Stage Of Hypertrophy Research Articles

Cardiac β-adrenoceptors, G-proteins and adenylate cyclase regulation during myocardial hypertrophy

The role of the β-adrenoceptor-G-protein-adenylate cyclase system in the pathogenesis of cardiac hypertrophy was studied. We have used a minipig model of pressure-overload cardiac hypertrophy secondary to aortic banding. Four groups of five animals were used: minipigs made hypertrophic were evaluated 2 months (CH2 group) and 9 months (CH9 group) later and compared to controls (C2 and C9 groups, respectively). A decrease in β-adrenergic receptor density and an increase in antagonist affinity were shown in left ventricular membranes of hypertrophied animals compared with controls. In both groups, CH2 and CH9, an increase in EC 50 for isopreterenol-stimulated adenylate cyclase activity, an increase in forskolin-stimulated adenylate cyclase activity and a diminished inhibition by carbachol of isoproterenol-stimulated adenylate cyclase were observed. In contrast, fluoride-stimulated adenylate cyclase activity was markedly increased only in the end stage of hypertrophy. α s-cholera toxin-catalysed ADP-ribosylation is increased in early hypertrophy and then decreases with late hypertrophy and a similar pattern is observed with α O pertussis toxin-catalysed ADP-ribosylation, whereas α i-ADP-ribosylation remains unchanged. Tissue content of G s-, G i- and G 0-proteins, as assessed by specific antibodies, was found unchanged in CH9 and CH2 groups when compared with that in C9 and C2 control groups, respectively. Modifications in G s functional activity in later hypertrophic stages, expressed as alterations in cholera toxin ADP-ribosylation and adenylate cyclase fluoride responsiveness, may be important in the pathogenesis of decompensation from compensated hypertrophy to cardiac failure.

Transdermal dihydrotestosterone treatment of 'andropause'.

Male ageing coincides on average with progressive impairment of testicular function. The most striking plasma changes are an increase in sex hormone binding globulin (SHBG) and a decrease in non SHBG-bound testosterone, which is the only testosterone subfraction effectively bioavailable for target tissues. In healthy subjects the bioavailable testosterone declines by approximately 1% per year between 40 and 70 years but a more pronounced decline has been observed in non-healthy groups, especially in high cardiovascular risks groups. Relative androgen deficiency is likely to have unfavourable consequences on muscle, adipose tissue, bone, haematopoiesis, fibrinolysis, insulin sensitivity, central nervous system, mood and sexual function and might be treated by an appropriate androgen supplementation. The potential risk for prostate has been the main reason for limiting indications of such treatment. Testosterone (T) and dihydrotestosterone (DHT) are two potent androgens which have opposite effects regarding aromatase activity, an enzyme present in prostate stroma and suspected to have a pathogenic influence through local oestradiol synthesis. T is the main substrate for aromatase and oestradiol synthesis while DHT is not aromatizable and, at sufficient concentration, decreases T and oestradiol levels. A 1.8 years survey of 37 men aged 55-70 years treated with daily percutaneous DHT treatment suggested that high plasma levels of DHT (> 8.5 nmol/l) effectively induced clinical benefits while slightly but significantly reducing prostate size. Early stages of prostate hypertrophy require synergic stimulation by both DHT and oestradiol, and suppressing oestradiol instead of DHT seems easier and better adapted to the specific situation of aged hypogonadic men.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo profile of myocardial energy metabolism of pressure-overloaded rat.

