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Adrenergic beta-blocking agents were given to 7 patients with advanced congestive cardiomyopathy who had tachycardia at rest (98 plus or minus 13 beats/min). The patients were on beta-adrenergic receptor blockade for 2 to 12 months (average 5-4 months). One patient was given alprenolol 50 mg twice daily and the other patients were given practolol 50 to 400 mg twice daily. Virus infection had occurred in 6 of the patients before the onset of symptoms of cardiac disease. All patients were in a steady state or were progressively deteriorating at the start of beta-adrenergic receptor blockade. Conventional treatment with digitalis and diuretics was unaltered or reduced during treatment with beta-blocking agents. An improvement was seen in their clinical condition shortly after administration of the drugs. Continued treatment resulted in an increase in physical working capacity and a reduction of heart size. Noninvasive investigations including phonocardiogram, carotid pulse curve, apex cardiogram, and echocardiogram showed improved ventricular function in all cases. The present study indicates that adrenergic beta-blocking agents can improve heart function in at lease some patients with congestive cardiomyopathy. Furthermore, it is suggested that increased catecholamine activity may be an important factor for the development of this disease, as has been shown in animal experiments.

The hemodynamic effects of 75 to 225 μg/kg prenalterol (PNL) intravenously were studied at rest and during exercise in eight patients with chronic congestive heart failure (CHF) after myocardial infarction (three patients), valvular surgery (three patients), and congestive cardiomyopathy (two patients). All had New York Health Association functional class III and IV CHF and were receiving digitalls and diuretics. With PNL at rest, left ventricular filling pressure (LVFP) fell from 17 to 12 mm Hg, cardiac index (CI) rose from 2.1 to 2.9 L/min/m 2 , heart rate (HR) increased mildly, systemic vascular resistance (SVR) decilned moderately, and peripheral arterial pressure was unchanged. During PNL exercise compared with control, LVFP rise was less and CI, HR, and SVR responses were similar; dyspnea and angina were reduced in most patients. The eight patients were then given PNL orally, 30 to 200 mg/day, versus placebo for 6 days with comparative evaluation by echocardiogram, systolic time intervals (STI), exercise test, and continuous ECG. With PNL orally five of eight patients improved symptomatically, ejection fraction increased from 0.44 to 0.53, and STI preejection period shortened by 10 msec, without change in resting HR or systemic arterial blood pressure. The incidence of ventricular premature beats was not increased. PNL orally vs placebo exercise capacity increased 10%. Thus PNL may be of value for long-term CHF treatment in addition to conventional therapy.

Twenty-eight patients with heart failure caused by congestive cardiomyopathy, which had been diagnosed according to the criteria of Goodwin and Oakley, were treated with beta-blocking agents for six to 62 months, except for four patients who died within two months. Repeated non-invasive investigations were performed before and during treatment as well as exercise tests and chest x-rays. The echocardiographic and pulse curve findings indicated an improvement in systolic and diastolic myocardial function. The ejection fraction increased from 0.32 +/- 0.02 to 0.42 +/- 0.04, and the third heart sound amplitude and rapid filling wave were significantly reduced. The functional classification improved in 15 patients while in 12 patients it remained unchanged and in one it deteriorated. During follow-up, 10 patients died, most of them suddenly. The mortality was lower than expected in this severely ill group of patients. The beneficial effect of chronic beta-blockade in patients with congestive cardiomyopathy suggests that catecholamines are involved in the pathogenesis of congestive cardiomyopathy, and that patients with congestive cardiomyopathy may have inappropriate sympathetic cardiac stimulation which can be reduced by chronic beta-blockade. It is suggested that beta-receptor blockade should be added to conventional treatment with digitalis and diuretics in all patients with severe myocardial failure caused by congestive cardiomyopathy.

