SEARCH · PubMed Health

Results for “Cardiac hypertrophy”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1979

Association of myocardial cell necrosis with experimental cardiac hypertrophy.

Cardiac hypertrophy was induced in rabbits by injecting thyroxine or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.

Animals↗

PubMed1975

Lysosomal and neutral hydrolase activity during the regression of cardiac hypertrophy.

Cardiac hypertrophy was produced in rats by constriction of the ascending aorta. Removal of the constricting band 10 days after operation resulted in rapid decline in left ventricular (LV) weight and total ventricular RNA. Activities of acid RNase and beta-glucuronidase were elevated 3 days after aortic constriction. Activities of cathepsin D and alkaline RNase were unchanges. Activities of cathepsin D and acid RNase were unchanged 1 and 3 days after removal of constricting band. Ca2+-activated, neutral protease (CAF) isolated from postmitochondrial muscle supernatant was partially purified and characterized. CAF specifically degrades alpha-actinin when incubated with isolated myofibriles in the presence of Ca2+.

Animals↗

PubMed1976

Coronary blood flow and myocardial O2 consumption in hypertrophied cardiac muscle in dogs.

In dogs with experimental cardiac hypertrophy in resting conditions, coronary blood flow and myocardial O2 consumption increased proportionately to the cardiac mass; coronary flow and O2 consumption per gram of myocardium, therefore, ranged within normal values. The coronary reserve, neasured as the percentage increase in the coronary blood flow from rest till peak flow during reactive hyperaemia, was noticeably reduced, because it was partially utilized, even at rest, and consequently the possibility of an increase in flow after exercise or stress was diminished.

Animals↗

PubMed1979

Augmented aftercontractions in papillary muscles from rats with cardiac hypertrophy.

Paired-pulse stimulation induced larger aftercontractions in papillary muscles from spontaneously hypertensive rats (SHR) than from normotensive Wistar-Kyoto rats (WKY). To determine whether aftercontraction exaggeration is a general characteristic of hypertrophied cardiac muscle, three models were examined: SHRs, deoxycorticosterone acetate (DOCA)-treated rats, and aorta-constricted rats. Responses of pipillary muscles from hypertrophied hearts tested under conditions conducive to aftercontraction generation were compared to pipillary muscles from WKY or sham-treated controls, respectively. Field-stimulated papillary muscles mounted in an oxygenated temperature-controlled physiologic salt solution were exposed to calcium concentrations of 2.5 and 5.0 mM, and temperatures of 27 degrees C and 17 degrees C. Although testing conditions influenced the contractile responses to single stimuli, there was no difference in active tension, time to peak tension, or one-half relaxation time between the three experimental groups and their respective controls. Paired-pulse stimulation induced aftercontractions that were enhanced in high-calcium and low-temperature solutions. Under these conditions, papillary muscles from hypertrophied hearts developed larger aftercontractions than did their respective controls.

Animals↗

PubMed1976

Control of protein balance in hypertrophied cardiac muscle.

The levels of intracellular proteins are determined by a balance between their rates of synthesis and degradation. During the development of regression of cardiac hypertrophy, both of these rates can be expected to change. Possible control sites of synthetic and degradation processes are discussed in this article. The following experimental results are presented: (1) Cardiac mitochondrial cytochromes accumulate early after imposition of pressure overload, as a result of an increased rate of synthesis and decreased rate of degradation. (2) The half-life of myosin heavy chains (HC) in the steady state was determined from incorporation kinetics, using leucyl-tRNA as precursor, to be 5-6 days. (3) The existence of a pool of newly synthesized myofilaments which are not fully incorporated into the core of myofibrils is indicated by the incorporation data.

Animals↗

PubMed1978

Synthesis and degradation of myocardial protein during the development and regression of thyroxine-induced cardiac hypertrophy in rats.

