Biomedical subjects
G C Sutton
Publications and source records attributed to G C Sutton.
Double-blind, randomised, cross-over comparison of oral captopril and enoximone added to diuretic treatment in patients with severe heart failure.
Enoximone (MDL 17043, 150 mg t.d.s.) and captopril (25 mg t.d.s.) were compared as additional treatment to diuretics in 13 patients with severe chronic heart failure in a cross-over, double-blind, and randomised trial. Each treatment was continued for one month. Heart failure was due to cardiomyopathy in six patients and ischaemic heart disease in seven. Exercise capacity and central haemodynamics at rest and on exercise were measured on entry to the study and after each treatment period. Cardiac index at peak exercise time and peak oxygen consumption were increased by both drugs, but there were no differences in these increases between the two drugs after one month's treatment. Minor differences were found in the biochemical and hormonal response to the two drugs. Those patients who improved on captopril also improved on enoximone.
Double-blind comparison of captopril alone against frusemide plus amiloride in mild heart failure.
Captopril alone as therapy for mild heart failure was compared with a combination of frusemide and amiloride in a double-blind randomised crossover trial in 14 patients who had previously been treated with diuretics. Although 10 patients remained stable on captopril alone, 4 patients deteriorated, with the development of pulmonary oedema of breathlessness. All 4 patients had had pulmonary oedema previously, unlike the patients who remained stable. Angiotensin converting enzyme inhibition alone is not sufficient treatment for patients with mild heart failure and a history of overt pulmonary oedema.
A comparison of hemodynamic effects of one-month oral captopril and enoximone treatment for severe congestive heart failure.
A double-blind, randomized, crossover trial was undertaken to compare the effect of enoximone (150 mg, 3 times daily) and captopril (25 mg, 3 times daily) added to conventional therapy with diuretics in the treatment of 13 patients with severe chronic heart failure. Each treatment was continued for 1 month. Heart failure was due to idiopathic dilated cardiomyopathy in 6 patients and coronary artery disease in 7. Hemodynamic measurements were made at rest and during exercise, on entry to the study and after each treatment period. The cardiac index at rest was 1.9 +/- 0.2 liters min-1 m2 (mean +/- 1 standard deviation) and did not change with either drug. Systemic vascular resistance at rest decreased with enoximone (p less than 0.05) and was unchanged with captopril. Systemic vascular resistance at peak exercise was not lowered by either drug. Both drugs caused an increase of cardiac index at peak exercise (p less than 0.04) and a prolongation of exercise time (p less than 0.05). No difference was detected between the hemodynamic response to the 2 drugs after 1 month treatment either at rest or during exercise.
Differences between acute and long-term metabolic and endocrine effects of oral beta-adrenoceptor agonist therapy with pirbuterol for cardiac failure.
The metabolic, hormonal and haemodynamic effects of oral pirbuterol, a new beta 2-adrenoceptor agonist, were studied acutely (n = 19) and after 3 months treatment (n = 11) in patients with severe heart failure receiving chronic frusemide therapy. In the acute study fasted patients (n = 10) showed reductions in plasma K+ (P less than 0.005) and cortisol (P less than 0.01) and increases in plasma glucose (P less than 0.005), insulin (P less than 0.01), lactate (P less than 0.005) and pyruvate (P less than 0.0025). These acute changes were less in unfasted subjects (n = 9). Maximal increase in stroke volume occurred at approximately half the plasma pirbuterol concentration required for maximal effect on plasma insulin. Treatment with pirbuterol for 3 months was associated with sustained increases in stroke volume and fasting plasma glucose and insulin, but there was loss of all other acute metabolic effects. Despite concurrent frusemide and digoxin therapy acute hypokalaemia caused no adverse effects. Hypokalaemia did not occur with chronic pirbuterol administration.
Yellow book, red alert: managing change in the NHS.
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Effects of combined alpha and beta adrenoceptor blockade in patients with angina pectoris. A double blind study comparing labetalol with placebo.
