The effects of felodipine in angina pectoris.

The clinical response to felodipine, in addition to a beta-blocker, was evaluated and compared with placebo in this double-blind cross-over study. Twenty patients with exertional angina pectoris completed the study. Felodipine reduced the number of angina attacks and the Glyceryl Trinitrate (GTN) consumption. The median exercise capacity was increased 33% after 4 weeks' felodipine treatment compared with placebo. At maximal exercise, systolic blood pressure and rate pressure product were reduced by felodipine while no change was seen in heart rate or ST-depression. Felodipine reduced both supine and erect blood pressure. The mean supine blood pressure at rest was 138/82 mm Hg after four weeks' placebo treatment compared with 114/71 mmHg after felodipine 5-10 mg b.i.d. Felodipine has overall a modest but significant anti-anginal benefit when combined with a beta-blocker.

Clinical value of Doppler echocardiography in the assessment of adults with aortic stenosis.

Continuous wave Doppler echocardiography was used to study 41 adults with clinically suspected aortic stenosis undergoing cardiac catheterisation. Non-invasive assessment of the severity of stenosis was made before catheterisation using electrocardiograms, chest radiographs, and cross sectional echocardiography in addition to clinical examination and assessment modified, where appropriate, by the result of the Doppler examination. Catheterisation gradients were obtained in 33 patients and correlated well with those obtained by Doppler examination particularly when simultaneous recordings were obtained. All patients with surgically significant stenoses were identified by non-invasive assessment including Doppler examination and overestimation was not found in any patient with a less than significant stenosis. Thus surgery can be recommended in patients with aortic stenosis without the need for previous cardiac catheterisation.

Comparative clinical efficacy of bepridil, propranolol and placebo in patients with chronic stable angina.

A randomised double-blind parallel group study was performed to compare the clinical efficacy of bepridil, a new calcium slow channel blocker, with that of propranolol and placebo in patients with chronic stable angina of effort. Efficacy was assessed objectively by dynamic exercise testing using an upright bicycle ergometer and subjectively by patient documentation of anginal frequency and nitrate consumption. The administration of bepridil resulted in a significant improvement in physical work capacity expressed as calculated maximal oxygen uptake (Vo2 max) and exercise time. This was associated with subjective improvement in terms of reduced anginal frequency. Despite baseline differences in exercise performance and anginal frequency between the three treatment groups, the beneficial effects of bepridil were statistically significant when compared to propranolol. Although minor electrocardiographic changes were noted, no adverse effects were evident when bepridil was prescribed in doses of up to 400 mg/day over a 10 week period.

Acylated streptokinase--plasminogen complex in patients with acute myocardial infarction.

BRL 26921 is the p- anisoyl derivative of the primary streptokinase-human plasminogen complex in which the acyl group is specifically located at the catalytic centre of the enzyme. Doses of BRL 26921 ranging from 5 mg to 25 mg were given intravenously or into a coronary artery to 12 patients with acute myocardial infarction. The complex was well tolerated and produced no serious bleeding. Coronary artery reperfusion was demonstrated angiographically in three patients. In most patients, fibrinogen, plasminogen, alpha 2 antiplasmin and alpha 2 macroglobulin levels fell and the level of fibrinogen degradation products increased acutely post treatment indicating systemic fibrinolytic activation. The degree of this activation was variable but was profound in some. It appeared to be dose related and modified by the presence of streptokinase antibodies. BRL 26921 appears less "selectively" thrombolytic in patients than had been expected from animal models.

Selective reactions in the analytical characterisation of steroids by gas chromatography-mass spectrometry.

The analytical characterization, by GC-MS, of individual compounds in mixtures of steroids, such as occur frequently in biological extracts, is difficult because of the close similarities in structure and properties of many components. The improved separating power of capillary (open-tubular) columns alleviates the problem, but does not solve it fully: for example, the coincidence of retention times of two different compounds may still be virtually complete. Comparative analyses on two distinctively different phases afford one valuable application of selectivity, but may not always be feasible when costly columns are required. Comparative analyses of the sample, before and after effecting its modification by well-defined reactions, are inexpensive and are particularly when selective transformations are used. The use of the microbial enzyme cholesterol oxidase as a selective oxidant for 3 beta-hydroxysteroids (chiefly limited to 4-ene, 5-ene and 5 alpha-types) is illustrated for a model mixture of androstanols related to the boar pheromone (5 alpha, 16-androsten-3 alpha-ol). Retention regularities and changes in mass spectra enhance the reliability of identifications. An exploratory application of cholesterol oxidase in the analysis of minor "polar" sterols in human serum is reported. Most of the known minor sterols are good substrates for the enzyme, and their transformation products yield distinctive GC-MS data, as exemplified for the 7 alpha- and 7 beta-hydroxycholesterols. Another convenient and versatile selective reagent is methaneboronic acid, which yields cyclic esters of suitably constituted diols. These derivatives have shorter retention times (on "non-polar" phases) than the di-TMS ethers, chiefly by virtue of their much lower molecular weights. The mass spectra of cyclic boronates generally show clear molecular ions, also fragmentations that complement the information obtainable from the di-TMS ethers. These features are illustrated for a group of diols and triols of the 5 alpha-pregnane series.

