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BACKGROUND: Coronary care units were developed in the 1960s as specially equipped and staffed areas where patients with acute myocardial infarction could be monitored and offered rapid resuscitation from life-threatening arrhythmias. Awareness of the morbidity and mortality of the wider spectrum of acute coronary ischaemia was unrecognized at that time. AIM: To examine the relative frequencies with which thrombolytic treatment and resuscitation from cardiac arrest are provided for patients with myocardial infarction in cardiac care units (CCUs), emergency departments (EDs) and other medical wards. DESIGN: Observational study. METHODS: We analysed records from the National Audit of Myocardial Infarction Project (MINAP) for 61 688 patients admitted to 230 acute hospitals in England and Wales during 2003, and who received a final diagnosis of myocardial infarction, for locations of initiation of thrombolytic therapy and of first cardiac arrest within hospital. RESULTS: Overall, 84% of 27 881 patients with ST-segment-elevation infarction, but only 42% of 30 382 patients with non-ST-elevation infarction, were admitted to a CCU. Of those receiving thrombolytic treatment for ST-elevation infarction, 68.3% of 21 595 did so in the ED. Within the first 4 h after arrival, the majority of episodes of cardiac arrest occurred in the ED: 709 (57%) vs. 488 (39%) in CCU, and 49 (4%) in medical wards. DISCUSSION: The traditional role of the CCU in providing early resuscitation and thrombolytic treatment for patients with ST elevation infarction has largely been devolved to the ED. The role of the CCU should be re-evaluated, and the service re-designed to provide specialist care for all presentations of acute coronary syndrome.

OBJECTIVE—To develop a performance indicator for acute myocardial infarction which would reliably measure success of treatment and which might provide an alternative to case fatality as an audited outcome. DESIGN—A two year audit of all cases of acute myocardial infarction and resuscitated cases of out of hospital cardiac arrest from coronary heart disease in patients under 75 years of age. Behaviour of patients in calling for help, performance of the ambulance services in treating out of hospital arrest, and of the hospitals in providing resuscitation and thrombolytic treatment are audited separately. SETTING—Four district general hospitals. AUDITED INTERVENTIONS—Resuscitation from cardiac arrest and thrombolytic treatment. MAIN OUTCOME MEASURES—Hospital case fatality and lives saved/1000 patients treated. RESULTS—Overall, the lives of 83/1000 patients were saved (95% confidence interval 70 to 96). Of these, 29 (35%) were saved by out of hospital resuscitation and 38 (46%) by in hospital resuscitation from cardiac arrest. It was estimated that 16 lives (19%) were saved by thrombolytic treatment. There were no significant differences in case fatality among the hospitals. CONCLUSIONS—Lives saved/1000 patients treated is an easily measurable index and assesses performance of the ambulance service as well as of the hospital. Because it is relatively insensitive to diagnostic definitions, it may provide a robust alternative to case fatality as a performance indicator. Keywords: acute myocardial infarction; audit; case fatality; outcome indicators

The aim of this study was to evaluate whether streptokinase (SK) may produce beneficial effects at the level of microvascular circulation in addition to coronary recanalization. Twenty mongrel dogs weighing 28.4 +/- 4.6 kg were randomized to receive SK (16,000-72,000 U/kg) or 20 ml saline (control) in an open-chest anterior descending artery occlusion (3 h) and reperfusion (2 h) model. Myocardial blood flow was measured by the radioactive microsphere technique and the state of microvascular circulation (red blood cell containing capillary counts and tissue red blood cell content) was evaluated in the infarcted subendocardial zone using computerized image analysis. The percentage (mean +/- SE) of cell-containing vessels normalized to nonischemic control areas was 166.5 +/- 7.5 in SK-treated infarcts while in untreated control infarcts it was more variable (130.0 +/- 15.6%) (2P > 0.1). The red blood cell content of infarcts treated with 2.0 megaunits SK was 3.9 +/- 0.6% compared with 6.7 +/- 0.9% in untreated control infarcts (2P = 0.029). Plasma viscosity was slightly reduced in SK-treated dogs (2P = 0.05), but no significant changes in blood fibrinogen, hemoglobin, blood flow, and high energy phosphate levels between control and SK-treated infarcts were observed. SK reduces congestion and results in more even reperfusion of the microvasculature in severely ischemic myocardium to which blood flow has been restored. This effect may be beneficial in the salvage and healing of clinical infarctions.

