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Biomedical subjects

T H Pringle

Publications and source records attributed to T H Pringle.

At least 37 records · Page 2Linked to original sources
PubMed1992

Circadian variation of white blood cell aggregation and free radical indices in men with ischaemic heart disease.

The fibrinolytic activity of blood has a circadian variation with increased thrombotic tendency in the morning. This may be a contributory factor to the circadian variation in the time of onset of thrombotic events. However, there has recently been increasing interest to the role of the white blood cells (WBC) and free radicals (FRs) in thrombosis. We have previously reported a circadian variation in WBC aggregation and FR status in normal volunteers. No one has yet studied possible circadian variations in these parameters in patients with stable ischaemic heart disease (IHD). Ten men with stable IHD had blood samples collected at four-hourly intervals from midday until midday the following day. The patients were ambulant until midnight at which time they went to bed and remained in bed until 0800 h. The following were measured on each sample: WBC aggregation, malondialdehyde (MDA) which is a product of lipid peroxidation by FRs; the FR scavengers, plasma thiol (PSH), red cell glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of increased FR activity. WBC aggregation and PSH had significant circadian variations, P < 0.015 and P < 0.001 respectively. The WBC aggregation peak was at 1200 h and trough at 1600 h, the PSH peak was at midnight and the trough at 0400 h. WBC behaviour and FR status influence the flow properties of blood. The largest rise in WBC aggregation occurred from 0800 h to 1200 h; such an increase in aggregation could predispose to microcirculatory occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

The effect of atenolol on dipyridamole 201Tl myocardial perfusion tomography in patients with coronary artery disease.

The effect of atenolol on dipyridamole 201Tl myocardial perfusion tomography was evaluated in 12 patients with angiographically proven coronary artery disease. The patients had dipyridamole 201Tl tomography performed after 7 days treatment with 50 mg atenolol and then repeated after a further 7 days treatment with placebo. The images were interpreted qualitatively by two experienced observers and quantitatively using the Bullseye technique. Qualitative analysis of the images revealed that four of the 12 patients had larger defects on their scans whilst receiving atenolol compared to placebo. The remaining eight patients had defects which were the same size on both treatments. The severity of defects assessed qualitatively was not significantly influenced by atenolol therapy (P = 0.13, McNemera's test). The results obtained with the Bullseye method did not demonstrate significant statistical differences for defect size, degree of reversibility or percentage reversibility whilst the patients were receiving atenolol or placebo (Wilcoxon Rank Sum Test). Atenolol increased the size of perfusion defects on dipyridamole 201Tl tomography qualitatively and quantitatively for four patients in this group of 12 with proven coronary artery disease. Although this did not achieve a high level of statistical significance physicians should be aware that atenolol can influence the images obtained at dipyridamole 201Tl tomography.

Adult↗
PubMed1992

Beta-adrenoceptor antagonists enhance white blood cell aggregation in patients with ischaemic heart disease.

The effects of beta-adrenoceptor antagonists, calcium channel blockers and long acting nitrates on white blood cell (WBC) aggregation were studied in patients with ischaemic heart disease. WBC aggregation was significantly increased by beta-adrenoceptor antagonists (P = 0.011) but was unaffected by either calcium channel blockers or long acting nitrates. Enhanced WBC aggregation promotes microvascular occlusion and damage.

Adrenergic beta-Antagonists↗
PubMed1992

Obstructive left ventricular hypertrophy. Reversibility of outflow tract obstruction by drug therapy.

We report the cases of four patients with secondary left ventricular hypertrophy (three due to hypertension and one to aortic stenosis) in whom Doppler echocardiography showed dynamic left ventricular outflow tract obstruction and marked impairment of diastolic filling. Each patient derived marked symptomatic benefit from treatment with either a beta-blocker (atenolol) or calcium antagonist (verapamil). Repeat Doppler studies in three patients revealed a substantial improvement in systolic and diastolic flow abnormalities. Ventricular outflow tract obstruction should be recognized as occurring in a subgroup of patients with secondary left ventricular hypertrophy, and its presence should be sought by Doppler echocardiography before embarking on therapy. Negatively inotropic or positively lusitropic agents such as beta-blockers and rate-limiting calcium antagonists appear to be logical therapy for this condition.

