow calcium channel inhibitor may be useful as initial therapy for hypertension, particularly for those patients in whom beta-adrenoreceptor blockers are contraindicated.

Circadian rhythm of blood pressure in patients dependent on ventricular demand pacemakers.

The reported circadian rhythm of blood pressure variability with a rise in pressure before awakening has been the subject of controversy. Previous studies have suggested that since heart rate continues to fall before awakening while blood pressure is rising these physiological variables are subject to different control mechanisms. To evaluate further the dissociation of heart rate and blood pressure changes in a group of patients with a fixed heart rate, 11 patients who were dependent on ventricular demand pacemakers underwent intra-arterial ambulatory blood pressure monitoring. Nine aged matched control subjects followed the same protocol. Circadian curves plotted from pooled hourly mean data showed that despite a fixed heart rate the circadian pattern persisted, although attenuated, with blood pressure rising several hours before its rapid rise on awakening. Physiological testing showed that despite a fixed heart rate systolic blood pressure rose in response to bicycle exercise, there was a postural fall in the blood pressure on tilting and a modified Valsalva response. There was considerable beat to beat variability resulting presumably from asychronous pacing. Hour to hour changes did not contribute to the differences between the two groups and were not responsible for attenuation of the circadian rhythm. It is concluded that blood pressure and heart rate control mechanisms may be dissociated, particularly in the period before awakening.

The safety of ambulatory intra-arterial pressure monitoring: a clinical audit of 1000 studies.

Between 1973 and 1981 1000 successful studies involving ambulatory monitoring of intra-arterial blood pressure were performed using percutaneous cannulation of the brachial artery. We have reviewed the clinical effects of these studies and 35 other cases where attempted cannulation was unsuccessful. One major complication occurred, when an infected haematoma arising at the cannulation site led to the formation of a false aneurysm. In only one other case was distal pulsation diminished following the study. There were 157 reported "minor" complications in 122 studies, including haematoma, haemorrhage, transient paraesthesiae in median nerve territory, and evidence of micro-emboli. A limited study using pulsed wave Doppler ultrasound revealed no significant alteration in arterial lumen size or flow in 20 subjects. The procedure was therefore associated with a much smaller incidence of clinical problems than has been reported with other investigations involving cannulation of the brachial artery.

Evaluation of the Remler M2000 blood pressure recorder. Comparison with intraarterial blood pressure recordings both at hospital and at home.

The Remler M2000 is a semiautomated device that has been used to collect epidemiological data and assess blood pressure variability. It has been subjected to limited evaluation in operation, however, and no studies of its accuracy away from the hospital or office environment have been undertaken. We recruited a group of 28 patients with essential hypertension who were undergoing intraarterial ambulatory blood pressure monitoring and compared the intraarterial recordings with those made with the Remler instrument both at home and in the hospital. The Remler recordings were also compared with simultaneous indirect blood pressure measurements made with the random zero sphygmomanometer. The mean difference between the Remler and intraarterial blood pressure recordings was -3/7 in the hospital and 7/0 at home. All standard deviations were greater than 10 mm Hg, indicating large between-subject variability. Overall, the relationship of the Remler M2000 readings to intraarterial pressures was as close if not closer than standard indirect sphygmomanometry and thus might provide useful data for epidemiological surveys or drug trials. It would appear that for accurate measurement of short-term blood pressure variation and 24-hour recording, intraarterial recording is the method of choice.

The role of a slow channel inhibitor, verapamil, in the management of hypertension.

The 'Oxford' system for continuous monitoring of the ambulatory blood pressure was used to assess the changes in blood pressure following therapy with the slow channel inhibitor, verapamil. Sixteen patients were studied on no therapy and following a minimum of 6 weeks therapy (dose range 120-160 mg t.d.s.). During each study patients underwent standardized physiological tests including tilt, isometric handgrip and dynamic bicycle exercise. Verapamil was demonstrated to produce a consistent reduction of blood pressure over most of the 24 h period studied but this was most marked during the day. Heart rate was also reduced. There was no postural hypotension and the absolute responses to dynamic and isometric exercise were reduced. The results demonstrate the antihypertensive efficacy of 'slow channel inhibitors' as represented by verapamil.

Effect on intra-arterial blood pressure of slow release metoprolol combined with placebo or chlorthalidone.

