bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF TIMOLOL ON PLATELET AGGREGATION IN CORONARY HEART DISEASE
Authors: Thaulow Erik , Kjekshus John , Erikssen Jan 
Published: August 2010

ABSTRACTThe immediate effect of beta‐blockers versus placebo in platelet function was studied in ten healthy men one hour after either 40 mg propranolol, 5 mg timolol or placebo was given. Both beta‐blockers had similar platelet effects. They increased the ADP‐threshold in a platelet aggregation test and reduced the plasma level of beta‐thromboglobulin whereas the primary aggregation remained unchanged. Forty‐four patients were given timolol 10 mg twice daily or corresponding placebo medication in a secondary prevention trial after a myocardial infarction. At rest and also immediately after a near maximal exercise test the platelet function was similar on timolol and placebo. During exercise a lower ADP‐threshold and a higher plasma level of beta‐thromboglobulin was observed irrespective of whether the patients received placebo or timolol. Thus, the acute platelet inhibiting effect of timolol observed after a single dose disappeared during chronic timolol treatment. During 24 hours continuous ambulatory ECG monitoring patients on timolol treatment had significantly less arrhythmias than patients on placebo. A general effect on platelets cannot explain this antiarrhythmic effect of timolol during chronic therapy.
EARLY INTRAVENOUS ATENOLOL TREATMENT IN SUSPECTED ACUTE MYOCARDIAL INFARCTION
Authors: Sleight Peter , Yusuf Salim , Peto Richard , Rossi Paulo , Ramsdale David , Bennett David , Bray Colin , Furse Lynette 
Published: August 2010

All patients suitable for beta blockade entering the coronary care units at Oxford and Manchester were studied in a randomised trial to determine whether administration of intravenous atenolol within 12 hours of chest pain reduced infarct size and ventricular arrythmias.Infarct size was measured using cumulative CKMB release and R wave changes from the standard ECG. The preliminary report on the first 214 patients showed prevention of infarction and a mean one third reduction in infarct size in patients with initial definite infarction (Yusuf et al, 1980).Reanalysis of the data when 400 patients were randomised confirmed the observations of the initial analysis. In patients with initial threatened infarction (n = 143), 59 % of control patients developed infarction compared to 37 % in the atenolol treated patients (2p <0.01). In 247 subjects with initial definite infarction, the percentage of the original R wave remaining was 34.5 ± 8 in the atenolol treated subjects (2 p < 0.0001). In 247 subjects with initial definite infarction, the percentage of the original R wave remaining was 34.5 ± 2.1 in the controls compared to 43.4 ± 2.1 in the atenolol treated patients (2p < 0.003).Although bradycardia and hypotension were commoner in atenolol treated subjects (44 and 23 respectively) compared to controls (18 and 8 respectively), this was easily reversible by stopping the drug or using atropine. Inotropic drugs were only needed in 4 atenolol and 2 control subjects. More control patients needed treatment for heart failure compared to the atenolol group in hospital and at discharge (2p < 0.10 and 2p < 0.05).Ventricular arrythmias were recorded using a 24 hour Medilog recorder in 47 atenolol and 47 control subjects. There was a significant reduction in the incidence of R on T (prematurity index < 1.0) ventricular ectopics (41 % AT v 90 % controls 2p < 0.001), a significant slowing of the rate of sustained ventricular tachycardia (mean 144 in AT v 165 beats / min control 2p < 0.02), a significant delay in the prematurity index of VT (1.70 in AT v 1.34 in controls (2p < 0.01) and coupling interval of VT (680 msec in AT v 503 msec in controls 2p < 0.01).In conclusion, early IV Atenolol decreases infarct size and reduces the incidence and severity of ventricular arrythmias in patients with acute myocardial infarctions. A larger study is required to assess if these physiological benefits lead to a reduction in early and long term mortality.
BETA BLOCKADE AND THE SECONDARY PREVENTION OF MYOCARDIAL INFARCTION
Authors: Hampton J. R. 
Published: August 2010