An evaluation of the effect on resting and exercise blood pressure of some first line treatments in hypertension.

Eighteen patients with idiopathic hypertension were studied to assess the anti-hypertensive control, both at rest and during exercise of increasing doses of hydrochlorothiazide, metoprolol and a combination of hydrochlorothiazide and metoprolol. Each active treatment period was given for four weeks with an intervening four week placebo period, with assessments made at 2 to 4 hours and 22 to 24 hours following tablet intake. The results show that the resting systolic and diastolic values for all active treatment periods were significantly different from placebo. During exercise, the systolic blood pressure levels were significantly reduced by all active treatments with the greatest overall reduction being achieved by either metoprolol or the metoprolol-hydrochlorothiazide combination. However, the exercise induced increase in systolic blood pressure was reduced by approximately 25% by both metoprolol and the combination product, when compared to placebo, but not by the diuretic alone.

Evaluation of digitalis in cardiac failure.

Ten patients in sinus rhythm with symptomatic cardiac failure participated in a study investigating the value of digitalis at rest and during dynamic exercise. A haemodynamic profile and left ventricular ejection fraction were measured before treatment, after intravenous ouabain, and after six weeks of maintenance treatment with digoxin. There was no significant change in the haemodynamic profile or in the left ventricular ejection fraction at rest after either glycoside. During exercise there was a significant reduction in left ventricular filling pressure from 39 +/- 3 mm Hg to 34 +/- 3 mm Hg (p less than 0.05) after ouabain and to 33 +/- 3 mm Hg (p less than 0.02) after digoxin. Cardiac index improved from 33 +/- 0.3 1/min/m2 to 4.0 +/- 0.4 l/min/m2 (p less than 0.01) after ouabain and to 3.8 +/- 0.4 l/min/m2 (p less than 0.01) after digoxin. During exercise stroke volume index and stroke work index also improved significantly with both glycosides. This was accompanied by an increase in left ventricular ejection fraction from 29 +/- 2% to 36 +/- 3% (p less than 0.05) after ouabain and digoxin. In this study both intravenous ouabain and maintenance treatment with oral digoxin exerted a modest positive inotropic effect in patients with cardiac failure in sinus rhythm. The haemodynamic benefit, however, was manifest only during exertion.

On-line computer-assisted exercise mapping.

The ability of exercise ECG body surface mapping to detect the presence and distribution of coronary artery disease was investigated in 76 patients presenting with chest pain. The ECG data were recorded from 16 leads regularly placed over the left praecordium. All 16 leads were input simultaneously to a PDP8 computer and 8-second samples were stored at rest, at the termination of symptom-limited exercise, and in the recovery period. ST isopotential surface maps were subsequently constructed. The presence and praecordial projection of ST abnormality were related to the arteriographic distribution of coronary disease. The ECG data were abnormal in 56 of 58 patients with coronary disease and permitted the identification of left anterior descending artery disease in 49 of 53, right coronary artery disease in 39 of 43, and circumflex artery disease in 24 of 30. Mapping separated those with single vessel from those with multiple vessel disease in 91% of patients with coronary disease. These preliminary results suggest that exercise ECG body surface mapping may provide an attractive non-invasive approach to the investigation of patients with coronary disease.

Bayesian analysis of stress thallium-201 scintigraphy.

