- [Show abstract] [Hide abstract] ABSTRACT: One of the secondary objectives of the MIAMI Trial which evaluated the role of the beta-1-selective blocker metoprolol in suspected acute myocardial infarction was to further assess whether early intervention with beta-blockade can limit infarct size. A total of 5,778 patients from 104 worldwide centres were randomized into the trial. Various enzymes such as aspartate aminotransferase (ASAT), creatine kinase (CK), CK MB, CK B, lactate dehydrogenase (LD) and LD isoenzyme I were analysed. All enzymes were used according to the clinical routine of the respective hospital, except ASAT which was analysed once daily for 3 days in the majority of cases and LD I which was analysed every 12 h for 72 h in a subsample. A consistent observation was the lower serum enzyme activity among patients receiving metoprolol and randomized early after onset of symptoms, whereas no difference between metoprolol and placebo was observed in patients treated later in the course. The results of the MIAMI Trial support previous observations that early institution of metoprolol therapy limits infarct size, as indicated by the maximum serum enzyme activity.
- [Show abstract] [Hide abstract] ABSTRACT: In 727 patients with acute myocardial infarction, different enzyme variables reflecting infarct size were related to the 5-year mortality rate. The maximum activity of serum heat-stable lactate dehydrogenase (LD), analyzed every 12 hours for 48 to 108 hours, was significantly associated with the 5-year mortality rate when patients with a first myocardial infarction were evaluated (p less than 0.001), and similarly (p less than 0.001) when patients with a previous myocardial infarction were included in the analyses. Very similar results were found when the maximum activity of aspartate aminotransferase (ASAT) analyzed once daily for 3 days was related to the mortality rate over 5 years, whereas the maximum activity of creatine kinase (CK) and CK subunit B analyzed every 6 hours for 48 hours in a subset of patients did not predict the outcome to the same extent. The results from LD and ASAT analyses clearly indicated that the association between infarct size and 5-year mortality rate was caused by the much higher mortality rate in patients with larger infarcts during the first year after onset of infarction, whereas after the first year, incidence of death appeared to be independent of the original infarct size. Thus we conclude that although a highly significant relationship between infarct size and overall 5-year survival was found, the mortality rate seemed to be higher in patients with larger infarcts, particularly during the first year after infarction.
- [Show abstract] [Hide abstract] ABSTRACT: Eighty-seven Nordic Hospital laboratories participated in a joint SCE-NORDKEM follow-up study of the long-term stability of the previously established calibration factors for a number of alpha-amylase routine methods based on six different substrates. Human control materials with 90% pancreatic, 90% salivary, and pure pancreatic alpha-amylases were measured by the participants. The data were plotted before and after calibration of each method using a human pancreatic calibrator with an assigned catalytic concentration of 390 U/l (Phadebas blue starch method, 37 degrees C). As in the previous study, carried out 9 months earlier, the pre-calibration values varied over a six-fold range. The post-calibration values of all methods except those based on a tetraose substrate showed an acceptable inter-laboratory comparability. As a temporary measure, SCE recommends that the Nordic laboratories calibrate the accepted routine methods by their individual calibration factor. Detailed suggestions for calibration procedures and a discussion of the principles of transferability will shortly be published by the SCE in this journal.
- [Show abstract] [Hide abstract] ABSTRACT: In 585 patients with a first myocardial infarction the enzymatically estimated infarct size was related to the clinical course during a 2-year follow-up. Infarct size was estimated from maximum heat-stable lactate dehydrogenase activity. A higher maximum serum activity was associated with a higher mortality rate, more treatment with diuretics, digitalis and antiarrhythmics and a lower frequency of return to work. Patients with smaller infarcts according to maximum serum activity, however, had a higher incidence of angina pectoris and a higher reinfarction rate. We conclude that although there is a strong association between serum enzyme activity and mortality during a 2-year follow-up, the relation with morbidity appears to be more complex.
- [Show abstract] [Hide abstract] ABSTRACT: Serum (S) enzyme activity of aspartate aminotransferase (ASAT, E.C. 18.104.22.168.), heat stable lactate dehydrogenase (LD, E.C. 22.214.171.124.), creatine kinase (CK, E.C. 126.96.36.199.) and CK-B subunit and the respective standard electrocardiograms (ECG) were compared in 463 patients with suspected acute myocardial infarction (MI) in order to evaluate sensitivity and specificity. Serum ASAT was analysed daily for 3 days, S-heat stable LD every 12 h for 48-108 h, S-CK and S-CK-B every 6 h for 48 h and ECG once daily for 3 days. All four enzymes had a high sensitivity, varying from 99% for LD to 97% for CK-B. The highest specificity was observed for CK-B and CK (98%) as compared with heat stable LD (91%) and ASAT (74%). Standard ECG showed a high specificity (96%) and a low sensitivity (80%).