24 patients with congestive cardiomyopathy (group I) were compared with a group of 13 controls with similar clinical findings and myocardial function who were selected retrospectively (group II) . All patients received digitalis and diuretics, but group I patients received beta-blockers as well. The survival-rate in group I patients (83%, 66%, and 52% after one, two, and three years respectively) differed significantly from that in group II subjects (46%, 19%, and 10%, respectively). This finding is supported by the demonstration that beta-blockade improved myocardial function in group I subjects. It is therefore suggested that beta-blockade prolongs survival in patients with congestive cardiomyopathy.

To evaluate the short- and long-term effects of beta-adrenergic blockade (metoprolol) as well as the reaction to withdrawal and readministration of metoprolol in severe heart failure, 33 patients (25 men and eight women; mean age, 47.6 +/- 14.0 years) with dilated cardiomyopathy were studied by right and left heart catheterization, right ventricular biopsy, two-dimensional and Doppler echocardiography, and external pulse recordings. Twenty-six of 33 patients survived more than 6 months, and 24 of the 26 patients improved their functional class (from mean 3.3 to 1.8, p less than 0.0001). These 24 patients were subjected to withdrawal of metoprolol until the number of symptoms increased and deterioration occurred as observed noninvasively (group 1, n = 16), whereas the eight patients did not deteriorate during a 12-month period (group 2). During long-term treatment with metoprolol, there was an increase in ejection fraction from 0.24 to 0.42 (p less than 0.0001), whereas there was a decrease in the left ventricular (LV) end-diastolic dimension (from 7.3 to 6.4 cm, p less than 0.0001), in the grade of mitral regurgitation (from 1.7 to 0.4, p less than 0.0001), and in the grade of tricuspid regurgitation (from 0.6 to 0.05, p less than 0.007). There was a decrease in pulmonary wedge pressure (from 23.8 to 10.7 mm Hg, p less than 0.0001), LV end-diastolic pressure (from 24.1 to 13.4 mm Hg, p less than 0.002), and systolic vascular resistance (from 1,782 to 1,499 dynes/sec/cm, p less than 0.04). There was an increase in systolic blood pressure (from 116 to 132 mm Hg, p less than 0.003), cardiac index (from 2.17 to 2.58 l/min/m2, p less than 0.005), and LV stroke work index (from 31 to 65 g.m/m2, p less than 0.0001). During withdrawal of metoprolol, the heart rate and left atrial dimension increased (p less than 0.0001), whereas ejection fraction decreased (p less than 0.0001). The 12 (of 16) patients in group 1 who survived the withdrawal period had metoprolol readministered, and subsequently, ejection fraction increased (from 0.23 to 0.33, p less than 0.002). Patients had a low number of ventricular beta-adrenergic receptors compared with healthy control subjects (30.3 +/- 2.9 vs. 97.4 +/- 8.7 fmol/mg protein, p less than 0.001), but long-term treatment with metoprolol caused a moderate up-regulation (from 30.3 +/- 2.9 to 49.0 +/- 7.1 fmol/mg protein, p less than 0.05), which may facilitate a more normal response to sympathetic stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

A total of 1395 patients aged 40 to 74 years were included in a double blind trial with the beta 1 selective blocker metoprolol in suspected acute myocardial infarction. Metoprolol was given intravenously (15 mg) as soon as possible after admission to hospital followed by 200 mg daily for three months. A placebo was given in the same manner. The severity of chest pain in the acute phase was calculated by recording the number of injections of analgesics given and the time from the start of blind treatment to the time when the last analgesic was given (duration of pain). The patients receiving metoprolol were given a lower mean number of injections of analgesics during the first four days and after randomisation than those receiving a placebo. The estimated duration of pain was shorter in the metoprolol group than in the placebo group. These effects were related to the initial heart rate, the initial systolic blood pressure, and the final site of the infarct as determined electrocardiographically. Thus metoprolol given in the acute phase of suspected or definite myocardial infarction appears to reduce the severity of chest pain.

