Biomedical subjects
I Hutton
Publications and source records attributed to I Hutton.
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.
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.
Serum oestradiol and ischaemic heart disease--relationship with myocardial infarction but not coronary atheroma or haemostasis.
Elevated oestradiol (E2) levels may be a risk factor for ischaemic heart disease in men, although the mechanisms for the elevation of oestrogen and for its adverse effects remain unclear. We have studied 100 Caucasian males undergoing elective coronary angiography for ischaemic chest pain and measured serum oestradiol, a profile of haemostatic tests, extent of coronary artery disease and evidence of previous myocardial infarction in order to assess any relationships which could explain the effect of elevated serum oestradiol levels. Levels were significantly higher in men with a history of myocardial infarction compared to those without (p less than 0.01), but were unrelated to the extent of coronary disease or to the haemostatic tests. These results suggest that the association of oestradiol with coronary events relates to myocardial infarction, not to atherogenesis, and is not due to any currently measurable alterations of haemostasis. Current beta-adrenoceptor blocker treatment was associated with lower oestradiol and thromboxane B2 concentrations (both, p = 0.06). These incidental findings suggest that further studies of the effects of beta-blockade on oestradiol and thromboxane metabolism are indicated.
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.
Cold pressor induced changes in regional left ventricular wall motion: specific but insensitive for coronary artery disease.
The incidence of new regional abnormalities of left ventricular wall motion induced by a peripheral cold stimulus has been examined in 75 patients who all underwent coronary arteriography. When analysis was carried out from a cine loop display a new wall motion abnormality had a sensitivity of 12% and a specificity of 100% for coronary artery disease. From stroke volume images the sensitivity was 35% and the specificity 87%. It is concluded that cold pressor induced wall motion changes are too insensitive to be a useful method of screening for coronary artery disease.
Haemodynamic effects of a new vasodilator drug, felodipine, in healthy subjects.
The haemodynamic effects of a new vasodilating drug, felodipine, were studied in eight, healthy, male subjects, aged 22-31 years. The drug was given as an oral solution in the dose of 0.15 mg/kg. Thirty-five minutes later further dose of 0.15 mg/kg was administered. Felodipine induced a pronounced decrease in diastolic blood pressure (maximal effect 15 +/- 4 mm Hg) and in the systemic vascular resistance. Cardiac output increased (maximum by 4.2 +/- 0.31/min), due to an increase both in the stroke volume and the heart rate. The maximal increase in the stroke volume (measured from echo cardiograms) and the heart rate were 33 +/- 5 ml and 23 +/- 3 beats/min, respectively. Felodipine caused a significant decrease in the pre-ejection period (23 +/- 3 ms) and an increase in the left ventricular ejection time (29 +/- 3 ms). The quotient PEP/LVET fell from 0.36 +/- 0.01 to 0.28 +/- 0.01. Significant activity of felodipine could be recorded at a plasma level of about 15 nmol/l. When the maximal haemodynamic effects were recorded the plasma level was about 40 nmol/l. After a cumulative dose of 0.30 mg/kg, there was a twofold variation in the maximal plasma level (from 31 to 61 nmol/l). The results of the present investigation are in agreement with previous haemodynamic studies in animals. It would appear that felodipine is a potent arteriolar vasodilator and it might well be of considerable value in the management of patients with hypertension or congestive cardiac failure.
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.
Effects of dazoxiben on transcardiac thromboxane levels and haemodynamics in coronary heart disease.
1 Plasma thromboxane levels were obtained from both the coronary sinus and aorta in patients with stable angina pectoris paced to angina, and in unstable angina patients before and after dazoxiben 100 mg. 2 Although there was a wide range of values in the different groups, dazoxiben significantly reduced plasma thromboxane levels in all patients. 3 Dazoxiben had no adverse effect on coronary and systemic haemodynamics, and atrial pacing time to angina was increased from 245 +/- 41 to 308 +/- 48s (P less than 0.01).
Prophylaxis of primary ventricular fibrillation with tocainide in acute myocardial infarction.