Aged↗
PubMed1991

Marfan syndrome affecting four generations of a family without ocular involvement.

Thirty eight relatives of a patient with Marfan syndrome were screened for the presence of this disorder. Marfan syndrome was newly diagnosed in living members of 4 generations in this family without evidence of ocular abnormality in any. After screening, 10 relatives were newly diagnosed as having definite, and 5 relatives as having possible, Marfan syndrome. Family screening has drawbacks as well as benefits for the patients. The main benefit is the identification and treatment of previously undiagnosed patients at risk of cardiac complications which are the major cause of mortality. The drawbacks include employment problems created for patients with Marfan syndrome as a direct consequence of our screening programme and the anxiety induced in previously asymptomatic family members who did not realize that they could be at risk. Also, the 4 adult patients with possible Marfan syndrome found it difficult to accept that a definite diagnosis could not be reached after they had been invited to attend a screening programme for a serious genetic disorder. This report illustrates the importance of screening all the relatives of a patient with Marfan syndrome to identify previously undiagnosed cases. However, before screening a family, the physician should be aware that a clear diagnosis may not be reached in all patients, and financial, psychological or social problems may arise as a result of the screening programme.

Adolescent↗
PubMed1988

Characterization of the beta-adrenoreceptors which mediate the isoprenaline-induced changes in finger tremor and cardiovascular function in man.

We have studied the contribution of beta 1- and beta 2-adrenoceptors to the isoprenaline-induced changes in heart rate, blood pressure, forearm blood flow, peripheral vascular resistance, and finger tremor. This was achieved by a comparison of the effects of atenolol 50 mg, ICI 118551 25 mg, propranolol 80 mg, atenolol 50 mg combined with ICI 118551 25 mg, propranolol 80 mg combined with ICI 118551 25 mg, and placebo. Atenolol 50 mg and ICI 118551 25 mg caused similar attenuations in the isoprenaline-induced changes in heart rate and diastolic blood pressure, but the responses after the combination of atenolol and ICI 118551 were similar to those after propranolol 80 mg. There was no difference in the forearm blood flow responses to isoprenaline after atenolol 50 mg and ICI 118551, but atenolol 50 mg did not reduce peripheral vascular resistance compared with placebo. Both responses after treatment with atenolol combined with ICI 118551 were similar to those after propranolol 80 mg. Finger tremor responses to isoprenaline were antagonized by ICI 118551 alone and in combination with propranolol and atenolol but not by atenolol alone, suggesting that the response is beta 2-adrenoceptor-mediated. We conclude that the cardiovascular responses to isoprenaline are mediated by both beta 1- and beta 2-adrenoceptors, whereas the finger tremor response is mediated by beta 2-adrenoceptors.

Adult↗
PubMed1988

The influence of cardiac staffing resources on permanent cardiac pacemaker implantation rates.

In Tayside region, from 1976 to 1986, the number of permanent pacemakers implanted per year more than doubled, with the increase particularly marked over the latter five years. In order to determine the factor(s) which had caused this increase in implantation rates, a retrospective analysis of patients undergoing pacemaker implantation during the period 1981-1986 was undertaken. No change in the number of elderly in the population, age of patients, mode of referral, waiting time before insertion or clinical indications for pacing was observed to account for this change. The advent of ambulatory ECG monitoring may have contributed to this increase, but the appointment of an extra cardiologist in Tayside in 1982 was believed to have been more important. These results suggest that the number of pacemakers implanted in a region is highly dependent on the number of cardiological staff in that region available for their insertion.

Aged↗
PubMed1987

A comparison of the cardioselectivity of five beta-adrenoceptor blocking drugs.

