Biomedical subjects

D J Ewing

Publications and source records attributed to D J Ewing.

At least 37 records · Page 2Linked to original sources

PubMed1992

Effect of captopril on cardiac parasympathetic activity in chronic cardiac failure secondary to coronary artery disease.

Thirty-two patients with chronic cardiac failure underwent 24-hour ambulatory electrocardiographic monitoring on 2 separate occasions: 20 patients before and during treatment with captopril, and 12 acting as controls. Heart rate variability was calculated by counting the number of times successive RR interval differences were greater than 50 ms (this measurement being a reliable index of cardiac parasympathetic activity). During treatment with captopril, group mean total counts increased to 1,032 (range 48 to 7,437) from 482 (range 23 to 6,120) (p = 0.002). There was no change in mean hourly waking or sleeping heart rates. In the control group, no changes were seen: group mean total counts on the first occasion were 340 (range 120 to 3,255) and on the second occasion 400 (range 154 to 3,300) (p = not significant). These results show that treatment with angiotensin-converting enzyme inhibitors increases cardiac parasympathetic activity in patients with chronic cardiac failure. This may be relevant to the improved prognosis of this group of patients when treated with angiotensin-converting enzyme inhibitors.

Adult↗

PubMed1992

Decreased cardiac parasympathetic activity in chronic heart failure and its relation to left ventricular function.

BACKGROUND: Activation of the sympathetic nervous system has been extensively studied in patients with chronic heart failure, but the parasympathetic nervous system has received relatively little attention. The objective in this study was to investigate cardiac parasympathetic activity in chronic heart failure and to explore its relation to left ventricular function. METHODS: Heart rate variability was measured from 24 hour ambulatory electrocardiograms by counting the number of times each RR interval exceeded the preceding RR interval by more than 50 ms (counts). This method provided a sensitive index of cardiac parasympathetic activity. RESULTS: Mean (range) of counts were: waking 48 (1-275)/h, sleeping 62 (0-360)/h, and total 1310 (31-7278)/24 h. These were lower than expected, and in 26 (60%) of the 43 patients counts fell below the lower 95% confidence intervals (95% CI) for RR counts in normal subjects. A significant correlation between total 24 hour RR counts and left ventricular ejection fraction was present (r = 0.49, p less than 0.05). CONCLUSIONS: These results indicate that most patients with chronic heart failure have reduced heart rate variability and therefore reduced cardiac parasympathetic activity. The degree of parasympathetic dysfunction is related to the severity of left ventricular dysfunction. This may be relevant to the high incidence of ventricular arrhythmias and poor prognosis of patients with chronic heart failure.

Adult↗

PubMed1991

Regulation of ANP secretion in insulin-dependent diabetes mellitus and the influence of autonomic neuropathy.

In order to determine the effect of diabetic autonomic neuropathy (DAN) on the atrial natriuretic peptide (ANP) response to dynamic stimuli, we studied the ANP response to 60 degrees head-up and 60 degrees leg-up tilt in diabetic subjects with (DAN + ve, n = 8) and without (DAN - ve, n = 8) evidence of autonomic neuropathy and seven matched non-diabetic controls. Mean baseline plasma ANP concentrations were similar in all three groups. Head-up tilt was associated with a fall in plasma ANP in all seven healthy controls (21.8 (16.8-30.7) to 16.8 (7.1-29.1), P = 0.06, mean (range)), seven of the eight DAN - ve (16.9 (6.5-33.7) to 8.5 (3.0-21.1), P = 0.015) and all eight DAN + ve subjects (27.3 (8.5-101.5) to 15.4 (1.0-67.6), P = 0.044). Leg-up tilt caused a rise in plasma ANP in six of the seven healthy controls (17.6 (7.5-27.9) to 22.4 (15.2-48.1), P = 0.041), six of the eight DAN - ve (12.5 (7.8-27.8) to 15.5 (7.3-31.3), P = 0.054) and seven of the eight DAN + ve subjects (18.2 (2.8-55.1) to 25.1 (4.5-92.8), P = 0.013). There was no significant difference in the fall in plasma ANP during head-up tilt or in the rise in plasma ANP during leg-up tilt between the three groups. We conclude that the regulation of ANP secretion is normal in diabetes mellitus, and is unaffected by the presence of autonomic neuropathy.

