Search

An ectopic origin of the coronary artery from the aorta beyond the sinotubular junction, a condition commonly referred to as 'coronary artery high take-off', has been described in man and C57BL/6 mice. The present paper reports this congenital coronary artery anomaly in the Syrian hamster (Mesocricetus auratus). Hearts from 14 individuals, aged 53-350 days, were examined by means of a corrosion-cast technique, scanning electron microscopy or histological and immunohistochemical techniques. In 11 hamsters, the right coronary artery was the ectopic vessel. In the other three animals there was a solitary coronary ostium in the aorta. In all cases, the ectopic coronary artery originated at an acute angle and a valve-like ridge was in front of the coronary artery ostium. The ectopic arteries examined microscopically showed an intramural trajectory within the aortic wall. In the hearts with a solitary ostium in the aorta, the left main coronary artery coursed between the aorta and the pulmonary artery. In man, all of these anomalous conditions place the individual at risk of myocardial ischaemia and sudden death. However, none of the affected hamsters had clinical signs of disease. Intimal thickenings of increasing size with age were present in the intramural coronary artery segment of eight hamsters aged 106 days or older, examined histologically. The present findings fit with the notion that coronary arteries with acute angle take-off and an intramural course are subjected to unusual wear and tear, leading to tissue changes in the vessel wall., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This study describes a rare congenital coronary artery anomaly in the Syrian hamster; namely, the separate origin of the obtuse marginal and left circumflex arteries which are the main components of the left coronary artery. The hearts of nine affected animals were examined by means of a corrosion-cast technique and histology. The hamsters belonged to a laboratory inbred family with a high incidence of coronary artery anomalies and bicuspid aortic valve. The aortic valve was tricuspid in three hamsters and bicuspid in the other six hamsters. In all cases, the right coronary artery was normal, whereas the left coronary artery main trunk was absent. The present anomalous coronary artery patterns could be classified into two main entities: (i) ectopic origin of the obtuse marginal artery from the right aortic sinus or from the right coronary artery, with the left circumflex artery arising from the left side of the aortic valve; and (ii) ectopic origin of both the obtuse marginal artery from the right aortic sinus or from the right coronary artery and left circumflex artery from the dorsal aortic sinus. In all cases, the obtuse marginal artery coursed to the right side of the heart through the ventral wall of the right ventricular outflow tract. When the left circumflex artery arose from the dorsal aortic sinus, it formed an acute angle with the aortic wall. This report seems to be the first to describe the separate origin of the main components of the left coronary artery in a non-human mammalian species. In man, the congenital coronary artery and aortic valve defects reported herein may entail the risk of clinical complications. However, none of the affected hamsters showed signs of disease.

This study describes the coronary artery distribution patterns associated with the anomalous origin of the left coronary artery from the right side of the aortic valve in Syrian hamsters. The hearts of 15 affected animals were examined by means of a corrosion-cast technique, histology and scanning electron microscopy. The hamsters belonged to a laboratory inbred colony with a high incidence of coronary artery anomalies and bicuspid aortic valves. The aortic valve was tricuspid in eight hamsters and bicuspid in the other seven. In all cases, the right coronary artery was normal, whereas the left main coronary artery trunk arose from the right aortic sinus or from the right side of the ventral aortic sinus when the aortic valve was bicuspid. In 12 specimens, the left main trunk crossed the infundibular septum and then divided into the left circumflex branch and the obtuse marginal branch. In another specimen, the course of the left main trunk was ventral to the right ventricular outflow tract; in the remaining two, it surrounded the aorta dorsally. In man, some of these distribution patterns may cause myocardial ischaemia and sudden death. The present findings prove that the origin of the left coronary artery from the right aortic sinus occurs in primitive mammals such as the Syrian hamster, suggesting that the defect may occur in other mammalian species. Its possible occurrence should be borne in mind in domestic animals, especially in those with signs of myocardial ischaemia after strenuous activity.