Cardiac energy metabolism of pressure-overloaded rat hearts was examined under in vivo and in vitro conditions. Two, 4 and 6 weeks after constriction of the abdominal artery, the hemodynamic and metabolic profiles of hearts in vivo and of perfused hearts were determined. Significant increases in left ventricular weight/body weight (30 to 45% increase relative to the sham group), systolic and diastolic blood pressure (22 to 33% increase) and pressure-rate product (31 to 33% increase) were observed 2, 4 and 6 weeks after the operation, and a slight but significant decrease in heart rate was observed at 2 weeks after the operation. Tissue hydroxyproline content increased (17 to 93%) with time after pressure-overload. These findings are indicators of pressure-overloaded cardiac hypertrophy. The total high-energy phosphates of the in vivo rat myocardium under artificial respiration were lower than those of sham-operated rat myocardium 2 (23%) and 4 weeks (21%), but not 6 weeks after aortic constriction. The maximal oxygen consumption rates of mitochondria, when determined in the skinned cardiac fibers, also decreased 2 (47%) and 4 weeks (36%), but reversed 6 weeks after pressure-overload. However, the myocardial ATP, a utilizing form of high-energy phosphate, of pressure-overloaded rat myocardium remained normal at all times after cardiac hypertrophy. This suggests that alterations in hemodynamic variables of in vivo pressure-overloaded rats may not be attributable to a reduction in the myocardial energy production. In the perfused hearts isolated from pressure-overloaded rats, tissue ATP levels were similar to those of sham-operated rats, although the tissue creatine phosphate tended to be reduced in the pressure-overloaded animals at all stages of cardiac hypertrophy examined. Only a marginal decrease in the tissue high-energy phosphate (13%) was observed 4 weeks after the operation relative to that of sham-operated rats. In contrast, the developed tension of the perfused pressure-overloaded rat hearts was consistently lower (27 to 36%) than that of the sham-operated rat hearts. The results suggest that the high-energy phosphate levels of pressure-overloaded rat myocardium in vitro are unlikely to account for the observed decline in cardiac contractile function. The reduction of myocardial high-energy phosphates of pressure overloaded rats may be due to an adaptative change rather than a causal events.

Mechanical and energetic changes in short-term volume and pressure overload of rabbit heart.

The mechanical and energetic consequences of a short-term volume overload (STVOL) hypertrophy and short-term pressure overload (STPOL) hypertrophy have been investigated in rabbits and compared with short-term sham-operated controls (STSOC). Hypertrophy was induced either by creating an aortocaval shunt (volume overload) or by banding the pulmonary artery (pressure overload). Suitable papillary muscles were excised from the hearts 8-10 days after the surgical procedure. At 27 degrees C and a stimulus frequency of 1.0 Hz, peak stress development of the STVOL preparations was significantly reduced from the control group, whereas no significant difference in peak stress development was evident between the STPOL and STSOC groups. Surprisingly, the STPOL preparations displayed pulsus alternans after only 8-10 days of inducing the overload. At steady-state conditions, the isometric 10%-90% rise times, the 90%-10% relaxation times, and the 1/2-widths were not significantly different between the treated and control groups. In isotonically contracting muscles working against a range of afterloads, the enthalpy (energy) and work output of the STVOL and STPOL preparations were depressed compared to the STSOC preparations; the differences were statistically significant for the STVOL group. Due to the parallel change in work and enthalpy, the mechanical efficiency was unaltered. A force-length-area (FLA) analysis, analogue of the pressure-volume-area (PVA) analysis, was applied to the isotonic data of this study. The isotonic enthalpy at the various load levels was plotted against the measured FLA and the data were fitted by linear regression. It was evident that the FLA correlated closely with the energy used. The STVOL and STPOL mean total energy:FLA regression lines lay parallel to but were below the STSOC line, signifying a drop in the activation heat, although this reduction did not achieve statistical significance. It is concluded that significant mechanical and energetic changes are evident after a short-term volume overload although earlier work has shown that these differences are absent at the later, compensated stage of hypertrophy. Changes associated with the pressure overload model suggest a disturbance in calcium regulation: this effect is also seen in long-term pressure overload.

Myocardial contractility, lusitropy and calcium responsiveness in young (50 days) and hypertrophied (180 days) cardiomyopathic hamsters

Contractility, lusitropy and responsiveness to the increase of external Ca 2+ concentration were studied in left ventricular papillary muscles of normal and cardiomyopathic Syrian hamsters (SCH) from the UM-X 7.1 strain, both at the onset of myolysis (50-day-old animals) and at the cardiac hypertrophy stage (180-day-old animals) in the absence of congestive heart failure. A marked decrease in all indices of systolic performance was observed in 180-day-old myopathic hamsters as compared to agematched controls. This was associated with (1) an impairment of the relaxation phase, (2) a loss of the load sensitivity of relaxation, and (3) a decrease in the inotropic and lusitropic responsiveness to Ca 2+. On the other hand, when some indices of contraction and the inotropic response to Ca 2+ were impaired in 50-day-old myopathic hamsters as compared to age-matched controls, relaxation phase and the lusitropic response to Ca 2+ did not alter. This study shows that, in the UM-X 7.1 myopathic hamsters at the earlier stage of the disease, alterations in calcium homeostasis and contraction seem to be the first determinant factors of the development of heart failure when relaxation is not impaired. Conversely, when cardiac hypertrophy has developed, impaired relaxation may worsen heart failure.