OBJECTIVE: To examine the clinical characteristics and 30-day fatality rate among patients with electrocardiograms (ECGs) ineligible for fibrinolysis in a consecutive series in four general hospitals in the UK. METHODS: We studied 2439 consecutive patients who were identified from regular ward visits, surveillance of results from hospital laboratories, and hospital discharge coding. RESULTS: Thirty percent (732) of patients did not have ECGs eligible for fibrinolysis therapy, while indications were uncertain in 55 (2%). Within the ineligible group, patients presenting with ST depression (n = 294) had a higher 30-day fatality rate than those with ST elevation or left bundle branch block (26% versus 17%; P < 0.001); they represented 40% of the group ineligible for fibrinolysis therapy, or 12% of the total cohort. Thirty-day fatality rates in patients presenting with pathological Q waves and no diagnostic ST segment changes (n = 130), those with T wave changes but no other abnormality (n = 168) and those with a normal ECG (n = 128) were 10%, 5% and 3%, respectively. Despite their high fatality rate, fewer patients with ST depression were admitted to coronary care units than those with ECGs eligible for fibrinolysis therapy (61% versus 85%; P < 0.001) and 23% did not receive heparin. The coronary anatomy in a subset of patients with ST depression showed two- or three-vessel disease in 79% and left main stenosis in 9%. The rates of coronary revascularisation were low in all groups (< 10%). CONCLUSION: Patients with ECGs ineligible for fibrinolysis therapy are a disparate group, with a high rate of fatality occurring in patients who present with ST depression. The high prevalence of multiple vessel coronary disease in patients with ST depression suggests that a more active management strategy is required.

OBJECTIVE: To confirm the validity of a previously described method for assessment of infarct artery patency involving serial measurements of creatine kinase activity by use of troponin T concentration as an independent plasma marker. DESIGN: Streptokinase (1.5 x 10(6) units) was given intravenously to 60 patients within 6 h of onset of prolonged chest pain and ST segment elevation, and blood was taken for measurement of troponin T concentration at baseline and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 h after starting treatment. Coronary arteriography was performed at 2.6 (SD 0.3) h. Plasma troponin T concentration was assessed by two methods: (1) as the absolute rise between 0 and 3 h; and (2) as the proportion of the total rise (from baseline to peak) over the same period. Accuracy for prediction of infarct artery patency, assessed by receiver operating characteristic curves, was compared for both methods of assessment using troponin T and was in turn compared with previously reported results on the same patients using serial measurements of creatine kinase activity. RESULTS: Sufficient values for prediction of patency using troponin T were available in 53 patients. A rise in troponin T between 0 and 3 h to > or = 9% of peak concentration predicted angiographic patency with sensitivity of 94% and specificity of 100%. By contrast, at the optimum cutoff for absolute rate of rise (0.5 micrograms/l/h) sensitivity was only 66% and specificity 86%. Comparable figures for creatine kinase were 92% and 91% (> or = 20% of peak by 3 h) and 62% and 78% (150 IU/l/h). Receiver operating curves confirmed better predictive accuracy for proportions over absolute rates of rise for both markers (P < 0.01). CONCLUSIONS: For accurate diagnosis of infarct artery patency using plasma markers it is necessary to express the rate of rise as a proportion of the peak level. Analysed in this way, both creatine kinase and troponin T are suitable for use in randomised trials of new thrombolytic or adjuvant drugs.