Within six hours of suspected acute myocardial infarction, 791 patients entered a randomised double blind study of combined intravenous and oral tocainide for the prophylaxis of primary ventricular fibrillation. Acute myocardial infarction was confirmed in 559 patients, of whom 278 had received tocainide. The study was terminated on the basis of a sequential statistical analysis which showed that in these patients tocainide was unlikely to reduce the incidence of primary ventricular fibrillation by as much as 50%, primary ventricular fibrillation having occurred in 4% of the tocainide and 2% of the placebo patients. Significantly fewer tocainide treated patients were withdrawn for other serious ventricular arrhythmias. Mortality (1% in the tocainide group and 2% in the placebo group) was low with no statistically significant differences between the active and placebo groups. Unwanted effects of treatment were infrequent and rarely troublesome both in patients with and without acute myocardial infarction. These results suggest that in the dosage used in this study tocainide does not exert an antifibrillatory action in the early phase of acute myocardial infarction.
Management of heart failure.
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The clinical use of inotropes in cardiac failure: dopamine, dobutamine, prenalterol and pirbuterol.
The impaired cardiac performance in patients with congestive cardiac failure may be improved by the introduction of inotropic therapy. Dopamine and dobutamine are both potent cardiac stimulants although their haemodynamic profile is different. Dobutamine would appear to be the more appropriate choice in cardiac failure because of the additional benefit of preload reduction although in the context of severe hypotension dopamine would be preferred. The need for intravenous administration, however, limits their clinical application. In acute studies, the oral agents prenalterol and pirbuterol, are effective in improving myocardial function; pirbuterol mainly due to peripheral vasodilatation and afterload reduction. There are few chronic studies but confirmation of sustained haemodynamic improvement is lacking. This could be due, either to the inexorable deterioration in cardiac function or to a reduction in the beta receptor population available for catecholamine stimulation.
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.
Cardiovascular effects of prenalterol on rest and exercise haemodynamics in patients with chronic congestive cardiac failure.
?The cardiovascular effects of the cardioselective beta, agonist prenalterol have been studied in nine patients with severe chronic congestive cardiac failure and in six patients with left ventricular dysfunction resulting from previous myocardial infarction. In the patients with cardiac failure intravenous prenalterol in a dosage of 1.5 microgram/kg bodyweight increased the cardiac index from 1.8 +/- 0.1 to 21.+/- 0.1 1/min per m2 and the left ventricular ejection fraction from 22 +/- 3 to 28 +/- 3%. There was a modest but significant increase in heart rate from 76 +/- 3 to 87 +/- 4 beats/min. Systemic vascular resistance fell from 2285 +/- 51 to 2041 +/- 534 dynes s-1 cm-5. On exercise, the left ventricular filling pressure fell from 33 +/- 6 to 26 +/- 3 and both cardiac index and stroke index increased by 13% and 16%, respectively. There was no significant change in heart rate or systemic blood pressure. In the patients with left ventricular dysfunction, coronary sinus blood flow increased from 107 +/- 11 to 133 +/- 12 ml/min but the increase in myocardial oxygen consumption was small and not significant (11.6 +/- 1.2 and 14.5 +/- 1.9 ml/min). In all patients there was no evidence that prenalterol was arrhythmogenic.
[New inotropic agents in the treatment of congestive heart failure].
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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.
Comparison of the vasodilator prazosin and the selective beta1 agonist prenalterol on rest and exercise haemodynamics in CHF.
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The combination of nifedipine and propranolol in the management of patients with angina pectoris.
1 A double-blind cross over study was carried out to assess the effects of the combination of nifedipine and propranolol in 25 patients with chronic stable angina pectoris at beta-adrenoceptor blockade. 2 Efficacy was judged objectively by a standardized exercise protocol using a bicycle ergometer and subjectively by patient assessment of anginal attack rate. 3 The combination of nifedipine and propranolol was shown to be effective with an increase in exercise time to angina and an increase in physical work capacity expressed in terms of calculated maximal oxygen uptake (VO2 max). There was an associated reduction in anginal attack rate. 4 The synergistic effect was even more pronounced after reduction in propranolol dosage to 50% of the beta-adrenoceptor blocking dose, reflecting the myocardial depressant effects of beta-adrenoceptor blocking drugs in these patients with coronary heart disease, some of whom had poor left ventricular function.