The progress of hypertrophic scars monitored by ultrasound measurements of thickness

Ultrasound scanning was used to measure the thickness of hypertrophic scars following burn injury. Scarred areas on patients receiving pressure therapy were monitored at regular intervals from the initial healing, through the hypertrophic stage, to maturation of the scars. The data, collected over a period of 30 months, allowed a comparison of scar development in children and adults and a comparison of the response at different anatomical sites. Measurements made on individual patients could be related to factors affecting the progress of their hypertrophic areas and provided a useful backup to visual assessment during pressure garment therapy.

Noninvasive assessment of cardiomyopathy development with simultaneous measurement of topical 1H- and 31P-magnetic resonance spectroscopy.

Background. It might be possible to estimate the metabolic derangement of cardiac muscle by topical nuclear magnetic resonance spectroscopy (MRS) in vivo without killing the animal. Methods and Results. By use of topical 1H- and 31P-MRS focused on the heart of Syrian hamsters with or without cardiomyopathy (CM; BIO 14.6 strain), the chemical constituents were measured in vivo nondestructively and repetitively at several stages of development of CM. A phantom experiment and two-dimensional plot of chain methylenes (CH2) of lipid/water ratio by 1H-MRS versus creatine phosphate (CP)/[beta-P]ATP ratio by 31P-MRS indicated that signal cross talk from the adjacent organs was negligible. Even before the onset of clinical or pathological manifestation of CM (7 weeks after birth), CH2/water ratio by 1H-MRS was lower in the CM group (7.3 +/- 0.7%) than in control (11.8 +/- 2.0%, p less than 0.05), and it decreased further at the hypertrophic stage (17 weeks, 4.1 +/- 0.7%, p less than 0.05) and the congestive stage (27 weeks, 4.3 +/- 0.9%, p less than 0.05). In contrast, the CP/[beta-P]ATP ratio by 31P-MRS started to decrease at the hypertrophic stage (1.90 +/- 0.18 versus 2.52 +/- 0.24, p less than 0.05) and decreased further at the congestive stage to 1.53 +/- 0.18 (p less than 0.01). These in vivo MRS data were confirmed by both biochemical assay and in vitro MRS analysis in heavy water after the animals were killed. Conclusions. A combination of topical 1H-MRS and 31P-MRS in vivo is promising for the noninvasive and sensitive assessment of cardiac muscle metabolism. Comparison of these MRS studies and biochemical analysis suggested not only the modification of water, lipid, CP, or ATP contents but also the reduction of flexibility or fluidity of lipids in cardiomyopathic heart.

Stimulatory guanine nucleotide-binding protein and adenylate cyclase activities in Bio 14.6 cardiomyopathic hamsters at the hypertrophic stage.

The Bio 14.6 cardiomyopathic Syrian hamster is an animal model of human idiopathic cardiomyopathy. The pathogenesis of the disease in this animal has not yet been clearly elucidated. It is well known that alpha- and beta-adrenergic receptors are increased in the myocardium of this animal, but that isoprenaline does not produce an augmented response. We examined the activity of cardiac stimulatory GTP-binding protein (Gs), which couple with beta-adrenergic receptors to stimulate adenylate cyclase, in Bio 14.6 cardiomyopathic hamsters at 90 and 160 days of age. The cardiac norepinephrine concentration was significantly increased in Bio 14.6 hamsters compared with control hamsters (F1B) at 90 days of age (1,739 +/- 120 vs 1,470 +/- 161 ng/g wet tissue weight, p less than 0.05). Cardiac forskolin-stimulated adenylate cyclase activities at 90 and 160 days of age were lower in the cardiomyopathic hamsters than in the F1B controls (90 days old: 98 +/- 24 vs 122 +/- 29 pmol/min/mg protein, p less than 0.05; 160 days old: 74 +/- 13 vs 124 +/- 28 pmol/min/mg protein, p less than 0.01). Cardiac Gs activities at 90 and 160 days of age were significantly lower in Bio 14.6 hamsters than those in F1B hamsters (90 days old: 204 +/- 42 vs 259 +/- 49 pmol/min/mg protein, p less than 0.05; 160 days old: 156 +/- 39 vs 211 +/- 60 pmol/min/mg protein, p less than 0.05). We thus demonstrated functional defects in cardiac Gs protein and adenylate cyclase activity in the Bio 14.6 cardiomyopathic hamsters at 90 to 160 days of age (the hypertrophic stage of cardiomyopathy).(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of proliferation or hypertrophy of chondrocytes in serum-free culture: the role of insulin-like growth factor-I, insulin, or thyroxine.