Systolic time intervals and the a/H ratio were recorded in 20 patients with uncomplicated acute myocardial infarction over a period of five days. The initial high heart rate and systolic blood pressure and the short PEP and ICT indicating a sympathetic overactivity were spontaneously normalized during the first week of infarction. LVET was reduced indicating a fall in stroke volume and the a/H ratio was unchanged at the high levels suggestive of elevated preload or LVEDP. In 10 patients with acute myocardial infarction and recurrent chest pain recordings on noninvasive parameters were made before and 30 min after intravenous injection of practolol. In addition, 7 patients with chest pain, classified as acute myocardial infarction, were given practolol. The average dose of practolol was 17.9 mg ranging from 5 to 30 mg. An almost immediate and pronounced relief of pain was observed in all patients and no signs of impaired left ventricular function appeared. The product of systolic blood pressure and heart rate was decreased by practolol and the PEP and the ICT were prolonged to normal values while no changes were seen in LVET and a/H ratio. On 126 occasions practolol was given in dosages ranging from 5 to 30 mg (mean 8 mg) to 75 patients with acute myocardial infarction and recurrent chest pain. A satisfactory pain relief was seen on 108 occasions. It is suggested that an inappropriate sympathetic overactivity is an important factor in provoking recurrent chest pain in acute myocardial infarction. Administration of the beta-adrenergic blocking agent practolol resulted in pain relief due to reduction of heart work and in severity of myocardial ischemia. The beta-blocking agent was well tolerated in the present study. Continuous beta-blockade during the whole hospital stay to patients with acute myocardial infarction seems to be a very attractive therapy in order to preserve the ischemic myocardium and limit the size of infarction.

The acute haemodynamic effects of prenalterol 75-225 micrograms/kg i.v. were studied at rest and during exercise in the supine position in 12 patients with chronic congestive heart failure secondary to myocardial infarction (6 pts), chronic valvular disease with valvular replacement (4 pts), ischaemic cardiomyopathy (1 pt) and post myocarditis (1 pt). In 5 of the 6 AMI patients the effect of prenalterol on myocardial oxygen consumption at rest was measured. Pulmonary artery end-diastolic pressure decreased significantly from 17 to 10 mm Hg at rest and from 31 to 21 mm Hg during exercise. Resting heart rate increased from 78 to 90 at rest but was unchanged during exercise. MVO2 in the 5 patients was unchanged or lower in 4 patients and increased in one in whom angina developed after prenalterol. In general, dyspnoea and angina during exercise were less pronounced after prenalterol. The calculated triple product was lower after prenalterol, especially during exercise, indicating lower myocardial oxygen consumption and probably less myocardial ischaemia.

The variability of chest pain is described in 389 patients with acute myocardial infarction. Whereas 17% were free from severe pain after arrival in hospital, 11% required more than 10 analgesic injections. In 27% of the series analgesics were given more than 24 h after arrival in hospital. Predictors for the severity of chest pain were the rate-pressure product and degree of chest pain soon after arrival in hospital as well as electrocardiographic signs of myocardial infarction at entry. Patients with more severe chest pain had a higher 2-year mortality rate and a higher incidence of ventricular fibrillation and congestive heart failure during hospitalization.

In a double-blind trial, 30 patients with suspected acute myocardial infarction with onset of symptoms within the previous 24 h were randomized to treatment with 10 mg nifedipine/placebo orally 4 times a day during hospitalization. All patients were given 15 mg metoprolol intravenously 20 min after the initial administration of nifedipine/placebo, and thereafter, 50 mg 4 times a day. The combined therapy resulted only in moderate changes in systolic blood pressure and heart rate compared with metoprolol alone. Three of the 15 patients in the nifedipine group versus 2 of the 15 in the placebo group were withdrawn because of hypotension and/or bradycardia. None was withdrawn because of congestive heart failure or A-V block. It is concluded that the combination of nifedipine and metoprolol seems to be a relatively well-tolerated combination in acute myocardial infarction.

