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[Effect of chronic stimulation of the negative and positive emotionogenic centers of the hypothalamus on development of cardiac arrhythmias].

Chronic experiments were conducted on 46 rabbits; a study was made of the changes in cardiac activity arising in prolonged (up to 1--2 weeks) electric stimulation of the ventro-median nuclei of the hypothalamus. Disturbances of the cardiac rhythm in the form of tachycardia, atrial flutter and fibrillation, ventricular extrasystole and paroxysmal ventricular tachysystole occurred mostly during the first days of stimulation and ceased after inderal infusion. Functional "weakness" of the cardiac pacemakers was revealed in the animals subjected to 1--2-week stimulation of the ventromedian nuclei. This was indicated by the post-stimulation suppression of the pacemaker automaticity and the appearance of Liciani's periods. Disturbances of the cardiac rhythm originating in stimulation of the ventromedian nuclei ceased in stimulation of the lateral hypothalamic field.

Animals

[Role of mitral valve dysfunction in the development of cardiac insufficiency in postinfarct cardiosclerosis].

The clinical suggestion on the dysfunction of the mitral valve in 20 patients with post-infarction cardiosclerosis was confirmed by ventriculography (8 persons) and in autopsy (12 persons). The paper presents a clinical characteristics of the both groups of patients, the indices of the central hemodynamics, the end diastolic pressure in the left ventricle of the heart, coronaroangiography, as well as morphometric data of the examination of the hearts and of the extent of the scar lesions of the myocardium in patients who died of congestive cardiac insufficiency against the background of postinfarction cardiosclerosis combined with the papillary muscle affection.

Adult

Collagen synthesis in the developing chick heart.

We have surveyed the amount and types of collagen synthesized in two regions of the chick heart during embryonic development. Cardiac tissues from successive periods of development were labeled with 3H-proline in short-term organ culture. The fraction of incorporated label present as collagen was estimated by comparison of TCA-soluble radioactivity before and after digestion with purified bacterial collagenase. This measure of collagen synthesis varied only slightly with the length of the labeling period and agreed with values obtained by labeling in ovo. In the developing outflow tract, the fraction of label present as collagen increased sharply during the period of truncal septation (5-9 days), rising from initial values of 6% at 3 days of incubation to a plateau of about 25% (10-19 days). In ventricular myocardium, this fraction rose gradually from 3 to 20% between 3 and 19 days of incubation. The types of collagen synthesized in developing heart were analyzed by limited pepsin digestion and acrylamide gel electrophoresis, using collagens synthesized in tendon, cartilage, skin, and lens capsule for comparison. The types of collagen synthesized in both cardiac regions changed in similar manner during development. During the first week of cardiac function, a substantial but progressively smaller fraction of total collagen synthesized was identified as Type IV. Synthesis of Type I collagen increased sharply during this period and predominated during the second half of development. Type III collagen was synthesized in trace amounts by the middle of development and constituted approximately one-sixth of total collagen synthesis just before hatching. Minor amounts of collagen identified as Type B collagen were synthesized throughout the latter two-thirds of development.

Animals

Epicardial pacemaker complicated by cardiac tamponade and constrictive pericarditis.

Following insertion of an epicardial pacemaker, our patient developed cardiac tamponade complicated by subacute constrictive pericarditis. Echocardiographic findings and intracardiac pressures were typical of constrictive pericarditis, which was confirmed at surgery. Although rare, these unusual complications should be considered in patients who develop evidence of reduced cardiac output following either transvenous or epicardial electrode placement.

Aged

RNA splicing and cardiovascular disease: a guide for cardiologists.

