Dynamics of the mass of the right ventricle of the heart and concentration of RNA in it during the process of "reverse" development of hypertrophy]

Experiments were conducted on male rats, 250-300 g in weight. Adaptation to high altitude hypoxia was created by placing the animals daily for 5 hours, into an altitude chamber, at an "altitude" of 6000 m. The degree of hypertrophy of the right ventricle and its RNA content was studied after 20 days of adaptation, as well as 2, 10, 20 and 40 days after cessation of hypoxia. Twenty days after the beginning of adaptation the muscle mass of the right ventricle the RNA concentration and amount in it was found to increase considerably. After cessation of hypoxia half of the acquired increase in the ventricle muscle mass was lost in 10 days, and half of the acquired increase in the RNA--as soon as in 2 days. Forty days after cessation of hypoxia the right ventricle mass and its RNA content in the adapted animals did not differ from the same indices in control rats.     

Response of the rat cardiovascular system to a moderate altitude in connection with endurance training

The authors investigated whether an altitude of 1,350 m would affect the rat cardiovascular system in the same way as genuine altitude hypoxia and the way it would take effect when combined with endurance training in the form of swimming It was found that 8 weeks spent at this altitude led to an increase in absolute and relative heart weight, to right ventricular hypertrophy, and to increased resistance of the myocardium to acute anoxia. Physical training at a moderate altitude resulted in an increase in the relative weight of the musculature of both the right and the left ventricle and of the septum. Unlike low altitude training, however, growth of the two compartments of the heart was proportional. The resistance of the myocardium of trained animals against anoxia was the same, irrespective of whether they trained at a low or a high altitude. The results show that even a moderate altitude is not a matter of indifference for the rat organism, but that it leads to characteristic manifestations of altitude hypoxia in the cardiovascular system.     

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.     

Myocardial hypertrophy in rats exposed to simulated high altitude

Myocardial hypertrophy in Sprague-Dawley adult rats exposed to hypobaric hypoxia (0.40 atmosphere of air/18 h daily for 7 days) in a hypobaric chamber was investigated. Changes in the myocardial mass were evaluated on the basis of the dry heart weight and expressed as mg/100 g of total body weight (mean +/- SEM). Data are presented indicating that: chronic hypobaric hypoxia causes a significant degree of myocardial hypertrophy in rats; hypertrophic process involves both ventricles (the right more than the left); removal of the hypoxic stimulus leads to the disappearance of hypertrophy when evaluated as an increase in dry heart weight; hypoxia affects the synthesis of a significant amount of connective tissue in the left ventricle, which is not exposed to pressure load. The r?le of neurohumoral factors (i.e., adrenergic stimulation and catecholamines) in the development of the ventricular hypertrophy is suggested.     

Growth of cardiac muscle cells during rat adaptation to altitude hypoxia

The weight of the right heart ventricle in 1.5-month-old rats kept after birth in the mountains of 3400 m altitude is higher and its muscle cell cytoplasm mass is much larger compared to those in 1.5-month-old animals raised at 800 m altitude. The hypertrophy of cells is not due to their polyploidization. Only a small increase in the relative number of polyploid cells takes place under high altitude hypoxia. The weight of the right ventricle and myocyte mass in 3-month-old rats kept 1.5-3 months after the birth at 3400 m altitude also increases, although this augmentation is significantly less than in the animals grown in the mountains for 1.5 months immediately after the birth. The myocyte ploidy of adult animals adapted to hypoxia does not essentially differ from that of 1.5- and 3-month-old control rats: about 80 per cent of these cells are polyploid. Thus, the growth of cardiac myocytes under the heart hyperfunction in the case of high altitude hypoxia proceeds mainly on the ground of the stable polyploid genome, as well as normal ontogenetic growth of these cells.     