BACKGROUND After thrombolytic therapy, long-term patency of the infarct-related artery may reduce arrhythmias, limit ventricular dilatation, and provide collaterals to another infarct zone if further infarction occurs. However, independent long-term prognostic value of infarct artery patency has not been shown. METHODS AND RESULTS We followed 312 patients with first myocardial infarction treated < 4 hours after pain onset with thrombolysis (streptokinase [n = 188] or recombinant tissue-type plasminogen activator [n = 124]). At 28 +/- 11 days, cardiac catheterization was performed. Flow of the infarct-related artery was assessed by the TIMI scoring system, and a scoring system relating coronary stenoses and flow to the amount of myocardium supplied was also used. Follow-up was for 39 +/- 13 months. Cardiac death occurred in 5.8% of patients, and there were two noncardiac deaths. Revascularization was performed in 11.5% of patients. On univariate and multivariate analysis, ventricular function (ejection fraction, P = .006 and .02, or end-systolic volume index, P = .01 and .06) was the most important prognostic factor. Patency of the infarct-related artery measured as TIMI 3 flow was marginally significant on univariate analysis (P = .08) but not on multivariate analysis (P = .2). Patency was an independent prognostic factor in univariate and multivariate analysis when measured as an occlusion score (amount of myocardium supplied by an occluded artery, P = .01 and < .05). When the ejection fraction was > or = 50%, only occluded arteries supplying > 25% of the left ventricle affected prognosis adversely. If the ejection fraction was < 50%, occluded arteries supplying < 25% of myocardium also adversely affected prognosis. Treadmill exercise duration 4 weeks after infarction was the only other prognostic factor identified. CONCLUSIONS Ventricular function and infarct-related artery patency are independent prognostic factors after thrombolytic therapy for acute myocardial infarction.

BACKGROUND We investigated whether the proportion of creatine kinase (CK) MM3 to total MM isoform, measured in a single blood specimen taken at 3 hours after starting intravenous administration of streptokinase to patients with developing myocardial infarction, would give reliable information on patency or occlusion of the infarct-related coronary artery. METHODS Fifty-nine patients received streptokinase 1.5 x 10(6) U intravenously within 6 hours of onset of prolonged chest pain and ST-segment elevation. Patency of the infarct-related coronary artery was assessed by arteriography at 2.6 +/- 0.3 (SD) hours after starting streptokinase. Creatine kinase MM isoforms were measured by chromatofocusing in blood taken at 3 hours after streptokinase. RESULTS A proportion of CKMM3 to total CKMM of greater than 50% was present in 34 of 34 patients (100%) with a patent, infarct-related artery at arteriography and whose peak total CK activity reached twice the upper normal limit for our laboratory (600 U/L). CKMM3/total CKMM was less than 50% in 14 of 18 patients (78%) in whom the infarct-related artery was occluded. In five of six patients with a nondiagnostic total CK rise (peak < 600 U/L), 3-hour CKMM3/total CKMM was less than 50% despite a patent artery. CKMM3 was not measurable in one patient. CONCLUSIONS A proportion of CKMM3/total CKMM of greater than 50% is highly sensitive for prediction of infarct artery patency at 3 hours after administration of streptokinase. However, the test used in this way is not reliable for patients with "prevented" myocardial infarction. Also, positive tests do occur in patients with angiographically occluded arteries, possibly signifying intermittent reperfusion and occlusion.

We measured levels of tissue plasminogen activator (t-PA) antigen in 100 patients within six hours of the onset of acute myocardial infarction, in 34 patients with chronic angina but no recent infarction, and in 36 normal subjects. We also assayed von Willebrand factor in the acute patients and in the normal subjects. Measurements were repeated in 40 acute patients at three weeks after myocardial infarction. Although resting levels of t-PA antigen were not significantly different from normal during myocardial infarction, the capacity of the vascular endothelium to release t-PA after five minutes of venous occlusion was impaired (p less than 0.01). The acute phase vessel wall release of von Willebrand factor was increased during acute infarction (p less than 0.01). We conclude that impairment of t-PA production is associated with acute coronary thrombosis, although it is not possible to differentiate between a causative role or a secondary response due to exhaustion of the t-PA producing mechanism.