ABSTRACTIn 1965 Snow reported a clinical trial in which treatment with propranolol significantly reduced mortality following myocardial infarction. Unfortunately the design of this trial was inadequate by modern standards, and the results must be discounted. None of the studies published since then have provided convincing evidence that beta blockers are useful following myocardial infarction.Survival after a myocardial infarction depends principally upon the amount of heart muscle that has been destroyed, and it is probably unreasonable to expect any treatment to reduce mortality by more than 20 or 30 %. In patients who survive an infarction for more than 48 hours, the expected fatality rate in the next year is approximately 15 %. To detect a reduction of this mortality to 10%, 2300 patients would be needed in the trial.The analysis of several of the published trials has been made difficult by a lack of data, the failure on the part of authors and journal editors to agree on a common method of presenting results, and disagreement as to whether results should be analysed on an «all patients – intention to treat» basis or by considering only «clinical effectiveness» among patients who remained on treatment. Examples of these problems will be given, together with a suggested scheme for data presentation.The 95 % confidence intervals of all the randomised and double blind studies of beta blockers after myocardial infarction show that by «intention to treat» analysis, none demonstrate a statistically significant reduction in mortality among treated patients. Only the practolol trial was of a reasonable size, but even here total mortality was not significantly reduced; the result is in any case of only theoretical interest. The trials showing a reduction of mortality in association with alprenolol treatment are not convincing, and the stratified trial design of one of these may have given misleading results because of the relatively small number of patients involved.
LIPID LOWERING AND ISCHAEMIC HEART DISEASE
Authors: Oliver M. F. 
Published: August 2010

ABSTRACTThere is a non‐linear discontinuos relationship between serum cholesterol, and LDL cholesterol, with IHD. There is no sound evidence that reduction of serum cholesterol below 200–210 mg/dl will reduce IHD incidence.It has not yet been shown that regression of advanced lesions in middle‐aged men can occur, but regression of cholesterol‐induced atheromatous lesions has been achieved in juvenile monkeys by discontinuing atherogenic diets.While the three major primary prevention trials of lowering raised serum cholesterol were all associated with reduction in non‐fatal mortality from IHD ‐ thereby supporting the lipid hypothesis ‐ all also showed an increase in non‐cardiovascular mortality.It is legitimate to raise doubts about the consequences on normal biological function of ageing cells of reducing cholesterol concentrations over many years.It is probably of little value to reduce raised serum cholesterol concentrations in patients with overt IHD, since their prognosis is largely determined by the extent of myocardial damage sustained and of coexisting thrombogenic tendency.Patients with familial hypercholesterolemia should be vigorously treated with a diet with a PIS ratio 1–5, cholestyramine and perhaps nicotinic acid also. The general population should be advised to reduce fat calories to below 30 per cent of total energy with no more than one‐third from saturated fat.
HEMODYNAMIC AND METABOLIC EFFECTS OF VASODILATORS, NITRATES, HYDRALAZINE, PRAZOSIN AND CAPTOPRIL IN CHRONIC ISCHEMIC HEART FAILURE
Authors: Chatterjee Kanu , Rouleau Jean‐Lucien 
Published: August 2010

ABSTRACTVasodilators like nitrates, hydralazine, captopril and prazosin all improve left ventricular function of patients with chronic ischemic heart failure. The influence of these vasodilator agents on coronary hemodynamics and myocardial oxygen consumption, however may bot be similar. With nitrates and captopril, improved left ventricular function is associated with decreased myocardial oxygen consumption; in contrast, with prazosin or hydralazine no consistent or significant change in myocardial oxygen consumption is observed. Thus, the metabolic cost for the improved left ventricular function with these vasodilator agents is not similar.
ORAL ANTICOAGULATION IN THE SECONDARY PREVENTION OF MYOCARDIAL INFARCTION
Authors: Loeliger E.A. 
Published: August 2010