Functional, morphologic and histochemical changes in the myocardium and their role in the development of cor pulmonale following pulmonary resection]

Functional, morphological and histochemical alterations were studied in 32 dogs within the period of 5 days--18 months after resection of 32-80% of the pulmonary tissue. According to the presence of hypertrophy of the heart right ventricle wall, morphological changes of the myocardium and disorders in the functional features of the cardiovascular activity all the animals were divided into 4 groups: 1--control animals; 2--experimental animals without hypertrophy of the right ventricle wall; 3--experimental animals with hypertrophy of the right ventricle wall in the stage of compensation; 4--experimental animals with hypertrophy of the right ventricle wall in the stage of decompensation. In the myocardium of the second group animals a decrease of aerobic processes and an increase of anaerobic ones were found to take place. The aerobic processes increased and the anaerobic processes decreased in the myocardium of dogs having hypertrophy of the right ventricle wall in the stage compensation. In the muscle of the decompensated pulmonary heart there occurred a pronounced decrease of aerobic and anaerobic processes, a disturbance of the protein and fat metabolism. All this resulted in a decreased contractive function of the myocardium with distrubed hemodynamics. The investigations have shown the interrelationships of morphological, histochemical and ECG alterations in the dynamics of the pulmonary heart development after resection of lungs.     

The relationship between the structure and activity of rat skeletal muscle mitochondria after thyroidectomy and thyroid hormone treatment

The fine structure of rat gastrocnemius muscle fibers has been studied after changes were induced in the basal metabolic rate (BMR) by thyroidectomy and L-thyroxine administration under anabolic conditions. Biochemical analysis of skeletal muscle mitochondrial respiration and phosphorylation from the same tissue preparations has been summarized, details having been published earlier (3). As estimated from electron micrographs, the total amount of mitochondria from thyroidectomized animals was enlarged 1.5 times over that from normal controls. The total amount of mitochondria from thyroidectomized or normal animals made hypermetabolic with thyroxine was increased 2.5 to 3.5 times over that from their corresponding controls. In all cases, there was an increase in the mitochondrial population and the profile ratio of cristae to matrix was also considerably increased, thus indicating both relative and absolute enlargements of the entire surface of the cristae per unit fiber. The major structural changes persisted for at least 3 weeks after the cessation of thyroxine treatment, by which time the elevated mitochondrial respiratory and phosphorylative activity had declined to normal values. The hypertrophy and increase in mitochondrial population was more prominent in the perinuclear and subsacrolemmic regions near blood vessels than in the interstices of the fibrils. The very long interfibrillar mitochondria found in both the hypo- and hypermetabolic tissues are more likely to be derived from outgrowths of the original mitochondria rather than from a fusion of smaller ones. These findings are compatible with the ideas expressed elsewhere (see 1, 3, 10) that, under conditions close to the physiological, thyroid hormones control mitochondrial metabolic activity by a subtle alteration in mitochondrial composition with respect to their respiratory and phosphorylative constituents. The possible application of using thyroid hormones in the study of biogenesis of mitochondria and the synthesis of mitochondrial constituents are discussed.     

Myocardial infarct in rats: right ventricular hypertrophy as a criterion of postinfarct left ventricular heart failure

The course of experimental myocardial infarction was accompanied by the growth response of the right ventricle (RV) in some rats. Rats with RV hypertrophy unlike ones without RV hypertrophy had depressed cardiac contraction force and velocity at rest as well as a minimal capacity to respond to functional stress. Dibunol (butylhydroxytoluene, 30 mg/kg) prevented the depression of cardiac contractility and RV growth. RV hypertrophy in the rats following left coronary artery ligation is the consequence of the left ventricle pump failure and resultant pulmonary hypertension. RV hypertrophy may be proposed as an index of postinfarct heart failure and its reduction as an index of the cardioprotective effect of various pharmacological interventions.     

Up-regulation of hexokinase1 in the right ventricle of monocrotaline induced pulmonary hypertension

Background

Pulmonary arterial hypertension (PAH) is a proliferative arteriopathy associated with a glycolytic shift during heart metabolism. An increase in glycolytic metabolism can be detected in the right ventricle during PAH. Expression levels of glycolysis genes in the right ventricle during glycolysis that occur in monocrotaline (MCT)-induced pulmonary hypertension (PH) remain unknown.

Methods

PH was induced by a single subcutaneous injection of MCT (50 mg/kg) into rats, eventually causing right heart failure. Concurrently, a control group was injected with normal saline. The MCT-PH rats were randomly divided into three groups according to MCT treatment: MCT-2 week, 3 week, and 4 week groups (MCT-2w, 3w, 4w). At the end of the study, hemodynamics and right ventricular hypertrophy were compared among experimental groups. Expression of key glycolytic candidate genes was screened in the right ventricle.