This study examined the effect of age on left ventricular (LV) function, assessed by contrast ventriculography 3 weeks after a first acute myocardial infarction in 312 patients who received thrombolytic therapy within 4 hours of the onset of infarction and in 83 patients who received placebo. Streptokinase was given to 188 patients and recombinant tissue-type plasminogen activator (rt-PA) to 124. Patients were divided into 2 age groups: less than 60 years (n = 244) and greater than or equal to 60 years (n = 151). Thrombolytic therapy improved ejection fraction in both age groups: from 54 +/- 13 to 59 +/- 11% (p = 0.021) in the younger group and from 50 +/- 14 to 57 +/- 13% (p = 0.004) in the older group. Ejection fraction was identical in streptokinase- and rt-PA-treated patients. Multifactor analysis of variance revealed that younger age and thrombolytic therapy were independently associated with improved ejection fraction. Thrombolytic therapy also reduced end-systolic volume (p = 0.001) by 14 ml in the elderly and 9 ml in the younger group. Minor bleeding complications were more frequent in the elderly and 3 serious hemorrhages occurred in patients greater than or equal to 60 years. These findings reveal that thrombolysis improves LV function in all age groups studied. Because increasing age is independently associated with a lower ejection fraction after acute myocardial infarction, thrombolytic therapy may confer greater benefits in older patients.

Objectives: To discover the circumstances of out of hospital cardiac death irrespective of resuscitation attempts. Design: Prospective community study over the two years 1994 and 1995. Setting: The health districts of Brighton, South Glamorgan, and York, UK. Subjects: 1290 victims of sudden death or cardiac arrest caused by coronary heart disease who were under 76 years of age. Interventions: Basic and advanced life support for witnessed cardiac arrests. Main outcome measures: Survival to reach hospital and for 30 days after the arrest. Results: 35 (35%) of 101 patients (mean age 64) whose arrest was witnessed by a doctor or paramedic survived for 30 days compared with 9 of 464 (2%) whose arrest was witnessed by a relative or bystander at home (mean age 66) and 15 of 200 (8%) whose arrest was witnessed in a public place (mean age 61). None of the 525 victims of an unwitnessed arrest survived but the majority of those whose arrest was witnessed had complained of new symptoms before the arrest. Victims who were given basic life support by relatives or bystanders had better survival (14 of 183 (8%)) than those who were not (10 of 481 (2%), p < 0.001). Of the 20% of arrests that occurred in public places, few were in places where public access defibrillators would now be available. Conclusions: The burden of out of hospital cardiac arrest is mainly in the home but most victims have premonitory symptoms. Public education to seek help urgently for new or prolonged chest pain seems the most promising method to address the problem.

Rescue thrombolysis appears to be safe and may be an alternative to angioplasty when normal epicardial blood flow is not achieved after administration of thrombolytic therapy in patients with acute myocardial infarction. Further trials are required to evaluate this approach.

To examine the clinical characteristics and 30-day fatality rate among patients with electrocardiograms (ECGs) ineligible for fibrinolysis in a consecutive series in four general hospitals in the UK.We studied 2439 consecutive patients who were identified from regular ward visits, surveillance of results from hospital laboratories, and hospital discharge coding.Thirty percent (732) of patients did not have ECGs eligible for fibrinolysis therapy, while indications were uncertain in 55 (2%). Within the ineligible group, patients presenting with ST depression (n = 294) had a higher 30-day fatality rate than those with ST elevation or left bundle branch block (26% versus 17%; P0.001); they represented 40% of the group ineligible for fibrinolysis therapy, or 12% of the total cohort. Thirty-day fatality rates in patients presenting with pathological Q waves and no diagnostic ST segment changes (n = 130), those with T wave changes but no other abnormality (n = 168) and those with a normal ECG (n = 128) were 10%, 5% and 3%, respectively. Despite their high fatality rate, fewer patients with ST depression were admitted to coronary care units than those with ECGs eligible for fibrinolysis therapy (61% versus 85%; P0.001) and 23% did not receive heparin. The coronary anatomy in a subset of patients with ST depression showed two- or three-vessel disease in 79% and left main stenosis in 9%. The rates of coronary revascularisation were low in all groups (10%).Patients with ECGs ineligible for fibrinolysis therapy are a disparate group, with a high rate of fatality occurring in patients who present with ST depression. The high prevalence of multiple vessel coronary disease in patients with ST depression suggests that a more active management strategy is required.

