Study of the factors influencing cardiac growth. I. Comparison of cardiomegaly induced by isoproterenol in euthyroid and thyroidectomized rats

The purpose of the present work was to study the cardiac growth-stimulating effect of IPR in hypothyroid animals, in which the in vitro sensitivity of the myocardium to beta-adrenergic agonists is significantly decreased. To determine the degree of myocardial enlargement, wet and dry ventricle weight and myocardial RNA, DNA and protein were measured. IPR administered to euthyroid rats in a dosage of 5 mg/kg/day for 4 days induced cardiomegaly. In thyroidectomized rats, a consistent depression of IPR-induced cardiomegaly was observed. This phenomenon appears to be in accordance with earlier observations showing a marked decrease in maximal beta-receptor level of ventricular membranes after thyroidectomy or PTU treatment.     

Thyroxine-induced cardiomegaly: assessment of nucleic acid, protein content and myosin ATPase of rat heart.

1 mg/kg L-thyroxine was administered to rats for 14 days to evaluate the potential of the hyperthyroid state to induce heart hypertrophy and its effect on myosin adenosine-triphosphatase (ATPase) activity. Evidence of hyperthyroidism such as weight loss, elevation of rectal temperature, increased heart rate and oxygen consumption, was observed in all treated rats. Cardiac enlargement was determined by comparison of wet and dry ventricle weights, myocardial RNA, DNA and protein content. Wet and dry ventricle weights and the level of cardiac RNA and protein were augmented by thyroxine treatment. ATPase activity of cardiac myosin was stimulated as the Ca2+ concentration in the incubation medium increased. No difference was found in Ca2+-activation, salt sensitivity or ATPase activity of unreacted and sulphydrylmodified cardiac myosins from euthyroid or hyperthyroid groups. The results showed that in hyperthyroid rats, in contrast to some other species, the biochemical mechanism responsible for the enhancement of cardiac contractility is not an increased myosin ATPase.     

Study of the factors influencing cardiac growth. III. Digitoxin treatment and thyroxine-induced cardiac hypertrophy in the rat

Thyroxine (T4) administered to rats in a dose of 1 mg/kg for 12 days induces cardiac hypertrophy. The purpose of the present study was to determine the effect of prophylactic + simultaneous digitoxin treatments on the development of T4-induced cardiac hypertrophy. Digitoxin (1 mg/kg body weight) was given per os, once daily for 6 days prior to T4 administration and continued simultaneously with T4 treatment. To determine myocardial enlargement, wet heart weight, myocardial nucleic acid and protein were measured. Digitoxin treatment induced a slight increase in wet ventricle weight and a significant elevation of myocardial RNA content (mg/ventricles) and concentration (mg/g). At the same time, the degree of T4-induced cardiac hypertrophy in digitoxin-treated and untreated animals was nearly the same. On the basis of these results it can be stated that--unlike the cardiac hypertrophy induced by pressure overload or hypoxia,--the T4-induced cardiac hypertrophy is not altered by digitoxin administration.     

Acute effects of isoproterenol on cellular autophagy. Inhibition in myocardium but stimulation in liver parenchyma

The influence of isoproterenol (IPR) on cellular autophagy was examined in left ventricular myocardium and in liver parenchyma of rats two hours after a subcutaneous injection of a low dose (3 mg/kg body weight). 4 animals were treated with IPR, 4 controls received Ringer solution. The average cytoplasmic volume fraction of the autophagic vacuoles (AV) was 1.6 X 10(-4) in the heart muscle of the controls. After treatment with IPR this value was reduced by 70% to 0.5 X 10(-4). This inhibition of cellular autophagy is interpreted as an initial anticatabolic reaction which might be responsible for the myocardial hypertrophy after chronic administration of IPR. An opposite influence of IPR was observed in the hepatocytes. The volume fraction of AV's increased twofold to 8.7 X 10(-4) after IPR, compared to 4.0 X 10(-4) in control animals. In the controls, the volume fraction of AV's in heart muscle was 57% of the value found in the liver. Comparing liver tissue after fixation by immersion and by perfusion, no statistically significant differences in the volume fractions and in the numerical densities of AV's were observed.     