The haemodynamic effects of a new beta 1-receptor agonist, 1-(4 hydroxyphenoxy) 3-isopropylamino-2-propanol, were studied in 25 patients after acute myocardial infarction using non-invasive methods. The drug caused an increase in systolic blood pressure and pulse pressure, without change in diastolic blood pressure, and a slight increase in heart rate and reduction in the pre-ejection period. These changes were greater in patients without a history of left heart failure. It is suggested that this cardioselective drug possesses positive inotropic activity but only slight positive chronotropic activity. The substance has been further investigated as a possible antidote to unwanted cardiac side effects of the cardioselective beta-blocker, metoprolol. The changes in the cardiovascular dynamics caused by metoprolol in patients with acute myocardial infarction were promptly reversed by this new beta 1-agonist. With its positive inotropic properties and its efficacy in reversing the effects of a cardioselective beta-blocker, the drug is a potentially useful pharmacological agent to support an acutely depressed myocardium in patients on beta-blocking agents.

Prognosis in congestive cardiomyopathy (COCM) with marked dilatation and heart failure is poor. A low rate of spontaneous recovery was observed. A high level of circulating catecholamines is often found, which may explain the common finding of resting tachycardia. An early series of COCM patients with tachycardia responded surprisingly well when chronic beta-blockade was added to the conventional treatment of failure. Later, even patients without tachycardia were included with a period of placebo preceding beta-blocker treatment in order to exclude patients with spontaneous recovery. Acute beta-blockade was surprisingly well tolerated, possibly because the reduction in contractility was compensated for by an increase in myocardial compliance. After long-term beta-blockade, improvement was observed after 6 months and further improvement was seen after 24 months. In patients improving functionally, there was reduction in heart size and left ventricular end diastolic diameter and increase in working performance. For the whole group, there was a decrease in rapid filling wave in apex cardiogram, reduction in third heart sound and increase in ejection fraction. Changes in the reverse way were seen in these three variables after beta-blocker withdrawal and relapse into heart failure occurred in 6/15 patients. Changes in diastolic function may be an early important effect of beta-blockade in COCM. Increase in survival was seen when beta-blocker-treated patients with COCM were compared to well matched COCM controls. It is suggested that increased sensitivity to sympathetic stimulation contributes to the pathogenesis in some patients with COCM and that improvement in myocardial function explains prolonged survival.

In a double blind study of metoprolol in the treatment of suspected acute myocardial infarction 698 patients (study group) received metoprolol and 697 a placebo (control group). Metoprolol was given in an intravenous dose of 15 mg as soon as possible after admission to hospital followed by 50 g by mouth four times a day for two days and thereafter 100 mg twice a day for three months. A placebo was similarly given. Congestive heart failure occurred in a similar percentage of patients in both the study (27%) and the control groups (30%). Its severity was estimated by calculating the total dose of frusemide given during the first four days in hospital. Less frusemide was given to patients treated with metoprolol compared with those given a placebo in the total series. An appreciably lower total dose of frusemide was given to patients included in the trial less than or equal to 12 hours after the onset of pain and treated with metoprolol compared with a placebo, while no difference was seen among patients treated later. The initial heart rate, systolic blood pressure, and infarct site affected the results.

The influence of naloxone on the effects of high frequency transcutaneous electrical nerve stimulation in angina pectoris induced by atrial pacing was studied in 11 patients with severe coronary artery disease. The patients were catheterised and treated with transcutaneous electrical nerve stimulation on two occasions, double blind and in random order, with a single intravenous dose of saline or with a single intravenous dose of 50 mg naloxone. Treatment with transcutaneous electrical nerve stimulation increased tolerance to pacing and significantly improved lactate metabolism with placebo and with naloxone. The positive effects of transcutaneous electrical nerve stimulation were thus reproducible and not reversed by single intravenous doses of naloxone. The results indicate that the effects of transcutaneous electrical nerve stimulation on the heart are not mediated by beta endorphin but they do not exclude activation of more short-acting opioids such as delta or kappa receptor agonists (met-enkephalin or dynorphin or both) because naloxone has a low affinity for these receptors. Non-opioid mechanisms may also be important.

