Improvement of myocardial perfusion after thrombolysis assessed by thallium-201 exercise scintigraphy

The effects of recanalization by early intracoronary streptokinasein acute myocardial infarction on myocardial perfusion werestudied in a subset of 236 out of 533 patients enrolled in aprospective multicentre trial, randomly allocated to eitherconventional treatment or to thrombolysis. Maximal symptom-limitedthallium-201 stress testing was performed nine to 14 (median12) weeks after the acute event in 236 patients with a firstmyocardial infarction, of whom 108 patients were allocated toconventional treatment and 128 patients to thromolysis. Three-viewthallium exercise and redistribution scintigrams were dividedinto eight segments. The number of normal thallium segmentsat redistribution was 5.3±1.6 (mean±SD) in thecontrol group and 5.8±1.6 in the thrombolysis group (P<0.01), indicating increased myocardial perfusion after earlythrombolytic treatment. This beneficial effect was particularlyevident in patients with a first anterior infraction with 4.8±1.6normal thallium segments in the control group and 5.9±1.6normal segments in the thrombolysis group (P <0.001). Therewas no difference in residual ischaemia during exercise betweenthe control and the thrombolysis group either in the patientswith anterior or in those with inferior infarction. It is concluded that early thrombolysis within 4 h after onsetof symptoms, in some of the patients followed by angioplastyor coronary artery bypass surgery, leads to sustained improvementof myocardial perfusion at rest without excessive ischaemiaduring exercise, particularly in patients with acute anteriorinfarction.     

Protection of myocytes against free radical-induced damage by accelerated turnover of the glutathione redox cycle

The primary defence mechanism of myocytes against peroxidesand peroxide-derived peroxyl and alkoxyl radicals is the glutathioneredox cycle. The purpose of the present study was to increasethe turnover rate of this cycle by stimulating the glutathioneperoxidase catalysed reaction (2GSHGSSG), the glutathione reductasecatalysed reaction (GSSG2GSH), or both, Neonatal rat heart cellcultures were subjected to a standardized protocol of oxidativestress using 80 µmol. l^–1 cumene hydroperoxide (CHPO)for 0–90 min. The consequences of this protocol were describedin terms of cellular concentrations of GSH, GSSG, NADPH andATP, formation of malondialdehyde (MDA), release of GSSG andof ATP catabolites, depression of contraction frequency, cellularcalcium overload, and enzyme release. Trolox-C, an analogue of vitamin E, accelerated the glutathioneperoxidase reaction leading to lowering of GSH concentrationand the GSH/GSSG ratio, less MDA formation, diminished negativechronotropy, delayed calcium overload, and less enzyme release.Glucose was used to accelerate the glutathione reductase reactionby supplying NADPH, leading to higher GSH concentration anda higher GSH/GSSG ratio, less MDA formation, diminished negativechronotropy, unchanged development of calcium overload, andless enzyme release. As a full turn of the glutathione redoxcycle involves both the peroxidase and the reductase reactions,the combination of Trolox-C and glucose was superior to eitherof the two alone: 90 min following addition of CHPO togetherwith Trolox-C and glucose, the GSH concentration and the GSH/GSSGratio were almost normal, MDA formation was extremely low, calciumoverload was markedly delayed, and enzyme release hardly occurredat all. Cells remained beating in the observation period of30 min. We conclude that the capacity of the glutathione redoxcycle to withstand oxidative stress can be increased by stimulationof either the peroxidase reaction or the reductase reaction,and that optimal redox cycling is achieved by stimulation ofboth reactions.     

Quantitation of global and regional left ventricular function by cine magnetic resonance imaging during dobutamine stress in normal human subjects

Magnetic resonance imaging (MRI) provides high-resolution imagesof the heart. However, physical exercise during MRI is difficultdue to space restriction and motion artefacts. To evaluate thefeasibility of MRI during stress conditions, dobutamine wasused as an alternative to exercise. Haemodynamics, ventricularvolumes and wall thickening were measured at rest and duringpeak dobutamine infusion (15 µg . kg^–1 . min^–1)in 23 normal human subjects. To calculate left ventricular volumes,eight short-axis views were obtained encompassing the left ventriclefrom base to apex. At six levels, percent systolic wall thickening(% WTh) was measured in 18 segments (20° intervals). Heartrate, systolic and diastolic blood pressures, stroke index,cardiac output and left ventricular ejection fraction increasedsignificantly during dobutamine infusion (all P values <0.001).In addition, % WTh increased significantly (P < 0.001 duringdobutamine compared to the control state at all levels exceptin the apical and low-left ventricular levels. Both in controlconditions and during dobutamine, segmental wall motion analysisshowed the highest % WTh at the posterolateral area and thelowest % WTh at the septal region (P <0.05). MRI clearly identifies wall motion dynamics and provides calculationsof segmental wall thickening and haemodynamic parameters. Dobutamineis a useful stress agent by virtue of its safety, operator controland its effects which resemble physical exercise.     

Myocardial (iso)enzyme activities, DNA concentration and nuclear polyploidy in hearts of patients operated upon for congenital heart disease, and in normal and hypertrophic adult human hearts at autopsy

To investigate biochemical characteristics of hypertrophic myocardium of young and adult humans, we analysed myocardial biopsies obtained from 28 mainly young patients undergoing cardiac surgery for congenital heart disease and 41 autopsied hearts from 18 adult normal and 23 hypertrophic human subjects. Myocardial activities of the enzymes creatine kinase and lactate dehydrogenase were independent of age during childhood, but decreased significantly with hypertrophy at adult age. Myocyte nuclei showed increased polyploidization during childhood which was progressive with age, and in the adult stage polyploidization was correlated with heart weight. Nevertheless myocardial DNA concentration fell under both conditions, which is to be ascribed to the 'diluting' effect of myocyte hypertrophy. Before an age of 8 years DNA concentration in the child heart material studied has reached the value found in adult nonhypertrophic hearts, although at that time polyploidization of myocyte nuclei in child hearts was only half the value found in adult non-hypertrophic hearts. Biochemical measurement of DNA concentration in peroperatively taken myocardial biopsies may contribute to the in vivo diagnosis of ventricular hypertrophy in quantitative terms, in combination with radiology, echocardiography and histology.     

Efficacy and Safety of Thrombolysis with Intravenous Streptokinase Initiated Prior to Ambulance Transport from Community Hospital to Tertiary Health Care Center

We studied the safety and efficacy of thrombolytic therapy for acute myocardial infarction initiated prior to ambulance transport. Two treatment regimens were compared in a prospective design: 40 patients (group A) received intravenous streptokinase 5 ± 10⁵ IU (SK-IV) prior to and during ambulance transport and were compared with 36 patients (group B) in whom the same dosage of streptokinase was given after arrival in our hospital. In all patients immediate coronary angiography was performed, followed by intracoronary streptokinase administration. Infarct size was assessed by cumulative release of α-hydroxybutyrate dehydrogenase. Apart from three episodes of ventricular fibrillation no procedure-related complications occurred during transport. Median time to SK-IV was 70 minutes in group A versus 125 minutes in group B (P < 0.001). At first visualization the infarct-related vessel was patent in 23 patients (58%) in group A and in 6 patients (17%) in group B (P < 0.001). Anterior wall infarction median infarct size in group A was 32% smaller than that in group B (P < 0.05). We conclude that SK-IV started before ambulance transport is safe, accelerates early reperfusion rate, and consequently leads to a further limitation of infarct size in patients with anterior wall infarction. (J Interven Cardiol 1989:2:3)