Cardiovascular diseases and erectile dysfunction: the two faces of the coin of androgen deficiency.

Traditionally, clinical conditions synonymous with the ageing male included cardiovascular disease (CVD), type 2 diabetes mellitus (DM) and sexual dysfunction, and were widely regarded as independent clinical entities. Over the last decade, interrelationship of clinical conditions has been convincingly demonstrated. Declining testosterone levels in the elderly, once regarded as an academic endocrinological question, appear to be central to the listed pathologies. It is now clear that erectile dysfunction is an expression of endothelial dysfunction. Testosterone deficiency is associated with an increased incidence of CVD and DM. The latter is often the sequel of the metabolic syndrome. Visceral obesity, a pivotal characteristic of the metabolic syndrome, suppresses the hypothalamic-pituitary-testicular axis leading to diminished testosterone production. Conversely, substantial androgen deficiency leads to signs and symptoms of metabolic syndrome. It is erroneous not to include testosterone measurements in the progress of the CVD, DM and erectile dysfunction. These conditions correlate strongly with testosterone deficiency.

Day case laparoscopic incisional hernia repair is feasible, acceptable, and cost effective.

BACKGROUND: Day case surgery is increasingly performed in the United Kingdom. Laparoscopic techniques have increased the number of conditions suitable for a day surgical approach. Findings have shown that laparoscopic incisional hernia repair (LIHR) is superior to conventional open techniques. This study aimed to show that day case LIHR is safe, produces a good clinical outcome, and is cost effective. METHODS: Day case laparoscopic repair was performed for 31 consecutive patients (10 men; median age, 67 years; range, 39-80 years). Data were entered prospectively into a database. Patients were discharged within 8 h committed to a 10-day course of oral diclofenac 50 mg three times daily and 2 tablets of codydramol four times daily. Follow-up evaluation was by telephone consultation. Hospital costs for LIHR and open repair were compared. RESULTS: All procedures were completed laparoscopically on a day case basis. Additional unsuspected defects were found in eight cases (25.8%). The median mesh size was 140 cm2 (range, 25-375 cm2), and the median body mass index (BMI) was 28.7 kg/m2 (range, 20-37.1 kg/m2). Operations were performed or supervised by a single consultant surgeon (S.J.W.). Six postoperative seromas resolved spontaneously. Two port-site infections required oral antibiotics, and one diathermy pad burn healed with simple dressings. The median analgesia requirement was 7 days (range, 0-152 days). There were no recurrences during a median follow-up period of 15 months (range, 3-24 months). There was a saving of 616 pounds sterling per procedure. CONCLUSIONS: Day case laparoscopic repair of incisional hernias is feasible and safe and has a good clinical outcome. The hospital costs are less than for open techniques.

Contemporary mortality due to acute myocardial infarction, unstable angina and exertional angina in a population in South East London.

BACKGROUND: Data on the contemporary mortality of coronary heart disease (CHD) are surprisingly sparse. AIM: To describe the contemporary mortality of all manifestations of CHD. DESIGN: Prospective follow-up of patients with a first presentation of CHD in a defined population. METHODS: We studied 537 patients with a first presentation of acute myocardial infarction, unstable angina or new exertional angina in Bromley Health Authority, London (population 295,000). Patients were prospectively monitored for cardiac and non-cardiac mortality for a median of 6 years. RESULTS: During a median 6 years follow-up, there were 88 (16%) deaths. Survival free from cardiac death was not significantly different between unstable angina (92%) and new exertional angina (94%), but was lower for acute myocardial infarction (84%). DISCUSSION: Mortality from CHD appears to be falling. However, efforts to prevent myocardial infarction should continue to be a priority, because on-going early mortality remains high. New exertional angina should be diagnosed and managed promptly, as its mortality is similar to that of unstable angina.

Epanolol. A new once-daily antianginal agent: dose finding and long term efficacy.