A single-blind study of prenalterol 20-200 mg daily in a slow-release tablet preparation and a placebo was performed in 15 patients with moderate to severe congestive heart failure (NYHA II-IV) to evaluate the haemodynamic and clinical effects of oral prenalterol. Non-invasive parameters in the measurement of cardiac output, stroke volume, pre-ejection period index (PEPI), PEP/LVET ratio, ejection fraction and mean Vcf were significantly improved, indicating beneficial effects of prenalterol on cardiac contractility. Systolic blood pressure, heart rate and rate-pressure product were slightly increased at rest but were considerably lower during exercise. Arrhythmogenecity was not seen in the patients studied. Subjective improvement was noted in the majority of patients as evidenced by a decreased frequency of dyspnoea, fatigue and angina. Unwanted effects, such as palpitations and transmitted arm pulsations, were transient and disappeared with dose adjustment, while the inotropic effect of the medication was maintained. The clinical response appeared to be sustained for up to 2 weeks of treatment, indicating non-development of tachyphylaxis.

In 585 patients with a first acute myocardial infarction the maximum activity of heat stable lactate dehydrogenase (EC 1.1.1.27) was correlated with mortality at three months. The patients participated in a double blind trial with metoprolol in acute myocardial infarction. In all patients not taking a beta blocker a highly significant correlation was found, but this was not evident in those who were. When patients with anterior or inferior infarctions treated with a placebo were analysed separately the correlation remained, as it did when the patients who were alive on the fourth day after the onset of pain were analysed separately. No correlation was observed between enzyme activity and three month mortality in these subgroups if only patients treated with metoprolol were included. In a subsample of only 171 patients it was found that the maximum activity of creatine kinase (EC 2.7.3.2) and creatine kinase subunit B did not correlate with three month mortality regardless of treatment. Thus it is concluded that when a sufficiently large number of patients are investigated there is a highly significant correlation between the enzymatic estimation of infarct size and early mortality in acute myocardial infarction. This relation did not persist when patients treated with beta blockade were analysed.

The pain-relieving effects of transcutaneous electrical nerve stimulation (TENS) were investigated in patients with severe angina pectoris first with respect to systemic and coronary hemodynamics and myocardial metabolism during pacing-induced angina and second in a controlled long-term study. Two series of patients with severe angina pectoris (NYHA class III to IV) were studied (13 patients in the pacing study and 23 in the long-term study). In the pacing-induced angina study there was increased tolerance to pacing (142 +/- 23 compared with 124 +/- 20 beats/min tolerated, p less than .001), improved lactate metabolism (2 +/- 36% compared with -18 +/- 43%, p less than .01), and less pronounced ST segment depression (2.3 +/- 1.1 compared with 2.9 +/- 2.6 mm, p less than 0.05) with TENS. In the long study the effects of TENS were measured by means of repeated bicycle ergometer test, frequency of anginal attacks, and consumption of short-acting nitroglycerin. TENS was used regularly for 1 hr three times per day. The TENS treatment group had increased work capacity (637 +/- 308 vs 555 +/- 277 W . min, p greater than .001), decreased ST segment depression (2.3 +/- 1.1 vs 3.6 +/- 1.6 mm, p less than .001), reduced frequency of anginal attacks (p less than .05), and reduced consumption of short-acting nitroglycerin per week (p less than .05) compared with the control group. The observed effects were mainly due to decreased afterload resulting from systemic vascular dilatation.

