Features of the contour of the inner surface of the cardiac ventricles and Thebesius-Vieussens vessels

Using certain morphological methods, relief peculiarities of the cardiac ventricle chambers, form and extent of the intertrabecular spaces, connections with the myocardial blood bed have been studied in 92 human hearts. Foramina, fissurae and excavations on the internal surface of the ventricles are the beginnings of the intertrabecular spaces, in their deep parts elements of the microcirculatory blood bed of the myocardium have openings. As demonstrate serial sections, there are not any immediate anastomoses between the myocardial arteries, veins and the intertrabecular spaces. This fact does not confirm the existing opinion that the smallest cardiac veins (Viessen-Thebesian vessels) belong to the arterio-venous anastomoses. A propose is made to use the term "the smallest cardiac veins" only to the veins that directly open into the auricular chambers.     

Gene expression of adrenomedullin in failing myocardium: comparison to atrial natriuretic peptide.

The expression of adrenomedullin (AM) and atrial natriuretic factor (ANF) were investigated in the myocardium of a rat model of chronic ischemic heart failure (CHF) compared with sham-operated controls. In addition, human myocardium of patients with end-stage heart failure due to idiopathic dilated cardiomyopathy compared with myocardium of normal subjects (NF) was studied. In CHF, similar AM levels but increased ANF expression were observed in left ventricular myocardium, as assessed by semiquantitative PCR. Functional experiments with freshly excised papillary muscles showed no influence of AM on myocardial contractility. In NF human myocardium, the expression of AM mRNA was threefold higher in atrial compared with ventricular tissue. In analogy, ANF mRNA was increased by approximately 15-fold in atrial tissue. In dilated cardiomyopathy, the expression of AM was significantly increased in right and left ventricles compared with NF. In parallel, ventricular ANF expression was enhanced.     

The development of the conduction system in the mouse embryo heart: I. The first embryonic A-V conduction pathway

In the 8-, 9-, and 10-day-old mouse embryos, the primitive atria are interconnected with the ventricles via the atrioventricular (A-V) canal. Due to the twisting process of the tubular heart, the wall of the A-V canal establishes continuity not only with the left ventricle but also with the bulbus and truncus arteriosus. At this stage of heart development, the A-V node and bundle have not yet appeared, and, thus, the atrial impulse must be conveyed to the ventricle by the muscle tissue of the wall of the A-V canal, in which two muscle cell layers have been observed. The inner layer extends deep into the left ventricular cavity and is interconnected with both the trabecular system and the ventricular (IV) septum, which begins to develop on the tenth day. In the inner dorsal wall of the A-V canal, the cells are large (～ 20 μm in diameter) and show a strong PAS reaction. It is likely that these large glycogen-rich cells from which the A-V node primordium develops on the eleventh day play the main role in the A-V impulse conduction. The muscle cells at the ventrolateral walls of the canal are small and form a loose spongy myocardium into which the connective tissue cells begin to penetrate on the tenth day, ultimately to form the annulus fibrosus. At the same time, the outer cell layer of the dorsal wall begins to deteriorate; the cells show vacuolar degeneration, myolysis, and shrinkage necrosis. This process appears to represent a programmed cell death, as was described in the bird heart (Pexieder, 1975). On the basis of morphological data, the sequence of atrioventricular activation before the appearance of the A-V node and bundle is discussed.     

Evolution of blood vessels of the heart wall

In progressive development of the organisms, the cardio-vascular system perfects, its construction is adequate to the level and character of the animal's metabolism. The hypobranchial arteries, forming in the subbranchial area in fishes, make the immediate source for the branching off the coronary arteries. Comparison of the data concerning the places where the cranial coronary arteries take their origin in amphibia, reptiles, birds and mammalia demonstrates that the evolutional process is directed towards transference of the places of their branching off on the ventral aorta, and then on the nearest distance to the heart. Certain data are obtained on evolution of the blood circulation pathways in the myocardium and, particularly, on presence of blood vessels in the spongy myocardium in Elasmobranchii, Chondrosteoideii, as well as in the alligator. The most important of the myocardial blood vessels at all stages of evolution is their connection with the cardiac chambers. At definite stages of phylogenesis, simultaneously with compactization of the myocardium and formation of veins from the intertrabecular spaces, the subepicardial and intramural veins unite into a single venous system, bringing blood to the cardiac cavity. In birds, mammalia and human being, the coronary vessels have reached a high degree of development, having penetrated by their branches into all layers of the cardiac wall, and thus they exclude the dependence of the myocardial blood supply from the blood that is present in the cardiac cavity.     

