Regional changes in ornithine decarboxylase activity and polyamine levels during thyroxine-induced cardiac hypertrophy

Ornithine decarboxylase activities (ODC) and polyamine levels were determined in five cardiac regions of the rat heart, following daily administration of 1 mg/kg of thyroxine, in the right and left atria, the right and left ventricles and the septum. The thyroxine stimulated ODC activity in all five regions of the heart. Enzyme activity in the left atrium and the septum peaked a day earlier than in other regions and the decline of ODC activity was slower. Putrescine in control animals was present in all regions except the right atrium, where its content was below detectable levels. Following the administration of thyroxine, the putrescine content of the left atrium, the right ventricle and the septum declined, while spermidine and spermine levels remained unchanged. In direct contrast to the other regions of the heart, thyroxine stimulated an increase in polyamines, as well as in weight which occurred exclusively in the left ventricle. These findings suggest a causal relationship between increased polyamines and hypertrophy.     

Exposure to intermittent high altitude induces different changes in adenylyl cyclase activity in hearts of young and adult Wistar rats

This study investigates changes of adenylyl cyclase activity in the heart of young and adult Wistar rats exposed to experimental conditions simulating high altitude hypoxia as a model for interpretation of some adaptive changes of adenylyl cyclase observed in human. The exposure of rats to intermittent high altitude (IHA) hypoxia (5000 m) showed significant adaptive changes. The right ventricular weight and the ratio of right/left ventricular weights of adult rats exposed to IHA were significantly increased when compared to appropriate controls; adaptive changes of cardiac adenylyl cyclase being dependent on the age of the animals. The isoprenaline-stimulated activity was higher in the left than in the right ventricle, and in both ventricles it was higher in young rats than in adult rats. When compared to controls, isoprenaline stimulation was decreased in the right ventricles of adapted young rats and, by contrast, it was increased in the left ventricles of adapted adult rats. This decrease and increase of adenylyl cyclase activity evoked by isoprenaline was paralleled by forskolin-induced adenylyl cyclase activity in these experimental groups. It seems therefore that the changes in the pattern of total adenylyl cyclase activity observed under IHA hypoxia may at least be partially explained by the changes of beta-adrenergic receptor susceptibility following IHA hypoxia.     

Exposure to Intermittent High Altitude Induces Different Changes in Adenylyl Cyclase Activity in Hearts of Young and Adult Wistar Rats

Abstract

This study investigates changes of adenylyl cyclase activity in the heart of young and adult Wistar rats exposed to experimental conditions simulating high altitude hypoxia as a model for interpretation of some adaptive changes of adenylyl cyclase observed in human. The exposure of rats to intermittent high altitude (IHA) hypoxia (5000 m) showed significant adaptive changes. The right ventricular weight and the ratio of right/left ventricular weights of adult rats exposed to IHA were significantly increased when compared to appropriate controls; adaptive changes of cardiac adenylyl cyclase being dependent on the age of the animals. The isoprenaline‐stimulated activity was higher in the left than in the right ventricle, and in both ventricles it was higher in young rats than in adult rats. When compared to controls, isoprenaline stimulation was decreased in the right ventricles of adapted young rats and, by contrast, it was increased in the left ventricles of adapted adult rats. This decrease and increase of adenylyl cyclase activity evoked by isoprenaline was paralleled by forskolin‐induced adenylyl cyclase activity in these experimental groups. It seems therefore that the changes in the pattern of total adenylyl cyclase activity observed under IHA hypoxia may at least be partially explained by the changes of beta‐adrenergic receptor susceptibility following IHA hypoxia.     

DNA synthesis in the ventricular myocardium of young rats exposed to intermittent high altitude (IHA) hypoxia. An autoradiographic study.