To investigate the current use of thrombolytic therapy in the management of patients with acute myocardial infarction and to determine the potential for an increased use of thrombolysis or percutaneous transluminal coronary angioplasty (PTCA).All hospitalised cases of acute myocardial infarction were identified in three health districts in the UK (population of 960,000) in patients under the age of 76 years during a 2-year period; 2439 patients had acute myocardial infarction, of whom 1264 (52%) received thrombolytic therapy. Failure to administer thrombolytic therapy was a result of the absence of diagnostic electrocardiograms in 712 (29.2%) patients, late presentation in 127 (5.2%), therapeutic error in 112 (4.6%), presence of a bleeding risk in 139 (5.7%) and other miscellaneous reasons in 80 (3.3%) patients. Thirty-eight of the 139 patients in whom bleeding risk was reported as a contra-indication could, in retrospect, have received thrombolytic therapy and a further 76 would have been suitable for primary PTCA.The potential for increasing the use of thrombolytic therapy seems to be limited and is unlikely to make a major impact on the in-hospital mortality from acute myocardial infarction. However, primary PTCA should be considered in those who are ineligible for thrombolysis because of bleeding risk as a contra-indication.

Objectives: To provide a contemporary account of the treatment and outcomes of acute coronary attacks in England and Wales and to identify strategies that might improve the outcome.

OBJECTIVE The primary purpose of this study was to assess the effects of 12 weeks of treatment with either troglitazone, an investigational thiazolidinedione that acts as an insulin-action enhancer, or placebo in patients with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS A total of 51 subjects with IGT between 24 and 77 years of age were enrolled in this multicenter, double-blind, placebo-controlled, parallel group study (troglitazone, 25 patients; placebo, 26 patients). Patients were randomly assigned to receive either 400 mg troglitazone (every morning [QAM]) or placebo (QAM). The main outcome measure was the oral glucose tolerance test (OGTT) assessing glucose, insulin, and C-peptide levels in the fasting state and every 30 min up to 2 h after ingesting the glucose load. Fasting serum levels of HbA1c, fructosamine, lipids, and blood pressure were also measured. RESULTS A total of 46 patients completed the study. The glucose, insulin, and C-peptide responses after a glucose load were significantly reduced at 6 and 12 weeks in the troglitazone treatment group. After 6 weeks of treatment, 75% (n = 18) of those taking troglitazone had improved to normal glucose tolerance, whereas only 38% (n = 9) of those of placebo showed improvement (P = 0.008). After 12 weeks of treatment, 80% (n = 16) of the troglitazone treatment group had normalized their glucose tolerance, while only 48% (n = 10) of those on placebo had converted to normal (P = 0.016). Fasting triglyceride levels in the troglitazone treatment group had decreased by 40 mg/dl (0.45 mmol/l) (P = 0.0016). Other lipid measurements, blood pressure, glycosylated hemoglobin, and fructosamine were normal at baseline for both treatment groups and remained normal throughout the study. CONCLUSIONS The glycemic response after a glucose load is statistically and clinically significantly improved for patients with IGT treated with troglitazone.