The effects of a combined alpha and beta receptor antagonist, labetalol, were investigated in 10 patients with chronic stable angina pectoris. The optimal dose was determined during an initial dose titration study when the patients were treated with 200 mg, 400 mg, and 600 mg (six patients) of labetalol a day. The effective dose was then compared with placebo in a double blind randomised study. The effects of the drug were monitored with angina diaries, treadmill exercise testing, and 48 hour ambulatory electrocardiographic ST segment monitoring. Plasma labetalol concentrations were measured during each treatment period. The mean effective antianginal dose of labetalol was 480 (SD 140) mg/day given by mouth twice a day. There was a dose related reduction in daytime and nocturnal heart rate, the frequency of pain was significantly reduced by 41%, and exercise duration was significantly increased by 44% with labetalol when compared with placebo. The frequency and duration of the episodes of ST segment depression were significantly reduced by 56% and 73% respectively with labetalol. Adverse effects resulted in a reduction of the dose of labetalol in two patients. Thus labetalol is an effective agent in the treatment of angina pectoris.
Solitary tumour metastasis: a rare cause of right ventricular outflow tract obstruction and sudden death.
The clinical features of a patient presenting with recent breathlessness indicated right ventricular outflow tract obstruction, while echocardiography suggested the presence of tumour in the right ventricle. Before further investigations could be instituted, she died suddenly. Autopsy revealed a haemopericardium secondary to rupture of the right atrium while the right ventricle was found to contain a tumour arising from most of its endocardial surface. Histology showed this to be a poorly differentiated mucous secreting carcinoma similar in appearance to her colonic carcinoma excised 8 years previously. There was no other evidence of metastatic disease.
Incoordinate left ventricular wall motion after acute myocardial infarction. Serial echocardiographic assessment.
Serial simultaneous M mode echocardiograms, phonocardiograms, and apexcardiograms were recorded and digitised in 20 patients with a first myocardial infarction immediately after and two, three, seven, and 56 days after hospital admission. Left ventricular maximum and minimum dimensions, normalised maximum rate of change of dimension during systole and diastole, and three previously defined indices of the coordination of left ventricular wall motion were measured. Incoordinate left ventricular wall motion was detected in all patients but was more pronounced in those with an anterior infarction (15) than in those with an inferior infarction (5). Although on the first three days after admission patients with heart failure (7) were indistinguishable echocardiographically from those without (13), differences became apparent later with an increase in left ventricular dimension and more pronounced evidence of incoordination in those with heart failure. In the first two days after admission patients with full thickness infarcts (14) were indistinguishable echocardiographically from those with partial thickness infarcts (6) despite the former being of much larger size as judged by the measurement of cardiac enzyme activity. Abnormal indices of coordination reverted to normal with time in patients with partial thickness infarctions, whereas only partial reversion of these indices occurred in those with full thickness infarctions. The use of digitised M mode echocardiograms is a sensitive means of detecting and following the evolution of incoordinate left ventricular wall motion in patients with an acute myocardial infarction whatever the position, type, or size of the infarct. Incoordination so detected is, however, quantitatively unrelated to infarct type or size or to the clinical state of the patient.
Bedside haemodynamic monitoring: experience in a general hospital.
Bedside right heart haemodynamic monitoring was carried out on 55 occasions over 18 months in the cardiac care unit of a district general hospital. The technique was used to assist in the management of 27 patients with acute heart failure by helping to select appropriate treatment. Although the catheters were flow guided, insertion and positioning were facilitated by fluoroscopy. The procedure was safe, with one complication arising; technical difficulties occurred in eight cases. Prediction of cardiac output and left ventricular filling pressure by clinical assessment proved to be accurate in only 55% of cases: in patients with acute heart failure there was a tendency to underestimate the cardiac output (25%) and overestimate the left ventricular filling pressure (37%), whereas in patients with chronic heart failure the filling pressure was more accurately estimated (71%). Haemodynamic measurement was often invaluable in selecting and adjusting treatment, particularly in critically ill patients.
Acute haemodynamic comparison of amrinone and pirbuterol in chronic heart failure. Additional effects of isosorbide dinitrate.