Epanolol is a new once-daily agent for the treatment of angina pectoris. This study was conducted in 2 parts. Firstly, a dose-finding study was performed using placebo and epanolol 100, 200, 300 and 400mg to assess the efficacy and safety of the drug. Once-daily epanolol 200mg was an effective dose, significantly reducing angina attack rate and increasing exercise duration and work output. At the same time, an improvement was noted in the patients' well-being and their ability to undertake normal daily activities. The 200mg dose regimen was used in a long term (12 months) assessment of the efficacy and safety of epanolol in the second part of this study. The efficacy of epanolol was clearly maintained throughout the full treatment period without adverse events or withdrawals as a result of treatment. The effectiveness and safety of epanolol are attributed to its selective beta 1-partial agonist activity. At rest, the degree of agonist activity (about 20% of that of isoprenaline) may prevent some of the untoward effects occasionally seen with full beta-blockers. During exercise, the antagonist activity becomes apparent and cardiac ischaemia is reduced.

Effect of partial agonist activity on the side effects of beta-blockade in patients with chronic stable angina.

Some side effects of the beta 1-adrenoceptor blocker atenolol may result from depression of cardiac output at rest. They may, therefore, be reduced by the use of drugs with beta 1-partial agonist activity, such as epanolol. We compared once-daily atenolol 100mg and epanolol 200mg in 20 patients reporting side effects while taking atenolol for chronic stable angina. A double-dummy, double-blind, crossover design was used to assess side effects by use of visual analogue scales and interviews, and antianginal efficacy by treadmill exercise tests and diary cards. In a comparison with atenolol, no significant differences in exercise time (686 +/- 11 seconds vs 685 +/- 10 seconds, maximum ST depression (1.02 +/- 0.09mm vs 1.07 +/- 0.08mm), time to 1mm ST depression (8.4 +/- 1.9 minutes vs 9.0 +/- 2.0 minutes), or days without angina (median 100% in both) were shown. All visual analogue scores were higher with epanolol (subjective energy 58.3 +/- 1.7 vs 54.3 +/- 1.5, well-being 61.8 +/- 1.8 vs 58.6 +/- 1.5 and warmth of extremities 68.4 +/- 3.6 vs 62.0 +/- 3.1). Although these differences did not attain statistical significance, 11 patients expressed a preference for epanolol and only 6 for atenolol. We conclude that, in this study, epanolol is as effective as atenolol as an antianginal agent for chronic stable angina. It improved the side effect profile in some but not all patients.

The role of captopril as single therapy in hypertension and angina pectoris.

Eighteen hypertensive patients with a resting diastolic blood pressure between 100 and 120 mmHg who also had angina and proven coronary arterial disease entered a dose titration study to evaluate the efficacy of captopril as a single therapy in hypertension and coexisting stable angina. Captopril was administered for 2 weeks at 25 or 50 mg three times daily and the patients evaluated subjectively and by maximal symptom limited treadmill exercise testing. In comparison to placebo captopril 25 mg and 50 mg dosage increased time to 1 mm ST depression from 188.2 +/- 24.4 sec on placebo to 337.6 +/- 29.5 and 364.2 +/- 36.2 sec respectively (P less than 0.01). The maximum ST segment depression was reduced from 2.5 +/- 0.25 mm on placebo to 1.4 +/- 0.22 mm on captopril 25 mg and 1.2 +/- 0.30 mm on captopril 50 mg (P less than 0.01). Exercise duration increased from 310.3 +/- 21.4 sec on placebo to 438.3 +/- 27.3 sec on captopril 25 mg and to 460.9 +/- 26.5 sec on captopril 50 mg (P less than 0.01). The resting systolic blood pressure decreased from 184.1 +/- 4.7 mmHg on placebo to 159 +/- 4.2 mmHg on captopril 25 mg and to 150.9 +/- 4.6 mmHg on captopril 50 mg (less than 0.01). Similarly, diastolic blood pressure decreased from 111.6 +/- 2.1 mmHg on placebo to 93.8 +/- 1.3 mmHg on captopril 25 mg and to 90.0 +/- 1.7 mmHg on captopril 50 mg (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of intermittent (eight hours off) transdermal nitrate therapy in stable angina.