In bone forming cartilage in vivo, cells undergo terminal differentiation, whereas most of the cells in normal articular cartilage do not. Chondrocyte hypertrophy can be induced also in vitro by diffusible signals. We have identified growth factors or hormones acting individually on 17-d chick embryo sternal chondrocytes cultured in agarose gels under strictly serum-free conditions. Insulin-like growth factor I or insulin triggered the first steps of chondrocyte maturation, i.e., cell proliferation and increased matrix deposition while the chondrocytic phenotype was maintained. However, cells did not progress to the hypertrophic stage. Proliferation and stimulated collagen production was preceded by a lag period, indicating that synthesis of other components was required before cells became responsive to insulin-like growth factor I or insulin. Very small amounts of FBS exerted effects similar to those of insulin-like growth factor I or insulin. However, FBS could act directly and elicited hypertrophy when constituting greater than 1% of the culture media. Basic FGF has been claimed to be the most potent chondrocyte mitogen, but had negligible effects under serum-free conditions. The same is true for PDGF, a major serum-mitogen. Under the direction of thyroxine, cells did not proliferate but became typical hypertrophic chondrocytes, extensively synthesizing collagen X and alkaline phosphatase.

Morphology of tissue components of layers of the rat myocardium in the early stages of myocardial hypertrophy

Morphology of tissue components of layers of the rat myocardium in the early stages of myocardial hypertrophy

Electron microscopic study on overacting inferior oblique muscles.

Overaction of the inferior oblique(IO) muscle is manifested by elevation of the adducted eye and from the clinical point of view there are two types of overaction. The primary type is of unknown cause, whereas the secondary type is usually related to the palsy of the ipsilateral superior oblique or contralateral superior rectus. An ultrastructural study on the overacting IO muscles was performed compared to normal IO muscles by electron microscopy. Of 16 biopsies of overacting IO muscles, four had primary overacting inferior obliques and twelve had secondary overacting inferior obliques due to paralysis of superior oblique muscle. Additional four IO muscle, obtained from patients with intraocular diseases served as control specimens. The most striking abnormalities were aggregations of mitochondria and degenerating mitochondrial profiles and increased vacuolization in primary and secondary overacting muscles. Many muscle fibers were in different stages of atrophy, and hypertrophy and regeneration of muscle fibers were sometimes visible. The results suggest that the primary overacting IO muscle might be the result of a paresis of the superior oblique muscle.

Postnatal development of cholinergic neurons in the rat: I. Forebrain

The postnatal development of cholinergic projection and local-circuit neurons in the rat forebrain was examined by use of choline acetyltransferase (ChAT) immunohistochemistry and acetylcholinesterase (AChE) histochemistry. Although regional nuances were apparent, a general trend emerged in which cholinergic projection neurons in the basal nuclear complex (i.e., medial septal nucleus, vertical and horizontal diagonal band nuclei, magnocellular preoptic field, substantia innominata, nucleus basalis, and nucleus of the ansa lenticularis) demonstrated ChAT-like immunoreactivity earlier in postnatal development than intrinsically organized cholinergic cells in the caudate-putamen nucleus and nucleus accumbens, although this disparity was less apparent for local circuit neurons in the olfactory tubercle and Islands of Calleja complex. Ontologic gradients of enzyme expression also existed in some regions. A lateral to medial progression of ChAT and AChE appearance was observed as a function of increasing postnatal age in the nucleus accumbens and rostral caudate-putamen nucleus. By comparison, a rostrocaudal gradient of expression of ChAT-like immunoreactivity was apparent within the basal nuclear complex. Moderate to intense ChAT positivity, for example, appeared first in the medial septal nucleus. Furthermore, compared to more caudal regions, a greater proportion of AChE-positive neurons in rostral aspects of the basal forebrain expressed ChAT immunoreactivity on postnatal day 1, a difference that was no longer present by postnatal day 5. Cholinergic neurons in all forebrain regions also underwent an initial stage of progressive soma and proximal-dendrite hypertrophy, which peaked during the third postnatal week, followed by a period of cell-body and dendritic shrinkage that persisted into the fifth postnatal week when adult configurations were reached. These soma and dendritic size increases and decreases were not correlated with the magnitude of postnatal ChAT expression, which increased progressively until adult levels were attained approximately by the third to fifth weeks after birth. Expression of AChE in putative cholinergic neurons appeared to precede that of ChAT, especially in the caudate-putamen complex. Staining intensity of AChE also incremented earlier than that of ChAT.