To compare a thromboxane antagonist (GR3219) with aspirin in patients with prolonged chest pain and ST segment depression to see if the frequency of attacks of chest pain was reduced.The trial was part of a study comparing GR3219 with aspirin, and streptokinase with placebo and comprised the GR3219/aspirin leg. Thirty one patients were randomly assigned to GR3219 80 mg twice daily and 28 to aspirin 300 mg daily. The patients were under the age of 76 and admitted to a coronary care unit within 6 hours of continuous chest pain. The ECG showed at least 1 mm of flat or down-going ST segment. The patients kept diaries of their pain over the subsequent 31 days.Seventy percent of patients developed further chest pain. There was no difference between the pattern of recurrent chest pain according to which drug was used.The hypothesis that specific thromboxane A blockade with GR3219 would be more efficacious than aspirin was not supported by these results.

In order to further define clinical and angiocardiographic predictors of long-term survival after myocardial infarction we followed 616 consecutive male patients under 60 years of age, survivors of a first (N = 455) or recurrent (N = 161) myocardial infarction, for 8.8 +/- 2.9 years. Patients had angiocardiography at 4-8 weeks after infarction; none had thrombolysis, but 33% had cardiac surgery, 14% on a clinical trial basis. Left ventricular end-systolic volume was the most powerful predictor of cardiac mortality; ejection fraction and end-diastolic volume added no further information. Myocardial score, a measure of the severity of coronary stenoses in relation to the amount of myocardium supplied, was of only borderline predictive value on multivariate analysis, possibly because any effect had been negated by coronary surgery. Administration of beta-blocker drugs had an independent effect of improving prognosis, while continued cigarette smoking worsened it. Age, status of index infarction (first or recurrent) and serum cholesterol did not affect survival. A trial of surgery, carried out in a subset of 200 of these patients who were relatively asymptomatic but had severe coronary disease, showed no survival advantage for intended surgical over non-surgical management. We conclude that a high left ventricular end-systolic volume remains the most important adverse prognostic factor after recovery from myocardial infarction.

Objective: The aims were to determine (1) the relationship between changes in contractile function (systolic shortening) and the appearance of diastolic dysfunction (postsystolic shortening) during progressive regional left ventricular ischaemia; (2) the effects of increased afterload (acute constriction of the descending thoracic aorta) on ischaemic contractile dysfunction; and (3) the effects of loading during ischaemia on load dependent relaxation. Methods: Regional myocardial function, using sonomicrometry, was measured in the short and long axes of the apex of the left ventricle of eight open chest anaesthetised dogs (16-20 kg). Progressive apical ischaemia was induced by graded reductions in left anterior descending coronary artery flow (critical constriction, ischaemia 1, ischaemia 2, total coronary occlusion, and postocclusive maximum reactive hyperaemia). Acute afterloading was induced by a snare placed around the descending aorta. Results: Consistent decreases in systolic shortening and increases in postsystolic shortening relative to the total segmental shortening in the short axis of the apical region were seen with worsening ischaemia. Aortic constriction increased the magnitude of apical postsystolic shortening and decreased apical systolic shortening in the short axis during critical constriction, ischaemia 1, and ischaemia 2. Long axis function changed in a qualitatively similar but quantitatively different manner. There was a significant decrease in the load dependency of relaxation with total coronary occlusion. Conclusions: (1) Changes in systolic and diastolic function occurred concomitantly as mild regional myocardial ischaemia developed and intensified; (2) afterloading significantly worsened regional systolic and diastolic dysfunction during mild ischaemia; and (3) progression of regional ischaemia resulted in loss of load dependent relaxation.