Thirty patients with essential hypertension participated in a double blind crossover trial in which they were randomly allocated to treatment with either once daily slow release metoprolol (200 mg) with placebo or once daily slow release metoprolol (200 mg) with chlorthalidone (25 mg). Ambulatory intra-arterial blood pressure was recorded continuously for 24-48 hours before treatment and two months after each change in regimen. The response of blood pressure and pulse rate to a standard exercise protocol that included supine rest and tilt, isometric, and dynamic bicycle exercise was measured during the same recording periods. Both treatments appreciably reduced blood pressure and pulse rate; mean daytime intra-arterial blood pressure was reduced from 174/95 mm Hg to 158/85 mm Hg by metoprolol plus placebo and to 143/78 mm Hg by metoprolol plus chlorthalidone. This reduction with the combined treatment was significantly greater than with metoprolol and placebo (p systolic = 0.001, p diastolic = 0.004). Mean night time pressures were reduced from 148/78 mm Hg to 139/75 mm Hg by metoprolol plus placebo and to 116/61 mm Hg by metoprolol plus chlorthalidone. Again the reduction in blood pressure was significantly greater with combined treatment (p less than 0.001) than with metoprolol plus placebo. Once daily slow release metoprolol is effective in controlling blood pressure, but this effect is greatly enhanced by the addition of a diuretic.

Nifedipine or verapamil as sole treatment of hypertension. An intraarterial study.

Intraarterial ambulatory blood pressures were recorded prior to and during therapy with two different calcium ion antagonists, nifedipine and verapamil, in two separate groups of patients. In the first group, nine patients were studied off therapy and following a minimum of 6 weeks of nifedipine treatment (dose range, 20 to 60 mg twice daily). A second group of 16 patients followed the identical protocol but were prescribed verapamil (120 to 160 mg, three times daily). During both studies, patients underwent standardized physiological tests including tilt, isometric handgrip, and dynamic bicycle exercise. Both verapamil and nifedipine caused a reduction in blood pressure over most of the 24 hours studied. Nifedipine did not affect heart rate whereas verapamil caused a reduction of approximately 10 bpm. Nifedipine and verapamil did not induce postural hypotension, and the absolute responses to dynamic and isometric exercise were reduced. These results show the efficacy of slow channel inhibitors in the management of essential hypertension.

Prazosin alone and combined with a beta-adrenoreceptor blocker in treatment of hypertension.

We recorded intra-arterial ambulatory blood pressure in 13 patients with essential hypertension before and after long-term twice-daily prazosin therapy (mean dosage 13.8 mg, SD 4.2 mg). Nine other patients with essential hypertension inadequately controlled with beta-adrenoreceptor blocking drugs were studied before and after the addition of long-term twice-daily prazosin therapy (mean dosage 8.8 mg, SD 6.7 mg). Ten patients, responders from both groups, then received once-daily prazosin, and intraarterial monitoring was repeated for a third time. Circadian curves from pooled hourly data showed no significant reduction of intra-arterial ambulatory blood pressure with prazosin alone. There was a slight reflex tachycardia. Nine patients receiving combination therapy showed a daytime reduction in blood pressure averaging 24/6 mm Hg (p less than 0.001). Postural hypotension was recorded in both groups. Once-daily prazosin failed to control the blood pressure after 1700 h in the group of 10 patients defined as responders. Following combination therapy the blood pressure was reduced by 19/14 mm Hg at the peak of isometric hand grip and by 25/9 mm Hg on dynamic bicycle exercise. These data indicate that prazosin as an antihypertensive agent is best used in combination therapy with beta-adrenoreceptor blockade.

Nifedipine tablets for systemic hypertension: a study using continuous ambulatory intraarterial recording.

The action of nifedipine tablets was examined in 17 patients with essential hypertension focusing particularly on the profile of blood pressure (BP) reduction over 24 hours resulting from both twice-daily and once-daily therapy (dose range 40 to 120 mg daily). This new formulation of nifedipine has a more prolonged and lower peak plasma level than an equivalent dose of nifedipine capsules. Our patients were fully ambulant and studied by continuous intraarterial recording techniques. BP responses during isometric and dynamic exercise testing were also observed. Within-patient comparisons of consecutive mean hourly systolic and diastolic BP showed a highly significant effect from twice-daily therapy (p less than 0.001) for nearly the entire day. Also, significantly lower BP was maintained during isometric and dynamic exercise. Mean hourly heart rates were not significantly altered. The profile of action of the single morning dose was initially similar, but its efficacy diminished from 6 P.M. to 8 A.M. on the following day. Side effects were not unduly troublesome and did not cause any patient withdrawals. Four patients developed mild ankle edema. Two others had facial flushing. Nifedipine given twice daily in tablet form, therefore, is an effective antihypertensive drug capable of lowering BP consistently over 24 hours in ambulant patients and during formal exercise testing. We suggest that this agent may be useful as initial therapy for systemic hypertension, although the tablets are not as yet widely available.