Triggered Activity As a Possible Mechanism for Arrhythmias in Ventricular Hypertrophy

To study the cellular mechanisms of arrhythmias occurring in cardiac hypertrophy, we performed standard microelectrode studies on papillary muscles isolated from control (group N) and hypertrophied ferrets right ventricles. Different stages of hypertrophy, induced by pulmonary banding, were studied: 10-22 days (group H1), 4-6 weeks (H2), and 5 1/2-6 months (H3). During the development of hypertrophy, under beta-adrenergic stimulation, triggered activity (TA) induced by delayed afterdepolarizations appeared in 2 of 5 muscles in group H1 and 8 of 8 in group H2. This arrhythmia was absent in N muscles, as well as in H3, despite a pronounced prolongation of the action potentials at 50% (100 +/- 9.3 msec in group H3 vs 67 +/- 5.7 msec in H2; P less than 0.01) and 90% of repolarization (225 +/- 8.7 in H3 vs 185 +/- 7.4 msec in H2; P less than 0.02). The presence of TA was associated with an increase in the intracellular calcium activity (144 +/- 60 nM in H2 vs 47 +/- 9 nM in N; P less than 0.05). TA properties were as follows. Triggering frequency increased as beta-adrenergic stimulation increased, as pacing cycle length (PCL) decreased, and as duration of the prestimulative pause increased. The duration of salvos of TA increased as duration of the prestimulative pauses increased (NS). The coupling interval of the first triggered beat decreased as PCL decreased (P less than 0.001). The minimal cycle length of salvos of TA was not modified by these parameters. It is concluded that delayed afterdepolarizations-induced TA may occur under beta-adrenergic stimulation during the first stages of ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

FLOODWATER TEMPERATURE AND STEM LENTICEL HYPERTROPHY IN MANGIFERA INDICA (ANACARDIACEAE)

One‐year‐old seedling trees of Mangifera indica L. cv. Peach were exposed to floodwater temperatures of 15, 22.5, or 30 C for at least 13 days. Immediately prior to flooding, and at daily intervals thereafter, trees were visually examined for evidence of lenticel hypertrophy. Although lenticel hypertrophy was first apparent after 5 days of submergence at 30 C, and after 6 days at 22.5 C, the mean number of days of flooding until lenticel hypertrophy was first observed was 6.6 and 8.1 for the 30 and 22.5 C treatments, respectively. Even after 28 days, lenticel hypertrophy did not occur on plants flooded at 15 C. Initial stages of lenticel hypertrophy were characterized by development of intercellular spaces in the phellem and production of additional phellem tissue by increased phellogen activity. Later stages of hypertrophy were characterized by development of intercellular spaces in the phellem and cortex. Tree survival was not affected by floodwater temperature or lenticel hypertrophy.

Diminished tolerance of prehypertrophic, cardiomyopathic Syrian hamster hearts to Ca2+ stresses.