Alternative splicing (AS) is a fundamental RNA processing mechanism, which generates different RNA transcripts and consequently different protein isoforms from a single gene. This increases the diversity of proteins within an organism and can fine-tune biological processes. This review examines how cardiac-enriched RNA-binding proteins establish heart-specific splicing programs governing aspects of cardiac development, function, and disease. Developmentally, coordinated sarcomeric isoform switches underpin the foetal-to-adult transition and further isoform rewiring in ion channel and kinase genes determine electrophysiology and excitation-contraction coupling. AS contributes to the pathogenesis of several cardiomyopathies and emerging datasets suggest that pathological hypertrophy engages distinct splicing signatures compared with physiological hypertrophy. This review summarizes diagnostic and prognostic opportunities arising from bulk, long-read, and single-cell/nucleus transcriptomics, which resolve cell type-specific isoforms and disease-associated switches. Circulating RNA biomarkers (including splice ratios and circularRNAs) may signify myocardial remodelling and arrhythmic risk. Integrative approaches that link AS with proteomics and genomics improve variant interpretation, reveal previously unannotated protein isoforms, and enable tracking of disease progression and therapy response. Finally, an outline of therapeutic strategies to modulate AS in cardiovascular disease (CVD), including antisense oligonucleotides, small molecules, and genome-editing modalities (CRISPR, base, and prime editing), is provided. The major challenges that remain before splice-targeting therapeutics can be targeted to treat cardiovascular disease are highlighted. Lessons from neuromuscular indications establish clinical feasibility of splicing correction and motivate translation to cardiology. Together, mechanistic insight, biomarker development, and therapeutic innovation position RNA splicing as a tractable axis for precision cardiovascular medicine.

Humans

Hypertension with mineralocorticoid administration to the Long-Evans rat.

1. The Carworth Long-Evans rat has been reported to develop adrenal-regeneration hypertension but not deoxycorticosterone acetate (DOCA) hypertension. Deficiency of a hypothalamic receptor for deoxycorticosterone which mediates saline polydipsia has been postulated to underlie this resistance. Since a mineralocorticoid etiology for adrenal-regeneration hypertension has been postulated and all mineralocorticoids are thought to act on common receptors, these previous reports are difficult to reconcile. 2. To determine if an absolute or relative resistance to mineralocorticoids is present, Charles River Long-Evans and Sprague-Dawley rats were given 40 mg (107 micromol) of DOCA pellets/rat or 250 microgrms (0.65 micromol) of 2 alpha-methyl-9-alpha-fluorocortisol/day subcutaneously. 3. Saline polydipsia occurred with both steroids with both rat strains, though significantly less with the Long-Evans rats. Both types of rats became hypertensive and developed cardiac and renal enlargement with both steroids. Hypertension developed more rapidly with 2 alpha-methyl-9 alpha-fluorocortisol. 4. Thus mineralocorticoid hypertension can be produced in the Charles River Long-Evans rat, and the development of adrenal-regeneration hypertension in this rat strain is not incompatible with a mineralocorticoid etiology for adrenal-regeneration hypertension.

Adrenalectomy

[Cardiac neurosis in everyday general medical practice (author's transl)].

From results of the study of 37 patients with cardiac neurosis, new conceptual relationships to explain this condition are developed. Cardiac neurosis is explained as a disturbance of the "psycho-neurovegetative self-regulation mechanism" (servomechanisms). The authors show how such a conception, which has been borrowed from the servomechanism technique, may favourably influence the diagnosis and therapy of this condition. It has been tried in that way to link the two opposites: organic and functional causes. Some therapeutic approaches adapted to the structure of everyday general medical practice are suggested.

Adrenergic beta-Antagonists

Cardiac arrest temperature: the effect of ethyl alcohol and carbon dioxide on baboons.

The effect of high inspired carbon dioxide concentrations and i.v. ethyl alcohol on the temperature at which cardiac arrest occurred was studied in chacma baboons. Alcohol-treated baboons developed cardiac arrest at a temperature of 24.3 degrees C (SD +/- 0.85) and control animals at 27 degrees C (SD +/- 1.30). There were no signs of cardiac failure before the occurrence of ventricular fibrillation.

Animals

Response of hypertensive adolescents to dynamic and isometric exercise stress.

