Does acute-phase beta-blockade reduce mortality in acute myocardial infarction by limiting infarct size?

The mechanism by which early intervention with beta-blockers reduces mortality in acute myocardial infarction is unclear. Therefore the effects of intravenous, followed by oral, metoprolol on indices of infarct size were studied in a double-blind fashion with a median delay of 6.75 hours from onset of symptoms. In 129 patients peak enzyme release and QRS score on the electrocardiogram were assessed, while myocardial perfusion score on thallium-201 scintigraphy was studied in 45 patients. There was a close correlation between all the indices of infarct size. While the correlation coefficients did not appear to be influenced by metoprolol treatment, the slope of the regression was affected. Peak aspartate aminotransferase and lactic dehydrogenase were lower by 11 and 7%, respectively, in the metoprolol-treated group, but no reduction was noted in QRS score or in thallium-201 perfusion defect size in the actively treated group. Thus, it seems likely that early intervention with metoprolol in acute myocardial infarction reduces mortality, not by limiting infarct size, but by some other mechanism.

Renal effects of nicardipine in essential hypertension: differences between acute and chronic therapy.

Previous reports have described improvements in renal function with acute administration of nicardipine. The purpose of this study was to determine if these improvements persist with continued treatment. Using single dose radio-isotopic techniques in six subjects with essential hypertension, evaluations of glomerular filtration rate and effective renal plasma flow were made prior to treatment during an intravenous nicardipine infusion of 80 micrograms/kg per h, and following 6 weeks of treatment with 30-40 mg, three times a day. Subjects were stabilized on a diet containing 100 mmol Na+, 80 mmol K+ and 1650 ml water. Blood pressure was similarly reduced with both acute (-45/26 mmHg) and chronic (-42/21 mmHg) therapy. Renal vascular resistance index fell with both acute (-39%) and chronic (-26%) treatment. Significant increases in effective renal plasma flow (+15%), urine volume (+121%), and urinary sodium (+168%) and calcium (+128%) elimination were seen with acute treatment. These parameters had returned to control levels after 6 weeks of treatment. No change was seen in glomerular filtration rate, filtration fraction, plasma renin activity or plasma aldosterone concentration. These data showed that the natriuresis and diuresis as well as the increase in effective renal plasma flow seen with the introduction of nicardipine therapy, did not persist during long-term treatment. There was no evidence of deterioration in any aspect of renal function during long-term therapy despite the significant reduction in renal perfusion pressure.

Beta-adrenergic blockade in acute myocardial infarction: a haemodynamic and radionuclide study.

While long term beta-adrenergic blockade, introduced in the convalescent stage of myocardial infarction, may reduce subsequent mortality, the value of early beta-blockade in the acute phase is less certain. Therefore, the influence of beta-blockade on left ventricular performance and eventual infarct size was assessed in 61 consecutive patients with acute myocardial infarction. Metoprolol (15 mg i.v. followed by 200 mg day-1 orally) or placebo was administered in a double-blind, randomised fashion with a median delay of 5.9 hours from onset of symptoms. After 15 days of double blind therapy all patients were started on open treatment with metoprolol. All patients underwent haemodynamic monitoring for 24 hours and serial radionuclide ventriculography and thallium 201 scintigraphy. In the first hour metoprolol produced a decrease in cardiac output (1.3 l min-1; P less than 0.001) due to a reduction in heart rate (15 min-1; P less than 0.001) and a decrease in left ventricular stroke work index (10.7 g m m-2; P less than 0.001) due to a reduction in mean arterial pressure (10 mmHg; P less than 0.001). There was then a gradual attenuation in these changes. While metoprolol produced an increase in pulmonary capillary wedge pressure and in both end-diastolic and end-systolic volumes (P less than 0.05), these changes were confined to patients with a baseline pulmonary capillary wedge pressure below the median of 13 mmHg mercury. There was no significant change in stroke volume or in ejection fraction in response to metoprolol. There was no significant difference between the groups in left ventricular performance, as assessed by radionuclide ventriculography, or in scintigraphic infarct size, either at the end of the 15 days double-blind treatment or after 3 months open treatment with metoprolol. Thus, early intervention with metoprolol in acute myocardial infarction appeared to reduce myocardial oxygen consumption with no adverse haemodynamic effect. However, metoprolol failed to preserve left ventricular function, or to reduce apparent infarct size. These data suggest that the modest reduction in mortality reported in the acute phase studies of beta-blockade in myocardial infarction, is unlikely to be due to infarct reduction. It is more likely to be due to a secondary prevention or to an antiarrhythmic effect.

Routine exercise testing or thallium-201 scintigraphy for prediction of cardiac events post-myocardial infarction?

The efficacy of 12 lead exercise testing and rest/exercise 201Tl scintigraphy as indicators of coronary anatomy and prognosis was compared in 46 low risk survivors of acute myocardial infarction. The non invasive procedures were performed at discharge, and cardiac catheterization was performed six weeks post discharge. On exercise testing, ST depression in leads remote from the site of infarction was considered to indicate multivessel disease and reversible ischaemia. On 201Tl scintigraphy, a perfusion defect remote from the site of infarction indicated multivessel disease, while a defect which reperfused at rest indicated reversible ischaemia. During the mean follow-up of 13 +/- 3 months, 14(30%) patients experienced cardiac events. Thallium scintigraphy was a more sensitive, but less specific, indicator of multivessel disease than exercise testing. Both exercise testing and 201Tl scintigraphy had a similar sensitivity (79% vs 79%), specificity (78% vs 88%) and predictive accuracy (78% vs 85%) for predicting subsequent cardiac events. Thus, in our patient population, 201Tl scintigraphy could not be demonstrated to be superior to routine exercise testing in low risk patients post myocardial infarction.