The formation, topographical location and calcification of cartilage in congenital bicuspid aortic valves of 235 Syrian hamsters aged 0--173 days were studied by histological, histochemical and immunohistochemical techniques. In all animals the aortic valve was bicuspid; it had two leaflets, ventral and dorsal, each supported by its own aortic sinus. In 141 valves, a more or less developed raphe was located in the ventral sinus. The remaining 94 valves were devoid of any raphe. The first sign of valvular chondrogenesis was the presence of small groups of cells embedded in a type II collagen-positive extracellular matrix. These cellular groups, which appeared as early as 2 days after birth, became converted into hyaline cartilage or fibrocartilage. A considerable proportion (67%) of the valvular cartilages developed within the first 6 weeks of life. The cartilaginous tissue was capable of forming anywhere along the attachments of the valve leaflets to their supporting sinuses. However, statistical analyses substantiated the observation that the bases of the sinuses and raphes were the valvular regions particularly prone to the development of cartilage. At these sites, the cartilage was usually hyaline and often became calcified. The findings were consistent with the assumption that intense mechanical stimulation plays an important role in the formation of the valvular cartilage. Moreover, these findings supplied new evidence that in the cardiac semilunar valves of Syrian hamsters, cartilage formation does not involve the aggregation of large numbers of cells before their differentiation into chondrocytes. The valvular hyaline cartilages appear to act as competent pivots, resisting mechanical tensions generated during the cardiac cycle. Deposition of calcium in the matrix can be regarded as a reinforcement process of the cartilaginous tissue. Finally, it is hypothesized that the formation of cartilage in the aortic valves of hamsters prevents dystrophic calcification of the valve, a pathological change that causes aortic stenosis in man, especially in patients with a bicuspid aortic valve.

The formation of cartilage in aortic valves of Syrian hamsters was studied using histological, histochemical and immunohistochemical techniques. The sample consisted of 281 specimens aged 0-363 days, all of which had a normal (tricuspid) aortic valve. The first sign of valvular chondrogenesis is the presence of small groups of cells embedded in a type II collagen-positive matrix. These groups of cells, which can appear as early as one day after birth, increase in size and differentiate into hyaline cartilage or fibrocartilage. From the fourth day of life, all hamsters examined displayed cartilaginous foci in the aortic valve. They were located along the fibrous attachments of the valve leaflets to their respective sinuses, including the valve commissures. A considerable proportion (76%) of cartilages formed within the first 40 days of life, that is during the period of time in which the histogenesis of the valve takes place. The present observations are consistent with the assumption that in mammals, the precursors of the aortic valve chondrocytes are neural crest-derived cells. Results of a statistical analysis substantiate that the incidence is significantly higher in (1) the territory that comprises the collagenous condensation of the ventral commissure and the ventro-lateral and proximal fibrous attachments of the right leaflet to its sinus, and (2) the proximal fibrous attachment of dorsal leaflet to its sinus. These findings together with data in the literature concerning the distribution of stress in each leaflet-sinus assembly of the valve during the cardiac cycle, suggest that mechanical action might play an inductive role in the formation of the cartilaginous tissue in the aortic valve of mammals. In addition, they point to the possibility that locally intense mechanical stimulation is responsible for the differentiation of the anticipated cartilaginous tissue into hyaline cartilage.

In the Syrian hamster, anomalies in the origin of the left coronary artery are significantly associated with the bicuspid condition of the aortic valve. In this species, bicuspid aortic valves are expressions of a trait, the variation of which takes the form of a phenotypic continuum, ranging from a tricuspid aortic valve with no commissural fusion to a bicuspid aortic valve with the aortic sinuses located in ventrodorsal orientation and devoid of any raphe. The intermediate stages of the continuum are represented by tricuspid aortic valves with a more or less extensive fusion of the ventral commissure and bicuspid aortic valves with a more or less developed raphe located in the ventral aortic sinus. The present study was designed to decide whether there is a gap between tricuspid and bicuspid aortic valves regarding the incidence of coronary artery anomalies, or whether this incidence varies according to the different tricuspid and bicuspid morphotypes of the continuum. The study was carried out in Syrian hamsters belonging to a single inbred family with a high incidence of tricuspid aortic valves with fusion of the ventral commissure, bicuspid aortic valves, and anomalies in the origin of the left coronary artery, i.e. single right coronary artery ostium in aorta, anomalous origin of the left coronary artery from the pulmonary artery, and anomalous origin of the left coronary artery from the dorsal aortic sinus. The specimens were examined by means of a stereomicroscope and, in several cases, scanning electron microscopy was also used. The relationships between anomalous coronary artery patterns and aortic valve morphologies were tested using a logistic regression model. The results obtained indicate that there is no discontinuity between tricuspid and bicuspid aortic valves regarding the incidence of coronary artery anomalies. The probability of occurrence of anomalous coronary artery patterns increases continuously according to the deviation degree of the aortic valve from its normal (tricuspid) design. The present findings suggest that in the Syrian hamster, the morphogenetic mechanisms involved in the formation of congenital anomalous aortic valves and anomalies in the origin of the left coronary artery, respectively, are strongly related from an aetiological viewpoint.