Results

We observed an increase in mean pulmonary arterial pressure, right ventricular systolic pressure and right ventricular hypertrophy index three weeks following MCT injection. Alterations in the morphology and structure of right ventricular myocardial cells, as well as the pulmonary vasculature were observed. Expression of hexokinase 1 (HK1) mRNA began to increase in the right ventricle of the MCT-3w group and MCT-4w group, while the expression of lactate dehydrogenase A (LDHA) was elevated in the right ventricle of the MCT-4w group. Hexokinase 2(HK2), pyruvate dehydrogenase complex α1 (PDHα1), and LDHA mRNA expression showed no changes in the right ventricle. HK1 mRNA expression was further confirmed by HK1 protein expression and immunohistochemical analyses. All findings underlie the glycolytic phenotype in the right ventricle.

Conclusions

There was an increase in the protein and mRNA expression of hexokinase-1 (HK1) three and four weeks after the injection of monocrotaline in the right ventricle, intervention of HK1 may be amenable to therapeutic intervention.     

Congestive heart failure in copper-deficient mice

Copper Deficiency (CuD) leads to hypertrophic cardiomyopathy in various experimental models. The morphological, electrophysiological, and molecular aspects of this hypertrophy have been under investigation for a long time. However the transition from compensated hypertrophy to decompensated heart failure has not been investigated in the study of CuD. We set out to investigate the contractile and hemodynamic parameters of the CuD mouse heart and to determine whether heart failure follows hypertrophy in the CuD heart. Dams of FVB mice were fed CuD or copper-adequate (CuA) diet starting from the third day post delivery and the weanling pups were fed the same diet for a total period of 5 weeks (pre- and postweanling). At week 4, the functional parameters of the heart were analyzed using a surgical technique for catheterizing the left ventricle. A significant decrease in left ventricle systolic pressure was observed with no significant change in heart rate, and more importantly contractility as measured by the maximal rate of left ventricular pressure rise (+dP/dt) and decline (-dP/dt) were significantly depressed in the CuD mice. However, left ventricle end diastolic pressure was elevated, and relaxation was impaired in the CuD animals; the duration of relaxation was prolonged. In addition to significant changes in the basal level of cardiac function, CuD hearts had a blunted response to the stimulation of the beta-adrenergic agonist isoproterenol. Furthermore, morphological analysis revealed increased collagen accumulation in the CuD hearts along with lipid deposition. This study shows that CuD leads to systolic and diastolic dysfunction in association with histopathological changes, which are indices commonly used to diagnose congestive heart failure.     

Sex Differences in the Beneficial Cardiac Effects of Chronic Treatment with Atrial Natriuretic Peptide In Spontaneously Hypertensive Rats

Introduction

The aim of this study was to investigate both the effects of chronic treatment with atrial natriuretic peptide (ANP) on systolic blood pressure (SBP), cardiac nitric oxide (NO) system, oxidative stress, hypertrophy, fibrosis and apoptosis in spontaneously hypertensive rats (SHR), and sex-related differences in the response to the treatment.

Methods

10 week-old male and female SHR were infused with ANP (100 ng/hr/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). SBP was recorded and nitrites and nitrates excretion (NOx) were determined. After treatment, NO synthase (NOS) activity, eNOS expression, thiobarbituric acid-reactive substances (TBARS) and glutathione concentration were determined in left ventricle, as well as the activity of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD). Morphological studies in left ventricle were performed in slices stained with hematoxylin-eosin or Sirius red to identify collagen as a fibrosis indicator; immunohistochemistry was employed for identification of transforming growth factor beta; and apoptosis was evaluated by Tunel assay.

Results

Female SHR showed lower SBP, higher NO-system activity and less oxidative stress, fibrosis and hypertrophy in left ventricle, as well as higher cardiac NOS activity, eNOS protein content and NOx excretion than male SHR. Although ANP treatment lowered blood pressure and increased NOS activity and eNOS expression in both sexes, cardiac NOS response to ANP was more marked in females. In left ventricle, ANP reduced TBARS and increased glutathione concentration and activity of CAT and SOD enzymes in both sexes, as well as GPx activity in males. ANP decreased fibrosis and apoptosis in hearts from male and female SHR but females showed less end-organ damage in heart. Chronic ANP treatment would ameliorate hypertension and end-organ damage in heart by reducing oxidative stress, increasing NO-system activity, and diminishing fibrosis and hypertrophy.     

