Hypercatecholaminemia is known to lead to the development of irreversible damage to the myocardium.The mechanism of this damage has not yet been explained, although it has been suggested that it is effected through excessive B-adrenergic stimulation [6, 7, i0]. Noradrenalin (NA), adrenalin (A), and isoproterenol (IP) give rise to different B-stimulating effects, and in this series IP is the most powerful B-agonist.The aim of this investigation was to compare the harmful action of catecholamines differing in their affinity for ~-receptors, by the use of two independent quantitative methods of assessing damage (biochemical and morphological) in experiments on a model of the isolated rat heart. EXPERIMENTAL METHODMale Wistar rats weighing 200-250 g were heparinized, and 20 min later they were anesthetized with thiopental sodium in a dose of 0.2 mg/g intraperitoneally.The thorax of the anesthetized animals was opened and the heart quickly removed and immersed in cold (4°C) perfusion medium.After cardiac activity had ceased the preparation was placed in the chamber of a Langendorff's perfusion system, the aorta was cannulated, and retrograde perfusion with oxygenated (96% 02 and 4% C02) modified Krebs--Henseleit solution in bicarbonate buffer (pH 7.4-7.5) at 37°C was started under a constant perfusion pressure of 80 cm water.L-Noradrenalin bitartrate, L-adrenalin bitartrate, and DL-isoproterenol hydrochloride were used (all reagents were from Sigma, USA).The following series of experiments were performed series I (control), in which the hearts were perfused with Krebs--Henseleit solution for 160 min of the experiment.In the experiments of series II solutions of catecholamines were used in the following concentrations NA and A 10 -7 and 10 -6 M, IP i0-~-i0 -4 M. The concentrations of catecholamines in the perfusion fluid were monitored by Doty's method [3]. The hearts were perfused in accordance with the scheme: 20 min --washing hearts to remove blood, 20 min --control perfusion, 60 min --perfusion with solution containing catecholamine, 60 min --perfusion with Krebs--Henseleit solution.In all series the perfusion fluid was collected every 20 min and the velocity of the coronary flow was measured. Aliquots of perfusion fluid, collected during this time interval, were taken for analysis of enzyme activity: creatine phosphokinase (CPK) and lactate dehydrogenase (LDH).The rate of relief of the enzyme was calculated and expressed as activity of enzyme liberated into the perfusion fluid during unit time (U/min), and as the total quantity of enzymes released into the perfusion fluid during the whole period of investigation (U). Activity of CPK and LDH was studied by the use of kinetic methods [2, 9] on a reaction velocity analyzer (from LKB, Sweden).Some hearts in all series of experiments were fixed in buffered 10% formalin solution and embedded in paraffin wax.Sections through the heart 5-7 ~ thick, cut in the frontal plane, were stained by Lie's method [5] and with Heidenhain's iron hematoxylin.A general assessment of the...
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