Adult↗

PubMed1991

Heart rate variability in patients with ventricular arrhythmias: effect of antiarrhythmic drugs. Antiarrhythmic Drug Evaluation Group (ADEG).

The purpose of this study was to investigate whether heart rate variability could be reliably assessed in patients with ventricular arrhythmias and to evaluate whether it is affected by antiarrhythmic drugs. The study was based on an analysis of 239 ambulatory electrocardiographic (ECG) recordings obtained from 67 patients with frequent and complex ventricular arrhythmias enrolled in the Antiarrhythmic Drug Evaluation Group (ADEG) study. In each recording, after exclusion of premature ventricular complexes, the number of times during a 24 h period in which two consecutive sinus RR intervals differed by more than 50 ms was calculated. The total 24 h count from each recording was then used as an index of heart rate variability. This method is a reliable marker of cardiac parasympathetic activity. Recordings were analyzed at baseline (n = 56), during long-term treatment with amiodarone (n = 17), flecainide (n = 22) or propafenone (n = 17) and after washout in selected patients (n = 5). Despite the presence of a different number of arrhythmias, total 24 h counts in the same patient appeared reproducible over time (r = 0.83 between two different recordings, n = 49, p less than 0.0001). Baseline counts (median 1,698, range 26 to 13,648) were not correlated (r = 0.15) with the number of arrhythmias. The three antiarrhythmic drugs had a disparate effect on total 24 h counts: no change was observed in patients treated with amiodarone (median percent change [delta %]-8, p = NS), whereas a significant (p less than 0.025) decrease occurred in patients treated with flecainide (median delta % -56%) or propafenone (median delta % -64%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Heart rate variability: an important new risk factor in patients following myocardial infarction.

After acute myocardial infarction, cardiac autonomic, and particularly parasympathetic, activity decreases, followed by a gradual return toward normal over the next few weeks and months. The easiest measurable index of autonomic activity is heart rate variability, which can be assessed in a number of different ways. Where heart rate variability is low after myocardial infarction, long-term survival is considerably reduced, independent of other known risk factors. This may be caused by patchy autonomic denervation, rendering the heart more susceptible to potentially fatal arrhythmias. Prophylactic drug therapy might reduce mortality in patients with low heart rate variability.

Autonomic Nervous System↗

PubMed1991

Autonomic neuropathy, QT interval lengthening, and unexpected deaths in male diabetic patients.

QT intervals were measured over RR intervals ranging from 500 ms to 1000 ms in 13 normal male subjects, 13 male diabetic subjects without and 13 with autonomic neuropathy. There was a close linear relationship between QT and RR in all subjects. The slope of the regression line was significantly greater in the autonomic neuropathy group than the normal group. Thirty-two male diabetic subjects with varying degrees of autonomic dysfunction had repeat QT measurements 3 (range 2-6) years later. QT and QTC lengthened significantly at the second visit, unrelated to age or time between recordings, but which corresponded with changes in autonomic function. Of 71 male diabetic subjects under 60 years followed for 3 years, 13 had died, 8 unexpectedly. Of those with autonomic neuropathy. QT and QTC were significantly longer in those who subsequently died, despite similar ages and duration of diabetes. We conclude that QT/RR interval relationships are altered in diabetic autonomic neuropathy, and that changes in QT length with time parallel changes in autonomic function. There may be an association between QT interval prolongation and the risk of dying unexpectedly in diabetic autonomic neuropathy.

Adult↗

PubMed1991

A double-blind crossover study of oral xamoterol in postural hypotension due to diabetic autonomic neuropathy.