The variation of the diagnostic value of stress Tl-201 scintigraphy with prevalence of coronary heart disease (CHD) in the population has been investigated using Bayesian reasoning. From scintigraphic and arteriographic data obtained in 100 consecutive patients presenting with chest pain, the sensitivity of stress Tl-201 scintigraphy for the detection of significant CHD was 90% and the specificity was 88%. From Bayes' Theorem, the posterior probability of having CHD for a given test result was calculated for prevalences of CHD ranging from 1% to 99%. The discriminant value of stress Tl-201 scintigraphy was best when the prevalence of CHD lay between 30% and 70% and maximum for a prevalence of 52%. Thus, stress Tl-201 scintigraphy would be an unsuitable diagnostic test where the prior probability of CHD is low, e.g., population screening programmes, and would add little where the clinical probability of having CHD is already high. However, where the prior probability of having CHD is intermediate stress Tl-201 scintigraphy may provide valuable diagnostic information.

Effect of blood pressure control on left ventricular hypertrophy in patients with essential hypertension.

1. Changes in left ventricular structure and function were assessed by echocardiography in 22 patients before and after 9 months blood pressure control. 2. Nine patients had normal baseline echocardiograms (group 1) and 13 had echocardiographic evidence of left ventricular hypertrophy (group 2). 3. Group 2 patients demonstrated significant reductions in posterior wall thickness (P < 0.01), septal wall thickness (P < 0.025) and left ventricular mass (P < 0.005). Only six of the 13 patients showed a reduction of greater than or equal to 3 mm in posterior wall thickness. The remainder showed no alteration or only a slight non-significant reduction. 4. The regression of voltage in some patients but not in others did not appear to be related to initial blood pressure, the extent of the fall in blood pressure or duration of follow-up. It was not possible to say whether any specific therapy was beneficial to regression since most of the patients were on multiple therapy.

Comparison of newer antiarrhythmic agents.

In the past decade a number of new antiarrhythmic drugs ahve been introduced. They have been extensively used in the acute phase of myocardial infarction. Few, if any, long-term comparative trials of these newer agents have been reported. Most of these newer agents have been shown to be able to reduce the frequency of ventricular arrhythmias but not the mortality rate. Beta blockers and some antiplatelet adhesive drugs, however, have reduced the mortality rate following myocardial infarction. There is a need for long-term properly stratified trials of these effective agents.

Serial measurements of left ventricular dimensions by echocardiography. Assessment of week-to-week, inter- and intraobserver variability in normal subjects and patients with valvular heart disease.

The week-to-week, inter- and intraobserver variation in left ventricular echocardiographic measurements has been studied in 10 normal male volunteers and in five patients with stable valvular disease. A two-way analysis of variance showed no statistically significant variation either from week to week or between observers. Furthermore the within observer variation was minimal. Calculation of the coefficient of variation allowed confidence limits to be applied to each of the six ventricular measurements, thus providing ranges of variation in follow-up studies using M-mode echocardiography.

Cholestyramine promotes receptor-mediated low-density-lipoprotein catabolism.

We studied the influence of cholestyramine (24 g per day) on receptor-mediated and receptor-independent low-density-lipoprotein catabolism in five women with heterozygous familial hypercholesterolemia. Cholestyramine lowered the level of circulating low-density-lipoprotein apoprotein by doubling (P less than 0.01) its fractional clearance via the receptor path, but fractional catabolism by the receptor-independent route remained unchanged. Moreover, although the absolute rate of catabolism of the apoprotein was not affected by treatment, the amounts handled by each pathway altered. Catabolism via the physiologically controllable receptor route increased by 71 per cent (P less than 0.05), but there was a 12 per cent drop in clearance by the nonreceptor pathway. These data demonstrate the utility of cholestyramine in promoting low-density-lipoprotein catabolism via its specific physiologic clearance pathway. They also show that heterozygotes with familial hypercholesterolemia can increase the activity of their low-density-lipoprotein receptors when presented with an appropriate stimulus.

The effects of propranolol and acebutolol on left ventricular function and coronary haemodynamics in the conscious dog with myocardial ischaemia.

1 The cardiovascular effects of the beta-adrenoceptor blocking drugs, propranolol and acebutolol, on regional coronary blood flow and left ventricular function have been investigated in the conscious dog with developing myocardial infarction. 2 Propranolol (1 to 1.5 mg/kg) or acebutolol (4 to 5 mg/kg) were administered intravenously 2 to 3 h after occlusion of the left anterior descending coronary artery. 3 Propranolol or acebutolol administration resulted in a relative increase in flow to the ischaemic area of the myocardium, particularly to the subendocardium. 4 Propranolol produced a greater reduction in heart rate and myocardial contractility than acebutolol. 5 These results demonstrate that beta-adrenoceptor blocking drugs reduce myocardial oxygen consumption and increase coronary flow to the ischaemic area of the myocardium after coronary artery occlusion in the conscious dog.