The Effect Of Breed, Age, And Sex On Myocardial Necrosis Produced By Isoproterenol In The Rat

Progressive hypertrophy and heart failure in β 1 -adrenergic receptor transgenic mice

“…Hypertrophic responses have been described for the G q pathway (25), and transgenic overexpression of G␣ q in the heart promotes the development of pressure-induced heart failure (26). Histological changes have long been known to occur in hearts in response to chronic treatment with isoproterenol (27) but have not been reported in the animals with Ϸ200-fold overexpression of the ␤ 2 -adrenergic receptor (12). Again, this result is compatible with the hypothesis that the ␤ 1 -subtype is better coupled to cardiac responses.…”

Effect of Glucose in Isoproterenol-Induced Necrotic Heart Under Anoxic Perfusion1

“…In our experimental con dition, however, increased concentration of glucose in the perfusion medium did not im prove the decrease of mechanical performance and did not enhance anaerobic glycolysis in the normal rat heart during anoxia, suggesting that glucose transport into heart tis sue was a rate-limiting factor of glycolytic flux. Rona and his associates (14) found that isoproterenol produced subendocardial ne crosis of uniform severity. Histological and electron microscopical studies were made on the heart of rats treated with isoproterenol and the general morphological features of the infarction in the rat heart were similar to those produced by ischemia (15).…”

Time course of Na, K-ATPase activity during development of isoproterenol-induced myocardial necrosis in rats

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Massive doses of catecholamines and, in particular, of the synthetic B-adenomimetic isoproterenol, produce infarct-like necrotic lesions in the myocardium of experimental animals [12]. A distinguishing feature of isoproterenol-induced necrosis of the myocardium is early damage to the sarcolemma of the cardiomyocytes, manifested as a sharp increase in its permeability for macromolecular tracers (horseradish peroxidase, ferritin, colloidal lanthanum, etc.)

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“…[2, 5, ii]. Unlike other models of myocardial pathology, such as ischemia, in isoproterenol necrosis the permeability of the intracellular membranes for macromolecules is distubed much later than the permeability of the sarcolemma [2, 5].It was this feature of isoproterenol necrosis (IN) which led us to study the activity of Na,K-ATPase, a biochemical marker of the sarcolemma, at different stages of development of the pathological conditions.The following time intervals were chosen, counting starting from the last injection of isoproterenol: 1 h, when the period of the B-adrenergic response of the vessels ended and passage of the tracers through the plasma membrane of the cardiomyocytes was beginning to be found [5]; 6 h, the time of the greatest increase in permeability of the aarcolemma for macromolecular tracers and Ca ++ [ii]; 24 h, when necrosis of the heart muscle has completely developed [12].To shorten the time between sacrifice of the animals and determination of enzyme activity as much as possible, the work was done on heart tissue homogenate [14], using an anatomically well-demarcated area--the apex of the left ventricle, where necrotic lesions are most marked [12], and the greatest increase in permeability for tracers is observed [ii]. Considering the vector character of Na,K-ATPase, i.e., that its aclivity depends on accessibility of ligands on different sides of the membrane and, consequently, on the degree of closure of the sarcolemmal particles formed during homogenization, parallel determinations of enzyme activity were made in the presence and absence of low concentrations of detergent, making the membrane completely permeable for all ligands and ensuring complete manifestation of Na,K-ATPase activity [3].…”

“…To shorten the time between sacrifice of the animals and determination of enzyme activity as much as possible, the work was done on heart tissue homogenate [14], using an anatomically well-demarcated area--the apex of the left ventricle, where necrotic lesions are most marked [12], and the greatest increase in permeability for tracers is observed [ii]. Considering the vector character of Na,K-ATPase, i.e., that its aclivity depends on accessibility of ligands on different sides of the membrane and, consequently, on the degree of closure of the sarcolemmal particles formed during homogenization, parallel determinations of enzyme activity were made in the presence and absence of low concentrations of detergent, making the membrane completely permeable for all ligands and ensuring complete manifestation of Na,K-ATPase activity [3].…”