Levels of protein, RNA, DNA, glycogen and lipid during growth and development of Daphnia magna Straus (Crustacea: Cladocera)

1. Protein, RNA, DNA, glycogen and lipid content were determined in Daphnia magna on days 0, 2, 4, 6, 8 and 21 of growth and development. The composition of D. magna as percentage of reconstituted dry weight was similar to other zooplankton with the exception of DNA content, which was lower than values previously reported.
2. The relative content of protein, RNA, DNA and reconstituted dry weight changed during the 21-day growth period, and these changes were related to growth rate and total growth of D. magna . RNA:protein, RNA: reconstituted dry weight, and protein:RNA : DNA ratios were highly correlated to relative growth rate and total growth as measured by protein content or reconstituted dry weight.
3. Addition of progeny biomass to adult biomass increased correlations between biochemical ratios and absolute growth rate, but had little effect on relationships involving relative growth rate or total growth.
4. The relationship between biomolecule ratios and growth established for D. magna grown under optimal conditions was not successful in predicting growth of D. magna reared under crowded conditions.
5. These data indicate that variation in biochemical ratios among life, stages of D. magna may be used to predict growth of organisms grown under similar conditions, but may not be extended to other situations. It is suggested, however, that variation in biochemical ratios in a particular life stage of a zooplankton species may be related to the productivity for that species.     

Anti-apoptotic potential of gymnemic acid phospholipid complex pretreatment in Wistar rats with experimental cardiomyopathy

Cardiomyocyte apoptosis in heart failure has been the topic of research in many recent studies. In the present investigation, the potential cardioprotective effect of gymnemic acid phospholipid complex (GPC) on myocardial apoptosis and cardiac function was studied in doxorubicin (DOX; 30 mg/kg/ip/single dose)-induced cardiomyopathy model in rats. Doxorubicin induced cardiomyopathy was evidenced by significant hemodynamic changes (increased systolic, diastolic, mean arterial pressure and heart rate), decreased heart weight to body weight ratio, increase in serum lactate dehydrogenase (LDH) and Ca2+ levels and decrease in myocardial Na+/K+ ATPase levels along with caspase-3 activation. A marked reduction in glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase levels along with increase in the levels of thiobarbituric acids (TBARS) were also observed in rat myocardium. In addition, DNA laddering observed on agarose gel electrophoresis and cardiac histopathology study further supplemented myocardial apoptosis. Pre-treatment with GPC significantly reduced DOX-induced cardiac toxicity, including improvement of hemodynamic variables and heart weight to body weight ratio, decreased serum Ca2+ level and LDH levels, myocardial caspase-3 levels, increased Na+/K+ ATPase levels and decreased myocardial TBARS levels and elevated antioxidant enzymes as compared to pathogenic control group. Further, the anti-apoptotic effect of GPC was verified by prevention of internucleosomal DNA laddering on agarose gel electrophoresis and attenuation of histopathological perturbations by doxorubicin. These observations demonstrate that GPC might serve as a cardioprotective formulation in DOX-induced cardiomyopathy in rats.     

Changes in dry weight, protein, deoxyribonucleic acid, ribonucleic acid and reserve and structural carbohydrate during aerobic growth cycle of yeast

1. Changes in dry weight, DNA, RNA, protein and reserve and structural carbohydrate were measured during the aerobic growth of yeast on 0.9% glucose in an aerobic synthetic medium. 2. After glucose had been consumed and during the growth of yeast on ethanol and acetate, the rate of formation of DNA remained about the same but the rate of increase of dry weight was greatly diminished. 3. During the second stage of growth the ratios dry weight/DNA, protein/DNA, RNA/DNA and carbohydrate/DNA decreased to about 30% of the corresponding values during the first stage of growth. 4. A higher fraction of the dry weight of the yeast cells could be accounted for by the reserve carbohydrate content of the cells during the second stage of growth. 5. By the end of the first stage of growth an increase in the reserve carbohydrate content of the cells was observed. Part of this reserve carbohydrate was consumed by the cells in the beginning of the second stage of growth. The possibility of adaptation of cells at the expense of their reserves is discussed.     

Effects of chronic caffeine ingestion on growth and myocardial function

Experiments were conducted to determine whether chronic caffeine consumption during early growth and development affected cardiac performance and development of adipose tissue. Dams were fed a nutritionally complete diet with or without the addition of 10 mg/kg caffeine during lactation. After weaning, the pups were maintained on this diet until they were sacrificed at 88 days of age. Body weight at the time of sacrifice was comparable for both groups. The hearts from caffeine-fed animals were significantly (P less than 0.05) larger based on both dry and wet weights although the dry weight/wet weight ratios were similar. Ventricular function curves were generated on each heart using an isolated working heart preparation. The isolated hearts of caffeine-fed rats exhibited a significant reduction in cardiac output, stroke volume, mean aortic pressure, and estimated myocardial work when compared to controls. The rats fed caffeine had greater plasma triglyceride levels with no significant differences in adipocyte size or number in the epididymal and perirenal depots. It is concluded that chronic caffeine intake from birth may alter cardiac function of the offspring.     