Intermittent high altitude (IHA) hypoxia (7000 m) increased the wet weight of the right ventricular myocardium of 30-day-old rats after two 4 h/day exposures. During the same period the number of DNA-synthesizing nuclei of both muscle and non-muscle cell types increased proportionally. After 4 such exposures to hypoxia the number of 3H-thymidine-labelled nuclei in both cell types increased further. In addition, the number of labelled nuclei increased significantly in the yet un-enlarged left ventricle. While there was no difference in the number of DNA-synthesizing cells between the right and left ventricles in control animals, a significant increase in the number of cells involved in DNA synthesis in the right ventricle was found in both groups of animals exposed to IHA hypoxia. These results show that DNA synthesis in myonuclei of the ventricular myocardium can be stimulated in 30-day-old rats, i.e. at the very end of the weaning period.     

三种正常大鼠磁共振成像心功能基础数据采集和分析

目的大鼠是常用的制备心脏病模型的实验动物,而磁共振成像（MRI）技术已经成为评价心脏病模型病理进程和药效的重要技术手段,但是目前国内外没有正常大鼠心脏的磁共振成像技术参数,影响了这一技术的应用。本文利用磁共振成像技术,采集和定量分析Wistar、Sprague-Dawley和Lewis三种常用大鼠的左、右心室功能参数,为心脏病模型制备和分析提供参考数据。方法利用7．0T高场强MRI心脏电影（CINE）序列,分析这三种常用大鼠活体心脏组织的左、右心室心功能参数。结果获得三种大鼠左、右心室的8—9周龄功能参数,包括：左、右心室的舒张末容积（EDV）、收缩末容积（ESV）、射血分数（EF）;左心室乳头肌层面舒张末期内径（EDD）、收缩末期内径（ESD）、短轴缩短率（Fs）、舒张末前后室壁厚度（EDAWT,EDPWT）、收缩末前后室壁厚度（ESAWT,ESPWT）、前室壁增厚率（AWT）和后室壁增厚率（PwT）;右心室乳头肌层面舒张末室壁厚度（EDWT）、收缩末室壁厚度（ESWT）和室壁增厚率（WT）等十八项心脏主要功能和结构的正常值。结论本研究获得的三种大鼠十八项心脏主要功能和结构的正常值,可作为心脏病模型制备成模判定和病理进程、药物评价的参考数据。     

Effect of ectopic excitation on the ventricular pump function in chicken

The pump function of the heart ventricles was studied in chest-open anaesthetized adult female chickens under sinus rhythm and ectopic excitation of different localization. The intraventricular pressure in the right and left heart ventricles was measured by insertion of catheters through the ventricular free walls. Maximum systolic pressure, end-diastolic pressure, contractility (dP/dtmax) and relaxation (dP/dtmin) of both heart ventricles, and duration of the asynchronous contraction time of the left ventricle were analyzed. It was revealed that reduction of the pump function of the left ventricle tends to be greater under right ventricular ectopic excitation compared with left ventricular one. In comparison with the sinus rhythm, the pump function of the right ventricle was preserved to a greater extent under stimulation of the left ventricular apex and was significantly impaired under right ventricular ectopic excitation. Relaxation of both heart ventricles was more susceptible to ventricular ectopic excitation than contractility, and was more vulnerable in the right ventricle than in the left one. The direction of changes of the pump function of the heart ventricles in chickens under ventricular ectopic excitation was similar to changes of the pump function of mammalian hearts.     

Proliferative processes in the myocardium in different parts of the heart during the creation of experimental myocardial infarct of the left ventricle in 2- and 3-week-old rats