A randomised, within patient comparison was made in patients with severe chronic heart failure, to study the acute haemodynamic effects of oral agents which have inotropic and vasodilator properties. A non-glycosidic non-adrenergic positive inotropic agent with vasodilator properties (amrinone) was compared with a beta-agonist which has vasodilator and positive inotropic effects (pirbuterol). To assess whether combined treatment with a venodilator might be advantageous, the effect of adding isosorbide dinitrate was studied. Oral amrinone or pirbuterol were given in random order to each of 13 patients, on successive days, and oral isosorbide dinitrate was added after two-and-a-half hours. Control values before amrinone or pirbuterol were similar, and both drugs increased cardiac index while reducing left ventricular filling pressure, right atrial pressure, and systemic vascular resistance. Heart rate and blood pressure were unchanged. The magnitude of the changes caused by amrinone and pirbuterol were not significantly different. The addition of isosorbide dinitrate caused further falls in left ventricular filling pressure and right atrial pressures, and a fall in heart rate with each drug. Other measurements remained unchanged. Although amrinone and pirbuterol have different pharmacological properties, their acute haemodynamic effects in patients with chronic heart failure are indistinguishable.
Symptoms, haemodynamics, and exercise capacity during long term treatment of chronic heart failure. Experience with pirbuterol.
An open study of long term treatment with an oral beta 2 agonist (pirbuterol 20 mg three times daily) was undertaken in 63 patients with severe chronic heart failure. During three months of treatment 20 (32%) patients died, of whom 16 were taking the drug at the time of death. Mortality was related to initial functional class (New York Heart Association classification: 23% in grade III and 75% in grade IV). Concomitant treatment with digoxin did not affect mortality. The drug was well tolerated by most patients but unwanted side effects necessitated withdrawal of the drug in six (10%). Thirty-five patients were continuing to take the drug after three months, of whom 22 reported symptomatic improvement and only four deterioration. There was a relation between symptomatic improvement and increase in exercise capacity. At initial haemodynamic assessment a single dose of pirbuterol increased the cardiac index by 34% and the stroke index by 21%. Left ventricular filling pressure fell by 23% and systemic vascular resistance by 22%. Haemodynamic reassessment after three months of continuous treatment in 29 patients showed maintained improvement in the group as a whole, although individual variation was considerable. There was no apparent relation between haemodynamic improvement and improvement in exercise duration and symptoms. Severe heart failure has a poor prognosis. Identification of those patients who may derive benefit from treatment with a particular drug is not yet possible.
Ventricular dysrhythmias following intravenous dipyridamole during "stress" myocardial imaging.
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A long-term prevention study with oxprenolol in coronary heart disease.
We carried out a randomized double-blind controlled secondary-prevention trial of oxprenolol over seven years. Forty milligrams of oxprenolol or placebo was given twice daily to 1103 men 35 to 65 years old who had an acute myocardial infarction between 1 and 90 months previously. Overall, there was no difference in mortality or cardiac events between the placebo and oxprenolol groups. The major influence on prognosis was the time at which treatment was started after infarction. In 417 patients in whom treatment was started within four months of infarction oxprenolol increased the six-year cumulative survival rate from 77 to 95 per cent (P less than 0.001). In 274 patients with treatment starting between 5 and 12 months of infarction the survival rate was similar in the two groups, but in 412 patients entered between 1 and 7 1/2 years after their first infarction oxprenolol reduced the six-year survival rate from 92 to 79 per cent (P = 0.002). The increased mortality in this latter group mainly occurred late after withdrawal from active treatment. The value of low-dose oxprenolol in secondary prevention appears to be confined to patients treated relatively soon after myocardial infarction.
Beta 2 adrenoceptor agonists. Pharmacology, metabolic effects and arrhythmias.
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Clinical studies with beta 2 adrenoceptor agonists in heart failure.
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Treatment of chronic heart failure with pirbuterol: acute haemodynamic responses.
Fifty-nine patients with severe chronic heart failure were given pirbuterol, a beta agonist with vasodilator and positive inotropic properties. The acute haemodynamic responses to both single (20 patients) and incremental doses (39 patients) were measured. Pirbuterol increased cardiac index and reduced left ventricular filling pressure and systemic vascular resistance with only small changes in heart rate and blood pressure. Maximal effects were observed at an average of 170 minutes after a single oral dose of pirbuterol. In the incremental dose studies the plasma pirbuterol concentration was found to increase with increasing doses and was related to the magnitude of the haemodynamic response. Pirbuterol was well tolerated, and no drug-related side effects were recorded. Oral pirbuterol clearly improved pump performance in these patients, the haemodynamic changes being consistent with vasodilatation as the dominant mechanism rather than a direct inotropic effect.
Single-dose and dose-response studies with oral pirbuterol, a new beta agonist in chronic heart failure.
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