ABSTRACTEvidence in favour of oral anticoagulant therapy (OAT) in patients suffering from an acute myocardial infarction has been published in 1977 by Chalmers and co‐workers (New Engl. J. Med.297, 1091). For OAT after discharge an International Review Group (IRG) concluded in 1970 that «anticoagulant therapy probably prolongs survival at least over two years, but that benefit is as a rule restricted to patients with a history of angina or previous infarction» (The Lancet,1, 203). Since the IRG finished their analysis, favourable results of four additional comparative studies have been published, three of which were double‐blind and performed in the Netherlands. These four studies demonstrated a beneficial effect of adequate oral anticoagulation. The latest study was performed to assess benefits and untoward reactions of long‐term OAT in the elderly. Results were published in November 1980 (The Lancet, 2,989). Mortality in the 738 patients who entered the trial, all of whom older than sixty years, having survived a transmural infarction, and having been on OAT for at least six months (mean: six years), was lower in patients on active treatment (p=0.016), due to the important difference in recurrent myocardial infarction (RMI). Fifty‐eight RMI's occurred in the placebo group as compared to only twenty in the AC group (p < 0.01). Fatal cerebrovascular accidents were evenly distributed over the two groups, with a preponderance of haemorrhage in patients on active treatment. No fatal extracranial haemorrhage occurred. Incidence and severity of bleeding complications were in agreement with good patient compliance. No significant relationship was found between the recurrence of infarction and either the age of the patient or the length of treatment before entering trial. The steadiness of the widening gap between the mortality and RMI's observed in the two groups indicates that the efficacy of OAT persisted throughout the entire observation period of two years.
COST‐BENEFIT ASPECTS OF POST‐MYOCARDIAL INFARCTION INTERVENTION
Authors: Wilhelmsson C. , Vedin A. , Wilhelmsen L. 
Published: August 2010

ABSTRACTAfter myocardial infarction the mortality during the first post hospital year declines from approximately 10 per cent to 5 per cent during the second year. The rates of non‐fatal recurrencies are similar. Mortality is related to age but not to the same extent to sex. Nonfatal recurrencies are, however, not related to age.Prediction of mortality is feasible by several prognostic models. Factors related to size of myocardial damage stand out as the important secondary risk factors for the years immediately after infarction. Most of these factors are not generally related to the risk of non‐fatal recurrencies. The proportion of cardiovascular deaths is 90 per cent during the first years and declines thereafter.Simplistically it may be said that the prognosis during the first years is related to the extent of the myocardial damage and thereafter primary risk factors become more important.Thus, it seems logical in the short‐term perspective to influence myocardial factors and related arrhythmias and in the long‐term perspective to influence primary risk factors which more likely operate on the vascular factors.Three preventive methods have demonstrated a positive benefit: 1) chronic beta‐blockade, 2) cessation of smoking, 3) by‐pass surgery in certain categories.After careful calculations it may be argued that at least half of the total mortality may be inhibited by beta‐blockade and cessation of smoking. The impact of coronary surgery, lipid lowering and reduction of high blood pressures is more difficult to assess.
Beta–Sympathetic Blockade with Chronotropic Compensation in the Management of Heart Disease
Authors: Geddes J. S. 
Published: August 2010

ABSTRACT.This presentation briefly describes the sympathetic and parasympathetic control of the heart, particularly in relation to coronary vascular effects. Autonomic disturbances following myocardial infarction and their significance are discussed. The influence of the autonomic system in chronic coronary heart disease is considered, particularly in relation to the beneficial effects which may be obtained by the combined use of beta–blocking drugs and cardiac pacing.Nine anginal patients with spontaneous or drug–induced bradycardia received temporary pacing and 27 others had pacemakers implanted. Pain was well controlled in the former group. Long term pacing produced worth–while benefit in 67% of the patients followed for periods up to 6 months, the figure falling to 50% among those followed for 24 months. Eight of the 27 relapsed. Thus, correction of bradycardia by pacing often produced a beneficial long term effect.A second group of 14 patients with ventricular arrhythmias was treated with beta–blocking agents combined with pacing. So far, 10 of these 14 have had their arrhythmias controlled either by the initial or by a modified drug regime.The results indicate that among patients with chronic coronary artery disease, beta–blockade to minimize cardiac sympathetic activity, coupled with pacing to prevent loss of chronotrophic control, often represents an effective combination for the management of refractory angina or arrhythmias.
Experimental Studies of Psychophysiological Factors in Sudden Cardiac Death
Authors: Verrier Richard L. , Lown Bernard 
Published: August 2010