As a result of 30 times repeated injections of 3H-thymidine (3HTdr) to neonate rats, beginning from days 13 or 21 post partum, ca. 20 and 10% of myonuclei in the left and right atria were labeled, respectively, while in both ventricles cumulative labeling of myocytes was nearly ten times lower. In rats of the same age with experimental infarction of the left ventricular myocardium the number of myonuclei labeled after 30-fold 3HTdr injections increased in atria up to 40-50%, in perinecrotic myofibers of the left ventricles up to 8-11%, and in myofibers of the left and right ventricle located far from the necrotic foci up to 3-4 and 2-3%, respectively. In some of rats subendocardial and/or subepicardial layers of the surviving left ventricular myocardium contained up to 15-35% of labeled myonuclei. Thus, in neonatal rats the extent of DNA synthesis reactivation in the nuclei of cardiomyocytes, the majority of which have recently completed normal ontogenetic proliferation, is, on the whole, of the same order as found in similar experiments on adult rats (Rumiantsev, Kassem, 1976; Oberpriller et al., 1984). However, still immature ventricular myocytes of neonatal rats resume mitotic cycle easier than those of adult animals which is evidenced not only by higher numbers of 3HTdr labeled myonuclei in subepicardial and subendocardial ventricular myocardia of some rats, but even more by reactivation of DNA synthesis in a limited fraction (2-3%) of the whole population of non-perinecrotic myocytes in both ventricles. Besides, reactive proliferation of cardiomyocytes in the atria of neonate rats, unlike in adults, starts on day 3 rather than on day 5 after infarction is induced. In the atria of neonatal rats polyploidization of myonuclei at later postinfarction stages is less pronounced than in adult rats which may be accounted for by formation of individual daughter nuclei during acytokinetic mitoses or, more seldom, by completion of cytotomy.     

Cumulative indices of DNA synthesizing myocytes in different compartments of the working myocardium and conductive system of the rat’s heart muscle following extensive left ventricle infarction

Ten successive³H-thymidine injections at 12h intervals (which is a little shorter than the adult heart myocyte S phase) were performed for labeling of the majority of cardiac myocytes synthesizing DNA at any moment of such a 5 days experiment. In the hearts of control unoperated rats ten-fold repeated³H-thymidine administration results in labeling of 2–3% myocyte nuclei, in both atria, ca. 1% of the specialized muscle cell nuclei in the atrioventricular conductive system, only occasional muscle cells being labeled in the working ventricular myocardium. When ten successive³H-thymidine injections were made between the 5th and 10th days following extended left ventricle infarction, the percentage of labeled myocytes in left and right atria reaches, respectively, 51.4±4.4% and 34.7±3.6%. In the left ventricle labeled muscle nuclei are accumulated predominantly (9.3±2.1%) within the thin subepicardial layer of the surviving myofibers, while myofibers located in other perinecrotic areas contained only 1.3±0.5% labeled muscle nuclei. The number of these nuclei in the atrioventricular system remains at the level observed in control hearts (up to 2%), approaching closely the zero level in the working myocardium of both the ventricles and interventricular septum, located at the considerable distance from the infarcted region. When similar experiments with ten-fold repeated³H-thymidine injections were performed between 15th and 20th post-infarction days the number of labeled myocyte nuclei was found to be reduced 4–6 times in atria, being changed rather a little in the perinecrotic ventricular myocardium and in the specialized myocardium of the atrioventricular system. Some possible reasons of the observed differences in the proliferative behaviour of cardiac myocytes in terms of their topology and/or specialization are discussed     

Capillarization of the myocardium of the yak

Organometric and histometric characteristics of various parts of the heart have been performed in the yak, a permanent inhabitant at altitudes of 3,000-5,000 m above the sea level. Forty hearts of mature animals have been studied. Morphometric investigations of capillaries in the muscle fibers have been carried out in the atrial walls, in the right and left auriculae. in the ventricles and in the papillary muscles. The data are presented for each cardiac part: they describe diameters, density and volume of the capillary network and muscle fibers. In order to estimate the degree of capillarization of the cardiac muscle tissue, a new parameter is suggested to be used, when analyzing the morphometric data. It characterizes ratio of capillaries volume. According to the criterion given, a significant difference is stated between the degree of capillarization in the myocardium of the right and left ventricles. We suppose that this adequately reflects an increased loading experienced by the right cardiac parts under a long-lasting effect of altitude factors.     