Cardiac hypertrophy was induced in rats by daily injections of L-thyroxine (1.0 mg/kg). Regression from hypertrophy was studied 4 days after discontinuing thyroxine. Isolated, Langendorff-perfused hearts were perfused with Krebs-Henseleit buffer, glucose, insulin, and amino acids. To measure protein synthesis, left ventricular tissue was assayed for incorporation of tritiated phenylalanine into protein. Indices of rates of protein degradation were obtained by measuring the release of cold phenylalanine after blocking protein synthesis with cycloheximide. After 3 days of thyroxine (when cardiac growth was maximally increased), the rate of protein synthesis increased by 22% (P less than 0.001). After 1 week, synthesis was 8% greater than control (P less than 0.05), and by 2 weeks (when hypertrophy was stable and the rate of cardiac growth was similar to controls), synthesis had returned to control levels. In hearts regressing from hypertrophy, synthesis was reduced to 68% of control (P less than 0.001). The rate of protein degradation was decreased by 12% (P less than 0.05) after 3 days of thyroxine, but was not different from control at 1 or 2 weeks. During regression, degradation was 12% below control (P less than 0.05). Changes in the release of several amino acids that are synthesized or metabolized in heart (e.g., alanine, glycine, serine) were different from changes in phenylalanine release. In conclusion thyroxine-induced cardiac hypertrophy and regression are accompanied by changes in protein synthesis and degradation, and amino acid metabolism. The predominant change in hypertrophy is increased protein synthesis with a minor contribution from reduced degradation. Regression of hypertrophy is accompanied by decreased synthesis, not increased degradation.

Amino Acids↗

PubMed1975

Ultrastructural features of degenerated cardiac muscle cells in patients with cardiac hypertrophy.

Degenerated cardiac muscle cells were present in hypertrophied ventricular muscle obtained at operation from 12 (38%) of 32 patients with asymmetric septal hypertrophy (hypertrophic cardiomyopathy) or aortic valvular disease. Degenerated cells demonstrated a wide variety of ultrastructural alterations. Mildly altered cells were normal-sized or hypertrophied and showed focal changes, including preferential loss of thick (myosin) filaments, streaming and clumping of Z band material, and proliferation of the tubules of sarcoplasmic reticulum. Moderately and severely degenerated cells were normal-sized or atrophic and showed additional changes, including extensive myofibrillar lysis and loss of T tubules. The appearance of the most severely degenerated cells usually reflected the cytoplasmic organelle (sarcoplasmic reticulum, glycogen, or mitochondria) which underwent proliferation and filled the myofibril-free areas of these cells. Moderately and severely degenerated cells were present in areas of fibrosis, had thickened basement membranes, and had lost their intercellular connections. These observations suggest that degenerated cardiac muscle cells have poor contractile function and may be responsible for impaired cardiac performance in some patients with chronic ventricular hypertrophy.

Adolescent↗

PubMed1976

Biochemical aspects of experimental cardiac hypertrophy.

In experimental cardiac hypertrophy induced by aortic constriction of rats, the hypertrophy was established after 5-7 days. The basic biochemical changes for increasing tissue mass; increases in protein, nucleic acid, and polyamine synthesis started to occur between 2 and 8 hours followed by an increase in uridine nucleotide pools via predominance of "salvage" pathway. Although the precise coupling mechanism between mechanical stress and biochemical changes is still obscure, an interval between increased load and DNA transcription may be quite short. Some of the key enzymes regulating these processes showed a biphasic response the reason of which is not clear. The established hypertrophied heart muscle showed a decrease in velocity of isotonic shortening and an increase in resting tension. The former alteration is referred to a decrease in myosin ATPase activity and an disorder in excitation-contraction coupling mechanism, and the latter is supposed to be due to an increase in collagen in heart muscle.

Adenosine Triphosphatases↗

PubMed1979

Effects of cardiac hypertrophy secondary to hypertension on the coronary circulation.

