Search PubMedSearch

Biomedical subjects

D G Julian

Publications and source records attributed to D G Julian.

At least 19 recordsLinked to original sources

Why do patients die after myocardial infarction?

Death during and following myocardial infarction can arise from a number of different causes. Some of them, such as early ventricular fibrillation and cardiac rupture, seem unrelated to infarct size. However, deaths occurring later during the course of infarction do seem to be related to the extent of myocardial damage and to such phenomena as infarct extension and expansion, and the mechanisms involved include cardiac failure and shock, and late arrhythmias. Preventive measures must be directed at the various mechanisms involved. Thrombolytic drugs, by limiting infarct size, prevent death from several causes, whereas beta-blockers seem mainly to operate by preventing early rupture, reinfarction, and late ventricular fibrillation. Aspirin prevents reinfarction. Angiotensin-converting enzyme (ACE) inhibitors may prove to have a beneficial role in the early phase by unloading the heart and later by preventing infarct expansion and subsequent cardiac failure.

Cause of Death

The APSAC interventional mortality study (AIMS) trial: mortality data.

The anistreplase (anisoylated plasminogen streptokinase activator complex or APSAC) intervention mortality study was designed as a double-blind, placebo-controlled study to test the effectiveness of anistreplase, 30 U administered intravenously within the first 6 hours of acute myocardial infarction. The primary endpoint of the study was mortality of all causes at 30 days and 1 year. Within 30 days, there were 77 deaths with placebo (17.8%) and 40 deaths (6.5%) with anistreplase, an odds reduction of 50.5% (p = 0.0006). By the end of one year, there had been a total of 113 deaths (17.8%) with placebo and 69 deaths (11.1%) with anistreplase, an odds reduction of 42.7% (p = 0.0007).

Acute Disease

Time as a factor in thrombolytic therapy.

There is abundant evidence from angiographic studies that reperfusion and/or patency rates are greater when thrombolysis is initiated earlier. Evidence of a reduction in infarct size has been provided by a number of studies, which have also suggested that earlier therapy preserves left ventricular function. The major intravenous thrombolytic mortality trials appear to confirm the importance of delivering therapy soon after the onset of symptoms e.g. GISSI and ISIS-2. However, the benefit reported in the first hour in GISSI may be questioned. Furthermore, it seems probable that those coming in late to trials are patients who did not have a sudden onset of symptoms, but whose symptoms persisted, perhaps with recurrent pain, or with heart failure symptoms. This may account for the fact that the benefit seen relatively late, particularly in ISIS-2, does not seem to accord with reperfusion, infarct size and LVEF findings. The true benefits of earlier therapy will be established only when patients are randomized to active therapy or placebo at one point in time and then switched to alternative therapy at a specified later time. This has been done in a small trial with alteplase in Belfast. The findings were suggestive but not conclusive of an improvement in LVEF in those treated earlier. The European Myocardial Infarction Project (EMIP) should go far towards answering the question. In most European cities the time between onset of symptoms and the initiation of skilled treatment for myocardial infarction is of the order of 5-6 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Fibrinolytic Agents

Increased survival after APSAC: 30-day and 12-month mortality data from the APSAC Intervention Mortality Study.

Preliminary analysis of mortality data from the anisoylated plasminogen streptokinase activator complex (APSAC) Intervention Mortality Study (AIMS) showed a 47% reduction in 30-day mortality (with a 95% confidence interval of 21 to 65%) for patients treated with APSAC within 6 hours of onset of acute myocardial infarction. After follow-up of 1,004 patients for 30 days after randomization in the double-blind, placebo-controlled, clinical trial, researchers found that 61 patients (12.2%) in the placebo group had died compared with 32 patients (6.4%) in the APSAC group (p = 0.0016). Incomplete follow-up of these patients for 1 year provided an estimated mortality of 19.4% in the placebo group and 10.8% in the APSAC group (log-rank test for survival to year p = 0.0006). Benefit was seen irrespective of age, site of infarction and time from onset of symptoms up to 6 hours.

Aged

An analysis of factors predisposing to neurological injury in patients undergoing coronary bypass operations.

In a prospective study of 312 patients undergoing elective coronary bypass surgery we evaluated 50 preoperative, intraoperative and postoperative factors with the aim of identifying predisposing causes for perioperative neurological morbidity. Factors which showed a significant association with the development of neurological complications included the duration and severity of heart disease before surgery; the presence of extracoronary vascular disease; history of cardiac failure; history of diabetes; difficulty in terminating bypass; intraoperative mean arterial pressure levels of less than 40 mmHg; a large drop in haemoglobin level during surgery; prolonged stay in the intensive therapy unit after operation; and abnormalities of blood pressure control in the postoperative period. The significance of these findings is discussed and a comparison made with data available from previous studies.

Adult

A controlled trial of GL enzyme in the treatment of acute myocardial infarction.

GL enzyme (hyaglosidase) is a highly purified component enzyme of hyaluronidase. A therapeutic trial was carried out in the treatment of suspected myocardial infarction among 1,488 patients presenting within 6 h of the onset of symptoms. No significant reduction in mortality at 6 months was observed in the GL group (15.7%) compared with the placebo group (16.4%). Mortality at 2 weeks was also unaffected by treatment (GL 10.3%; placebo 10.9%).

Clinical Trials as Topic

Prevention of tolerance to nitroglycerin patches by overnight removal.