Although abnormal myocardial calcium homeostasis in the cardiomyopathic hamster (CMH) has been documented in the hypertrophic stage of the disease, the Ca2+ tolerance before the hypertrophic stage has not been investigated. We studied isovolumic contractile function in response to a variety of Ca2+ stresses including increases in perfusate [Ca2+] (Cao), the Ca2+ channel agonist Bay K 8644, and alpha- or beta-adrenergic agonists of isolated perfused hamster hearts from 24-45-day-old male CMH, BIO 14.6 strain, and age- and sex-matched F1B strain controls. The coronary flow at a constant perfusion pressure did not differ between two groups at baseline or after any Ca2+ stress. At a Cao of 1.0 mM, neither end-diastolic pressure (EDP) nor developed pressure (DP) nor half relaxation time (RT1/2) during stimulation at 1-3 Hz differed between the two groups; as Cao was increased up to 10 mM, CMH hearts showed a lower threshold for the occurrence of a Ca2+ overload profile: EDP and RT1/2 increased to a greater, and DP to a lesser, extent in CMH than in control hearts. To determine whether calcium influx via Ca2+ channels mediates the lower threshold for Ca2+ overload in CMH hearts, we measured resting pressure and scattered laser light intensity fluctuation (SLIF) in unstimulated hearts. Prior studies have shown that SLIF is generated by microscopic tissue motion caused by diastolic spontaneous sarcoplasmic reticulum Ca2+ release and that SLIF amplitude reflects the extent of cell and sarcoplasmic reticulum Ca2+ loading. The Ca(2+)-dependent increase in resting pressure in unstimulated hearts was highly correlated with an increase in SLIF, and this relation was steeper in CMH than in control hearts. CMH hearts also showed a reduced threshold for the occurrence of a Ca2+ overload profile in response to the adrenergic receptor agonists and the Ca2+ channel agonist during electrical stimulation in a Cao of 2.0 mM: maximum DP achieved with each agonist was significantly less and the dose-response curves to each agonist were shifted leftward in CMH versus control hearts. In CMH hearts EDP began to increase at a significantly lower concentration of each agonist, and the maximum extent of increase in EDP in response to all agonists was significantly enhanced compared with control hearts. In response to beta-adrenergic or Ca2+ channel agonists, neither resting pressure nor SLIF in unstimulated hearts increased in control or in CMH hearts. In contrast, in response to alpha-adrenergic stimulation, both SLIF and resting pressure increased to a greater extent in CMH than in control hearts.(ABSTRACT TRUNCATED AT 400 WORDS)

Expression of the preproenkephalin A gene in the heart of cardiomyopathic hamsters

The expression of the preproenkephalin A gene (Enk gene), which codes for the precursor of enkephalins, was investigated in the heart of hamsters with a hereditary cardiomyopathy at four different stages of the disease: the prenecrotic stage (30 days), the necrotic stage (60 days), the hypertrophic stage (120 days), and the final stage (200 days). In control atria and ventricles, the relative abundance of the Enk mRNA, as assessed by Northern blot analysis, did not change upon ageing. In the ventricles of cardiomyopathic hamsters, however, it increased about two- to three-fold at the necrotic stage, but was unaltered at the other time points studied; whereas in the atria, it progressively decreased to reach about half that of control hamsters at the final stage. Enkephalin levels, as measured by radioimmunoassay, decreased at 60 days in both the atria and ventricles of control hamsters, and also in the atria of cardiomyopathic hamsters, and remained stable thereafter, corresponding to one-third to one-half of those at 30 days. However, in the ventricles of cardiomyopathic hamsters, the peptide level decreased only slightly, the consequence being that at 60, 120, and 200 days, it was about two- to three-fold that of control hamsters. The lack of correlation between peptide levels and the relative abundance of the Enk mRNA suggests that translational and (or) post-translational mechanisms are important in the control of the expression of the Enk gene in the heart of hamsters.

Changes in left ventricular diastolic filling during the development of left ventricular hypertrophy: Observations using Doppler echocardiography in a unique canine model

To examine changes in diastolic left ventricular filling during the development of left ventricular hypertrophy, serial pulsed Doppler echocardiographic studies were performed in a canine model of left ventricular hypertrophy induced by neurogenic pressor episodes. This model is unique since left ventricular hypertrophy develops without sustained hypertension. The neurogenic pressor episodes produced progressive increases in left ventricular mass of 17% by 3 weeks ( p < 0.03) and of 23% by 9 weeks ( p < 0.001). During the course of hypertrophy development, there were no changes in resting heart rate, blood pressure, left ventricular volumes or ejection fraction, or end-systolic wall stress. However, peak early filling (peak E) velocity decreased from 65 ± 5 cm/sec to 53 ± 4 cm/sec by 3 weeks ( p < 0.05) and remained depressed at 9 weeks. In addition, peak E/A (the ratio of early to late peak filling) decreased by 3 weeks ( p < 0.01) and the contribution of atrial filling to total left ventricular diastolic filling increased by 9 weeks ( p < 0.005). There were significant correlations between the changes in left ventricular mass and the change in peak E velocity at 3 weeks ( r = -0.92, p < 0.001) but not at 9 weeks. These data indicate that left ventricular filling abnormalities occur early in the course of the development of left ventricular hypertrophy, are not a result of loading alterations related to sustained hypertension, and do not change significantly following increasing stages of hypertrophy.