Age-related changes in the cardiomyocyte population of the heart ventricles of white rats

The total number of muscle cells and their nuclei in the rat ventricle walls at the age from 3 to 30 months was counted by means of alkaline dissociation of the prefixed myocardium. The total number of cardiomyocytes and their nuclei was shown to increase on the second year of life, this increase being much more pronounced and attaining the maximum much earlier in the right ventricle than in the left one. At the senile age (30 months) the number of cardiomyocytes in the ventricles decreases but the mean size of cells increases. Possible sources of replenishment of the population of cardiomyocytes are discussed.     

Regulation of cardiac adrenomedullin-mRNA in different stages of experimental heart failure

Adrenomedullin (AM) is a peptide hormone with vasodilating and natriuretic properties. AM plasma concentrations are elevated in heart failure. Whether cardiac AM-mRNA synthesis is increased in heart failure is not known. We measured AM-mRNA/GAPDH-mRNA in all four heart chambers in compensated and overt heart failure in rats with two different sizes of aortocaval shunt. Left and right atrial AM-mRNA expressions were unchanged in both heart failure models. Similarly, left and right ventricular AM-mRNA expressions were unchanged in compensated heart failure. In overt heart failure, however, the AM-mRNA expression was significantly increased in the left ventricle (145+/-20 vs. 100+/-3% of control, p<0.05). The right ventricular AM-mRNA expression was significantly increased only in a subgroup of animals with pulmonary congestion (lung weight >2.0 g, 141+/-16 vs. 100+/-11% of control, p<0.05). Ventricular AM concentrations were elevated in both ventricles in overt heart failure. AM plasma concentrations were significantly higher in the subgroup with pulmonary congestion than in rats with compensated heart failure (496+/-95 vs. 143+/-7 pmol/l, p<0.01). These data indicate that ventricular AM-mRNA expression and AM concentrations were upregulated only in advanced stages of heart failure. However, the exact contribution of cardiac AM synthesis to the increased AM plasma levels remains to be established.     

Ploidy in the hearts of elderly patients

The DNA-ploidy of the left and right ventricular wall in 48 patients aged 80-98 years was investigated by scanning cytophotometry. The great variation in nuclear ploidy previously described in the heart muscle was shown to persist during the ninth decade. In addition, the percentage of nuclei with more than 2C DNA content in both ventricles correlated with the degree of coronary stenosis, and in the right ventricle with the presence and severity of pulmonary emphysema, and with the duration of digitalis therapy where this drug was given.     

Effect of intermittent high altitude hypoxia on the structure and enzymatic activity of cardiac myosin

The time course of structural and enzymatic changes in cardiac myosin was studied in the right and left ventricle of rats exposed to intermittent high altitude (IHA) hypoxia. In the controls, ATPase activity and myosin structure in both ventricles was the same. After the third exposure to simulated high altitude (2 600 m), myosin enzymatic activity rose significantly in the left ventricle and a significant right-left difference appeared. In the next phase of adaptation (11 exposures, 6 000 m), myosin ATPase activity fell in both ventricles and the right-left difference disappeared. After the 16th exposure (7 000 m), enzymatic activity increased again in both ventricles and attained control values. IHA also produced significant structural changes in cardiac myosin, particularly in the rigaht ventricle. The changes were characterized by the formation of myosin aggregates with significantly lower ATPase activity that the myosin monomer. The time course and localization of structural and enzymatic changes in cardiac myosin corresponded to the morphological damage to the heart fibres.     