The efficacy of intermittent (16 h on/8 h off) transdermal nitrate therapy (0.4 mg/h) was assessed in 46 patients with chronic stable angina, all but one of whom were on concomitant beta-blocker and/or calcium antagonist therapy. The study was a randomised, double-blind placebo-controlled crossover with two consecutive 7-day treatment periods, conducted at two centres. Prior to entry into the study patients were screened for exercise test reproducibility and nitrate response. Patch efficacy was determined by maximal symptom limited treadmill stress testing (Bruce protocol) and subjective diary card data. Analysis of variance showed that active treatment significantly improved time to onset of angina (P < 0.001), time to 1 mm ST-segment depression (P < 0.001) and total exercise duration (P < 0.001) compared with placebo from 385.7, 310.8 and 458.1 s to 455.7, 385.2 and 497.1 s, respectively. Nitrate patch therapy significantly reduced diastolic and systolic blood pressures without significantly increasing resting heart rate. There was a marginal reduction in the incidence of angina attacks and sublingual nitroglycerine consumption during active treatment. We conclude that intermittent transdermal nitrate therapy significantly improves exercise tolerance in patients with chronic angina pectoris and that this improvement occurs in addition to conventional anti-anginal therapy.

A randomised double-blind crossover study of isosorbide mononitrate and nifedipine retard in chronic stable angina.

In order to evaluate and compare the efficacy and safety of nifedipine retard and isosorbide-5-mononitrate as monotherapy in the treatment of stable angina, 18 patients with abnormal exercise electrocardiograms and angiographically proven coronary arterial disease were studied in a randomised placebo controlled double-blind crossover study comparing isosorbide 20 mg twice a day, sustained released isosorbide 40 mg once daily and nifedipine 20 mg twice a day each given for two weeks. Patients were assessed subjectively by counting the frequency of anginal attacks and glyceryl trinitrate consumed and objectively by maximal symptom-limited treadmill stress tests performed at "trough" therapeutic blood levels on the last day of each treatment period. There were no significant differences in all parameters between entry and run-out placebo. Compared to placebo, all three active treatments showed significant improvement in exercise time to 1 mm ST segment depression, amount of maximum ST segment depression and exercise duration. All three active treatments also significantly reduced the consumption of glyceryl trinitrate and frequency of anginal attacks. There were no significant differences between active treatments. Thus similar clinical improvements were produced by nifedipine retard and isosorbide, both being shown to be equally effective starting therapy for the treatment of patients with stable angina pectoris. Although anginal frequency was reduced by one third and exercise time increased residual symptoms and exercise ischaemia suggest that nifedipine retard and isosorbide may be more clinically useful in combination therapy. Neither demonstrated tolerance after two weeks of therapy.

Does atenolol improve physical and psychological function after coronary artery bypass surgery: a controlled study.

A double-blind prospective randomized trial of atenolol (100 mg once daily) was carried out on 88 patients (78 men) awaiting coronary artery bypass graft surgery. Standardized ratings of both psychiatric morbidity and functional capacity were made before, 3 months (n = 82) and 12 months (n = 81) after surgery. One year after surgery men in the atenolol group had a significantly shorter treadmill exercise time than those on placebo (7.21 +/- 0.28 min vs 8.32 +/- 0.40 min; p less than 0.05), but the frequency of reported anginal attacks during the year was similar in both drug groups. Improvement in functional capacity (measured in exercise time) in the 71 men following surgery was related to both physical and psychological variables assessed before the operation. Men with more severe occlusive disease, lower neuroticism and higher extraversion scores pre-operatively showed greater percentage improvement in exercise time after surgery. Women had significantly levels of psychiatric morbidity and shorter treadmill exercise time than men both before and after surgery. Of the psychiatric and psychological variables, only ratings of Type A behaviour fell significantly in the atenolol group (170.9 +/- 5.3 vs 163.0 +/- 5.2; p less than 0.05). This change, which is probably not clinically important, occurred independently of any reduction in either overall psychiatric morbidity score or ratings of somatic symptoms mediated by beta-adrenergic receptors. The atenolol group reported more side-effects of both psychological and physical symptoms than the placebo group. We do not recommend the routine use of atenolol after bypass graft surgery. Our findings failed to support the suggestion that Type A characteristics may reflect an underlying sympathetic nervous system reactivity.