Recent reports have suggested that xamoterol, a beta 1 adrenoceptor partial agonist with 43% intrinsic sympathomimetic activity improves symptomatic postural hypotension in patients with primary autonomic failure. To evaluate the use of xamoterol in eleven insulin dependent patients with diabetes mellitus who had postural hypotension (over 20 mmHg systolic blood pressure) secondary to autonomic neuropathy, we performed a double-blind, randomized, placebo controlled crossover study with xamoterol (200 mg bd orally) for 1 month. Treatment with xamoterol raised supine systolic blood pressure by 11 mmHg but a reduced standing systolic blood pressure by 11 mmHg with an increase in the standing-supine systolic blood pressure difference. No significant differences were observed in symptom score, HbA1 or plasma glucose. We conclude that oral xamoterol raises supine systolic blood pressure but paradoxically lowers standing systolic blood pressure further in insulin dependent diabetes mellitus. Xamoterol is unlikely to be of value in the management of postural hypotension in diabetic patients with autonomic neuropathy.

Adrenergic beta-Agonists↗

PubMed1991

Heart rate variability and cardiac arrhythmias in patients with chronic renal failure.

Heart rate variability was measured from 24-h electrocardiograms in 61 patients with end stage chronic renal failure. The method used counts the number of times successive RR intervals differ by more than 50 ms over the 24-h period, and is a reliable indicator of cardiac parasympathetic activity. Also analysed were the frequency and type of ectopic beats and other arrhythmias. Twenty-one subjects (34%) had varying numbers of ventricular ectopic beats, and twelve (20%) had frequent supraventricular ectopics. Total 24-h count values were abnormal in 30 (76%) of the 41 subjects whose tapes were technically suitable for this analysis. There were no sex differences, but those patients maintained on haemodialysis had significantly lower counts than those on continuous ambulatory peritoneal dialysis. We conclude that about three-quarters of patients with chronic renal failure have abnormal cardiac parasympathetic activity. This may increase susceptibility to cardiac arrhythmias and sudden death and contribute to the high mortality of patients with chronic renal failure.

Adolescent↗

PubMed1991

Twenty four hour heart rate variability: effects of posture, sleep, and time of day in healthy controls and comparison with bedside tests of autonomic function in diabetic patients.

Heart rate variability was measured in 77 healthy controls and 343 diabetic patients by a count of the number of beat-to-beat differences greater than 50 ms in the RR interval during a 24 hour ambulatory electrocardiogram. In the healthy controls the lower 95% tolerance limits for total 24 hour RR interval counts were approximately 2000 at age 25, 1000 at 45, and 500 at 65 years. Six controls confined to bed after injury had normal 24 hour patterns of RR counts, while eight other controls showed loss of diurnal variation in both heart rate and RR counts during a period of sleep deprivation. RR counts in ten controls on and off night duty increased during sleep whenever it occurred. Nearly half (146) the 343 diabetic patients had abnormal 24 hour RR counts. The percentage of abnormal RR counts increased with increasing autonomic abnormality assessed by a standard battery of tests of cardiovascular autonomic function. A quarter of those with normal cardiovascular reflex tests had abnormal 24 hour RR counts. There were close correlations between 24 hour RR count results and the individual heart rate tests (r = 0.6). The assessment of cardiac parasympathetic activity by 24 hour RR counts was reliable. The diurnal variations in RR counts seen in the controls were probably related to sleep rather than either posture or time of day. The method was more sensitive than conventional tests of cardiovascular reflexes.

Adolescent↗

PubMed1991

Hand skin blood flow in diabetic patients with autonomic neuropathy and microangiopathy.