Cell transplantation with a catheter-based approach: an efficient method for the treatment of heart failure with multiple lesions

Cell transplantation is emerging as a potential therapeutic approach for the treatment of heart failure. At present, popular methods of cell delivery may not be efficient in perfusing cells through the whole myocardium. We have developed a novel catheter-based method for global transplantation of cells. Heart failure was induced in rabbit by intravenous administration of doxorubicin. Autologous bone marrow mononuclear cells were transplanted into failing hearts via the root of the aorta. Bilateral sinus aortae and coronary arteries were visualized by angiography during the cell transplantation procedure; there was no intraprocedural death. Four weeks after cell transplantation, there was an improvement in the mean left ventricular ejection fraction from baseline 72.13% to 81.54% (P = 0.034). Transplanted cells were observed throughout the cardiac layers of left and right ventricles. In conclusion, cell transplantation through the root of the aorta is a useful approach to globally supply cells into the heart.     

An Operation Designed to Promote the Growth of New Coronary Arteries,Using a Detached Omental Graft: A Preliminary Report

The human greater omentum exhibits a marked affinity for inflamed surfaces, to which it supplies numerous blood vessels. To achieve myocardial revascularization by omental graft the root of the aorta, the epicardium over both ventricles and the serosal layer of the pericardium were removed in 17 animals. A piece of greater omentum was removed from the abdomen, unfolded and wrapped around the entire heart, and fixed by interrupted sutures to the base of the aorta. Myocardial ischemia was created at the time of operation by ameroid constriction of coronary arteries. Vessels, arteriolar or larger, were found to grow from the root of the aorta, the myocardium and the pericardium into the detached free omental graft, which apparently acted as a conveyer for new vessels, including new coronary arteries, to reach the myocardium.     

Cardiac neural crest is necessary for normal addition of the myocardium to the arterial pole from the secondary heart field

In cardiac neural-crest-ablated embryos, the secondary heart field fails to add myocardial cells to the outflow tract and elongation of the tube is deficient. Since that study, we have shown that the secondary heart field provides both myocardium and smooth muscle to the arterial pole. The present study was undertaken to determine whether addition of both cell types is disrupted after neural crest ablation. Marking experiments confirm that the myocardial component fails to be added to the outflow tract after neural crest ablation. The cells destined to go into the outflow myocardium fail to migrate and are left at the junction of the outflow myocardium with the nascent smooth muscle at the base of the arterial pole. In contrast, the vascular smooth muscle component is added to the arterial pole normally after neural crest ablation. When the myocardium is not added to the outflow tract, the point where the outflow joins the pharynx does not move caudally as it normally should, the aortic sac is smaller and fails to elongate resulting in abnormal connections of the outflow tract with the caudal aortic arch arteries.     

Intramural chronotopography of myocardial depolarization in the heart ventricles of the pig (Sus scrofa domesticus)

Multichannel synchronous cardioelectrotopography is used to analyze the sequence of myocardial depolarization in the ventricles of the pig heart. Formation of early depolarization areas has been established in subendocardium of interventricular septum and in the base of papillary muscles of the left ventricle; of multiple foci-in the thickness of myocardial walls; of areas of late depolarization-in subepicardium of the dorsolateral side of the left ventricle. In pig heart ventricles, as compared with other ungulates (reindeer and sheep) there are revealed differences in location of areas of the early and late depolarization areas and the breakthrough of excitation wave onto subepicardium.     

Myocardium at the base of the aorta and pulmonary trunk is prefigured in the outflow tract of the heart and in subdomains of the second heart field

Outflow tract myocardium in the mouse heart is derived from the anterior heart field, a subdomain of the second heart field. We have recently characterized a transgene (y96-Myf5-nlacZ-16), which is expressed in the inferior wall of the outflow tract and then predominantly in myocardium at the base of the pulmonary trunk. Transgene A17-Myf5-nlacZ-T55 is expressed in the developing heart in a complementary pattern to y96-Myf5-nlacZ-16, in the superior wall of the outflow tract at E10.5 and in myocardium at the base of the aorta at E14.5. At E9.5, the two transgenes are transcribed in different subdomains of the anterior heart field. A clonal analysis of cardiomyocytes in the outflow tract, at E10.5 and E14.5, provides insight into the behaviour of myocardial cells and their progenitors. At E14.5, most clones are located at the base of either the pulmonary trunk or the aorta, indicating that these derive from distinct myocardial domains. At E10.5, clones are observed in subdomains of the outflow tract. The distribution of small clones indicates proliferative differences, whereas regionalisation of large clones, that derive from an early myocardial progenitor cell, reflect coherent cell growth in the heart field as well as in the myocardium. Our results suggest that myocardial differences at the base of the great arteries are prefigured in distinct progenitor cell populations in the anterior heart field, with important implications for understanding the etiology of congenital heart defects affecting the arterial pole of the heart.     