Efficacy of nifedipine and isosorbide mononitrate in combination with atenolol in stable angina.

Many patients with angina pectoris whose symptoms are not completely controlled by beta-blockers are treated with several types of drugs, but it is not clear whether addition of a calcium-channel antagonist and/or a nitrate confers any advantage over beta-blockade alone. 18 patients receiving atenolol for stable angina pectoris completed a double-blind, randomised, crossover trial of atenolol treatment plus placebo, isosorbide mononitrate, nifedipine, and mononitrate and nifedipine (triple therapy). The patients were assessed subjectively and by treadmill exercise testing and 24 h ambulatory electrocardiographic recordings at the end of each 4-week treatment period. There were no significant differences among the treatment periods in angina attack rates, glyceryl trinitrate consumption, exercise duration to onset of angina or 1 mm ST depression, or duration of symptomless ischaemia. Total exercise duration was longer on atenolol plus mononitrate than on atenolol alone (mean difference 46 [95% confidence interval 18-88] s; p = 0.005), atenolol plus nifedipine (36 [2-71] s; p = 0.04), or triple therapy (28 [6-61] s; not significant). In 12 patients the exercise time was shorter on triple therapy than on atenolol plus mononitrate alone. Although "maximum" antianginal treatment with two or three drugs is commonly accepted, this approach confers no substantial advantage over optimum beta-blockade as monotherapy. If a second drug is needed, there is a slight advantage in favour of isosorbide mononitrate, but if this is not effective, treatment should be changed rather than added. Many patients with angina pectoris seem to be pharmacologically overtreated.

Raised exercise diastolic blood pressure as indicator of ischaemic left ventricular dysfunction.

91 (16.8%) of 541 consecutive patients investigated for chest pain or after recent uncomplicated myocardial infarction had a rise in diastolic blood pressure (DBP) of more than 15 mm Hg during a symptom-limited treadmill test. 63 also had electrocardiographic evidence of ischaemia, but 28 did not have 1 mm ST segment depression, of whom 24 had angiographic evidence of more than 70% stenosis of two or more major coronary arteries. 55 of these 91 patients underwent coronary artery bypass surgery; repeat angiography in 22 at 12 months showed an improved left ventricular ejection fraction in 18 who had a normal postoperative DBP response, but no change in ejection fraction in the 4 who still had an abnormal rise in DBP on exercise. Exercise-induced ischaemia may cause a reversible fall in cardiac output that sometimes leads to reflex vasoconstriction and a rise in DBP before a fall in systolic blood pressure or ECG evidence of ST segment depression. An abnormal DBP response to exercise may identify some patients at high risk of myocardial infarction who might otherwise have false-negative exercise tests.

Physical and psychological correlates of severe heart disease in men.

Seventy eight men were assessed one month before coronary artery bypass graft surgery using standardized measures of psychiatric morbidity and personality as well as a measure of emotional expression (the CECS). All patients had at least one coronary vessel occluded by 75% or more of its diameter, and functional capacity was assessed by calculating the exercise treadmill time (in seconds) for each patient. Most of the variance in exercise treadmill time was accounted for by the following variables: young age, short duration of symptoms, and less severe angina. Only one of five men was designated a psychiatric 'case'. The only psychological measure significantly associated with atherosclerosis was expression of fear (on the CECS). A measure of Type A behaviour (Bortner score) was related to exercise treadmill time, but not to any of the angiographic or clinical indices of coronary heart disease (CHD). Like other measures of Type A behaviour, the Bortner scale is psychometrically impure and has doubtful validity. More valid behavioural variables (such as those measured by the CECS) require further investigation. Future studies on the relation between psychological factors and the extent of CHD should take account of not only sex differences but also patients without significant CHD: high rates of psychiatric morbidity in such patients confound the relation between psychological trait measures and atherosclerosis.