ABSTRACT. Earlier research in the field of sudden cardiac death is reviewed. Such studies were largely oriented towards the provocation of myocardial injury and asystole in normal animals. However, such investigations constitute an inadequate model to describe the clinical appearance of sudden death, where underlying coronary disease is often present and the precipitating event is usually ventricular fibrillation rather than asystole.This report describes a series of studies designed to investigate the processes underlying cardiac vulnerability and the influence upon it of various psychological stresses. It is concluded that the primary mediator of ventricular vulnerability is the sympathetic nervous system. The efferent vagus appears to exert some protective influence against arrhythmias due to adrenergic stimulation. An appropriate clinical strategy for the treatment of malignant arrhythmias would therefore involve attempts to decrease cardiac sympathetic drive whilst at the same time enhancing vagal tone. Treatments are described which aim to bring this situation about by the use of clonidine, morphine sulphate, 1–tryptophan and tyrosine. The use of neurochemical agents in this context appears promising.
Socio–Economic Status as a Coronary Risk Factor: the Oslo Study
Authors: Holme I. , Helgeland A. , Hjermann I. , Leren P. 
Published: August 2010

ABSTRACT. The association between socioeconomic status, measured by a combination of income and education, and CHD mortality has been studied in a cohort of 40–49 year old Oslo men.Socio–economic status was significantly associated with CHD mortality. However, the lowest CHD mortality was found in social status Group III (middle class) and this could not be explained by the risk factor gradients seen among those studied.Although the number of fatalities is small (68 CHD deaths during 4.5 years) socio–economic status seems to be independently associated with coronary risk after adjusting for serum cholesterol, systolic blood pressure and cigarette smoking.
Single–dose pharmacokinetics of labetalol in healthy young men
Authors: Nyberg Gunnar , Hansson Roy , Tietz F. 
Published: August 2010

ABSTRACT. Single doses of labetalol (200 mg i.v. over 5 min, 200 and 400 mg orally) were given to five helthy men on three different occasions. Plasma levels were followed for up to 25 h and blood pressure for 5 h.The elimination half–life was 1.6 to 8.5 h for the first 8 h. The oral bioavailability ranged from 4 to 23%. All doses induced a significant fall in systolic blood pressure at 2 h, the peak effect occurring at 30–120 (mean 63–72) min. After intravenous administration the peak supine blood–pressure fall was significant for both systolic and diastolic blood pressure and occurred 16 min after administration.
Short–term influence of a post–synaptic α–adrenoceptor blocking drug (prazosin) on carbohydrate metabolism
Authors: Waern A. Urban , Berne Christian , Wibell Lars , Lithell Hans 
Published: August 2010

ABSTRACT.Since sympathetic nervous activity is intimately involved in the regulation of hormonal and metabolic responses, it may be assumed that antihypertensive drugs acting on adrenergic receptors will interfere with metabolic control mechanisms.We have therefore evaluated the effect of the selective α1–adrenoceptor blocker prazosin on intravenous glucose tolerance and insulin response in a group of 6 healthy subjects. Ninety minutes after a single oral dose of 2 mg prazosin we observed a significant (p < 0.05) fall in K–value (mean decrease from 1.7 to 1.0), which was accompanied by a blunting of the early insulin response. The acute effects of prazosin closely resemble those observed after 6–8 weeks of treatment with therapeutic doses of prazosin in hypertensive women. It is postulated that the effect of prazosin is mediated by an increase in circulating catecholamines acting on the pancreatic β–cell α2–adrenoceptors, which are responsible for the wellknown inhibitory action af α–adrenergic agents upon the release of insulin.
Haemodynamic effects of β–receptor blockade during acute administration and chronic treatment
Authors: Jensen Henrik AErenlund 
Published: August 2010

ABSTRACT. In early essential hypertension, an increase in cardiac output (CO) is seen in about twothirds of the patients. In established essential hypertension, CO is usually normal or subnormal, while total peripheral resistance (TPR) is increased.Treatment with β–adrenergic blocking agents accentuates these haemodynamic changes; in particular CO is further decreased. Comparison of the effects of β–blockers with and without β1–selectivity and instrinsic activity reveals slight differences in the haemodynamic responses. Although none of the β–blockers normalizes the haemodynamics, satisfactory blood–pressure reduction may be achieved at rest and during exercise with minimal side effects.
Peripheral vasodilatation in the treatment of hypertension. Prazosin compared with hydralazine in patients not responding to β–receptor blockade
Authors: Malmberg Lars , Fagerberg Sven–Erik , Frithz Göran 
Published: August 2010