Persistent pulmonary hypertension results in reduced tetralinoleoyl-cardiolipin and mitochondrial complex II + III during the development of right ventricular hypertrophy in the neonatal pig heart

Persistent pulmonary hypertension of the newborn (PPHN) results in right ventricular (RV) hypertrophy followed by right heart failure and an associated mitochondrial dysfunction. The phospholipid cardiolipin plays a key role in maintaining mitochondrial respiratory and cardiac function via modulation of the activities of enzymes involved in oxidative phosphorylation. In this study, changes in cardiolipin and cardiolipin metabolism were investigated during the development of right heart failure. Newborn piglets (<24 h old) were exposed to a hypoxic (10% O(2)) environment for 3 days, resulting in the induction of PPHN. Two sets of control piglets were used: 1) newborn or 2) exposed to a normoxic (21% O(2)) environment for 3 days. Cardiolipin biosynthetic and remodeling enzymes, mitochondrial complex II + III activity, incorporation of [1-(14)C]linoleoyl-CoA into cardiolipin precursors, and the tetralinoleoyl-cardiolipin pool size were determined in both the RV and left ventricle (LV). PPHN resulted in an increased heart-to-body weight ratio, RV-to-LV plus septum weight ratio, and expression of brain naturetic peptide in RV. In addition, PPHN reduced cardiolipin biosynthesis and remodeling in the RV and LV, which resulted in decreased tetralinoleoyl-cardiolipin levels and reduced complex II + III activity and protein levels of mitochondrial complexes II, III, and IV in the RV. This is the first study to examine the pattern of cardiolipin metabolism during the early development of both the RV and LV of the newborn piglet and to demonstrate that PPHN-induced alterations in cardiolipin biosynthetic and remodeling enzymes contribute to reduced tetralinoleoyl-cardiolipin and mitochondrial respiratory chain function during the development of RV hypertrophy. These defects in cardiolipin may play an important role in the rapid development of RV dysfunction and right heart failure in PPHN.     

Nifedipine does not impede clenbuterol-stimulated muscle hypertrophy.

The mechanism(s) responsible for beta2-adrenergic receptor-mediated skeletal muscle and cardiac hypertrophy remains undefined. This study examined whether calcium influx through L-type calcium channels contributed to the development of cardiac and skeletal muscle (plantaris; gastrocnemius; soleus) hypertrophy during an 8-day treatment with the beta2-adrenergic receptor agonist clenbuterol. Concurrent blockade of L-type calcium channels with nifedipine did not reverse the hypertrophic action of clenbuterol. Moreover, nifedipine treatment alone resulted in both cardiac and soleus muscle hypertrophy (6% and 7%, respectively), and this effect was additive to the clenbuterol-mediated hypertrophy in the heart and soleus muscles. The hypertrophic effects of nifedipine were not associated with increases in total beta-adrenergic receptor density, nor did nifedipine reverse clenbuterol-mediated beta-adrenergic receptor downregulation in either the left ventricle or soleus muscle. Both nifedipine and clenbuterol-induced hypertrophy increased total protein content of the soleus and left ventricle, with no change in protein concentration. In conclusion, our results support the hypothesis that beta2-adrenergic receptor agonist-induced muscle hypertrophy is mediated by mechanisms other than calcium influx through L-type calcium channels.     

Decreased PGC1-α levels and increased apoptotic protein signaling are associated with the maladaptive cardiac hypertrophy in hyperthyroidism

Hyperthyroidism can lead to the activation of proteins which are associated with inflammation, apoptosis, hypertrophy, and heart failure. This study aimed to explore the inflammatory and apoptotic proteins involved in the hyperthyroidism-induced cardiac hypertrophy establishment. Male Wistar rats were divided into control and hyperthyroid (12 mg/L L-thyroxine, in drinking water for 28 days) groups. The expression of inflammatory and apoptotic signaling proteins was quantified in the left ventricle by Western blot. Hyperthyroidism was confirmed by evaluation of T3 and T4 levels, as well as cardiac hypertrophy development. There was no change in the expression of HSP70, HIF1-α, TNF-α, MyD88, p-NFκB, NFκB, p-p38, and p38. Reduced expression of p53 and PGC1-α was associated with increased TLR4 and decreased IL-10 expression. Decreased Bcl-2 expression and increased Bax/Bcl-2 ratio were also observed. The results suggest that reduced PGC1-α and IL-10, and elevated TLR4 proteins expression could be involved with the diminished mitochondrial biogenesis and anti-inflammatory response, as well as cell death signaling, in the establishment of hyperthyroidism-induced maladaptive cardiac hypertrophy.     