OBJECTIVE: To determine whether changes in hand skin blood flow in diabetic men could be demonstrated with liquid crystal contact thermography and to assess the relative effects of autonomic neuropathy and microangiopathy on these changes. RESEARCH DESIGN AND METHODS: Thirty-four diabetic and 12 age-matched nondiabetic men comprised the study. The diabetic men were categorized according to standard cardiovascular autonomic function tests and the presence or absence of background or proliferative retinopathy and/or proteinuria. Bilateral hand thermograms were measured at rest and after immersion of the right hand in ice-cold water. RESULTS: Diabetic men with definite or severe autonomic neuropathy (n = 13) had a high frequency of anisothermal baseline thermograms (77 vs. 25% in nondiabetic subjects, P less than 0.05). After ice-cold water immersion, right-hand recovery was abnormally slow (514 +/- 157 arbitrary U, area under the curve) compared with nondiabetic men (685 +/- 135 arbitrary U, P less than 0.01). Diabetic men with proliferative retinopathy (n = 8) all had definite or severe autonomic neuropathy and showed the same abnormalities. Diabetic men with nor or early autonomic changes showed normal thermographic patterns. CONCLUSIONS: These results are consistent with increased palmar arteriovenous shunt blood flow or capillary closure in the hands of diabetic patients with definite or severe autonomic neuropathy. They indicate that thermoregulatory reflex changes in hand skin blood flow are controlled by the autonomic nervous system. It is possible, however, that diabetic microangiopathy, associated with the presence of proliferative retinopathy, also independently affects hand skin blood flow.

Adult↗

PubMed1990

Sequential autonomic function tests in HIV infection.

Cardiovascular autonomic function tests were carried out on 22 men at varying stages of HIV infection. Thirteen were asymptomatic, seven had persistent generalized lymphadenopathy, and two had Kaposi's sarcoma. Pupil cycle times were also measured. Except for one subject with definite autonomic abnormalities, all the rest had almost normal test results. There were no correlations between individual tests of immune function and the autonomic test results. The tests were repeated 9-18 months later in 12 men, four of whom were taking zidovudine at that time. Although there was evidence of progression of HIV-associated immune dysfunction, there was no significant deterioration in autonomic function. In the single patient with abnormal autonomic function, these changes appeared to reverse on treatment with zidovudine.

Adult↗

PubMed1990

QT interval length and diabetic autonomic neuropathy.

QT interval length was measured in ECG recordings from three groups of age-matched male subjects: 36 normal subjects, 41 diabetic patients without (DAN-ve), and 34 with (DAN+ve) autonomic neuropathy. ECG samples were selected from previously recorded 24-h ECGs on the basis of a clearly defined T wave and a steady RR interval over 2 min of around 750 ms (80 beats min-1). There were no significant differences in RR interval between the groups. The two diabetic groups had slightly longer QT measurements (normal 365 +/- 14 (+/- SD) ms, DAN-ve 373 +/- 18 ms, DAN+ve 375 +/- 23 ms, p = 0.05), and corrected QT (QTc) values (normal 423 +/- 15 ms, DAN-ve 430 +/- 20 ms, DAN+ve 435 +/- 24 ms, p = 0.05). Ten diabetic patients fell above our defined upper limit of normal for QTc (greater than mean + 2SD). There was a significant correlation in the DAN-ve group between the QT indices and 24-h RR counts (QT r = -0.38, p less than 0.01; QTc r = -0.40, p less than 0.01). We conclude that there are some small alterations in QT interval length in the steady state in diabetic autonomic neuropathy. The changes appear to be due to autonomic impairment, rather than diabetes per se.

Adult↗

PubMed1990

The clinical features of non-diabetic autonomic failure.

Eighty patients with symptomatic autonomic failure were referred to one physician. A definite diagnosis was made from suggestive symptoms and severely abnormal cardiovascular reflex tests. Just over half had 'primary' autonomic failure (PAF), either associated with Parkinsonism (PD), multiple system atrophy (MSA) or alone (PAF). The remainder had 'secondary' causes, which were empirically classified into five groups--associated with amyloidosis, peripheral neuropathies, carcinomas, as part of a complex clinical picture, and a number of miscellaneous causes. Diabetic patients were excluded from this series. The majority with PD or MSA were referred by neurologists, while most of those with PAF or secondary autonomic failure were referred by physicians. A high proportion of patients with MSA, amyloidosis and carcinomas are now dead. Autonomic failure may present in a variety of ways and to any medical speciality. Awareness of the possibility of an autonomic component in any complex clinical problem is a prerequisite to correct diagnosis and appropriate treatment.

Adult↗

PubMed1989

Vasopressin secretion in diabetic subjects with and without autonomic neuropathy: responses to osmotic and postural stimulation.