SUMMARYPrazosin was compared with hydralazine in 39 patients (mean age 49 years), who were already on β–blockade for arterial hypertension. They all had a resting DBP > 100 mm Hg on propranolol 80 mg b i d. They were randomly allocated to prazosin or hydralazine treatment. Blood pressure was measured after 4, 8 and 12 weeks. We noted a significant fall in blood pressure in both groups, in most cases to normotensive levels. Side–effects and other variables of interest are discussed. Together with β–blockade, i e propranolol, both prazosin and hydralazine give good blood–pressure control and no important differences could be found.
Inotropic, chronotropic and dromotropic effects of prenalterol, a new cardiostimulant drug
Authors: Moore E. N. , Aberg G. , Spear J. F. , Hodess A. B. , Herrmann I. , Adler G. 
Published: August 2010

ABSTRACTPrenalterol (H 133/22) is an adrenergic β–receptor stimulator which unlike isoproterenol is both orally active and has a long duration of action. The inotropic, chronotropic and dromotropic effects of prenalterol were investigated in pentobarbital anaesthetized dogs. Prenalterol was found to increase left ventricular maximum dP/dt in a dose–dependent manner up to a dose level of 50 μg/kg. Additional doses resulted in only small further increases in cardiac contractility. Electrophysiological studies were done to compare the effects of prenalterol and isoproterenol on sinus node and ventricular pacemaker function. Complete AV block was produced by electrocauterization of the His bundle. Prenalterol accelerated both ventricular and sinus node pacemakers at doses up to 50 μg/kg. The increase in ventricular rate was greater than the increase in sinus rate following supramaximal inotropic doses of prenalterol, yet no ventricular extrasystoles were ever observed. Similar acceleration of the ventricular and sinus node pacemakers were observed by infusion of isoproterenol. Prenalterol and isoproterenol accelerated AV nodal conduction and ventricular conduction but had little effect upon His–Purkinje conduction. Sinus node reset time was abbreviated as was the functional and effective refractory periods of the atrium and AV nodes.
Pharmacokinetics of prenalterol in healthy subjects and patients with congestive heart failure
Authors: Rönn O. 
Published: August 2010

ABSTRACT1. Prenalterol is rapidly and completely absorbed after oral administration with peak concentrations reached after 30 minutes.2. Prenalterol is rapidly distributed to extravascular tissues after intravenous administration.3. The extent of bioavailability after administration of prenalterol as a solution is about 25% of an intravenous dose. After administration of 20 mg prenalterol in a controlled release preparation the bioavailability is increased to about 45%.4. The half–life of the elimination phase is close to 2 hours.5. 60% of an intravenous dose and 15% of an oral dose is eliminated unchanged by renal excretion. The rest is mainly excreted as the sulphate ester of prenalterol.This presentation deals with the pharmacokinetic properties of prenalterol. The results have been obtained mainly from studies in healthy subjects after acute administration of the drug both intravenously and orally, but some preliminary data on the pharmacokinetics of prenalterol In patients with cardiac failure will also be presented.The studies were performed in six healthy male volunteers 22 to 25 years of age and with a mean weight of 78 kg. The subjects were in good health as judged from clinical and laboratory examinatlons. Prenalterol was administered on occasions separated by at least three days and was given in a randomised order. The subjects arrived at the laboratory after having fasted overnight. A standardised meal was given 3 and 6 hours after drug administration.Prenalterol was administered as prenalterol hydrochloride, a salt freely soluble In water. A single dose of 2.5 mg prenalterol was infused intravenously over 5 min. Oral prenalterol was given as a solution together with 100 ml of water in doses of 2.5, 5.0 and 10.0 mg. Three of the subjects received the intravenous dose and the oral dose of 2.5 mg as tritiated compound.