Isometric handgrip and dynamic exercise stress tests were performed on 109 hypertensive and 74 normotensive subjects 14 to 17 years old. The hypertensive subjects had resting systolic or diastolic pressures persistently above the 95th percentile on four consecutive examinations. Blood pressures and ECGs were recorded during isometric handgrip (25% maximum effort for four minutes) and bicycle ergometry until the subject was exhausted. The hypertensive subjects increased systolic pressure by an average 16 mm Hg with isometric exercise and 53 mm Hg with dynamic exercise. Control subjects had similar pressure changes, averaging 18 and 54 mm Hg, respectively. During isometric handgrip stress, diastolic pressures increased 12 mm Hg in hypertensive subjects and 18 mm Hg in control subjects. Only two hypertensive adolescents developed systolic pressures exceeding 200 mm Hg during dynamic exercise stress, and none developed systolic pressures above 200 mm Hg during isometric exercise stress. None of the normotensive or hypertensive subjects developed cardiac arrhythmias and the prevalence of ST segment depression during maximal stress was less than 2% in both groups. Therefore, in adolescents with mild to moderate hypertension the risk of developing significant ECG or hemodynamic abnormalities during mild isometric or heavy dynamic exercise is small. We believe the decision to restrict physical activity of an adolescent with elevated pressures should be based on the development of abnormal ST segment depression, cardiac arrhythmias, or excessive blood pressures at the time of exercise stress testing.

Adolescent

Biochemical aspects of cardiac muscle differentiation. Deoxyribonucleic acid synthesis and nuclear and cytoplasmic deoxyribonucleic acid polymerase activity.

DNA synthesis and DNA polymerase activity have been measured in terminally differentiating cardiac muscle of the rat. Incorporation of [3H]thymidine into DNA essentially ceases by the 17th day of postnatal development. Cardiac muscle of neonatal rats contains at least two molecular species of DNA polymerase: a 3.5 S DNA polymerase that can be extracted from nuclei with 0.2 m potassium phosphate and a 6 to 8 S soluble cytoplasmic DNA polymerase. The nuclear DNA polymerase in crude extracts has a pH optimum of 9.0 and is more active with native DNA than with denatured DNA as the primer-template. The cytoplasmic DNA polymerase in crude extracts has a pH optimum of 7.5 and is more active with denatured DNA. The activity of the 6 to 8 S cytoplasmic DNA polymerase decreases 80-fold from day 1 to day 17 after birth, which correlates temporally with the reduced rate of DNA synthesis. The activity of the 3.5 S nuclear DNA polymerase remains relatively constant throughout postnatal development. Mixing experiments (assay of neonatal enzyme extracts with adult enzyme extracts) gave additive results, suggesting that the decline in 6 to 8 S DNA polymerase activity apparently is not due to the presence of absence of soluble activators or inhibitors at different times during development. These studies may provide a system which can be used to investigate the control of DNA synthesis and cellular proliferation during the terminal stages of cardiac muscle differentiation.

Aging

[Contractile myocardial proteins and their enzymatic activity in hypertensive disease and coronary atherosclerosis].

An investigation into the fractional composition of myocardial proteins and ATP-ase activity of myosine in 86 persons, who during their lifetime suffered from hypertensive disease and coronary incompetence, revealed significant changes therein. An increased content of actomyosine complex proteins in hypertensive disease was superseded by their considerable diminution in the event of developing cardiac insufficiency, which was at that accompanied by declining ATP-ase activity of myosine. The development of acute myocardial infarction led to a still drastically reduced concentration of sarcoplasmatic and contractile proteins of the heart muscle, as well as to their diminished enzymatic activity.

Adenosine Triphosphatases

Effects of hyaluronic acid on cardiac cushion tissue cells in collagen matrix cultures.

To initiate the experimental exploration of the role of extracellular macromolecules in influencing developmental events in the heart, a 3-dimensional substrate culture model of the developing cardiac cushion was devised. One cardiac jelly component, hyaluronic acid, was tested for its effects on morphology and migratory capacity of cushion tissue cells within the collagen matrix substrate. Hyaluronate treatment resulted in: (1) an increase in the number and extent of filopodia, reflected as an increase in cell surface area, and (2) an increase in migratory capacity, reflected as an increase in maximum depth to which cells migrate through the collagen lattice. These results suggest one major role for hyaluronate in the early cardiac cushion is the promotion of a high level of motility capability in the newly seeded cushion tissue cells, required for the key event of cell migration across the developing cushion.