The cardioselectivities of five beta-adrenoceptor antagonists were compared. Six normal subjects received, in a double-blind random order, 200 mg acebutolol, 50 mg atenolol, 10 mg betaxolol, 100 mg metoprolol, 80 mg propranolol, and placebo. All beta-adrenoceptor antagonists produced a similar reduction in exercise tachycardia. Isoprenaline infusions in incremental doses were given. Dose-response curves were constructed and the doses of isoprenaline required to increase heart rate by 25 beats/min (I25), forearm blood flow by 3 ml/100 ml/min (IF3), and finger tremor by 200% (IT200), and decrease diastolic blood pressure by 25 mm Hg (ID25), after each treatment were compared. After propranolol, I25, ID25, IF3, and IT200 were greater (p less than 0.02) than after atenolol, betaxolol, and metoprolol; I25, ID25, and IT200 were greater than after acebutolol. After acebutolol I25, ID25, and IF3 were greater than after atenolol and betaxolol; IT200 was greater than after betaxolol. Atenolol and betaxolol caused less reduction in the isoprenaline-induced changes in blood glucose, plasma potassium, lactate, renin activity, and serum insulin than propranolol. Acebutolol caused less attenuation of blood glucose and plasma lactate, and metoprolol less attenuation of plasma renin activity, than propranolol. It is concluded that acebutolol, atenolol, betaxolol, and metoprolol cause less blockade of beta 2-adrenoceptors than propranolol, and atenolol and betaxolol are more cardioselective than acebutolol.

Adrenergic beta-Antagonists↗
PubMed1987

The assessment in man of the beta-adrenoceptor blocking activity and cardioselectivity of H-I 42 BS, a long acting beta-adrenoceptor blocking drug.

The pharmacokinetic and pharmacodynamic effects of the beta-adrenoceptor antagonist H-I 42 BS were examined in healthy subjects. In an open dose ranging study, H-I 42 BS 50, 100, 200 and 400 mg were given as single oral doses to four subjects. H-I 42 BS 400 mg caused maximum reduction in exercise heart rate (20.4 +/- 1.0%--mean +/- s.d.) at 4 h and still reduced exercise heart rate at 96 h (18.4 +/- 7.2%). Seven subjects received in double-blind, randomised order, single oral doses of H-I 42 BS 50, 100 and 200 mg, atenolol 50 and 100 mg and placebo. H-I 42 BS 400 mg was given in a single blind manner as the last dose of the study. Both H-I 42 BS and atenolol reduced supine and standing heart rate and systolic blood pressure (P less than 0.05) although atenolol had the more marked effect. The maximum percent reduction of exercise heart rate after H-I 42 BS 50 mg was 10.9 +/- 7.1%, after 100 mg was 18.7 +/- 5.8%, after 200 mg was 20.6 +/- 6.4% and after 400 mg was 21.9 +/- 8.2%. H-I 42 BS 400 mg still caused 11.0 +/- 3.5% reduction at 168 h. Atenolol 50 mg caused maximum percent reduction of exercise heart rate of 26.0 +/- 6.0% but did not reduce exercise heart rate after 24 h. The mean peak plasma concentrations for all doses of H-I 42 BS occurred at 5.1 +/- 1.5 h. The plasma elimination half-life was 47.6 +/- 8.1 h. There was a linear correlation between the dose and AUC0-infinity (r = 0.97). The cardioselectivity of H-I 42 BS and atenolol was compared. Six subjects received in double-blind random order H-I 42 BS 100 and 400 mg, atenolol 50 mg and placebo. After each dose, graded infusions of isoprenaline were given until the heart rate increased by 50 beats min-1. Dose-response curves for heart rate, diastolic blood pressure, forearm blood flow and finger tremor were constructed. There was no difference in the dose-response curves for forearm blood flow or finger tremor after H-I 42 BS 400 mg or atenolol 50 mg. Atenolol 50 mg caused more attenuation (P less than 0.01) of the diastolic blood pressure response. These results indicate that H-I 42 BS is a cardioselective beta-adrenoceptor antagonist with a long duration of action in man.

Adrenergic beta-Antagonists↗
PubMed1987

The assessment of the beta-adrenoceptor blocking activity and cardioselectivity of Koe 3290 in normal subjects.

