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Biomedical subjects

I Hutton

Publications and source records attributed to I Hutton.

At least 73 records · Page 4Linked to original sources

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 Significantly fewer tocainide treated patients were withdrawn for other serious ventricular arrhythmias.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.

Anti-Arrhythmia Agents

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.

Catecholamines

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.

Adult

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.

Adrenergic beta-Agonists

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.

Bayes Theorem

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.

Adult

Relation between extent of coronary artery disease and blood viscosity.

Blood viscosity (shear rate 100/s) and its major determinants (packed cell volume, plasma fibrinogen concentration, and plasma viscosity) were measured before coronary angiography in 50 men aged 30-55 and related to the extent of coronary artery disease. Twenty-six men had extensive disease (stenosis of two or three major coronary vessels), and 24 had either stenosis of one vessel or no stenosis. The 26 men with extensive disease had significantly higher mean blood viscosity than those with mild or no disease and 25 healthy controls (p less than 0.001). The increased viscosity was due partly to a higher packed cell volume and partly to a higher fibrinogen concentration; plasma viscosity was not significantly increased. These differences could not be explained by smoking history. These results suggest an association between increased blood viscosity and extensive coronary artery disease in men, which merits further investigation.

Adult

A prospective randomized trial of tocainide in patients following myocardial infarction.

One hundred forty-six patients with recent acute myocardial infarction were grouped at random into those treated with tocainide, an oral analogue of lignocaine, or placebo and followed up for 6 months. In addition to standard investigations, a 24-hour ambulatory taped ECG recording was obtained prior to randomization and thereafter at 2, 8, 16, and 24 hours after discharge. The ECGs were analyzed by means of an automated, computerized reporting system. Forty-two patients had significant ventricular arrhythmias, 10 of whom had effective plasma levels of tocainide compared with 27 patients on placebo (P < 0.005). In the placebo patients with increasing mobilization there was a consistent rise in the number of ventricular ectopic beats per day. There was no such increase in the tocainide patients (P < 0.01). Side effects were few and the incidence of central nervous system side effects was similar in both the tocainide and placebo groups. There was no conclusive evidence of myocardial depression, heart rate and blood pressure being unchanged over the 6-month period. Although ventricular arrhythmias were suppressed, the number of patients in the study was too small to draw conclusions regarding the mortality rate.

Anilides

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.

Acebutolol

Haemodynamic effects of prenalterol in patients with coronary heart disease.

The haemodynamic effects of prenalterol, a new selective beta-1 adrenoreceptor agonist, have been studied in patients with coronary heart disease. The drug was administered intravenously in a dosage of 0.5 to 2.5 micrograms/kg body weight to 20 patients undergoing coronary angiography and to 10 patients with a recent myocardial infarction, who had clinical evidence of left ventricular dysfunction. Left ventricular performance was enhanced in both groups of patients--left ventricular dP/dt (max) increased by 33 per cent and the systolic time intervals, pre-ejection period, and the ratio of pre-ejection period and left ventricular ejection shortened by 28 and 21 per cent, respectively. Cardiac output and stroke volume increased with no change in heart rate nor in left ventricular filling pressure. These results indicate that prenalterol enhances the contractile state of the myocardium without altering heart rate, and suggest that prenalterol could be of value in the management of patients with coronary heart disease, who have impaired left ventricular function.

Adrenergic beta-Agonists

The pharmacokinetics of slow-release procainamide.

Procainamide was given to 20 patients with normal renal function as an i.v. bolus of 500 mg followed by 1.0 or 1.5 g eight-hourly by mouth in the form of a slow release preparation (Durules). 97.6 +/- 27.1 (SD)% of the oral procainamide was absorbed, the absorption half life being 1.54 h. The elimination half life following the oral formulation was 6.0 +/- 0.8 h, compared to a mean of 3.4 +/- 0.4 h following i.v. administration. Elimination half life following i.v. administration was slightly related to acetylator status, being 2.75 +/- 0.9 h in fast acetylators, and 4.4 +/- 2.4 h in slow acetylators. This dependence on acetylator status was not seen in half life following oral administration. Total body clearance, steady state plasma procainamide and N-acetylprocainamide were not significantly dependent on acetylator status, although a few patients who are slow acetylators had unexpectedly low clearance and high steady state procainamide concentrations when given the higher dose.

Biological Availability

Magnesium metabolism in patients with coronary heart disease.

1. The oral absorption of magnesium, its myocardial uptake and exchangeable magnesium have been studied in patients with coronary heart disease and controls using the radioactive isotope magnesium-28. 2. No significant difference in oral absorption or myocardial uptake was found between patients and controls. 3. The exchangeable magnesium per kg body weight was significantly lower in the patients than in the controls.

Adult

Chemotherapy of sarcomas of the limbs by regional perfusion.

From 1957 to 1975, 113 patients with sarcoma of the extremities have been treated with chemotherapy by regional perfusion, either alone or as an adjunct to excisional surgery. Perfusion alone in 54 patients was associated with an early response rate of 83%, but only four patients had complete regression of tumor for longer than three months. When perfusion was followed by immediate or delayed excision, better results were obtained. In 49 Stage I patients and in 24 Stage II patients, cumulative survivals of 66% and 59% were obtained at five years and 66% and 51% at 10 years. The procedure has also been useful in saving functional limbs by converting tumors to operability, and in the palliation of pain and ulceration.

Adolescent