Chick heart peptidergic innervation: localization and development

Localization and development of chick heart peptidergic innervation (Substance P, VIP and Somatostatin) were investigated by means of immunofluorescence technique. The peptidergic component of the heart innervation was observed, for the first time, in older than 11 day chick embryos, i.e., subsequently to the appearance of the cholinergic component. The peptidergic structures achieve nearly full development in about 16-17 day embryos. Substance P is the most represented of the three peptides. It is localized both in nerve bundle fibers and in isolated fibers within the myocardium, the pericardium, the vessel walls; it is also present in fibers of some heart base ganglia. VIP is mostly contained in some thick single fibers travelling along the vessel walls of the heart base, the myocardium and the pericardium. Some VIP immunoreactive cells were also observed in the base ganglia. Somatostatin is mostly contained in some ganglia cells, whilst thin Somatostatin-immunoreactive fibers form a rich plexus among the atrial and ventricular myofibers, without contacting the vessel walls.     

Light and electron microscopic studies of the murine heart after repeated administrations of ciguatoxin or ciguatoxin-4c.

After repeated ip and oral administrations of ciguatoxin (CTX) and ciguatoxin-4c (CTX-4c), one of the derivatives of CTX, to male ICR mice at a dose of 0.1 microgram/kg for 15 days, resulted in marked swelling of cardiac cells and endothelial lining cells of blood capillaries in the heart was observed. Single doses caused no discernible pathological changes. Damage to the capillaries was followed by prominent effusion of serum and erythrocytes into the interstitial spaces of the myocardium occurred. Swelling of the endothelial lining cells of capillaries caused narrowing of the lumen and accumulation of blood platelets in capillaries, which resulted in multiple single cell necroses of cardiac muscle cells. Within 1 month after the treatments of these phycotoxins, myocytes and capillaries appeared to be normal. Effusion in the interstitial spaces resulted in formation of bundles of dense collagen, which persisted for 14 months. Diffuse interstitial fibrosis was prominent in septum and ventricles, accompanied by bilateral ventricular hypertrophy. A single dose of 0.7 micrograms/kg ip resulted in severe acute heart injuries, followed by diffuse myocardial fibrosis.     

Effect of localization of the ectopic excitation site on the sequence and duration of depolarization in the ventricular epicardium in dogs

The depth of the myocardial wall ectopic focus was found to affect spatial and temporal characteristics of the depolarization process in the heart ventricular surface. Duration of the ventricular epicardial depolarization under the ectopic foci located in subendocardial and intramural layers of the myocardium was shorter than in epicardial stimulation of the ventricles. A dependence of the ectopic excitation duration on the pacing site localization in the epicardium, was revealed. The shortest duration of the depolarization occurred under electrical stimulation of the apex and ventral part of the interventricular septum, whereas the longer one--under pacing the left ventricular base.     

Pressure overload and neurohumoral activation differentially affect the myocardial proteome

Treatment with monocrotaline causes pulmonary hypertension in rats. This results in severe pressure overload-induced hypertrophy of the right ventricles, whilst the normally loaded left ventricles do not hypertrophy. Both ventricles are affected by enhanced neuroendocrine stimulation in this model. We analyzed in this model load-induced and catecholamine-induced changes of right and left ventricular proteome by two-dimensional gel electrophoresis, tryptic in-gel digest, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. All analyzed animals showed right ventricular hypertrophy without signs of heart failure. Changes of 27 proteins in the right and 21 proteins in the left ventricular myocardium were found. Given the hemodynamic features of this animal model, proteome changes restricted to the right ventricle are caused by pressure overload. We describe for the first time a potentially novel pathway (BRAP2/BRCA1) that is involved in myocardial hypertrophy. Furthermore, we demonstrate that increased afterload-induced hypertrophy leads to striking changes in the energy metabolism with down-regulation of pyruvate dehydrogenase (subunit beta E1), isocitrate dehydrogenase, succinyl coenzyme A ligase, NADH dehydrogenase, ubiquinol-cytochrome C reductase, and propionyl coenzyme A carboxylase. These changes go in parallel with alterations of the thin filament proteome (troponin T, tropomyosin), probably associated with Ca(2+) sensitization of the myofilaments. In contrast, neurohumoral stimulation of the left ventricle increases the abundance of proteins relevant for energy metabolism. This study represents the first in-depth analysis of global proteome alterations in a controlled animal model of pressure overload-induced myocardial hypertrophy.     

Study of the impact of intramyocardial implantation of stem cells on myocardial perfusion and contractility in patients with coronary heart disease concurrent with postinfarct cardiosclerosis and chronic heart failure

OBJECTIVE: to study of intramyocardial implantation of cultured bone marrow stem cells on myocardial perfusion and contractility in the surgical treatment of patients with coronary heart disease (CHD) and chronic heart failure (CHF), by synchronized single-photon emission computed tomography (SSPECT) of the myocardium. SUBJECTS AND METHODS: The study included 11 patients. Intramyocardial injection of cell injections into the myocardial periscarring areas was made at coronary bypass surgery. All the patients underwent 99mTc myocardial SSPECT MIBI before and 3, 6, 12 months after surgery. RESULTS AND CONCLUSIONS: Implantation of bone marrow stem cells into the left ventricular myocardium favorably affects left ventricular remodeling and contributes to the improvement of myocardial perfusion and contractility, as evidenced by 99mTc.     