Effect of embryonal organ-specific RNA on myocardial hypertrophy]

The relative weight of the heart and the thickness of muscular fibers in the left ventricular myocardium of rats were evaluated 70-91 and 120-227 days after creating stenosis of the abdominal portion of the aorta. Half of the animals were inoculated with cardiac type-specific embryonal RNA, the rest of the animals being intact. The data were treated by the variational statistical technique, by dispersion and mathematic analyses. Administration of RNA decreased the rate of myocardial hypertrophy development.     

Changes in the composition of the excurrent duct system of the rat testis during postnatal development.

The gross composition of the testicular excurrent duct system of the rat was examined and compared along the length of the duct and with samples of testis, bladder and liver. Changes in composition with age were examined by analysing tissue from animals at postnatal ages of 19, 36, 48, 60, 90 and 120 days. In adult animals, testicular tissue was characterized by having the lowest dry weight, accompanied by low levels of total protein, lipid, RNA and glycogen; DNA, phospholipids and sialic acid were at levels similar to other tissues. A high proportion of the total protein was soluble. The ductuli efferentes plus initial segment of the epididymis were characterized by high levels of total lipid. The caput epididymidis contained a low level of total protein but a high level of acid-soluble phosphorus. The cauda epididymidis had a low dry weight and low levels of total protein, soluble protein, and lipid, but high levels of acid-soluble phosphorus, DNA and sialic acid. The ductus deferens contained small amounts of RNA and DNA but had a high dry weight, high total protein, soluble protein and glycogen. Several trends were apparent with increasing age. Dry weight increased in the ductuli efferentes plus initial segment, whilst total protein decreased in the caput and cauda epididymidis. Total lipid increased in the ductuli efferentes plus initial segment and acid-soluble phosphorus and sialic acid increased in all other segments of the excurrent duct system. In all segments the content of RNA and DNA decreased as the animals matured. The concentration of calcium and magnesium in the excurrent duct system was not significantly different from those levels found in the liver. High levels of spermine and spermidine were confirmed in the prostate, and were also detected in the testis, caput epididymidis and cauda epididymidis, but at a much lower concentration.     

Acetaldehyde and cardiac protein synthesis in the rat in vivo

Protein synthesis was measured in the hearts of rats exposed to acetaldehyde vapour for 21 days. Exposure to acetaldehyde significantly increased heart weight (expressed as % body weight) but was without effect on the rate of synthesis of mixed cardiac proteins. Concentrations of RNA in the hearts were not altered by acetaldehyde exposure, indicating no change in RNA activity for protein synthesis.     

老年缺血性心力衰竭的心脏DNA甲基化编码重编程与心肌细胞焦亡、铁死亡的关联

摘要 目的：探讨老年缺血性心力衰竭的心脏DNA甲基化编码重编程与心肌细胞焦亡、铁死亡的关联性。方法：2019年12月到2021月2月,选择在本院诊治的老年缺血性心力衰竭115例作为心衰组,同期选择在本院体检的非心血管疾病老年人群115例作为对照组。检测心脏DNA甲基化编码重编程、心肌细胞焦亡、铁死亡指标表达情况并进行相关性分析。结果：心衰组的心脏DNA甲基化编码重编程指标-miR-92a、miR-130a相对表达水平高于对照组（P<0.05）。心衰组的Caspase-1蛋白、Caspase-4蛋白相对表达水平高于对照组（P<0.05）。心衰组的铁调素含量高于对照组（P<0.05）。在两组230例入选者中,Spearsman相关分析显示：缺血性心力衰竭与miR-92a、miR-130a、半胱氨酸蛋白酶1（Caspase-1）、半胱氨酸蛋白酶4（Caspase-4）、铁调素存在正向相关性（P<0.05）。Logistic回归分析显示：miR-92a、miR-130a、Caspase-1、Caspase-4、铁调素为导致缺血性心力衰竭发生的重要因素（P<0.05）。结论：老年缺血性心力衰竭患者多伴随有心脏DNA甲基化编码重编程与心肌细胞焦亡、铁死亡,后三者与缺血性心力衰竭的发生存在关联性,也是导致缺血性心力衰竭发生的重要因素。     