Reciprocal change in ST segment in acute myocardial infarction: correlation with findings on exercise electrocardiography and coronary angiography.

The clinical relevance of reciprocal changes in the ST segment occurring at the time of acute myocardial infarction was studied prospectively in 85 consecutive uncomplicated cases. Reciprocal depression of the ST segment was defined as depression of 1 mm or more in electrocardiogram leads other than those reflecting the infarct. All patients underwent maximal, symptom limited treadmill stress testing two weeks after the infarct and coronary angiography six weeks after infarction. Forty six patients had inferior, 34 anterior, and five true posterior infarction. Of the 51 patients with reciprocal changes, 45 (88%) developed exercise induced ST segment depression in areas remote from the infarction zone. At angiography all 45 patients were shown to have stenoses greater than 70% in at least two major vessels. Four patients had negative exercise electrocardiograms and were sequently shown to have single vessel disease subtending their infarct, and the remaining two patients had a false negative treadmill test result. Of the 27 patients without reciprocal changes, 21 (78%) had negative treadmill stress test results associated with single vessel coronary disease. Five had positive stress test results and multivessel coronary disease, and one had a false negative stress test result. The remaining seven patients had ST segment elevation without Q wave formation in the reciprocal areas and were assessed separately. Of these, six had positive stress test results and multivessel coronary disease and one had a negative stress test result and single vessel coronary disease to the infarct area. Twenty one patients with anterior infarcts (62%) and 27 with inferior infarcts (59%) had reciprocal changes. No differences emerged in the relation between infarct site, reciprocal change, and presence of additional coronary disease. At follow up of the 51 patients with reciprocal changes in the ST segment 36 had become symptomatic, of whom 29 had undergone coronary artery bypass surgery. By contrast, only four of the 27 patients without reciprocal changes in the ST segment had developed symptoms, and two of these had undergone coronary revascularisation. Reciprocal ST segment depression at the time of acute myocardial infarction may identify patients with severe coronary disease who are at risk of subsequent cardiac events and appears to be as reliable as results of early postinfarction treadmill stress testing in predicting the underlying coronary anatomy. When the electrocardiogram does not show reciprocal changes treadmill testing provides valuable additional information.

Increased diastolic blood pressure response to exercise testing when coronary artery disease is suspected. An indication of severity.

One hundred and two consecutive patients with a history of chest pain or recent previous myocardial infarction underwent maximal treadmill stress testing and coronary angiography. The diastolic blood pressure response to exercise was evaluated independently of ST segment change and systolic blood pressure. In the presence of a normal systolic blood pressure response an increase in diastolic blood pressure of 15 mm Hg on at least two determinations during the same stage of exercise was considered abnormal. In 99 patients an accurate diastolic reading was possible. Of these, 61 had a normal diastolic blood pressure response; in 25 of these the ST segment was ischaemic and seven had three vessel coronary artery disease. Thirty eight patients had an abnormal diastolic blood pressure response and 27 of these had an ischaemic ST response. Of the 11 with a negative ST response for ischaemia one had left main stem disease, seven three vessel disease, and three two vessel disease. Patients with an abnormal diastolic response had greater ST depression with more angina at a reduced workload than those with a normal diastolic response. In patients with chest pain an abnormal increase in diastolic blood pressure on exercise reflects severe coronary artery disease. Although no false positives occurred in this study there was an appreciable number of false negatives (sensitivity 46%) in both patients with chest pain and those with infarction. An abnormal diastolic response therefore represents a useful additional diagnostic indicator of coronary artery disease when the ST segment response is normal or borderline. When the diastolic pressure becomes increased with or without ST changes the likelihood of severe coronary artery disease is increased.