Relation between expression of TNF alpha, iNOS, VEGF mRNA and development of heart failure after experimental myocardial infarction in rats.

An injury to the heart due to myocardial infarction (MI) may progress to heart failure. Among factors, whose interactions promote remodeling of ischemic myocardium, the increased expression of tumor necrosis factor alpha (TNFalpha), inducible nitric oxide synthase (iNOS) and Vascular Endothelial Growth Factor (VEGF) was found. However, little is known about the temporal and spatial relation between expression of iNOS, cytokine TNFalpha, and growth factor VEGF during pathological process of development of heart failure after the myocardial infarction. Male Sprague-Dawley rats were used for experimental myocardial infarction. The procedure was performed by anterolateral thoracotomy and snearing LAD with the metal clip. The hemodynamic measurements were done with the Langendorff preparation converted into a working heart system. The hemodynamic parameters were recorded at day 6, 11, 28, 40 and the myocardium for gene expression was collected at day 1, 4, 11, 28, 40. Control group was sham operated rats. The VEGF, TNFalpha, iNOS, and GAPDH genes were detected by RT-PCR assay from samples taken at border zone of myocardial infarction. Expression of isoform VEGF120 was found at day 1 and 4 after MI, whereas isoforms VEGF164 and VEGF188 along with expression of TNFalpha and iNOS was found at day 1, 4, 11, 28, 40. No expression of examined genes was detected in the myocardium of control rats. The expression of studied factors was parallel with development of heart failure after myocardial infarction assessed by hemodynamic measurements. These findings confirm the postulated involvement of TNFalpha, iNOS and growth factor VEGF in the remodeling of the myocardium and development of heart failure after experimental myocardial infarction.     

Histochemical studies of enzymes of the energy metabolism in postimplantation rat embryos

Using histochemical procedures for the detection of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), and cytochrome c oxidase (cytox), we investigated the levels of these enzymes of the energy metabolism in postimplantation rat embryos (9.5-12.5 days of gestation). On day 10.5 of gestation, the neural tube, somites, myocardium, and mesenchyme displayed moderate levels of LDH activity; this activity gradually increased in strength, so that, on day 12.5 of gestation, intense LDH activity was uniformly distributed in these intraembryonic tissues. In contrast to LDH, distinct regional differences in the distribution of SDH and cytox were detected. On day 10.5 of gestation, the myocardium exhibited weak to moderate SDH and cytox activity, and on day 11.5, the myocardial activity of these enzymes had become moderate to intense. However, in all other embryonic tissues, e.g., the neural tube and somites, only weak SDH and cytox activity was present. On day 12.5 of gestation, the myocardium displayed very intense SDH and cytox activity, whereas the mantle layer of the neural tube, the spinal ganglia, and the myotomes exhibited only moderate levels of SDH and cytox activity. In the matrix of the neural tube and mesenchyme, these enzyme activities remained at low levels. At electron microscopy, cytox activity was detectable in the spaces between the inner and outer membranes as well as in the intracristal spaces of mitochondria. In general, cytox activity increased in parallel with the differentiation of mitochondria (i.e., increased mitochondrial numbers and size, and the development of mitochondrial cristae), but when the distribution of the cytox activity was considered in detail, it was found to differ among mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Continuity of Right and Left Ventricular Myocardial Sinusoidal Spaces and its Relation to Right Ventricular Implants

Evidence is presented which indicates that blood leaving side branches of an internal mammary artery implanted into the anterior wall of the right ventricle flows from the tunnel in which it lies through myocardial sinusoidal spaces of the anterior right ventricular wall across the midline to fill corresponding spaces in the anterior wall of the left ventricle and thence is carried to the left coronary sinus. The myocardial sinusoidal spaces of right and left ventricles have been well outlined, using injections of polyvinyl acetate and the technique of digestion casts. We have been able to show that there is no barrier between the myocardial sinusoids of the right circulation and those related to the anterior descending branch of the left coronary artery. In structure, these myocardial sinusoidal spaces are quite different from the intramyocardial coronary arteriolar zones which, in 93% of human hearts, are separated from one another without collateral communication.The continuity of the right and left ventricular myocardial sinusoids explains why implantation of a right internal mammary artery into the anterior wall of the right ventricle combined with a corresponding left implant, epicardiectomy and free omental graft, has been so effective in our hands in the treatment of far-advanced human coronary artery insufficiency.