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The ultrastructure of selentum-deficient rat hearts
J Mol Cell Cardiol 19 (Supplement III) (1987)
190
THE U L ~ OF S~.~qIIFrDEFICIENT RAT HEARTS. R. Myklebust, K. Ytrehus, J. RJ_ngstad, O.D. Mj~s. Institute of Medical Biology, University of Tr~nsr Norway. Seleniur~ (Se) is an essential constituent of the peroxide metabolizing enzyme glutathione peroxidase. In this study the ultrastructure of Se-deficient rat hearts was investigated. Se-deficient hearts and control hearts were perfused for 20 rain in a Langendorff system and then perfusion-fixed using McDowell's fixative. For quantification of ultrastructural changes merphometry was used. From each heart 5 randomly selected biopsies were investigated, and frc~ each biopsy 5 randomly selected micrographs were taken. No signs of dar~ges were observed in the control group. In the Se-deficient group, however, mitochondrial swelling and filamental disorganizaticn were observed. The total n~nber of myocytes on the micrographs were counted and classified as either normal or damaged. No damaged cells were found in the control group, whereas 9% of the cells had clear signs of damage in the Se-deficient group. Cellular volume fractions were calculated using the point-counting method. Volture fraction of intracellular edema was 1.5% ,in .Se-def~cient hearts. No difference was found in volume fraction of mitochondria. This study indicates that Se-deficiency can lead to myocardial cell damage.
191 EXAMINATION OF THE CARBIOTOXIC EFFECTS OF ORGANIC PHOSPHOROACIO ESTER COMPOUNDS IN EXPERIMENTS WITH ISOLATED RAT HEARTS L. Nagymajt4nyi, I . Besi. Oepartment of Hygiene and Epidemiology, U o i v e r s i t y Medical School Szeged, Szeged, Hungary Cardiac data obtained from people poisoned l e t h a l l y by organic phosphate esters as w e l l as in v i v o animal experiments have shown before t h a t these compounds have i r r e v e r s i b l e c a r d i o t o x i c e f f e c t s which are independent of the c h o l i n e r g i c system, and are affected by the chemical s t r u c t u r e of the agents. In the course of experiments made with i s o l a t e d r a t hearts changes i n the function of h e a r t caused by c e r t a i n phosphate esters were examined by analysing the mechanogram and the action potentials of the heart by a computer processing elaborated by the authors. It was found that the agents had made a negative influence on the mechanic and electric function of the heart to varying degree, pharmacons affecting the ion transport of the membrane acted on the toxic process and partly diminished the harmful influence.
192
E F F E C T OF P R A J M A L I N E ON A T R I O V E N T R I C U L A R R E F R A C T O R I N E S S A N D C O N D U C T I O N . M. N~neth, J. Gy. Papp, L. Szekeres. Department of Pharmacology, University Medical School, Szeged, Hungary. Prajmaline is known to be a Class I antiarrhythmic drug characterized by the ability to block fast sodium channels in the working myocardium. The effect of this drug on the function of the atrioventricular (AV) conducting system has been little studied. The present work was designed to analyze the efficacy of prajmaline (0.i to 0.5 mg/l) in different portions of the AV conducting pathway in ccmioarison with other Class I (lidocaine, 5 mg/l ; mexiletine, 2 rag/l) and also with Class IV (verapamil, O.i mg/l ; diltiazem, O. 2 n~/i) antiarrhythnic drugs, utilizing a nticroelectrophysiological procedure elaborated for rabbit cardiac preparations (L. Szekeres, J.Gy. Papp (Eds.): The Pharmacological Protection of the Myocardium, Pergamon Press - Akad~miai KiadS, OxfordBudapest, pp. 191-195, 1986). Prajmaline preferentially prolonged the His-Purkinje (H-P) and His-ventricular (H-V) conduction time and effective refractory period. To a lesser extent the atrio-Hisian (A-H) conduction time and effective refractory period were also increased in the presence of the drug. The effect of lidocaine and mexiletine was similar to that of prajmaline, whereas verapamil end diltiazem had virtually no influence on the H-P and H-V oonduction and refractoriness, but significantly prolonged the A-H interval and refractory period. The results seem to support the view that prajmaline has predc~inant Class I and some subsidiary Class IV antiarrhythmic properties.
