[Effect of vitamin E on cardiac muscle function and metabolism during anoxia and after reoxygenation (author's transl)].
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Biomedical subjects
Publications and source records attributed to C M Caldarera.
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Treatment of perfused rabbit heart with reserpine causes a decrease of incorporation of labelled precursors into RNA species of subcellular fractions and polyamines. Ornithine decarboxylase, S-adenosylmethionine decarboxylase and cytoplasmic Mn2+-stimulated polyadenylate polymerase activities are not modified. Addition of noradrenaline to reserpine-treated perfused hearts enhances, compared with the control, the incorporation of precursor into RNA in all subcellular fractions other than the nuclear one, restores incorporation of labelled putrescine into polyamines, enhances ornithine decarboxylase and S-adenosylmethionine decarboxylase activities and causes a 12-fold increase in cytoplasmic Mn2+-dependent polyadenylate polymerase activity. After treatment with noradrenaline the increase in radioactivity was found solely in AMP after hydrolysis of microsomal RNA to nucleoside monophosphates.
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Environmental oxygen is shown to have a regulatory role in growth rate and the mechanism of gene de-repression in chick-embryo heart cells; it modulates the intracellular concentration of polyamines, and this appears to be closely related to histone acetylation.
An experimental study on myocardial viability after acute occlusion of the left anterior descending coronary artery (LAD) for period of six hours is described. For this study 24 adult dogs were used in which an acute myocardial infarction for an area of 20-30% of left ventricul were obtained with ligatures completely occluding the LAD and his collaterals. Following ligature release, on the LAD only, ECG, BP, VCP and histology were studied with the general clinical conditions. The Authors affirm that clinical and ECGraphic data became worse after reperfusion; instead histological data show the possibility of recovery of many muscolar cells of ischemic and neighbouring areas.
The behaviour of some enzymatic activities, such as monoamino oxidase (MAO), diamino oxidase (DAO), catalase, peroxidase and creatin chinase (CPK) have been studied both in blood serum and myocardial tissue of acute infarcted dogs (obtained by coronary occlusion). The most significant results are the changes of the DAO activity (--50% from the control) and peroxidase activity (+60%), 6 hours after acute ischemia. The effect of reperfusion was studied 2 hours later. A recovery of DAO activities was shown, while the peroxidase activities stayed elevated. All the enzymatic activities studied were evaluated in the serum, under the same experimental conditions. An increase of all these activities was observed until 6th hour of coronary occlusion. The reperfusion of acute ischemia, after six hours, causes a further increase of CPK and MAO activities and a decrease of catalase peroxidase and particulary evident DAO activities. The results of this experiment show that reoxygenation, under our experimental conditions, increases a further enzymatic release and in part causes a metabolic recovery of heart muscle.
Free nucleotide, polyamine and nucleic acid synthesis was studied in myocardial acute ischemia and reperfusion. An early stimulation of biosynthesis of these compounds was observed during ischemia, than later, a remarkable decrease of their specific radioactivity appeared. Reperfusion experiments cause a significant increase of nucleic acids and related compound biosynthesis. The results indicate that the biochemical mechanism of myocardial protein synthesis, under our experimental conditions are not irreversibly damaged by ischemia. In fact, the reperfusion causes a remarkable recovery of nucleic acid, free nucleotide and polyamine specific radioactivity. The changes during the period of infarction and subsequent reperfusion show that polyamines play a key role in myocardial ischemia and reperfusion.
The relationship between polyamines and RNA synthesis was studied by considering the action of spermine on histone acetylation in perfused heart. In addition, the effect of methylglyoxal bis(guanylhydrazone), inhibitor of putrescine-activated S-adenosylmethionine decarboxylase activity, on RNA and polyamine specific radioactivity and on acetylation of histone fractions was also investigated in perfused heart. Different concentrations of spermine and/or methylglyoxas bis(guanylhydrazone) were injected into the heart, 15 min after beginning the perfusion. The results demonstrate that spermine stimulates the specific radioactivity of RNA of subcellular fractions. Acetylation of the arginine-rich histone fractions, involved in the regulation of RNA transcription, is enhanced by spermine. The perfusion with methylglyoxal bis(guanylhydrazone) causes a decrease in the specific radioactivity of polyamines and RNA, and in acetylation of histone fractions. However, spermine is able to reverse the methylglyoxal bis(guanylhydrazone) inhibition when injected simultaneously. From these results we may assume a possible role for spermine in the regulation of RNA transcription.
A close relationship has been observed between polyamine, as spermine and spermidine, and nucleic acid synthesis during heart hypertrophy, induced in the rats experimentally, by physical exericse (swimming). The role of spermine on RNA synthesis has been studied by perfusion experiments of the heart. Spermine is able to stimulate myocardial RNA synthesis of all subcellular fractions. The biochemical mechanism of this phenomenon may be explained by the results of histone acetylation under the action of spermine, showing an increased radioactivity of F 2aI and F 2a2 arginine-rich histone fractions. This suggests that spermine may act modulating histone acetylation, with a consequence on the gene transcription mechanism.
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