Maternal undernutrition induces differential cardiac gene expression in pulmonary hypertensive steers at high elevation

Pulmonary hypertension, characterized by elevated pulmonary arterial pressure (PAP) and right ventricular hypertrophy, is caused by decreased atmospheric oxygen at high altitude. We hypothesized that maternal undernutrition programs right ventricle gene expression and sensitivity to increasing PAP at high altitude (2,183 m). On day 30 of gestation, forty Angus x Gelbvieh cows received diets to induce either gain (Control) or loss of body weight (Restricted) until day 125 of gestation. On day 126 of gestation, Restricted cows were realimented to achieve the same body weight as Controls by day 250. Parturition occurred naturally. PAP, which ranged from 40 to 114 mmHg, was determined in 15-mo-old steers from Control or Restricted cows before necropsy. At necropsy, hearts were collected from steers, separated into right and left ventricles, atria, and septa and weighed. Ventricular thickness was recorded. Eight Affymetrix bovine microarrays were screened [four high PAP (two Control and two Restricted) and four low PAP (two Control and two Restricted)] with right ventricle mRNA. This analysis revealed that pentraxin-related protein, interferon-related developmental regulator, and peroxisome proliferator-activated receptor-gamma coactivator-1alpha were differentially expressed (P < 0.05) in steer right ventricle from high-PAP cows compared with low-PAP cows. Also, activation peptide and pancreas cationic trypsinogen, alpha-actin, similar to ubiquitin carboxylesterase, were differently expressed (P < 0.05) in steers from Restricted cows compared with those from Control cows. Upregulated genes in high-PAP right ventricle have been associated with pathological cardiac hypertrophy. It is concluded that right ventricle gene expression may be differentially programmed by maternal undernutrition in the fetus during early gestation and may be detrimental to health and longevity of offspring, particularly at high altitude.     

An allometric comparison of the mitochondria of mammalian and reptilian tissues: The implications for the evolution of endothermy

Summary The effects of body size and phylogeny on metabolic capacities were examined by comparing the mitochondrial capacities of 6 mammalian and 4 reptilian species representing 100-fold body weight ranges. The mammals examined included 3 eutherian, 2 marsupial and a monotreme species and the reptiles 2 saurian, 1 crocodilian and 1 testudine species. The tissues examined were liver, kidney, brain, heart, lung and skeletal muscle. Allometric equations were derived for tissue weights, mitochondrial volume densities, internal mitochondrial membrane surface area densities, tissue mitochondrial membrane surface areas both per gram and per total tissue and summated tissue mitochondrial membrane surface areas. For the mammals and reptiles studied a 100% increase in body size resulted in average increases of 68% in internal organ size and 107% in skeletal muscle mass. Similarly, total organ mitochondrial membrane surface areas increase in mammals and reptiles by an average 54% and for skeletal muscle by an average 96%. These values are similar to increases in standard (54 and 71%) and maximum (73 and 77%) organismal metabolism values found by other authors for mammals and reptiles respectively. Although the allometric exponents (or rates of change with increasing body size) of the mitochondrial parameters in mammals and reptiles are statistically the same, in general the total amount of mitochondrial membrane surface area in the mammalian tissues are four times greater than found in the reptilian tissues. These differences were not the result of any single ‘quantum’ factor but are the result of the mammals having relatively larger tissues with a greater proportion of their volume occupied by mitochondria and to a lesser extent increases in the internal mitochondrial membrane surface area densities. Mitochondrial volume density from this present study would appear to be the major factor involved in changing weight specific metabolism of tissues both as a result of changes in body size and in the evolution of endothermy in mammals from reptiles.     

Expression of neural cell adhesion molecule immunoreactivity in hypertrophic myocardium

Myocardial neural cell adhesion molecule (N-CAM) is temporally regulated, being expressed during cardiac morphogenesis and innervation and suppressed in the adult heart. We have investigated the plasticity of N-CAM expression in hypertrophic muscle using the rat model of chronic hypoxia to selectively induce right ventricular hypertrophy over a 14 day time course. Sarcolemmal and intercalated disc N-CAM immunostaining was more extensive in the ventricular myocardium of hypoxic rats compared to normoxic controls. Quantitative assessment of the immunoreactivity in tissue extracts demonstrated a selective increase in the amount of N-CAM immunoreactivity in the hypertrophic myocardium of the right ventricle of rats exposed to hypoxia and this was associated with an increase of the 125 kDa isoform. We conclude that myocardial hypertrophy may be a factor influencing N-CAM expression in the heart and adhesion molecules may have a role in cardiac remodelling.     