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190
THE U L ~ OF S~.~qIIFrDEFICIENT RAT HEARTS. R. Myklebust, K. Ytrehus, J. RJ_ngstad, O.D. Mj~s. Institute of Medical Biology, University of Tr~nsr Norway. Seleniur~ (Se) is an essential constituent of the peroxide metabolizing enzyme glutathione peroxidase. In this study the ultrastructure of Se-deficient rat hearts was investigated. Se-deficient hearts and control hearts were perfused for 20 rain in a Langendorff system and then perfusion-fixed using McDowell's fixative. For quantification of ultrastructural changes merphometry was used. From each heart 5 randomly selected biopsies were investigated, and frc~ each biopsy 5 randomly selected micrographs were taken. No signs of dar~ges were observed in the control group. In the Se-deficient group, however, mitochondrial swelling and filamental disorganizaticn were observed. The total n~nber of myocytes on the micrographs were counted and classified as either normal or damaged. No damaged cells were found in the control group, whereas 9% of the cells had clear signs of damage in the Se-deficient group. Cellular volume fractions were calculated using the point-counting method. Volture fraction of intracellular edema was 1.5% ,in .Se-def~cient hearts. No difference was found in volume fraction of mitochondria. This study indicates that Se-deficiency can lead to myocardial cell damage.
191 EXAMINATION OF THE CARBIOTOXIC EFFECTS OF ORGANIC PHOSPHOROACIO ESTER COMPOUNDS IN EXPERIMENTS WITH ISOLATED RAT HEARTS L. Nagymajt4nyi, I . Besi. Oepartment of Hygiene and Epidemiology, U o i v e r s i t y Medical School Szeged, Szeged, Hungary Cardiac data obtained from people poisoned l e t h a l l y by organic phosphate esters as w e l l as in v i v o animal experiments have shown before t h a t these compounds have i r r e v e r s i b l e c a r d i o t o x i c e f f e c t s which are independent of the c h o l i n e r g i c system, and are affected by the chemical s t r u c t u r e of the agents. In the course of experiments made with i s o l a t e d r a t hearts changes i n the function of h e a r t caused by c e r t a i n phosphate esters were examined by analysing the mechanogram and the action potentials of the heart by a computer processing elaborated by the authors. It was found that the agents had made a negative influence on the mechanic and electric function of the heart to varying degree, pharmacons affecting the ion transport of the membrane acted on the toxic process and partly diminished the harmful influence.
192
E F F E C T OF P R A J M A L I N E ON A T R I O V E N T R I C U L A R R E F R A C T O R I N E S S A N D C O N D U C T I O N . M. N~neth, J. Gy. Papp, L. Szekeres. Department of Pharmacology, University Medical School, Szeged, Hungary. Prajmaline is known to be a Class I antiarrhythmic drug characterized by the ability to block fast sodium channels in the working myocardium. The effect of this drug on the function of the atrioventricular (AV) conducting system has been little studied. The present work was designed to analyze the efficacy of prajmaline (0.i to 0.5 mg/l) in different portions of the AV conducting pathway in ccmioarison with other Class I (lidocaine, 5 mg/l ; mexiletine, 2 rag/l) and also with Class IV (verapamil, O.i mg/l ; diltiazem, O. 2 n~/i) antiarrhythnic drugs, utilizing a nticroelectrophysiological procedure elaborated for rabbit cardiac preparations (L. Szekeres, J.Gy. Papp (Eds.): The Pharmacological Protection of the Myocardium, Pergamon Press - Akad~miai KiadS, OxfordBudapest, pp. 191-195, 1986). Prajmaline preferentially prolonged the His-Purkinje (H-P) and His-ventricular (H-V) conduction time and effective refractory period. To a lesser extent the atrio-Hisian (A-H) conduction time and effective refractory period were also increased in the presence of the drug. The effect of lidocaine and mexiletine was similar to that of prajmaline, whereas verapamil end diltiazem had virtually no influence on the H-P and H-V oonduction and refractoriness, but significantly prolonged the A-H interval and refractory period. The results seem to support the view that prajmaline has predc~inant Class I and some subsidiary Class IV antiarrhythmic properties.
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