- [Show abstract] [Hide abstract] ABSTRACT: Ischemic myocardial injury is the main cause for myocardial dysfunction after open-heart surgery and the main cause for ischemic damage is imbalance between energy demand and energy supply before, during, and after aortic cross clamping [1, 2]. The major steps taken to prevent myocardial injury are cooling and cardiac arrest. In patients with ischemic heart disease uneven distribution of cold cardioplegic solution will occur, resulting in impaired cooling of poststenotic areas, as shown by thermography . Ischemia induces liberation of catecholamines from the nerve endings in the myocardium , which together with the raised sympathetic activity during cardiopulmonary bypass  increases the metabolic rate, with resulting energy depletion and increased ischemic damage. The energy supply during the ischemic period relies to a great extent on glycolysis or glycogenolysis.
- [Show abstract] [Hide abstract] ABSTRACT: Systemic glucose uptake was studied in 31 patients during 4 hr starting 1 hr after open heart surgery, using the hyperinsulinemic "clamp" technique at different plasma insulin levels and at a glucose concentration of 6 or 10 mmol/liter. Possible metabolic side effects related to the glucose uptake were studied by measurements of urinary catecholamine excretion, O2 consumption, CO2 production, and arterial PCO2. A peak systemic glucose uptake of 7.0 +/- 0.4 mg/kg body weight/min was found at a plasma insulin concentration of 3192 +/- 150 mU/liter and a blood glucose concentration of 10.2 +/- 0.1 mmol/liter. No significant difference was found in urinary catecholamine excretion compared to control patients. O2 consumption was unaltered while a 15% increase in CO2 production was observed.
- [Show abstract] [Hide abstract] ABSTRACT: A double-blind trial with the beta 1-selective blocker metoprolol in suspected acute myocardial infarction and during 3 months' follow-up included 1395 patients, aged 40-74 years, 698 on metoprolol and 697 on placebo. In order to further evaluate the tolerability to beta-blockade in the elderly, the total series was divided into 2 groups according to median age (61 years) and into quartiles, the lowest quartile (40-57 years) being compared with the highest (67-74 years). The decrease in heart rate and systolic blood pressure after intravenous metoprolol in the acute phase was similar in the elderly and the younger patients. Hypotension was observed more often in the metoprolol-treated than in the placebo-treated younger patients, while no difference was observed in the elderly. Bradycardia was observed more often in the metoprolol group in both age groups, while there was no difference regarding the incidence of congestive heart failure in either the younger or in the elderly patients. The effect on mortality, serious ventricular arrhythmias and chest pain seemed to be similar in different age groups. From the present series we conclude that hemodynamic reactions and tolerability to beta-blockade can be expected to be similar in elderly and younger patients.
- [Show abstract] [Hide abstract] ABSTRACT: In 709 patients with definite acute myocardial infarction (MI) the appearance of raised serum enzyme activity was related to onset of symptoms. Heat stable lactate dehydrogenase (LD), creatine kinase (CK) and CK B were analysed. A gradual increase in the incidence of raised enzyme activity in the first blood sample was seen for up to 18 hours after the onset of MI for all 3 enzymes. The incidence of raised enzyme activity in the first blood sample was higher for CK and CK B than for heat stable LD up to 24 hours after onset of MI, but thereafter a similar incidence was found. The median time between onset of symptoms and estimated appearance of raised serum enzyme activity was 6.2 hours for heat stable LD versus 4.3 hours for CK and 4.1 hours for CK B. A wide variation was however found. Infarct localization and chronic treatment with betablockade might affect these results. The clinical course including short- and long-term survival was similar in patients with early and later appearance of enzymes.
- [Show abstract] [Hide abstract] ABSTRACT: In 592 patients with an acute myocardial infarction different enzymatic estimations of the infarct size were compared. Heat stable lactate dehydrogenase (LD) was analysed every 12 hours for 48-108 hours. Aspartate amino transferase (ASAT) was analysed once daily for 3 days. In a subgroup creatine kinase (CK) and creatine kinase subunit B (CK B) were analysed every 6 hours for 48 hours. A strong positive correlation was observed between the peak activity of the different enzymes (r-values varying between 0.81 and 0.85). The peak activity of heat stable LD, CK and CK B were strongly related to the area under the enzyme curve (r-values varying between 0.94 and 0.98). A substantial decrease in estimated infarct size was observed in a large number of patients when intervals between sampling increased, most often found for CK B. It is concluded that the calculated peak activity of heat stable LD, ASAT, CK and CK B seems to give a similar information about the infarct size in the majority of patients with acute myocardial infarction. Analyses of the area under the enzyme curve do not deviate from calculated peak enzyme activity.