Cardiac electric field at the period of depolarization and repolarization of the frog heart ventricle

Multichannel mapping of electrical field on heart ventricle epicardium and the body surface in frogs Rana esculenta and Rana temporaria was performed at periods of the ventricular myocardium depolarization and repolarization. The zone of the epicardium early depolarization is located on epicardium of the ventricle base posterior wall, while the late depolarization zone—on its apex and on the base anterior wall. The total vector of sequence of the ventricle epicardium depolarization is directed from the base to the apex. The zone of the early repolarization is located in the apical area, while that of the late one—in the area of the base. On the frog body surface the cardioelectric field with the cranial zone of negative and the caudal zone of positive potentials is formed before the appearance of the QRS complex on ECG. At the period of the heart ventricle repolarization the zone of the cardioelectric field negative potentials is located in the cranial, while that of the positive ones—in the body surface caudal parts. The cardioelectric field on the frog body surface at the periods of depolarization and repolarization of the ventricle myocardium reflects adequately the projection of sequence of involvement with excitation and of distribution of potentials on epicardium.     

Protein kinase C isozymes in hypertension and hypertrophy: Insight from SHHF rat hearts

Chronic hypertension results in cardiac hypertrophy and may lead to congestive heart failure. The protein kinase C (PKC) family has been identified as a signaling component promoting cardiac hypertrophy. We hypothesized that PKC activation may play a role mediating hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat heart. Six-month-old SHHF and normotensive control Wistar Furth (WF) rats were used. Hypertension and cardiac hypertrophy were confirmed in SHHF rats. PKC expression and activation were analyzed by Western blots using isozyme-specific antibodies. Compared to WF, untreated SHHF rats had increased phospho-active (10-fold), (4-fold), and (3-fold) isozyme expression. Furthermore, we analyzed the effect of an angiotensin II type 1 receptor blocker (ARB) and hydralazine (Hy) on PKC regulation in SHHF rat left ventricle (LV). Both the ARB and Hy normalized LV blood pressure, but only the ARB reduced heart mass. Neither treatment affected PKC expression or activity. Our data show differential activation of PKC in the hypertensive, hypertrophic SHHF rat heart. Regression of hypertrophy elicited by an ARB in this model occurred independently of changes in the expression and activity of the PKC isoforms examined. (Mol Cell Biochem 270: 63–69, 2005)     

Protective effect of peptide semax (ACTH(4-7)Pro-Gly-Pro) on the rat heart rate after myocardial infarction

Semax, a member of ACTH-derived peptides family, was used in treatment of ischemic stroke in patients. It decreased neurological deficiency and reduced NO hyperproduction in the rat brain caused by acute cerebral hypoperfusion. We suggest that semax is also capable of protecting the rat heart from ischemic damage 28 days after myocardial infarction (MI) induced by left descendent coronary artery occlusion. Semax (150 microg/kg) was given i. p. in the operating day twice: 15 min and 2 hours after coronary occlusion, and once a day for the following 6 days. In 28 days after infarction, the MI group developed cardiac hypertrophy, cell growth was caused mainly by the increase of contractile filaments not supported by the appropriate mitochondrial growth that indicated an impaired energy supply of the cells. Moreover, cardiac hypertrophy was accompanied by decreased mean arterial blood pressure and cardiac contractile function and increased left ventricular end-diastolic pressure. Pharmacological change of cardiac afterload revealed that, in 28 days after MI, the rat heart was not able to change its contractile performance in response to either increase or decrease of systemic blood pressure, and as a result could not maintain its diastolic pressure. All these changes obviously reflect development of heart failure. Semax did not affect cardiac work but partially prevented end-diastolic pressure growth in left ventricle as well as ameliorated cardiomyocyte hypertrophy and disproportionate growth of contractile and mitochondrial apparatus, thus exerting beneficial effect on the left ventricular remodeling and heart failure development late after myocardial infarction.