1. The beta-adrenoceptor antagonist activity, cardioselectivity and antilipolytic properties of Koe 3290 were investigated in healthy subjects. 2. Koe 3290 12.5, 25, 50 and 100 mg, atenolol 25, 50 and 100 mg and placebo were given in double-blind randomised order to eight subjects. All doses of both Koe 3290 and atenolol reduced supine, standing and exercise heart rate (P less than 0.02). From 2 to 8 h after administration the exercise heart rate after Koe 3290 100 mg was similar to that for atenolol 50 mg. 3. The cardioselectivity of Koe 3290 and atenolol was compared. Koe 3290 50, 100 and 150 mg, atenolol 50 and 100 mg and placebo were given to six subjects in a double-blind random order. Isoprenaline dose-response curves were constructed for cardiovascular parameters and finger tremor. 4. For doses which were equipotent at the beta 1-adrenoceptor (Koe 3290 100 mg and atenolol 50 mg) atenolol caused less attenuation of heart rate, diastolic blood pressure, forearm blood flow and finger tremor (P less than 0.02). 5. There was no difference in the isoprenaline-induced changes in serum free fatty acids, blood glucose, plasma lactate or potassium after Koe 3290 and atenolol. Koe 3290 attenuated the rise in serum insulin more than atenolol (P less than 0.02). 6. Koe 3290 is an effective beta-adrenoceptor blocking drug in man. It is not as cardioselective as atenolol and does not possess specific antilipolytic properties.

Adrenergic beta-Antagonists↗
PubMed1986

An external automatic device to detect ventricular fibrillation.

An analysis of a micro-processor-based system to detect cardiac arrest rhythms was made in a series of 84 cardiac arrests in 78 patients. The ECG was sensed using 2 external ECG/defibrillator pads applied to the chest wall. In 5 arrests, the initial rhythm was continuous electrical pacing in addition to the cardiac arrest and these were not included in the analysis. Of the remaining 79 arrests there were 15 in which the initial rhythm was ventricular fibrillation and 14 were correctly detected by the system (sensitivity 93%). In the remaining 64 arrests the initial rhythm was not ventricular fibrillation and 62 were correctly identified (specificity 97%). A high specificity is required in any device employing automatic detection of ventricular fibrillation. Continuous electrocardiographic recordings of the cardiac arrests were analysed every 8 to 18 s: of 223 sections showing ventricular fibrillation, 165 were correctly determined by the system, i.e. sensitivity 74%, where the rhythm was not ventricular fibrillation, of the 5002 sections 4953 were correctly detected by the system, i.e. specificity 99%. The percentage accuracy of detection of ventricular fibrillation varied from 25-100% (mean 81%) and for detection of non-ventricular fibrillation from 57-100% (mean 99%) in every 8 to 18 s section of ECG tracing per cardiac arrest episode. Thus the automatic detection of cardiac arrest rhythms is feasible with a high degree of accuracy.

Adolescent↗
PubMed1986

Pharmacodynamic and pharmacokinetic studies on bufuralol in man.

Observations were made in eight subjects who exercised before and at 1, 2, 4, 6, 8 and 24 h after the double-blind oral administration of placebo, bufuralol 7.5, 15, 30, 60 and 120 mg and propranolol 40 and 160 mg. The exercise heart rate remained constant after placebo. Bufuralol 7.5 mg and propranolol 40 mg reduced exercise heart rate up to 6 and 8 h respectively after dosing but bufuralol 15, 30, 60 and 120 mg and propranolol 160 mg were still active at 24 h. The lowest exercise heart rate occurred at 2 h after all active treatments. Bufuralol 60 and 120 mg produced similar reduction in exercise tachycardia as propranolol 40 mg but less than propranolol 160 mg. Plasma levels of bufuralol and its two major metabolites were measured. The peak plasma concentrations of bufuralol occurred at 1.5 h after 7.5 mg and at 2 h after the other doses of bufuralol. In six subjects the plasma elimination half-life of bufuralol was 2.61 +/- 0.18 h and in the other three subjects 4.85 +/- 0.35 h. There was a corresponding longer time to peak concentration and plasma elimination half-life of the two metabolites in these three subjects. These findings show that bufuralol is a potent beta-adrenoceptor antagonist with partial agonist activity. It has a long duration of action and there is bimodal metabolism of the drug in man.

Adrenergic beta-Antagonists↗
PubMed1986

Effects of ICI 141,292 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man.