For many years clinicians have suspected that hypertrophied ventricles have an inadequate coronary circulation. Recent studies have confirmed early observations that flow per gram in hypertrophied ventricles is normal at rest. However, coronary vascular resistance is greatly increased when hypertension is the cause of left ventricular hypertrophy. Studies that have employed labeled microspheres to assess regional myocardial perfusion have shown that the transmural distribution of myocardial perfusion is often abnormal in dogs with left ventricular hypertrophy. In addition, studies of cardiac hypertrophy in many animal models have shown that maximal coronary vasodilatation is limited substantially. Furthermore, when hypertrophied hearts are subjected to a physiologic stress that induces coronary vasodilatation, endocardial underperfusion occurs frequently. Thus, studies in animals suggest that cardiac hypertrophy adversely affects the coronary circulation. The availability of new techniques for estimating phasic and transmural coronary blood flow in man should make it possible to extend these studies to patients with cardiac hypertrophy.

Adenosine↗

PubMedDate not supplied

The pathways of protein synthesis and degradation in normal heart and during development and regression of cardiac hypertrophy.

The half-life of cardiac myosin heavy chains (HC) was determined, with leucyl-tRNA as precursor, to be 5.4 days. Myosin HC are labeled more rapidly than actin; myosin light chains (LC1 and LC2) are labeled more slowly than HC. The observed differences are attributable to heterogeneity in the half-lives, e.g., actin, and to the effect of dilution by the existing macromolecular precursor pool (LC1 and LC2). Cardiac and skeletal muscle contain a population of filaments that can be released from myofibrils by ATP-relaxing solution. The easily released filaments (ERF) are devoid of alpha-actinin and M-protein. Labeling of ERF is more rapid than that of residual myofibrils. Cardiac and skeletal muscle contains calcium-activated neutral protease, which selectively removes alpha-actinin when incubated with isolated myofibrils. During development of pressure-induced cardiac hypertrophy, the labeling of LC2 is increased. In regressing cardiac hypertrophy the activities of free and total cathepsin D and of acidic RNase are unaltered.

Actins↗

PubMed1975

Cardiac hypertrophy in spontaneously hypertensive rats.

The energy metabolism of cardiac hypertrophy in spontaneously hypertensive rats (SHR) was studied chronologically by histochemical and in part chemical methods. The activities of various enzymes, such as glucose-6-phosphate dehydrogenase (G6PDH), lactate dehydrogenase (LDH), isocitrate dehydrogenase, succinate dehydrogenase, beta-hydroxybutylate dehydrogenase (beta-HBDH) and monoamine oxidase (MAO) in the cardiac muscle were determined histochemically. beta-HBDH activity was greatly increased in the stage of developing hypertension in SHR. LDH activity increased simultaneously with the rise of beta-HBDH activity. Moreover, MAO activity increased markedly in later stages when the blood pressure was already elevated in SHR. To confirm the histochemical findings of beta-HBDH activity, the mitochondrial fraction of cardiac muscle was subjected to chemical assay. The chemical findings of myocardial beta-HBDH in SHR corresponded well with the histochemical findings. The myocardial beta-HBDH activity in SHR increased markedly at the age of 5 to 9 weeks, while no or minimal activity was found in controls of the same age. No significant difference of beta-HBDH activity was observed between SHR and controls in the mitochondrial fraction from the diaphragm and liver. The increase of beta-HBDH activity in the cardiac muscle of SHR prior to the development of cardiac hypertrophy suggests that the metabolism of ketone bodies may play an important role in providing the energy necessary for the development of cardiac hypertrophy in SHR.

Animals↗

PubMed1979

Quantitative ultrastructural aspects of cardiac hypertrophy.

Following a transient increase in relative mitochondrial volume which lasts but a few days, cardiac hypertrophy in response to pressure- or volume-overload is characterized by a preferential growth of contractile elements resulting in a decreased mitochondria/myofibrils volume ratio. At least under some conditions, the number of mitochondria/unit area increases as does the organelles surface/volume ratio. If the functional overload persists for a long period of time, e.g. 12-15 months, relative mitochondrial volume is decreased further. Unlike the imbalance in growth of mitochondria and myofibrils, the total surface area (sarcolemma plus T-System) enlarges in proportion to the increase in cell volume. While most of the components which are altered during hypertrophy become normalized as cardiac hypertrophy regresses, the process is slower than the imbalance associated with cellular enlargement. Most models of cardiac hypertrophy differ from normal growth in that the latter is characterized by proportional growth of all cellular components. In contrast, hypertrophy associated with exercise results in proportional growth in cellular components. The idea that growth of various cellular organelles is regulated by separate mechanisms is gaining support. Both sympathectomy and noreprinephrine depletion normalize the growth of mitochondria and myofibrils, while thyroxine treatment stimulates a preferential growth of mitochondria. Current evidence, therefore, suggests that myocardial cell growth probably involves complex processes which may vary with different conditions associated with the stimulus invoking enhanced cellular enlargement.