Lung mechanics and connective tissue proteins in diabetic Bio-Breeding/Worcester Wistar rats

We studied lungs of spontaneously diabetic Bio-Breeding/Worcester (BB/W) Wistar rats which resemble human insulin-dependent diabetes mellitus. Compared with the age-matched control group, the body weight of the diabetic rats tended to be smaller and lung wet and dry weight were similar, but lung dry weight, relative to body weight and to lung wet weight, was significantly larger. Both air and saline lung volumes were reduced in the diabetic rats, and volume-pressure (V-P) curves expressed as a percent of maximal lung volume were significantly shifted downward and to the right of those in the control group over the midportion. Total DNA and RNA contents were similar in both groups, whereas protein content and concentration and protein/DNA and RNA/DNA ratios were significantly reduced in the diabetic rats. In contrast, content and concentration of 4-hydroxy-L-proline, elastin, and crude connective tissue were significantly higher in the diabetic group. We conclude that the increase in connective tissue proteins in the BB/W rats is most likely responsible for the shift in the V-P curves.     

CHANGES IN CHROMATIN TEMPLATE ACTIVITY AND THEIR RELATIONSHIP TO DNA SYNTHESIS IN MOUSE PAROTID GLANDS STIMULATED BY ISOPROTERENOL

Chromatin template activity of mouse parotid glands increases after a single injection of isoproterenol (IPR), a procedure that causes, after a lag period of 20 hr, a marked stimulation of DNA synthesis and cell division in salivary glands of rodents. The increase in chromatin template activity occurs as early as 1 hr and peaks between 6 and 10 hr after IPR, paralleling previously reported changes in the incorporation of uridine-³H into total cellular RNA of mouse parotids. Template activity was measured in vitro in a system in which parotid gland chromatin was incubated with an exogenous RNA polymerase isolated from Escherichia coli. Similar results were obtained when template activity of parotid gland chromatin was assayed using an homologous RNA polymerase from mouse liver. Chromatin template activity in mouse parotids was also studied after the administration of drugs capable of inducing in salivary glands both DNA synthesis and secretion or secretion alone. The results indicate that the increased chromatin template activity occurring 6 hr after IPR is related to the subsequent onset of DNA synthesis. Furthermore, the increased chromatin template activity caused by IPR is inhibited by the previous administration of puromycin, an inhibitor of IPR-stimulated DNA synthesis.     

Manifestations and Mechanism of SARS-CoV2 Mediated Cardiac Injury

Coronavirus disease 2019 (COVID-19), a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) had resulted in considerable morbidity and mortality. COVID-19 primarily posed a threat to the respiratory system and violated many different organs, including the heart, kidney, liver, and blood vessels with the development of the disease. Severe patients were often accompanied by cardiac injury, and once the heart gets damaged, the mortality of patients will significantly increase. The main clinical manifestations of cardiac injury range from myocarditis, heart failure (HF), arrhythmia, and Takotsubo cardiomyopathy (TCM). A high abundance of angiotensin-converting enzyme II (ACE2) on the membrane of cardiomyocytes makes it possible that the virus can directly attack cardiomyocytes as subsequently evidenced by the detection of spike protein and virus RNA in autopsy cardiac tissues. The secondary myocardial injury through systemic inflammatory and immune response also caused obvious cardiac damage. The pathological manifestations of heart tissue were diverse, varied from mild cardiomyocyte edema, myocardial hypertrophy, cardiomyocyte degeneration, and necrosis to severe myocarditis caused by lymphocyte and macrophage infiltration. However, the mechanism of heart injury was still unclear. Here, we summarized the clinical manifestations and mechanism of SARS-CoV2 mediated cardiac injury, providing a reference for cardiac treatment in critically ill patients.     

Limitation of heart growth in neonatal piglets by simvastatin and atorvastatin: comparison with pravastatin

The pig heart grows rapidly in the first few days after birth. We examined the effects of simvastatin, atorvastatin, and pravastatin on heart growth in piglets. After vehicle, 2 mg x kg(-1) x day(-1) simvastatin, 2 mg x kg(-1) x day(-1) atorvastatin, or 4 mg x kg(-1) x day(-1) pravastatin were administered orally for 6 days, the thoracic cavity was opened, and the heart was removed under pentobarbital sodium (30 mg/kg ip) anesthesia. The heart was perfused to remove residual blood. After the heart was blotted dry, the right and left ventricular free walls were dissected. Each free wall was weighed and used for determination of DNA, RNA, and protein concentrations and mitogen-activated protein (MAP) kinase activity. Simvastatin and atorvastatin resulted in smaller increases with age in the weight, concentrations of RNA and protein, and activity of MAP kinase in the left ventricular free wall, whereas pravastatin did not. The parameters of heart growth in the right ventricular free wall were not appreciably affected by either drug. The blood pressure and heart rate were not changed by the treatments. These results suggest that simvastatin and atorvastatin interfere with heart growth in neonatal piglets after birth, especially in the left ventricular free wall.     