The clinical role of thallium-201 scintigraphy in the management and prognosis of coronary artery disease.

The clinical impact of thallium-201 (Tl-201) scintigraphy in coronary artery disease was reviewed in 162 consecutive patients referred for routine investigation. Normal Tl-201 images were obtained in 86 of the 102 studies undertaken for diagnostic purposes. Eighty-one (94%) of the 86 were spared diagnostic coronary arteriography; 5 proceeded to coronary arteriography for persistent symptoms (1 had double vessel disease, 2 had single vessel disease only, 2 had normal arteriograms). Conversely, coronary arteriography was normal in 2 of 16 patients (12.5%) with unequivocal image defects. Tl-201 scintigraphy was performed as a functional complement to coronary arteriography in 60 patients, influencing the decision for surgery in 36 and determining the presence or absence of myocardial ischaemia in 24 patients with equivocal coronary arteriograms. Normal data were obtained in 9 patients. Of the 95 patients with normal Tl-201 scintigrams, only 5 (5.2%) required further investigations or intervention (4 arteriograms, 1 coronary angioplasty) over a follow-up period of 18 +/- 1 months, none suffered myocardial infarction and none died. There were no deaths in either the diagnostic or complementary group, irrespective of the result of the Tl-201 scintigram, during the mean follow-up period of 18 months. These data confirm both the valuable role of Tl-201 scintigraphy in the management of patients with suspected or proven coronary artery disease and the excellent prognostic value of a normal Tl-201 scintigram.

Prognostic investigations after myocardial infarction: a comparison of radionuclide angiography and 201Tl scintigraphy.

The ability of pre-discharge thallium Tl201 scintigraphy and radionuclide angiography (RNA) to predict subsequent cardiac events was investigated in 46 apparently low-risk survivors of a first acute myocardial infarction. All patients underwent selective coronary arteriography at 3 months post-discharge. At the time of the initial investigation, half were beta-blocked, and thereafter, all patients were given prophylactic beta-blockade. During a mean follow-up period of 12 +/- 4 months, 14 patients (30%) experienced cardiac events, i.e. recurrent myocardial infarction (3 patients), angina pectoris (13 patients) and coronary surgery (8 patients). No patient died during the follow-up period. Of the 14 with subsequent cardiac events, 11 were identified by the presence of a reversible perfusion defect at 201Tl scintigraphy, while 7 exhibited abnormal left ventricular exercise reserve on RNA. The predictive accuracy of 201Tl (85%) for subsequent cardiac events exceeded that of RNA (56%; P less than 0.01) and of arteriographic multi-vessel disease (65%; P less than 0.05). The sensitivity of the non-invasive techniques was not influenced by beta-blockade at the time of investigation. Thus, 201Tl scintigraphy appears to be the more accurate technique for the assessment of the prognosis of apparently low-risk patients following myocardial infarction. The accuracy of the technique was not reduced by beta-adrenergic blockade.

Platelet inhibitory drugs: an in vivo method of evaluation in patients.

The measurement of platelet deposition in human thrombi is essential for the evaluation of platelet-inhibitory drugs and prosthetic materials for use in patients. The rate of 111Indium-labelled platelet accumulation on Dacron arterial grafts was measured in 27 patients randomised to take either aspirin and dipyridamole (ASA + DPM) or placebo. Autologous platelets were labelled and re-injected seven days following surgery and the graft thrombogenicity index calculated as the daily rise in the ratio of emissions from the graft over a reference site. The mean (+/- SD) thrombogenicity index in 12 patients undergoing femoro-popliteal bypass was 0.25 +/- 0.09 on placebo and 0.16 +/- 0.07 on ASA + DPM started pre-operatively (p less than 0.05). Post-operative ASA + DPM therapy started two days following platelet labelling in 15 patients with aorto-femoral grafts also significantly reduce thrombogenicity to 0.12 +/- 0.05 compared with 0.25 +/- 0.08 on placebo (p less than 0.01). In the latter patients the ratio of emissions from the graft over reference fell significantly on starting ASA + DPM, suggesting a net loss of platelets from the graft. These results indicate that the rate of in vivo platelet accumulation on Dacron grafts can be quantitated and that ASA + DPM reduced this rate in man.

Imaging of 111In-labelled platelets--a new method for the diagnosis of deep vein thrombosis.

A radionuclide method for detecting established thrombi at all sites in the lower limb would have several advantages. Autologous platelets were labelled with 150 microCi (5.5 MBq) indium-111-oxine and re-injected into patients who were imaged with a gamma camera and data processed by a medical computer. Areas of increased uptake on imaging were correlated with the sites of thrombi identified by bilateral ascending venography. Venography in 27 patients identified 12 unilateral and 5 bilateral thrombi. On the day following the re-injection of labelled platelets, imaging identified thrombi at 13 sites in 24 limbs giving an overall correlation with venography of 84.4 per cent, correlation for the calf and thigh being 79.5 per cent and 89.1 per cent respectively. In the thigh 57.1 per cent of thrombi were identified by imaging and 52.9 per cent in the calf. Activity over thrombi was at least 20 per cent higher than in adjacent areas or at similar sites in the contralateral leg. Herapin therapy is considered to affect the detection of deep vein thrombus adversely by this technique. The technique offers a useful method for the diagnosis of both early and established thrombi at any site in the lower limb.