In 585 patients having an acute myocardial infarction for the first time the relationship was investigated between estimated infarct size and the incidence of ventricular fibrillation and treated ventricular tachycardia during hospitalization. The size of the infarct was estimated from analyses of heat stable lactate dehydrogenase (LD) (EC 1.1.1.27.) in serum collected every 12 hr for 48-108 hr. All patients participated in a double-blind comparison of the beta 1-selective blocker metoprolol with placebo in suspected acute myocardial infarction. A correlation was observed between the enzymatically estimated infarct size and the incidence of ventricular fibrillation and treated ventricular tachycardia in patients on placebo (P less than 0.001), while this could not be demonstrated in patients on the beta-blocker (P greater than 0.2). In placebo treated patients there was a correlation between the maximum heat stable LD activity and early ventricular fibrillation (P = 0.034), late ventricular fibrillation (P less than 0.001), primary ventricular fibrillation (P = 0.002) as well as secondary ventricular fibrillation (P = 0.034). It is concluded that there seems to be a relatively strong correlation between the final size of the infarction and the occurrence of severe ventricular arrhythmias. Treatment with beta-blockade appeared to disturb this correlation.

During a double-blind trial in which patients with suspected myocardial infarction received metoprolol or placebo, we analyzed the occurrence of ventricular tachyarrhythmias. Metoprolol (15 mg intravenously) was given as soon as possible after admission, and thereafter 200 mg was given daily for three months. Antiarrhythmic drugs were given only for ventricular fibrillation and sustained ventricular tachycardia (greater than 60 beats per second). Definite acute myocardial infarction developed in 809 of the 1395 participants, and probable infarction in 162. Metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia. However, there were 17 cases of ventricular fibrillation in the placebo group (697 patients) and only 6 in the metoprolol group (698 patients, P less than 0.05). During the hospital stay significantly fewer patients receiving metoprolol (16) than placebo (38) (P less than 0.01) required lidocaine. In a separate analysis of 145 patients, metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia during the first 24 hours of treatment. Despite a lack of effect on less serious ventricular tachyarrhythmias, metoprolol had a prophylactic effect against ventricular fibrillation in acute myocardial infarction.

In 1350 patients with suspected acute myocardial infarction, serum potassium was analysed in the emergency ward. The effect of metoprolol was compared with placebo in a double-blind randomized trial. Metoprolol increased serum potassium from 4.11 +/- 0.02 mmol/l to 4.27 +/- 0.02 mmol/l (P less than 0.001) during the 1st day after hospital admission, whereas serum potassium levels remained fairly constant in patients given placebo during the same time (4.11 +/- 0.02 to 4.14 +/- 0.02 mmol/l; P greater than 0.2). Similar results were obtained when analysing patients with a confirmed myocardial infarction separately. The effects appeared homogeneously distributed in subgroups related to sex, clinical history, infarct site, infarct size and delay time from onset of symptoms to start of treatment. We conclude that early treatment with the beta-1-selective blocker metoprolol in patients with suspected acute myocardial infarction increases serum potassium.

This study reports the mortality over a 5-year-period determined a double-blind trial, which evaluated the effect of early intervention with metoprolol in suspected acute myocardial infarction. In all, there were 1,395 randomized patients, 698 and 697 of whom were allocated to metoprolol 200 mg daily and placebo treatments, respectively, for the first 3 months. Thereafter, the two groups were treated in a similar fashion implying beta-blockade to a majority. Within the first 3 months, mortality in the metoprolol group was 5.7% versus 8.9% of the placebo group (p = 0.02). This difference persisted after 2 years (metoprolol 13.2%; placebo 17.2%; p = 0.04). Over a 5-year-period, 24.2% of the patients who originally were allocated to metoprolol had died as compared to 25.7% of those originally allocated to placebo (p greater than 0.2). Among patients in whom treatment started early (less than or equal to 8 hours after onset of pain = the median delay time), enzyme activities in the metoprolol group was lower (p = 0.03) than in the placebo group. Mortality during the first 2 years among these patients treated early was lower in the metoprolol (11.8%) than in the placebo group (17.3%; p = 0.04). Corresponding figures after 5 years were 22.0% and 25.3%, respectively (p greater than 0.2). Among patients in whom treatment started later than 8 hours onset of pain, there was neither any difference in enzyme activity nor in mortality after 2 and 5 years. It can be concluded that early treatment with metoprolol in suspected acute myocardial infarction reduced mortality during the first 3 months compared with placebo. The difference persisted after 2 years. However, 5 years after randomization, no significant difference in mortality was observed between the two treatment groups.