Animals

Acute intravenous administration of potassium chloride to furosemide pretreated dogs.

Twelve male mongrel dogs were used for this study; six were untreated (control) and six were given intravenous furosemide (1 mg/kg) daily for seven consecutive days before each study. Each animal received intravenous KCl 0.8, 1.6 or 3.2 mMol/kg/hr for one hour, but only one dose for each study and at least seven days were allowed between studies. The animals were given thiopentone for tracheal intubation and mechanically ventilated, maintaining a PaCO2 of 4.0 to 4.5 kPa (30-35 torr) and anaesthetized with nitrous oxide-oxygen and halothane. Daily administration of furosemide reduced serum potassium from 4.48 to 4.09 mMol/1 with no significant change in serum sodium. A greater number of furosemide-pretreated animals (6 vs 3) developed cardiac dysrhythmias during non-lethal intravenous KCl at 0.8, 1.6 mMol/kg/hr. The furosemide-pretreated group tended to succumb at a lower serum potassium concentration (12.2 vs 13.8 mMol/I, P less than 0.05) and developed earlier onset (44 vs 54 min, P less than 0.05) of cardiac standstill or ventricular fibrillation following intravenous KCl at 3.2 mMol/kg/hr. Cardiac output, heart rate and mean arterial pressure were significantly elevated during serum concentrations of 6.9-9.1 mMol/1, while no statistically significant changes were observed for stroke volume and peripheral resistance. There were no significant differences of urinary potassium excretion between the untreated and treated groups when like doses of KCl were infused. These data suggest that acute infusion of KCl in furosemide-pretreated dogs may not be an effective means of treating hypokalaemia and could be hazardous.

Animals

Cardiac tamponade resulting from pericardial extramedullary hematopoiesis: a case report and review of the literature.

A patient with an unusual myeloproliferative disorder, characterized by hepatosplenomegaly, myelofibrosis, ringed sideroblasts, and conversion to acute myeloblastic leukemia developed cardiac tamponade secondary to pericardia extramedullary hematopoiesis. Diagnostic criteria are discussed. Irradiation and systemic chemotherapy were successful in controlling the effusion.

Adolescent

Cardiac tamponade in myxedema.

Pericardial effusions are frequently found in myxedema and , when present, are asymptomatic and usually of no hemodynamic consequence. We report a patient with ascites and pericardial effusion due to myxedema who developed cardiac tamponade following abdominal paracentesis. This case emphasizes that treatment of patients with myxedematous chronic pericardial effusions should include avoidance of those measurements which may reduce venous filling pressure or effective cardiac output regardless of the thyroid status.

Adult

Systemic stress in the production of cardiac thrombosis in hypercholesterolaemic rats.

An experimental study to elucidate the effects of feeding a high fat diet, hypercholesterolaemia and superadded acute and chronic stress on the production of cardiac thrombosis was carried out in rats. The high fat diet contained 25 percent butter rat providing 45 percent calories from fat which produced significant increase of serum cholesterol and other lipids. Acute stress was induced by two injections of adrenaline on a single day which caused a marked transient alteration of haemodynamics. Chronic stress was of two types, physical and metabolic. The physical stress was induced by repeated exposure of the rats to electric shock or roller drum exercise, while metabolic stress was caused by repeated injection of ACTH. Rats of both acute and chronic stress groups showed variable degree of medial degeneration, hyaline and fibrinoid intimal deposits and calcification in coronary arteries. Cardiac thrombi were seen in 30 percent animals subjected to adrenaline shock. Among the chronic stress procedure 17 percent rats exposed to electric shock and only one rat of the ACTH group developed cardiac thrombosis but no thrombus was detected in those exposed to roller drum exercise. The myocardium showed patchy necrosis with or without calcification, Spontaneous mortality was maximum following acute adrenaline shock (25 %) while electric shock caused mortality in 17 percent animals. The other procedures did not lead to spontaneous mortality. This study highlights the significant role of high fat intake, hypercholesterolaemia and systemic stress in the pathogenesis of acute cardiac thrombosis and myocardial necrosis/infarction.

Adrenocorticotropic Hormone