The beta-adrenoceptor blocking properties and cardioselectivity of ICI 141, 292 were investigated in healthy male subjects. Seven subjects received in random order oral doses of ICI 141,292 20, 50, 100, 200 and 400 mg, atenolol 50 and 100 mg and placebo. ICI 14 292 had no effect on supine heart rate which was reduced by atenolol 100 mg. ICI 141,292 50, 100 and 200 mg had no effect on standing heart rate which was reduced by 400 mg at 2 h. Both doses of atenolol caused greater reductions. The maximum percent reduction of an exercise tachycardia after ICI 141,292 200 mg (23.9 +/- 3.7%) and 400 mg (24.3 +/- 5.2%) were similar to atenolol 50 mg (27.3 +/- 4.7%) but less than atenolol 100 mg (30.8 +/- 2.9%) (P less than 0.02). Six subjects received in random order single oral doses of ICI 141,292 100, 200 and 400 mg, atenolol 50 mg, propranolol 40 mg and placebo. Following each dose each subject received graded infusions of isoprenaline sulphate until heart rate increased by 40 beats min-1. Dose-response curves were constructed for the changes in heart rate, finger tremor, blood pressure and forearm blood flow produced by each infusion. At the 4 micrograms min-1 dose of isoprenaline, ICI 141,292 200 mg caused more attenuation than atenolol 50 mg but less than propranolol 40 mg in the changes of heart rate, diastolic blood pressure and finger tremor (P less than 0.02). ICI 141,292 400 mg caused more attenuation of the changes of all parameters than atenolol 50 mg but less attenuation of the changes in diastolic blood pressure and finger tremor than propranolol 40 mg (P less than 0.02). These results indicate that ICI 141,292 is a cardioselective beta-adrenoceptor antagonist with partial agonist activity.

Adrenergic beta-Antagonists↗
PubMed1986

Automatic detection of cardiac arrest rhythms prior to automatic external cardiac defibrillation.

The detection and correction of ventricular fibrillation at the earliest time after its onset is essential to ensure long-term survival. During successive cardiac arrests the rhythms occurring were sensed by using disposable pre-gelled ECG defibrillator pads placed in the anterior-anterior position. Simultaneously with the treatment, the arrest rhythms were analyzed continually every 8 to 18 seconds by a microprocessor system. This system sampled digitally the electrocardiogram, and the algorithm looked for absence of the isoelectric segment, irregular energy density spectrum, and irregular wave shape. The analysis was displayed visually as ventricular fibrillation (VF) or non-VF, and simultaneously the ECG and system's analysis were recorded on tape. Later, the system's interpretation of the rhythm was compared with the ECG record. There were 46 males and 32 females. Their ages ranged from 14 to 85 years, with a mean of 63 years. Twenty-nine patients had sustained an acute myocardial infarction. In the remaining 49 patients, there were a variety of causes for cardiac arrest, including heart failure, vasovagal syncope, cardiomyopathy, and postoperative cases. We report in detail the process and results.

Journal Article↗
PubMed1983

The systemic and coronary haemodynamic effects of felodipine in patients with coronary heart disease.

The cardiovascular effects of felodipine, a new arteriolar vasodilator, were studied in 22 patients with coronary heart disease. There were significant falls in blood pressure and systemic vascular resistance of 16 and 38% respectively (P = 0.001), thus affecting after-load. Cardiac index and stroke index increased by 35 and 12% respectively. There was reflex tachycardia--from 75 +/- 3 to 85 +/- 3 b.p.m. (P = 0.005). Coronary sinus blood flow increased from 134 +/- 9 to 191 +/- 17 ml/min (P less than 0.005) and myocardial arterio-venous oxygen difference narrowed from 12.1 +/- 0.5 to 9.0 +/- 0.4 vols% (P less than 0.001) indicating less oxygen usage. With the heart rate held constant by atrial pacing, cardiac index and stroke index increased by 30 and 26% (P less than 0.001), whilst systolic blood pressure and systemic vascular resistance fell by 20 and 29% (P less than 0.001). This would suggest that the improved haemodynamics were largely secondary to after-load reduction.

Adult↗
PubMed1983

Prolongation of the QT interval during therapeutic starvation: a substrate for malignant arrhythmias.

Retrospective examination of weekly electrocardiograms of 13 patients on zero calorie intake for 97 +/- 25.4 d (mean +/- standard deviation) for morbid obesity demonstrated a significant progressive reduction in QRS voltage by the seventh week. There was a significant prolongation of the QTc interval in the group during the eighth week and in seven patients the QTc had lengthened beyond normal by the end of the fast. The importance of these changes is illustrated by one patient with QTc prolongation who sustained two cardiac arrests due to torsade de pointes. We recommend regular in-patient electrocardiographic monitoring for obese patients on therapeutic starvation.

Adult↗