The arterial levels of norepinephrine and epinephrine were estimated in 14 patients with severe coronary artery disease in order to assess the catecholamine metabolism during pacing-induced angina pectoris and to evaluate the effects of transcutaneous electrical nerve stimulation (TENS). Arterial levels of epinephrine and norepinephrine increased significantly during pacing to angina pectoris (p less than 0.05 and p less than 0.001, respectively), indicating that maximal atrial pacing induced an increase in sympathetic tone. At the corresponding pacing rate during TENS, myocardial lactate production was improved (p less than 0.01) and the ST segment depression was less pronounced (p less than 0.05). The maximal pacing rate during TENS was 141 +/- 24 compared to 123 +/- 19 (p less than 0.01) and the heart rate-blood pressure product was also significantly higher (p less than 0.01), suggesting an elevation of the anginal threshold by TENS. Systemic vascular resistance and systolic blood pressure were significantly reduced (both p less than 0.01). These beneficial results may be caused by a decrease in left ventricular afterload as reflected by a fall in systolic blood pressure and may be explained by reduced sympathetic activity. TENS may decrease the sympathetic activity either directly or indirectly as a consequence of pain inhibition. This hypothesis is supported by the fact that arterial levels of epinephrine and norepinephrine dropped during TENS in TENS responders.

The effect of beta-adrenorecptor stimulation on the volume of the urinary bladder in 16 neurologically normal humans without symptoms of micturition disturbances was investigated. Terbutaline, a selective beta2-adrenoceptor stimulating agent, was tested in 9 persons and isoprenaline, a general beta-adrenoceptor stimulating agent, was tested in 7 persons. After terbutaline the maximum increase in the bladder volume was 10% and on an average aroung 5%. After isoprenaline the maximum increase in the bladder volume was 15% and on an average around 5%. Terbutaline as well as isoprenaline administration resulted in tachycardia and an increased pulse pressure. The tachycardia was somewhat more marked after isoprenaline. In conclusion, only a small increase in the volume of the urinary bladder was noted after beta-adrenoceptor stimulation in neurologically normal humans without symptoms of micturition disturbances, in contrast to effects achieved in some patients with urgency. Terbutaline seems to have less cardiac effects compared to isoprenaline and is therefore to be preferred when beta-adrenoceptor stimulation is required in patients with urgency.

Chest pain is the most obvious marker of ischemia in acute myocardial infarction (MI) and is the primary symptom leading to hospitalization of the patient. A variety of pharmacologic and other measures have been used to control chest pain in acute MI, ranging from pure analgesics, particularly narcotics or tranquilizers,’ to drugs that have a direct or indirect effect on the ischemic myocardium.2,3 Control of pain in acute MI is important, since persistent chest pain in itself induces adverse systemic circulatory effects and adverse effects on the coronary circulation and on the myocardium via autonomic reflexes, principally mediated via sympathetic efferent nerves, but also to some degree via the vagus. The satisfactory relief of pain with morphine, for example, is considered to block such adverse effects. It has also been reported that morphine will cause preload reduction.4 However, high doses of morphine, the most widely used analgesic in acute MI, have been shown to have a potent stimulatory effect on the vagus nucleus in the pons5 and also to increase plasma catecholamines.6z 7 Morphine may also have an indirect inotropic effect on the myocardium,8 that may increase the oxygen demand of the ischemic myocardium. Such properties of morphine may theoretically lead to an increase in ischemia when high doses are required and may increase the need for other drugs to control the ischemic chest pain in acute MI. One must also realize that considerable depression of ventilation might occur in patients requiring high doses of narcotics for pain relief. There is good reason to believe that pain relief induced by means other than pure analgesics reflects improvement of the ischemic condition