Expression of anchorin CII mRNA by cultured chondrocytes

The establishment of a cell culture system promoting chondrocyte differentiation has been utilized to better characterize phenotypic stages of chondrogenesis at the cellular level. Although the expression of the type II collagen gene has been studied during "in vitro" chondrocyte differentiation, little is known about the expression of the gene coding for its receptor: anchorin CII. The modulation of the anchorin mRNA steady state level in chick embryo chondrocytes at different developmental stages is described here.The anchorin mRNA level was low in dedifferentiated chondrocytes, progressively increased after the cell transfer into suspension (a condition promoting differentiation), reached its maximal value after 4 weeks and decreased after 5 weeks.Therefore anchorin CII mRNA reaches its maximum level in hypertrophic stage II chondrocytes.

Purification and characterization of a high-molecular-weight protein induced in rat serum during the development of cardiac hypertrophy

A relatively high-molecular-weight polypeptide was found in rat serum within 6 h after aortic constriction in experimental animals. This polypeptide persists for about 7 days of the postoperative period and disappears at later stage of hypertrophy (40%). Further, fractionation and purification of this protein through DEAE-Sepharose and gel filtration chromatography have revealed that this protein is a single polypeptide and its relative molecular weight is 135 kDa. Immunoprecipitation and immunofluorescence microscopic analysis have indicated the presence of the above polypeptide in the nuclear fraction of heart cells. Studies on phosphorylation in vitro have revealed that this protein is a phosphoprotein. DNase I sensitivity and hybridization using a muscle specific gene probe have indicated the involvement of this protein in template associated changes in heart nuclei. Further the possibility of this protein being synthesized by heart cells indicates that this protein could traverse back and forth between heart cells and the extracellular fluid, suggesting an autocrine/paracrine role for this protein during the development of cardiac hypertrophy.

Calcium sensitivity of isometric tension in intact papillary muscles and chemically skinned trabeculae in different models of hypertensive hypertrophy

STUDY OBJECTIVE - The aim was to examine the contractile state, the inotropic response to [Ca2+]e and the Ca2+ sensitivity of the contractile proteins in different models of hypertensive hypertrophy in an early stage of evolution (3-4 weeks). DESIGN - Renal hypertension was induced by placing a silver clip around the left renal artery. The contralateral kidney was either removed (1K-1C) or left untouched (2K-1C). Hypertension through sodium overload was produced by administration of deoxycorticosterone and 1% NaCl drinking water. (DOCA rats). Active and passive length-tension curves were performed to evaluate basal contractility at Lmax and passive stiffness of cardiac muscle. The inotropic responsiveness to [Ca2+]e and the Ca2+ sensitivity of the contractile proteins were also evaluated. EXPERIMENTAL MATERIAL - Papillary muscles and skinned trabeculae from the left ventricle of male Wistar hypertensive and age matched normotensive rats were used. MEASUREMENTS AND RESULTS - Cardiac hypertrophy was similar in all hypertensive groups. In 2K-1C and 1K-1C rats, basal contractility was not significantly different from controls. In DOCA rats, developed tension and time to peak tension (TTP) were significantly greater than controls. The inotropic response to [Ca2+]e was depressed in 2K-1C and increased in DOCA rats. In DOCA rats, increasing [Ca2+]e produced an increase in TTP greater than in controls. No differences were detected in muscle passive stiffness or in Ca2+ sensitivity of the contractility proteins among the different groups. CONCLUSIONS - In the earlier stages of hypertensive hypertrophy, differences in basal contractile state and/or inotropic responsiveness appear to be more related to the initiating cause of hypertensive hypertrophy than to the degree of hypertrophy itself. These differences cannot be attributed to changes in Ca2+ sensitivity of the contractile system.