The effect of proflavine on HeLa cells

1. The effect of proflavine on the metabolism of RNA, DNA and protein of HeLa cells was studied. 2. The synthesis of RNA, DNA and protein was progressively inhibited by concentrations of proflavine up to 43mum. 3. There was no simple relationship between the degrees of inhibition of synthesis of RNA, DNA and protein by increasing concentrations of proflavine: the synthesis of RNA was most readily inhibited, and the synthesis of protein was relatively insensitive. 4. A concentration of 22mum-proflavine inhibited synthesis of RNA and DNA and caused a progressive loss of RNA from both nucleus and cytoplasm without any accompanying loss of DNA or dry weight from the cells. 5. The rapidly labelled RNA in the nucleus was preferentially degraded and was not transferred in a stable form to the cytoplasm.     

家族性扩张型心肌病的分子遗传研究进展

扩张型心肌病是一种以左心室和,或右心室扩大、心肌收缩功能受损为主要特征的心肌疾病,是除冠心病和高血压以外导致心力衰竭的主要病因之一。家族性扩张型心肌病约占扩张型心肌病的35％。目前为止,发现的和扩张型心肌病相关的基因突变主要是心肌蛋白基因突变和细胞骨架蛋白基因突变,此外还有线粒体DNA的突变和能量代谢相关的基因突变。本文对引起家族性扩张型心肌病的分子遗传进展进行了总结。     

Anti-nutritional effects of a moderate dose of soybean agglutinin in the rat

This study was conducted to investigate the effects of a moderate dose of purified soybean agglutinin on performance and nitrogen digestibility in rats as well as to determine its effects on the protein, DNA and RNA content of the small intestine and pancreas. Twenty-four Sprague - Dawley rats were randomly allotted into one of four groups for a 10-day nitrogen balance experiment. The four groups of rats were fed 7 g of a casein-cornstarch based diet or a similar diet supplemented with 0.1, 0.2 or 0.4 mg/g purified soybean agglutinin. All experimental diets were adjusted to an identical nutrient level. Dose of soybean agglutinin had no significant effect on rat performance. Incorporation of soybean agglutinin in the diet reduced apparent protein digestibility and the utilization of dietary protein by increasing nitrogen loss from the faeces and urine. Fresh pancreatic weight increased in rats fed soybean agglutinin at a level of 0.4 mg/g in the diet compared to the control, but the dry pancreatic weight and the protein content of the pancreas did not differ among the four groups. However the DNA and RNA content of the pancreas had a tendency to increase with a higher level of soybean agglutinin. The weight of the jejunum and its protein, DNA and RNA content were not significantly affected by soybean agglutinin, but the dry weight and the RNA of the jejunum tended to increase with higher levels of soybean agglutinin in the diet. In conclusion, purified soybean agglutinin, at moderate levels in the rats diet, had negative effects on digestive function, such as nitrogen digestibility, nitrogen retention and nitrogen balance. As the level of soybean agglutinin increased, the effects became more pronounced. Meanwhile, hypertrophy of the pancreas was observed with higher doses of soybean agglutinin incorporation in the diets.     

Malnutrition and the heart.

Earlier concepts that the heart is spared in malnutrition have been shown to be incorrect. Inadequate intake of protein and energy results in proportional loss of skeletal and myocardial muscle. As myocardial mass decreases, so does the ability to generate cardiac output; however, various compensatory factors come into play. Nutritional supplementation for malnourished patients reverses the compensatory factors and may increase the short-term potential for heart failure. Severe cardiac debility results in poor nutrition, which may in turn produce unsuspected but clinically significant myocardial atrophy. Nutritional support may play a role in improving cardiac function in selected patients with cardiac cachexia who are being prepared for cardiac surgery and in patients with rapid weight loss who are at risk for sudden death due to arrhythmias. Malnutrition is common in hospitalized patients, and many patients in hospital now receive nutritional supplementation; both facts have important cardiac implications.