For clinical prognosis, LV function is best described in terms of ejection fraction (EF) or end-systolic volume (ESV). Because deterioration of LV function is the most important adverse prognostic factor for patients after recovery from myocardial infarction, any agent which improves function should improve long-term survival. Clinical trials in which LV function has been measured have shown that early administration of all the presently available thrombolytic drugs improves LV function. There is, however, no evidence that one drug is better than another for preservation of LV function. Indeed in our double-blind comparison of streptokinase (SK) with tissue plasminogen activator (tPA) in which intervention was made at 2.5 +/- 0.6 h after onset, EF at 3 weeks after infarction was 58 +/- 12% for SK (n = 116) vs 58 +/- 12% for tPA (n = 124). The 95% confidence limit for the difference was 0 +/- 3%. Patency rates on the infarct-related artery at 3 weeks were similar in the two groups (75% SK, 76% tPA). Besides reflecting infarct size, LV function is also influenced by healing of the infarct, infarct expansion and LV remodelling. Two clinical trials have shown that captopril treatment started at 1-4 weeks after infarction and continuing for 1 year can prevent progressive LV dilatation in patients who have not received thrombolysis. One possible explanation for our own finding of similar effects of SK and tPA on LV function at three weeks after infarction, despite presumably more rapid reperfusion in patients given tPA, is that later reperfusion with SK prevented infarct expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

The high incidence and greater odds ratio of cough among Chinese patients taking ACE inhibitors raises the possibility of an enhanced susceptibility to this adverse effect among the Chinese.

The majority of readers of this article are likely to be hospital based clinicians whose experience of acute myocardial infarction is necessarily limited to examination of the survivors of a storm which has already taken its major toll. As has always been the case, most deaths from heart attack occur outside hospital and are medically unattended, as are about one quarter of non-fatal infarctions which are “silent” with no or atypical symptoms. For out-of-hospital deaths, even if a necropsy is carried out, it is in the majority of cases impossible to determine whether death had been caused by a developing infarction or by re-entrant ventricular fibrillation starting at the borders of a myocardial scar. Finally, it is impossible strictly speaking nowadays to speak about “natural” history. The history is inevitably “unnatural” in that it has in many cases been modified by treatment. In the most recent study performed in the UK,1, 74% of 1589 deaths from acute coronary heart attacks in people under 75 years of age occurred outside hospital; the proportion of out-of-hospital to total deaths varied inversely with age from 91% at age

EDITOR,—The North of England Stable Angina Guideline Development Group has provided concise and authoritative recommendations for the management of stable angina in primary care.1 They do not, however, say anything about …

Regional uptake of 99mTechnetium diphosphonate was compared with regional myocardial blood flow 6, 12 and 24 h after the onset of myocardial infarction in dogs, and with regional creatine kinase depletion 24 h after the onset. Uptake of the imaging agent increased from 6 to 24 h, but no consistent relationship could be demonstrated between regional myocardial blood flow and regional uptake of the diphosphonate nor between uptake and regional creatine kinase depletion at the centre or border of the infarct. In addition, inappropriately high levels of 99m Technetium uptake could be demonstrated in the epicardial layer of the normal tissue surrounding the infarct. We conclude that diphosphonate uptake is not quantitatively related to the severity of ischaemia, and that use of this substance for imaging may over-estimate myocardial infarct size.

In order to compare the time-course of disappearance of macromolecules and electrolytes from ischaemic myocardium, measurements of creatine kinase and lactate dehydrogenase activity and myoglobin, K+ and Na+ concentration were made on myocardial extracts from dogs which had left anterior descending coronary artery ligation for 3, 6, 12 and 24 h (4 groups of 6 dogs each). Intensity of ischaemia was assessed by myocardial blood flow measured with 15+/- 5 micrometers microspheres at 15 min after ligation. Creatine kinase and lactate dehydrogenase activities and K+/Na+ concentration ratios were at all times correlated with the magnitude of collateral blood flow in the ischaemic myocardium, while myoglobin concentration was correlated with blood flow only at 12 and 24h. Comparisons of the intensity of depletion at the various times after ligation showed that K+, K+/Na+ and creatine kinase had all reached a steady state at 12 h after ligation while lactate dehydrogenase and myoglobin had still to reach a steady state at 24 h. We conclude that these indices are mutually supportive markers of the intensity of ischaemia of 24 h duration, but K+ or K+/Na+ may be the most reliable indices for shorter periods of ischaemia of 3 to 6 h duration.