Choline acetyltransferase activity and distribution in rat hearts after bilateral cervical vagotomy

The activity of choline acetyltransferase (ChAt; E.C. 2.3.1.6) measured as the bromoacetylcholine-sensitive portion of the maximal rate of acetylcholine synthesis has been determined in homogenates of nine regions of the heart of control rats and rats sacrificed 72-74 h after bilateral cervical vagotomy. When related to the content of protein, the activity of ChAT was lowered by 30% in the atria and unchanged in the ventricles of vagotomized rats. The highest absolute decline caused by vagotomy was observed in the sinoatrial region; it was somewhat less in the rest of the right atrium and in the interatrial septum and considerably less in the left atrium. It is concluded that preganglionic parasympathetic fibres supply mainly the sinoatrial region and the right atrium, and that they do not branch to the ventricles. Preganglionic ChAT nts about 30% of total ChAT activity in the atria. The sinoatrio-ventricular gradient in the distribution of ChAT in the heart is due to uneven distribution of both the pre- and postganglionic ChAT pools (i.e., of both the pre- and postganglionic cholinergic nerve fibres and nerve cell bodies).     

Quantification of messenger ribonucleic acid for atrial natriuretic factor in atria and ventricles of Dahl salt-sensitive and salt-resistant rats

The levels of atrial natriuretic factor (ANF) and the mRNA for ANF were measured in the left ventricles of Dahl salt-sensitive (S) and salt-resistant (R) rats. ANF and ANF mRNA were both much higher in ventricular tissue of newborn rats of both strains compared to young adults, which represents the normal developmental pattern. There was no strain difference between S and R when the rats were young (1.5 months of age), but in older animals (8.5 months of age), when S rats were markedly hypertensive, there was a 5- to 10-fold increase in both left ventricular ANF and left ventricular ANF mRNA in S, but not R, rats. Atrial ANF mRNA was not similarly increased in hypertensive S rats. The ANF levels present in ventricles could not be accounted for by contamination with plasma ANF. Moreover, HPLC analysis of the forms of ANF in ventricles of newborn and hypertensive S rats showed that immunoreactive ANF in ventricles was present mainly in the same precursor form found in atria and not the shorter peptide form found in plasma. Northern blot analysis showed that ANF mRNA for atria and ventricles were the same size. It is concluded that in the S rat the heart left ventricle responds to hypertension by increasing production and storage of ANF.     

Relative hypertrophy of the right ventricle in silver foxes selected for domestication behavior

Silver foxes selected for domestication behavior were found to have relative hypertrophy of the right heart ventricle, which was 21% as enlarged in males and 18% as enlarged in females as compared with non-domesticated animals. It was established by stereological methods that hypertrophy occurs mainly at the expense of an increase in the absolute and relative content of myofibrils in cardiomyocytes, with the absolute total volume of the mitochondria being equal both in domesticated and non-domesticated animals. It was shown by means of dissociated cell counts that in both animal groups, the absolute number of cardiomyocytes and their nuclei in the right ventricles is approximately similar. It is suggested that there is a relationship between right heart ventricle hypertrophy in domesticated foxes and variation in the balance of sympathetic and parasympathetic effects.     

Metabolic enzyme response in the pressure-overloaded heart of weanling and adult rats

Weanling and adult rats were subjected to left ventricular pressure overload induced by abdominal aortic constriction. At 5 days or 5 weeks postsurgery, the left ventricle (LV) was dissected, weighed, and metabolic marker enzyme activities (mumole/g/min) of tissue homogenates were measured. Enzymes representing glycolytic (phosphofructokinase (PFK] and mitochondrial (citrate synthase (CS) and malate dehydrogenase (MDH] metabolisms were evaluated. Five days of pressure overload had detectable, but statistically nonsignificant effects on left ventricles of both weanling and adult rats. Sustained pressure overload (5 weeks) increased LV weight by 52 and 39% in weanling and adult rats, respectively. PFK activity was 24 +/- 1 (mean +/- SE) in control weanlings and was unaltered in any of the other groups. LDH isoenzyme composition was estimated by substrate inhibition (ratio 0.33/10 mM pyruvate). With normal heart development, the LDH ratio increased from 1.89 +/- 0.06 to 2.03 +/- 0.08. Pressure overload had no influence on the adult LDH ratio. Developmental LDH responses were not observed in weanling LV after 5 weeks of aortic constriction (1.74 +/- 0.06). The product of CS activity and LV weight was used to estimate mitochondrial mass in the ventricle. Mitochondria accumulated at a rate of about 5% increase per day over the intervening 5-week period of normal heart growth. Pressure overload for 5 weeks in weanling rats elicited net accumulation of mitochondria at a rate of about 9% increase per day. Mitochondrial accumulation in the adapting adult rat heart amounted to less than 1% increase per day. The results indicate that qualitative and quantitative differences exist between young and adult animals in their heart enzyme adaptive responses to pressure overloading. Divergent metabolic adaptations may contribute to heart functional differences in the enlarged heart of weanlings and adults.     