- [Show abstract] [Hide abstract] ABSTRACT: Thirty middle-aged, moderately obese men with untreated mild hypertension were allocated to two groups of 15 men each. Both groups were placed on energy-reduced diets (5.1 MJ/day) for 9-11 weeks which resulted in similar losses of body mass (8.5 kg). In group I the low energy diet was supplemented with sodium chloride leading to no change in urinary sodium excretion. During dieting there were significant reductions of plasma renin activity (PRA) and urinary excretion of noradrenaline and aldosterone. Heart rate but not mean arterial pressure (MAP) decreased significantly. Then followed a period of sodium restriction which resulted in a significant decrease in MAP and an increase in aldosterone excretion. In group II there was a reduction of sodium intake by about 80 mmol as judged from determinations of urinary sodium excretion. In this group the energy restriction was not accompanied by any changes in PRA or urinary excretion of aldosterone, whereas urinary noradrenaline excretion, heart rate and MAP decreased significantly. Urinary adrenaline excretion remained unchanged. It is concluded that the hypotensive response to moderate energy and sodium reduction cannot be explained by changes in the renin-aldosterone. system.
- [Show abstract] [Hide abstract] ABSTRACT: In 80 patients who underwent heart surgery the incidence of electrocardiographic (ECG) changes after the operation was analysed. A precordial grid containing 24 leads and leads II, III and aVF was used. Electrocardiographic measurements were taken the day before the operation and again 5 days after the operation. New Q-waves were observed in 2 patients (2.5%) in the 24 precordial leads, in 2 patients in leads II, III and aVF, and in one patient in both precordial leads and leads II, III and aVF. New T-wave inversions were observed in 20 patients (25%) in the 24 precordial leads, in 5 patients (6%) in leads II, III and aVF, and in 3 patients in both precordial leads and leads II, III and aVF. A similar serum enzyme activity was observed both in patients developing Q-waves as well as T-wave inversions compared with cases in whom ECG changes did not appear.
- [Show abstract] [Hide abstract] ABSTRACT: In 179 patients with anterior myocardial infarction the electrocardiographically estimated infarct size was related to serum enzyme activity. A precordial map containing 24 precordial positions and the peak activity of heat stable dehydrogenase (LD; EC 188.8.131.52) were used. A positive correlation was found between the area at risk (initial sum of ST-elevation) and the peak LD activity (r = 0.48 - 0.55; p less than 0.001). When the final Q-and R-wave amplitude were related to peak enzyme activity a better correlation was observed (r = 0.56 - 0.68; p less than 0.001). The sum of R-waves (sigma R) and the sum of Q-waves (sigma Q) in the 24 precordial leads were related to sigma R and sigma Q in five precordial standard leads. A good correlation was found between the two ECG methods (r = 0.75 - 0.83; p less than 0.001), indicating that an increased number of precordial leads gives information regarding the extent of infarction similar to that obtained with the routinely used standard leads. It is concluded that in the individual patient, serum enzyme activity and the final Q-and R-wave changes can give different information about infarct size. If, however, these two independent methods are used in a large number of patients in intervention studies they will probably give similar information about relative influence of the intervention on the mean infarct size.
- [Show abstract] [Hide abstract] ABSTRACT: In 585 patients having an acute myocardial infarction for the first time the relationship was investigated between estimated infarct size and the incidence of ventricular fibrillation and treated ventricular tachycardia during hospitalization. The size of the infarct was estimated from analyses of heat stable lactate dehydrogenase (LD) (EC 184.108.40.206.) in serum collected every 12 hr for 48-108 hr. All patients participated in a double-blind comparison of the beta 1-selective blocker metoprolol with placebo in suspected acute myocardial infarction. A correlation was observed between the enzymatically estimated infarct size and the incidence of ventricular fibrillation and treated ventricular tachycardia in patients on placebo (P less than 0.001), while this could not be demonstrated in patients on the beta-blocker (P greater than 0.2). In placebo treated patients there was a correlation between the maximum heat stable LD activity and early ventricular fibrillation (P = 0.034), late ventricular fibrillation (P less than 0.001), primary ventricular fibrillation (P = 0.002) as well as secondary ventricular fibrillation (P = 0.034). It is concluded that there seems to be a relatively strong correlation between the final size of the infarction and the occurrence of severe ventricular arrhythmias. Treatment with beta-blockade appeared to disturb this correlation.