SUMMARY 1. Plasma levels of propranolol were measured fluorometrically in patients with angina pectoris and in patients admitted to the Coronary Care Unit with acute myocardial infarction. 2. In thirty patients with stable angina pectoris, plasma propranolol levels varied almost linearly with doses between 10 and 120 mg during 6-hourly chronic oral administration. Plasma levels greater than 100 ng/ml produced 70–80% reduction in the tachycardia induced by strenous exercise on a treadmill. 3. In nineteen patients with acute myocardial infarction given oral propranolol, 20 mg 6-hourly, peak as well as trough plasma levels of the drug increased progressively but remained below 100 ng/ml in all except two patients during the first 24 h after their admission to the Coronary Care Unit. 4. The data suggest that the use of low and fixed doses of propranolol may not produce adequate plasma levels or significant β-adrenoceptor blockade in the early stages of acute myocardial infarction in man.

The value of intraaortic balloon counterpulsation in limiting infarct size and improving survival was studied in patients with early transmural myocardial infarction complicated by acute heart failure. Thirty such patients, previously well, were randomly assigned to counterpulsation (14 patients) or standard therapy (16 patients). Counterpulsation was begun 4.8 to 13.7 hours (mean 7.1) after the onset of pain and continued for less than 1 to 11 days (mean 4.5). Peak creatine kinase was 1,794 ± 846 IU/liter (mean ± standard deviation) in patients receiving counterpulsation compared with 1,688 ± 908 for those receiving standard therapy; cumulative creatine kinase was 3,590 ± 1,936 IU/liter for patients receiving counterpulsation and 2,945 ± 1,803 for those receiving standard therapy. Hospital mortality was similar (counterpulsation, 7 of 14; standard therapy, 7 of 16 [p = 0.05 for 25 percent mortality reduction]) as was mortality at follow-up (counterpulsation, 8 of 14; standard therapy, 10 of 16 [p = 0.09 for 25 percent mortality reduction]). Functional class at follow-up examination 1 to 36 months (mean 15) after infarction was also similar in the two groups. Counterpulsation did not appear to modify infarct size or to alter morbidity or mortality when initiated as primary therapy 4.8 to 13.7 hours after the onset of symptoms of myocardial infarction.

Measurement were made of the interaction of 8Kr, 133Xe, CH3I (131I) and I2 (131I) with various silver zeolites and activated charcoals under varying relative humidities and temperatures. Results show silver zeolite has significantly less interaction with noble gases and high adsorption efficiencies for CH3I making it superior to charcoal for airborne radioiodine monitoring. The penetration of airborne iodine activity into the silver zeolite filter bed was also examined. CH3I penetrated slightly deeper than I2 at the same air flow velocity; however, at 17.4 feet per minute, no more than 5% of the iodine activity in either form penetrated deeper than 1 cm into the filter bed. The sensitivity of the iodine-131 activity detection system was found to be approximately 2.5% (1% = 2.22 x 104 counts per minute/?Ci) at the 364 Kev photopeak with a 100 Kev energy window width.

A modified method for the measurement of total creatine phosphokinase release from venous blood samples taken four-hourly after myocardial infarction has been used in 43 patients admitted to a Coronary Care Unit. The fractional decay rate (Kd) of enzyme activity has been measured by a standardized method in each patient, and accuracy of the calculation of total enzyme release has been improved by allowance for individual variations in decay rate, and discarding of data from which decay rates cannot be measured within confidence limits of less than plus or minus 15 per cent. Total enzyme release was greater in cases of transmural infarction than in patients with subendocardial infarction, and showed a good positive correlation with clinical indices of the extent of myocardial damage. As noted by previous workers, this method allows for the measurement of the rate as well as the extent of enzyme release, and so should prove useful in the clinical evaluation of therapeutic agents which might accelerate or retard the rate of myocardial necrosis in patients with acute myocardial infarction.