Effect of sustained hypobaric hypoxia during maturation and aging on rat myocardium. I. Mechanical activity.

Long-lasting cardioprotection may be attained by chronic hypoxia. The basal parameters of contractile function and their response to hypoxia/reoxygenation were measured under isometric conditions, in papillary muscles isolated from left ventricle of rats that were submitted to 53.8 kPa in a hypobaric chamber from 7 wk of age and for their lifetime and of their siblings kept at 101.3 kPa. During acclimatization, hematocrit increased, body weight gain decreased, and heart weight increased with right ventricle hypertrophy. Papillary muscle cross-sectional area was similar in both control and hypoxic groups up to 45 wk of exposure. Developed tension (DT) was 34-64% higher in rats exposed to hypoxia for 10, 26, and 45 wk than in their age-matched controls, whereas resting tension was unchanged. Maximal rates of contraction and relaxation showed a similar pattern of changes as DT. Recovery of DT and maximal rates of contraction and relaxation after 60-min hypoxia and 30-min reoxygenation was also improved in adult hypoxic rats to values similar to those of young rats. Heart acclimatization was lost after 74 wk of exposure. Results are consistent with the development of cardioprotection during high-altitude acclimatization and provide an experimental model to study the mechanisms involved, which are addressed in the accompanying paper.     

Myosin types and fiber types in cardiac muscle. I. Ventricular myocardium

Antisera against bovine atrial myosin were raised in rabbits, purified by affinity chromatography, and absorbed with insolubilized ventricular myosin. Specific anti-bovine atrial myosin (anti-bAm) antibodies reacted selectively with atrial myosin heavy chains, as determined by enzyme immunoassay combined with SDS-gel electrophoresis. In direct and indirect immunofluorescence assay, anti-bAm was found to stain all atrial muscle fibers and a minor proportion of ventricular muscle fibers in the right ventricle of the bovine heart. In contrast, almost all muscle fibers in the left ventricle were unreactive. Purkinje fibers showed variable reactivity. In the rabbit heart, all atrial muscle fibers were stained by anti-bAm, whereas ventricular fibers showed a variable response in both the right and left ventricle, with a tendency for reactive fibers to be more numerous in the right ventricle and in subepicardial regions. Diversification of fiber types with respect to anti-bAm reactivity was found to occur during late stages of postnatal development in the rabbit heart and to be influenced by thyroid hormone. All ventricular muscle fibers became strongly reactive after thyroxine treatment, whereas they became unreactive or poorly reactive after propylthiouracil treatment. These findings are consistent with the existence of different ventricular isomyosins whose relative proportions can vary according to the thyroid state. Variations in ventricular isomyosin composition can account for the changes in myosin Ca2+-activated ATPase activity previously observed in cardiac muscle from hyper- and hypothyroid animals and may be responsible for the changes in the velocity of contraction of ventricular myocardium that occur under these conditions. The differential distribution of ventricular isomyosins in the normal heart suggests that fiber types with different contractile properties may coexist in the ventricular myocardium.