Isosorbide-5-mononitrate--effective monotherapy in chronic stable angina.

Isosorbide-5-mononitrate (ISMN) is not subject to first-pass metabolism and has more predictable blood concentrations than isosorbide dinitrate. In order to evaluate its efficacy as monotherapy in patients with chronic stable angina, 14 patients were studied. All had angiographically proven coronary artery disease and were limited by angina on a treadmill exercise test. After a 2-week placebo period ISMN was administered in a single-blind fashion with the dosage being titrated at 2-week intervals. The dosage increments were 20 mg once daily, 20 mg twice daily, 40 mg once daily and 40 mg twice daily. Patients were assessed subjectively by anginal attack rate and glyceryl trinitrate (GTN) consumption and objectively by treadmill exercise testing at 12 hours post dosage. ISMN increased the exercise ability significantly on all dosage regimes. However, a significant reduction in ST depression occurred only with the twice-daily regime. The increased exercise performance was associated with a significant decrease in anginal attack rate and GTN consumption from the 20 mg b.i.d. increment. ISMN is an effective antianginal agent with a more favourable profile in twice-daily dosage. Whilst no significant differences emerged between 20 mg and 40 mg twice daily, individual variation occurred, indicating a need for dosage flexibility.

The relationship between QT interval and heart rate during physiological exercise and pacing.

Conventional doctrine states that the QT interval is related to heart rate in an inverse exponential relationship, so that with increasing rate the QT interval shortens. This relationship has recently been studied in a group of patients undergoing physiological exercise stress tests, atrial pacing stress test, and in a further group of patients with complete heart block undergoing exercise at a fixed ventricular rate controlled by cardiac pacemaker. Examinations of recordings made during physiological exercise do show the expected shortening in QT interval, we believe that this shortening is only in part due to the intrinsic effect of increased rate as patient who were atrially paced to similar rates and within the same age group showed only a small decrease in measured QT interval and patients undergoing exercise at fixed ventricular rate showed shortening in QT interval which was related to the independent atrial rate. It appears, therefore, that the QT interval is governed mainly by extrinsic factors and not intrinsically rate related. The physiological control of QT interval is being used now to construct a cardiac pacemaker which senses the interval between the delivered stimulus and the evoked T wave so that the stimulus-evoked T wave interval could be used to set the subsequent escape interval and subsequently the overall pacing rate. Physiological control of cardiac pacing rate using conventional unipolar lead systems and independent of atrial activity is possible and currently being investigated.

Early exercise testing and coronary angiography after uncomplicated myocardial infarction.

In a prospective study 61 patients aged 55 years or less with uncomplicated myocardial infarction underwent treadmill stress testing at two weeks and coronary angiography at six weeks after infarction. Of the 44 patients who had a positive stress test, 43 had additional severe coronary artery disease confirmed by coronary angiography. Of the 17 patients who had a negative stress test for additional disease, coronary angiography identified only single-vessel disease in the infarct area in 15. The sensitivity of the stress test was 95% and the specificity 94%, though the number of patients in the study was small. Thus, exercise testing has considerable potential for the early identification of multiple-vessel disease in patients with uncomplicated myocardial infarction.

Emerging patterns of heart disease in HIV infected homosexual subjects with and without opportunistic infections; a prospective colour flow Doppler echocardiographic study.