Summary. In eight patients with valvular AS myocardial extraction of insulin was determined before and after intravenous infusion of 25 g of glucose. There was a significant extraction of insulin after the glucose infusion which was related to the arterial insulin concentration. It was also related to the gradient over the stenotic valve, which may explain the low plasma insulin levels previously found in patients with valvular aortic stenosis.

Prognosis in congestive cardiomyopathy (COCM) with marked dilatation and heart failure is poor. A low rate of spontaneous recovery was observed. A high level of circulating catecholamines is often found, which may explain the common finding of resting tachycardia. An early series of COCM patients with tachycardia responded surprisingly well when chronic beta-blockade was added to the conventional treatment of failure. Later, even patients without tachycardia were included with a period of placebo preceding beta-blocker treatment in order to exclude patients with spontaneous recovery. Acute beta-blockade was surprisingly well tolerated, possibly because the reduction in contractility was compensated for by an increase in myocardial compliance. After long-term beta-blockade, improvement was observed after 6 months and further improvement was seen after 24 months. In patients improving functionally, there was reduction in heart size and left ventricular end-diastolic diameter and increase in working performance. For the whole group, there was a decrease in rapid filling wave in apex cardiogram, reduction in third heart sound and increase in ejection fraction. Changes in the reverse way were seen in these three variables after beta-blocker withdrawal and relapse into heart failure occurred in 6/15 patients. Changes in diastolic function may be an early important effect of beta-blockade in COCM. Increase in survival was seen when beta-blocker-treated patients with COCM were compared to well-matched COCM controls.

1. A haemodynamic and myocardial metabolic study was performed to compare effects of maximal atrial pacing and the cold pressor test (CPT) in patients with angina pectoris. Twelve patients (group I) had angiographically severe coronary artery disease, while 16 patients (group II) had normal coronary angiograms. 2. At maximal pacing, angina developed in all patients in group I, and myocardial lactate production was found in eight of 12 patients. In group II, 12 out of 16 patients experienced chest pain, but only two patients had myocardial lactate production. Neither angina nor myocardial lactate production was present in any patient in either group during CPT. 3. Coronary sinus flow increased and coronary vascular resistance decreased significantly in both groups at maximal pacing (P 4. In conclusion, maximal pacing was a more effective method of provocation of angina pectoris than CPT. The reactions of coronary sinus flow and coronary vascular resistance were different in group I than in group II. However, because of the variability of response in patients with normal coronary arteries, CPT cannot be used to distinguish patients with coronary artery disease from patients with no such disease.

It is known that the heart will adapt to actual demand by increasing or decreasing its size through different mechanisms. In this presentation, the possible role of catecholamines in regulating heart protein synthesis and developing cardiac hypertrophy and cardiomyopathy is discussed. Injecting animals with catecholamines has been found to induce cardiac hypertrophy. In vitro perfusion of rat heart in the presence of catecholamines has been found to induce a time-dependent and dose-dependent stimulation of amino acid transport and incorporation into proteins. Acute haemodynamic effects of catecholamines increase cardiac performance while long-term treatment seems to cause depression of cardiac function, especially during ischaemic conditions. Chronic beta-blockade in patients with primary congestive cardiomyopathy improved both cardiac function and clinical condition in more than half the patients. Furthermore, a beneficial effect on survival was also found, when compared with a matched control group. It is hypothesised that catecholamines may play a role in developing cardiac hypertrophy as well as congestive cardiomyopathy.