This investigation assesses the extent of tolerance development with nitroglycerin patches and whether tolerance might be prevented by overnight patch removal. On commencing therapy, active patches significantly prolonged exercise time (3.5 hours after patch application) in comparison with placebo, with an accompanying reduction in ST-segment depression at maximal common workload. Patients then received continuous or 12-hour-daily intermittent patch therapy, in a double-blind fashion, for 7 days. Exercise testing was repeated before and after active patch application, on the eighth day of each treatment phase. During continuous therapy, beneficial effects on exercise time and ST depression were abolished. By contrast, during intermittent therapy, prolongation of exercise time and reduction in ST-segment depression still occurred, on testing 3.5 hours after active patch application. These results confirm previous studies showing a high degree of tolerance during continuous therapy with nitroglycerin patches and suggest that tolerance can be prevented by 12-hour-daily intermittent therapy.

Administration, Cutaneous

Quality of life after myocardial infarction.

The long-term physical and psychologic well-being of patients who have sustained a myocardial infarction is dependent on skilled care during the first hours. Although the immediate preservation of life is the first priority, the relief of symptoms and anxiety and the protection of the myocardium are of short- and long-term importance not only to the quantity but also to the quality of life. Pain relief, particularly in the prehospital phase, is often inadequate. Fear, triggered by pain, may be aggravated by the environment; aggressive (and often unnecessary) measures and the inhuman use of technology may interfere with personal care. Intensive observation is essential for the control of dangerous arrhythmias; the early use of fibrinolytic agents and beta blockers limits the extent of myocardial damage and reduces mortality. The effectiveness of therapy for cardiac failure and shock is questionable. The value of invasive monitoring and of inotropic drugs is uncertain, although the relief of symptoms by diuretic agents and vasodilator drugs is not in doubt. Success in the management of myocardial infarction depends on a highly individualized approach.

Adrenergic beta-Antagonists

Neuro-ophthalmological complications of coronary artery bypass graft surgery.

In a prospective study of neurological complications of coronary bypass surgery, detailed pre- and post-operative bedside ophthalmological evaluation was undertaken in 312 patients. Post-operative neuro-ophthalmological complications developed in 80/312 (25.6%) patients and included: areas of retinal infarction (17.3%); retinal emboli (2.6%); visual field defects (2.6%); reduction of visual acuity (4.5%) and Horner's syndrome (1.3%). Neuro-ophthalmological complications were not observed in a control group of 50 patients undergoing major peripheral vascular surgery. Ten of 75 patients reviewed at 6 months still had detectable neuro-ophthalmological abnormalities, but functional disability occurred only in those with persistent visual field defects. Multivariate analysis revealed that extra-coronary vascular disease, severe and prolonged duration of heart disease prior to operation, and large drop in haemoglobin level during surgery may predispose to neuro-ophthalmological complications.

Adult

Anisoylated plasminogen streptokinase activator complex versus placebo. A preliminary multicentre study of safety and early mortality in acute myocardial infarction.

90 patients were enrolled into this preliminary multicentre study of the efficacy and safety of 30 units intravenous anisoylated plasminogen streptokinase activator complex (APSAC) compared with placebo in patients with acute myocardial infarction. 45 patients received APSAC and 45 placebo; the groups were similar for age, weight and site of infarction. There were significantly more women treated with APSAC (p less than 0.02). The mean time to treatment was 3.3 hours after symptoms of myocardial infarction for APSAC and 3 hours for placebo. The 30-day mortality was 7 patients in the placebo group and 1 in the APSAC group (p = 0.058). Adverse events were generally minor and were of similar overall frequency in both groups. There were more haemorrhagic events with APSAC, from which all patients recovered, and more cardiovascular events with placebo including 2 deaths from cardiogenic shock. APSAC showed a trend towards a reduction in 30-day mortality. Experience from this study has led to the initiation of the APSAC in myocardial infarction multicentre mortality study (AIMS).

Anistreplase

Factors influencing the choice of first-line treatment in chronic ischaemic heart disease.

The three categories of antianginal drugs--nitrates, beta-blockers, and calcium antagonists--are approximately equally effective in preventing angina. However, there is a marked intraindividual variation in response, which is only partly explained by differing underlying mechanisms. Choice of drug depends largely on other factors, such as whether or not there is severe myocardial or pulmonary dysfunction, whether there are side effects, and whether there is concomitant hypertension, a history of myocardial infarction, or arrhythmias. There is no "optimal" drug. Treatment has to be individualised.

Chronic Disease

Long-term intellectual dysfunction following coronary artery bypass graft surgery: a six month follow-up study.

As part of a prospective study of neurological and neuropsychological complications of coronary bypass surgery, 259 patients underwent psychometric assessment before operation and at seven days and six months after operation using a battery of 10 standard tests of intellectual function. This report describes the natural history of intellectual dysfunction soon after surgery and the incidence and functional impact of late neuropsychological impairment. The mean neuropsychological scores for the whole group remained unchanged or improved compared with levels before operation for the majority of the 10 tests. Analysis of the test scores for individuals showed that 147 of 259 (57 per cent) patients showed deterioration on at least one test score at six months. The degree of impairment was usually mild. One hundred and thirty of the 147 patients showed mild cognitive dysfunction (score deterioration on one or two tests) and only 17 patients had moderate or severe impairment (score deterioration on three or more tests). Detectable neuropsychological deterioration at six months often did not matter to the patient in functional terms. Seventy-one per cent of these patients had no significant symptoms; 27 per cent had minor symptoms and only 2 per cent were seriously disabled. Of the patients unemployed at six months, in only one case was intellectual impairment the factor preventing return to work. A search for possible predisposing factors for long-term intellectual dysfunction was made using a multivariate analysis of 91 variables for each patient. Cardiac failure before surgery and global impairment of left ventricular function were the only factors showing significant correlation.

Adult