Aging↗

PubMed1975

Growth hormone in cardiac hypertrophy induced by nephrogenous hypertension.

Current evidence about the role of growth hormone in cardiac hypertrophy is ambiguous. The purpose of this investigation was to determine whether growth hormone was an important element in the cardiac hypertrophy induced by systemic hypertension. Male rats with either an intact hypophysis or a hypophysectomy were bilaterally adrenalectomized, and corticoids were replaced with exogenous deoxycorticosterone and hydrocortosone. Hypophysectomized rats were further treated with thyroxine, testosterone, and, where appropriate, bovine growth hormone. Selected groups of rats were made hypertensive by means of a surgical compression of the renal capsule which produced systemic hypertension. The magnitude of the hypertension was measured in awake rats by means of a tail plethysmograph and compressing tail-cuff. The hormone replacement program re-established systolic blood pressures in sham-operated, hypophysectomized rats to levels observed in intact-hypophysis, sham-operated rats. Thus, hypertensive, hypophysectomized rats obtained pressures above both hypophysectomized and intact-hypophysis, sham-operated rats. Hypertensive rats with an intact hypophysis and hypophysectomized rats with growth hormone developed cardiac hypertrophy. In spite of the hormone therapy, the above normal systemic blood pressures, and low mortality hopophysectomized rats without growth hormone did not develop cardiac hypertrophy.

Animals↗

PubMed1976

Heart volume and myocardial connective tissue during development and regression of thyroxine-induced cardiac hypertrophy in rats.

To determine whether development and regression of cardiac hypertrophy are accompanied by changes in heart volume and to learn whether a change in heart volume is associated with changes in the myocardial connective tissue, cardiac hypertrophy was induced in rats by administration of thyroxine. Rats were given L-thyroxine for 4 weeks. Heart volume was estimated radiologically in vivo at the start of the experiment and at 1- or 2-week intervals for 7 weeks. At each of these stages a number of rats were killed, their hearts were weighed and determinations were made of the myocardial contents of DNA, of collagen measured as hydroxyproline, and of glycosaminoglycans, measured as uronic acid. After thyroxine treatment the ratio of left heart ventricle weight to body weight and of heart volume to body weight rose significantly. The increase in heart weight was greater than the increase in heart volume. At the same time, there was a significant decrease in the concentration of hydroxyproline. After discontinuation of thyroxine treatment heart volume, heart weight and the concentration of myocardial collagen returned to normal within 2 weeks. However, the total amount of myocardial collagen was still less than normal at 2 weeks. The results suggest that the decrease in the amount of myocardial collagen associated with thyroxine-induced cardiac hypertrophy--because it results in a weakening of the supporting properties of the myocardial connective tissue framework--might contribute to a slight increase in in vivo heart volume.

Animals↗

PubMed1979

Molecular aspects of cardiac hypertrophy.

Despite continuous interest in cardiac hypertrophy, our knowledge of its molecular aspects is still elementary. Recently, however, several advancements of particular interest have been made: (a) Nuclei of muscle and nonmuscle cells have been separated, allowing for the first time the study of nuclear activity in specified cells (18). (b) Cardiac growth induced by pressure-overload (72) or by hormone treatment (26) has been shown to lead to myosin of altered ATPase, and strong evidence suggests that new species of myosin molecules thus appear. (c) The basis for assessment of protein synthesis and degradation has been established (46, 48). (d) Methods are being developed to supplement radioautography in evaluating cell proliferation (42, 59, 69). (e) In spontaneously hypertensive rats it has been shown that blood pressure might not be the sole factor responsible for cardiac enlargement, but that hypertrophy can be the result of genetic cardiovascular abnormality (19, 66). (f) A hypothesis relating the extent of energy utilization to the nuclear activity via NAD+ metabolism has been proposed, which allows for experimental verification (43).

