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Biomedical subjects

K Wildenthal

Publications and source records attributed to K Wildenthal.

At least 37 records · Page 2Linked to original sources
PubMed1980

Effect of thyrotoxicosis and recovery on myocardial protein balance.

Thyroid hormone, given in vivo or in vitro, exerts an anabolic effect on the heart. The hypertrophy that is produced by daily thyroxine injections in vivo is mediated primarily by an increase in protein synthesis. The changes in protein balance seem to be mediated at least in part by a direct action of thyroid hormone on heart cells, independent of secondary changes in hemodynamic or neurohumoral factors (although these might well contribute to the final effects in vivo, of course). The cardiac catabolism that accompanies regression of thyroxine-induced hypertrophy is characterized by a marked reduction in protein synthesis, not by an acceleration of protein breakdown.

Animals↗
PubMed1980

Lysosomal alterations in hypoxic and reoxygenated hearts. II. Immunohistochemical and biochemical changes in cathepsin D.

Sublethal hypoxic injury in rat and rabbit hearts was accompanied by a biochemical redistribution of cathepsin D activity from the particulate to the supernatant fraction of the tissue homogenate, which was partially reversible on reoxygenation. Immunofluorescent staining for cathepsin D failed to reveal major anatomic release of the acid hydrolase until necrosis was present, suggesting that the earlier biochemical redistribution was primarily a result of increased lysosomal fragility during homogenization, with significant intracellular diffusion of the enzyme occurring only as irreversible damage took place. Hypoxia produced enlargement of both cathepsin-D-staining lysosomes and nonstaining vacuoles, as well as their aggregation. These changes were intensified during reoxygenation and recovery of reversibly damaged hearts, suggesting a possible role for the lysosomal-vacuolar apparatus in myocytic repair following hypoxic injury.

Animals↗
PubMed1980

Lysosomal alterations in hypoxic and reoxygenated hearts. I. Ultrastructural and cytochemical changes.

Rabbit hearts perfused under hypoxic conditions underwent progressive subcellular damage, which becomes irreversible by one hour. During the first 20 minutes of perfusion, minor dilation of mitochondria and condensation of nuclear chromatin were the only salient features of cell injury. By 40 minutes moderate mitochondrial swelling was evident in hypoxic myocytes. Moreover, an increase in degenerating mitochondria and autophagic vacuoles was apparent. Reperfusion after either 20 or 40 minutes of hypoxia restored contractility, and injured myocytes underwent a cellular repair process that involved a dramatic increase in lysosomal autoplagy. One hour of hypoxia yielded irreversibly injured myocytes. Upon reoxygenation, some of these cells displayed typical changes of necrosis, but others apparently underwent an abortive repair process involving the formation of large, probably nonfunctional lysosomes. These observations suggest that lysosomal autophagy is important in the efforts at repair that cardiac cells initiate during and after hypoxia.

Acid Phosphatase↗
PubMed1980

Resistance to ischemic damage in hearts of starved rabbits: Correlation with lysosomal alterations and delayed release of cathepsin D.

Prolonged starvation produces dramatic changes both in the lysosomal properties of the heart and in its energy stores and, therefore, might be expected to alter some of the characteristic cardiac responses to ischemia. To test this possibility we ligated the circumflex coronary artery of rabbits that had been fed normally or starved for 6 days. Ultrastructural evidence of myocytic damage following 30 to 120 minutes of ischemia was much less severe in the starved animals than in the normally fed group. The development of signs of irreversible injury (e.g., osmiophilic densities in mitochondria) was delayed for 1 hour or more by starvation. A similar delay occurred in the biochemical redistribution of cathepsin D activity and in the cytoplasmic release of acid hydrolases from lysosomes and sarcoplasmic reticulum. These results indicate a marked protective effect of starvation against myocardial ischemia. In addition, both in starved and in fed animals, ischemically induced release of lysosomal enzymes was closely linked temporally to the development of subcellular damage.

Acid Phosphatase↗
PubMed1980

The role of lysosomes in the heart.

In many tissues there is strong evidence that lysosomes and lysosomal hydrolytic enzymes play important roles in the normal turnover of tissue proteins and other macromolecules. Alterations in the activities and/or availability of lysosomal enzymes are believed to be responsible for alterations in the rate of degradation of many tissue components. It has also been suggested that abnormal release and activation of lysosomal enzymes during ischemia and other potentially lethal events may contribute to the tissue damage that ultimately ensues. Proof that lysosomes are important in cardiac physiology and pathology has not yet been obtained. Circumstantial evidence tends to link lysosomal alterations with changes in protein degradation following many interventions, but this is not always the case. Ischemia is accompanied by leakage of lysosomal enzymes into the cytosol before signs of irreversible damage have appeared, but this association may be coincidental rather than causal. Investigation in the area of cardiac lysosomes has increased markedly in the past 5-10 years. With the development of improved techniques for measuring lysosomal function in heart tissue, there is every reason to expect major breakthroughs in this area of research in the near future.

Animals↗
PubMed1979

Influence of a phosphodiesterase inhibitor on the chronotropic effects of glucagon and norepinephrine in fetal mouse hearts.

Fetal mouse hearts develop tachycardia in response both to norepinephrine and to glucagon, but although adenylate cyclase is stimulated and adenosine 3':5'-monophosphate (cyclic AMP) elevated by norepinephrine, no measurable changes are produced by glucagon. To test further the possible independence of glucagon chronotropy from the cyclic AMP system, the effects of a phosphodiesterase inhibitor were evaluated. The dose-response curve to norepinephrine was shifted to the left by the phosphodiesterase inhibitor 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro7-2956), but the dose-response curve to glucagon was unaltered. Thus, 10(-6) M norepinephrine produced an increase of 40 +/- 5 beats/min in hearts pretreated with Ro7-2956, as compared to an increase of 22 +/- 3 in control hearts (P less than .01). In contrast, 10(-6) M glucagon produced a rate increase of 25 +/- 4 beats/min in treated hearts vs. 26 +/- 4 beats/min in controls. These data are compatible with the hypothesis that adenylate cyclase and cyclic AMP are involved in the chronotropic response of the fetal mouse heart to norepinephrine but not to glucagon.

Animals↗