We studied 124 homosexual men aged 36.7 +/- 7.6 years (range 23-57) using Doppler echocardiography. One hundred and one patients (Group A) had had acquired immunodeficiency syndrome for 1.6 +/- 1.0 years and 23 patients (Group B) had had HIV infection without opportunistic infections for 3.2 +/- 2.3 years. Doppler echocardiography was normal in 31% of Group A patients and in 61% of Group B. Pericardial effusion was found in 44 Group A patients (44%) and two Group B patients (9%). In Group A, left ventricular dilatation and/or dysfunction were found in 20 patients (20%), aortic root dilatation and regurgitation in eight patients (8%) and an intracardiac echogenic mass in seven patients (7%); in Group B one patient (4%) had an intracardiac mass. Forty-four (44%) Group A patients had cardiac presentations, and of these 22 had cardiomegaly with clinical signs of heart failure; 10 patients had tachyarrhythmias compared to only two in Group B. Although the CD4 lymphocyte count (%) was significantly lower in Group A than in Group B (5.4 +/- 6.1 vs 13.3 +/- 7.3, P < 0.001), the presence of pericardial effusion, left ventricular dysfunction, right-sided cardiac enlargement or the duration of HIV infection, did not relate to the CD4 level in either group. Although often not diagnosed clinically, cardiac involvement in patients with AIDS is a clinical reality, with pericardial effusion, cardiomyopathy and left ventricular dysfunction appearing to have a high prevalence in male homosexual patients with AIDS. These clinical and echocardiographic findings are associated with clinically apparent intercurrent opportunistic infections, rather than the HIV virus per se, or the severity of infection as reflected by the CD4 count.

Oral labetalol in the management of stable angina pectoris in normotensive patients.

The efficacy of labetalol, an alpha and beta receptor antagonist, was evaluated in 12 normotensive patients with stable angina pectoris in a single blind dose ranging study. After a two week period of placebo treatment, labetalol was given in doses of 100, 150, 200, and 300 mg twice daily, each for two weeks. Frequency of angina attacks decreased from 9.4 (SEM 2.3)/week in the control period to 7.3 (2.8), 5.2 (2.6), 3.8 (1.8), and 3.3 (1.9)/week in the four successive treatment periods. In the same periods the number of glyceryl trinitrate tablets consumed decreased from 7.0 (2.6)/week to 5.8 (3.3), 3.9 (2.9), 2.7 (1.8), and 2.6 (2.1)/week. Maximal symptom limited treadmill exercise tests were performed three and 12 hours after dosage at each dose. Exercise tolerance (expressed as seconds of the Bruce protocol) increased from 266 (44) with placebo to 306 (44), 369 (50), 396 (48), and 413 (51) in the four treatment periods. This improvement was accompanied by a significant blunting of the heart rate and blood pressure responses to exercise. Trough point exercise tolerance did not differ significantly from that at three hours after dosage. Thus labetalol is effective as an antianginal agent at doses of 150-300 mg twice daily and is well tolerated by the normotensive patient with angina.

Early exercise testing and elective coronary artery bypass surgery after uncomplicated myocardial infarction. Effect on morbidity and mortality.

One hundred and nineteen consecutive patients were studied prospectively after uncomplicated myocardial infarction by maximal exercise electrocardiography at two weeks and coronary angiography at six weeks. At angiography 87 patients had a stenosis greater than 70% in one major coronary artery supplying residual viable myocardium outside the infarction zone. In 82 (94%) of these the 12 lead maximal exercise electrocardiogram correctly identified these areas of ischaemic but viable myocardium. Based on ST criteria alone five patients had a false negative exercise electrocardiogram for additional disease. Nevertheless, three developed angina or a significant fall in systolic blood pressure or both at a low workload. On the basis of the anatomical lesions, symptoms, and the results of the European Coronary Surgery Study Group 55 patients were allocated for surgery. Of these, 54 underwent coronary artery bypass grafting within three months of myocardial infarction. One patient died perioperatively and another died after a reinfarction at four months while awaiting surgery. The remaining 53 were symptom free during a mean follow up period of 37 months. Sixty four patients received medical treatment. At angiography 32, 24, and eight patients had one, two, and three vessel coronary disease respectively. The exercise electrocardiogram correctly predicted the anatomy in 60 (94%), with two false positive and two false negative results for additional disease. The eight patients with three vessel disease treated medically had generalised inoperable disease, and at follow up three had died after a further infarction and five remained symptomatic with full medical treatment. Thus of those designated as at high risk and considered suitable for surgery the 37 month survival was 53 or 54 patients treated surgicall7y.