Adenosine Triphosphatases↗

PubMed2026

Phosphoproteomics identification of ERK-dependent activation of Rps6kb1 in cardiac hypertrophy.

Cardiomyocyte growth is tightly controlled by multiple signaling pathways. Identification of master kinases in this process is essential in exploring potential targets for the treatment of pathological cardiac hypertrophy and heart failure. Here we identified the mTOR-independent activation of ribosomal protein S6 kinase b1 (Rps6kb1) during cardiomyocyte growth. By utilizing phosphoproteomics in primary neonatal rat ventricular myocytes, we revealed Rps6kb1 as one of most activated kinases under growth stimulation. We further demonstrated the role of Rps6kb1 phosphorylation in pathological cardiac hypertrophy and heart failure. We showed that the phosphorylation of multiple sites in Rps6kb1, including T367 in the kinase domain and S418/T421/S424 in the C-terminal domain, is not directly regulated by the activity of mTOR but coupled with the activation of the MEK1/ERK axis. In mice, cardiomyocyte-specific deletion of Rps6kb1 significantly inhibited both constitutively active ERK- and pressure overload-induced cardiac hypertrophy. In contrast, cardiomyocyte-specific overexpression of wild-type Rps6kb1, rather than the phosphorylation-defective mutant, elevated cardiac hypertrophy and augmented pressure overload-induced heart failure. In conclusion, our findings reveal that the MEK/ERK axis primes Rps6kb1 activation through phosphorylation of 2 separate domains of Rps6kb1, which may play an essential role in cardiac hypertrophy and heart failure under hemodynamic stress.

Animals↗

PubMed1978

Alterations in activities of cyclic nucleotide systems and in beta-adrenergic receptor-mediated activation of cyclic AMP-dependent protein kinase during progression and regression of isoproterenol-induced cardiac hypertrophy.

Initial and transient increases in the basal levels of cyclic GMP in the heart were noted prior to cardiac hypertrophy in rats administered isoproterenol. Increased levels of cyclic AMP-phosphodiesterase (in both the soluble and particulate fractions) and stimulatory modulator of cyclic GMP-dependent protein kinase, however, were associated with the progression, or the state, of cardiomegaly, with their levels returning to the control values upon regression of the hypertrophy. The levels of cyclic GMP phosphodiesterase in the soluble fraction were lower, whereas those in the particulate fraction were higher, in the hypertrophied heart than the control. In cardiac hypertrophy, the maximal activity ratio(--cyclic AMP/+cyclic AMP) of cyclic AMP-dependent protein kinase in the incubated minced heart caused by isoproterenol was lower, whereas the concentration of isoproterenol required to increase the activity ratio half-maximally was higher than controls; the reduced responsiveness to the drug, however, was reversed when the hypertrophy regressed. These observations, taken collectively, appear to suggest that the desensitization of the beta-adrenergic mechanism seen in the cardiac hypertrophy produced by repeated administration of isoproterenol is associated with adaptive modifications in certain parameters of the cyclic nucleotide systems.

Animals↗

PubMed1975

Myocardial mechanics at various stages of the cardiac hypertrophy induced by a transitory work load in the rat.

Cardiac hypertrophy was induced in rats by abdominal aortic constriction lasting 5-28 days. In other rats, release of aortic constriction after 5 or 15 days led to hypertrophy regression, which was completed within 15 days. Left ventricular papillary muscle study during cardiac hypertrophy demonstrated an early but transitory decrease of tension development and shortening velocity, a prolonged contraction duration, a slowed relaxation, and a reduced response to changes in the stimulation rate. After hypertrophy regression, the prolongation of contraction persisted; mechanical performance was similar to control, except for increased peak isometric tension in early released animals. These findings indicated that anomalous excitation-contraction coupling may be related to the hypertrophy process itself and that prolonged contraction could act as a compensatory mechanism.

Animals↗