- [Show abstract] [Hide abstract] ABSTRACT: In 581 patients with acute myocardial infarction (MI), the time lapse from estimated onset of infarction to estimated peak serum (S) enzyme activity was evaluated. Heat-stable lactate dehydrogenase (LD; E.C. 220.127.116.11) was analyzed every 12 h for 48-108 h after arrival in hospital (n = 581) and creatine kinase (CK; E.C. 18.104.22.168.; n = 224), and creatine kinase subunit B (CK-B; n = 211) were analyzed every 6 h for 48 h. Peak S-LD was observed between 14 and 110 h after estimated onset of MI (mean 46.6 +/- 0.6 h), peak S-CK was observed between 8 and 58 h (mean 25.0 +/- 0.6 h), and peak S-CK-B was also observed between 8 and 58 h (mean 22.8 +/- 0.7 h) after onset. In 86% of patients, peak LD was reached within 60 h after onset of MI, in 78%, peak CK was reached within 30 h, and in 82%, peak CK-B was observed within 30 h after onset of MI. A weak correlation was found between duration of pain and time lapse to S peak enzyme activity (r = 0.25 -0.27; p less than 0.001), while there was no correlation between S peak activity and time lapse from onset of MI to S peak activity. It is concluded, that although in the majority of patients with MI, peak serum-enzyme activity is reached within a predictable amount of time after estimated onset of MI there is wide variation, difficult to establish from the clinical course, among individual patients.
- [Show abstract] [Hide abstract] ABSTRACT: The Göteborg Metoprolol Trial was a double-blind, placebo-controlled, stratified trial aimed at evaluating the effect of the beta 1-selective blocker, metoprolol, in suspected acute myocardial infarction and during 2 years of follow-up. The primary end-point was 3-month mortality (blind treatment period). Secondary end-points were 2-year mortality, indirect signs of infarct size, chest pain, arrhythmias and tolerability. The entry criteria were fulfilled in 2,802 patients, 1,395 of whom were included in the trial. Treatment started as soon as possible after arrival in hospital with intravenous administration followed by oral treatment for 3 months. All patients were randomized 48 hours or less after estimated onset of infarction and 69% were randomized at 12 hours or less. The blind treatment had to be withdrawn in 19% of all randomized patients before the end of the 3-month follow-up.
- [Show abstract] [Hide abstract] ABSTRACT: In 1,375 patients serum activity of heat-stable lactate dehydrogenase (LD; E.C.22.214.171.124.) was analyzed every twelfth hour for 48 to 108 hours. The mean maximum LD activity was 11.1 +/- 0.4 mu kat X 1(-1) in the metoprolol group vs 12.4 +/- 0.5 mu kat X 1(-1) in the placebo group (p = 0.054). In patients in whom treatment was started 12 hours or less after the onset of pain, a 17% reduction in LD activity was observed (p = 0.009) and similar results were found in patients randomized 8 hours or less. Groups in which the effect after metoprolol treatment was more pronounced were those with an initially higher heart rate and also those with anterior myocardial infarction.
- [Show abstract] [Hide abstract] ABSTRACT: In 194 patients with inferior wall acute myocardial infarction (MI) defined from ECG, the initial ST elevation and final Q- and R-wave changes in leads II, III and aVF were related to peak serum enzyme (heat stable lactate dehydrogenase) activity. Positive correlations were observed between initial ST elevation and peak LD (r = 0.54; p less than 0.001) and between peak LD and the final Q- and R-wave changes (r = 0.45; p less than 0.001). Peak LD activity was strongly related to the incidence and severity of congestive heart failure, and to mortality after 90 days and 2 years. A similar relationship could not be demonstrated between ECG findings and clinical outcome.
- [Show abstract] [Hide abstract] ABSTRACT: In 563 patients with acute myocardial infarction and no previous myocardial infarction, the estimated infarct size was related to the estimated duration of pain and the amount of analgesics given. The size of infarction estimated from analyses of heat-stable lactate dehydrogenase (EC 126.96.36.199) at 12-hour intervals for 48-108 h and from Q- and R-wave changes in the ECG correlated positively, although weakly with duration of the pain and the amount of analgesics given. These data support the hypothesis that larger infarcts, as a group, evolve over a longer time period than smaller infarcts and that the duration of pain in many patients might be an indicator of the infarct size. In the individual patient, however, one cannot predict the size of the infarction from the severity of pain.
University of GothenburgGoeteborg, Västra Götaland, Sweden