1. The release of arginine vasopressin (AVP) after an osmotic stimulus and head-up tilt was assessed in diabetic subjects with and without autonomic neuropathy. 2. Six diabetic subjects with (DAN +ve) and five without (DAN -ve) evidence of autonomic neuropathy and five normal subjects were infused with 5% (w/v) NaCl at a rate of 0.05 ml min-1 kg-1 body weight for 120 min. Blood pressure, heart rate and plasma AVP were measured over this period. 3. Seven DAN +ve, six DAN -ve and six normal subjects were tilted head-up to 45 degrees for 120 min. Blood pressure, heart rate and plasma AVP were measured during the study. 4. Infusion of 5% (w/v) NaCl produced appropriate rises in plasma osmolality and plasma AVP levels which did not differ between the three groups, confirming the normal osmotic release of AVP in the diabetic subjects. 5. During head-up tilt, there were no differences in AVP responses between the three groups, despite a major hypotensive stimulus in the DAN +ve group. 6. We conclude that osmotic release of AVP is normal in diabetes, but that cardiovascular release of AVP is impaired in diabetic subjects with cardiovascular reflex evidence of autonomic neuropathy, reflecting an afferent defect.

Adult↗

PubMed1989

Evaluation of oral cisapride and metoclopramide in diabetic autonomic neuropathy: an eight-week double-blind crossover study.

Nineteen diabetic patients with autonomic neuropathy were enrolled in a double-blind crossover study of cisapride, metoclopramide and placebo. Symptoms were evaluated from diary cards and from assessments undertaken at the end of each eight week treatment period. Measurements of oesophageal transit, gastric emptying and whole gut transit were made before treatment began and at the end of each treatment period. Three patients dropped out early in the study, and the results from 16 patients were analysed. The severity of autonomic neuropathy, judged from cardiovascular reflex tests, correlated with delayed oesophageal transit and prolonged gastric emptying, but abnormal oesophageal transit and gastric emptying were often unrelated to the presence of upper gastrointestinal symptoms. Neither cisapride nor metoclopramide had a statistically significant effect on oesophageal transit, gastric emptying or whole-gut transit, nor was any significant effect on symptoms identified, although a trend towards reduced nausea and vomiting with metoclopramide and reduced epigastric fullness and diarrhoea with cisapride was suggested. Upper gastrointestinal symptoms correlate poorly with objective abnormalities of gastrointestinal motor function in diabetes. In consequence, the symptomatic benefit to be expected from correction of these motor abnormalities remains uncertain.

Adult↗

PubMed1989

Abnormal cardiovascular reflexes in patients with gastro-oesophageal reflux.

Using five non-invasive tests, abnormalities of cardiovascular reflex function were found in 20 of 50 patients with gastro-oesophageal reflux. Abnormalities of pupil cycle time, an index of non-vagal parasympathetic function, were found in only a few patients, implying that the cardiovascular abnormalities observed were not part of a generalised parasympathetic defect. The findings are consistent with the hypothesis that an abnormality of vagal function may contribute to the pathogenesis of gastro-oesophageal reflux.

Adolescent↗

PubMed1989

Cardiac parasympathetic activity during the early hours of acute myocardial infarction.

Cardiac parasympathetic activity was assessed in 21 patients during the first 24 hours of acute myocardial infarction by measuring abrupt beat by beat changes in RR interval, which are expressed as "RR counts". Eleven patients had inferior wall infarction and 10 had anterior wall myocardial infarction. The whole recording period was analysed in 11 patients (five inferior and six anterior), and intermittent hourly periods were analysed in all 21 subjects. Mean RR counts were significantly lower in patients with anterior than inferior infarction, and below the normal range. Although mean heart rates were faster in the group with anterior infarction, there was a dissociation between RR counts and mean heart rate that was consistent with RR interval variability being an independent measure of parasympathetic activity. This study indicates that cardiac parasympathetic activity during acute myocardial infarction can be simply and reliably assessed from continuous electrocardiographic recordings, and it showed significantly lower cardiac parasympathetic activity in patients with anterior infarction.

Adult↗

PubMed1989

Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients.

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.

Adult↗