We report a 72-year-old woman with severe congenital stenosis of the left coronary artery orifice and clinically significant atherosclerotic changes in both the right and left coronary arteries. The stenotic ostium was located at the point at which the left and posterior aortic valve leaflets joined to form the left commissure, just at the distal vertex of the left interleaflet triangle, between the left and posterior aortic sinuses. The right coronary artery was more developed in size than usual, whereas the left coronary artery consisted of a short left main coronary trunk that bifurcated into left anterior descending and left circumflex arteries. The left coronary artery system was filled retrogradely through two vessels proceeding from the right coronary artery, namely, the conal artery and a well-developed branch that ran across the interventricular septum. This abnormal arrangement of the coronary arteries showed striking functional similarities with atresia of the left main coronary artery. Current knowledge on the morphogenesis of the coronary arteries suggests that the present anomalous coronary artery pattern resulted from the penetration of the anticipated left coronary artery system into the aorta at a totally erroneus site. This hindered the normal development of the ostium, which subsisted as a punctiform, practically nonfunctional opening.

Background: Bicuspid aortic valve is the most frequent congenital cardiac malformation in humans. However, the morphogenesis of the defect is still unknown. Previous work showed that, in the Syrian hamster, congenital bicuspid aortic valves with the aortic sinuses arranged in ventrodorsal orientation are expressions of a trait the variation of which takes the form of a continuous phenotypic spectrum, ranging from a tricuspid aortic valve with no fusion of the ventral commissure to a bicuspid aortic valve devoid of any raphe. The present study was designed to elucidate the mechanism involved in the formation of bicuspid aortic valves in Syrian hamsters as a possible starting point for further investigation of this process in humans., Methods: The sample examined consisted of 80 embryos, aged between 10 days, 16 hours and 13 days, 1 hour postcoitum. Most (n = 59) of the embryos belonged to a laboratory-inbred family of Syrian hamsters with a high incidence of bicuspid aortic valves. The study was carried out using scanning electron microscopy and histological techniques for light microscopy., Results: Twenty-three embryos showed a still undivided conotruncus. In all of these cases there were six mesenchymal semilunar valve primordia protruding into the lumen of the conotruncus. In a further 29 embryos, the conotruncus had just divided into the aortic and pulmonary channels; the embryos were at the beginning of the valvulogenesis. In 13 of these 29 embryos there were three well-defined aortic valve cushions, right, left, and dorsal, whereas in the other 16, the right and left valve cushions were more or less fused toward the lumen of the aorta; when they were completely fused, only two aortic valve cushions, a ventral and a dorsal, could be identified. In the remaining 28 embryos, the aortic valve cushions showed a marked degree of excavation. In 23 of these cases, the valve exhibited a basically tricuspid architecture, whereas it was unequivocally bicuspid in the other five., Conclusions: All variants of the aortic valve morphologic spectrum occurring in the Syrian hamster develop from three mesenchymal valve cushions, right, left, and dorsal, after normal septation of the conotruncus. The bicuspid condition of the aortic valve is not the consequence of improper development of the conotruncal ridges, conotruncal malseptation, valve cushion agenesis, or lesions acquired after a normal valvulogenesis. Fusion of the right and left valve cushions at the beginning of the valvulogenesis appears to be a key factor in the formation of bicuspid aortic valves. Each aortic valve acquires its specific morphology prior to the end of the valvulogenetic process.

The condition of the aortic valve and the origin of the coronary arteries were examined in 2413 Syrian hamsters aged between 1 and 823 days, belonging to nine inbred laboratory families. The specimens were studied with either a stereomicroscope, a corrosion-cast technique, or histological techniques (light microscopy). The aortic valve was tricuspid in 1823 (75.5%) cases, and bicuspid in the remaining 590 (24.5%). In all bicuspid aortic valves there were two aortic sinuses, a ventral and a dorsal, each supporting one cusp. The left coronary artery arose from the dorsal aortic sinus in 71 (2.9%) hamsters, eight of which died unexpectedly between ages 1 and 622 days. In 29 (40.8%) of the 71 cases, the aortic valve was tricuspid and the right coronary artery originated from the right aortic sinus. In the remaining 42 (59.2%) cases, the aortic valve was bicuspid and the right coronary artery arose from the right side of the ventral aortic sinus. Results of a chi 2 contingency test demonstrated that the frequency of left coronary artery arising from the dorsal aortic sinus significantly increased when the aortic valve was bicuspid. This fact, together with previously reported data on coronary artery anomalies in the Syrian hamster, suggests that the left coronary artery arising from the dorsal aortic sinus may be an expression of a single morphogenetic defect which is expressed as bicuspid aortic valve in some cases, anomalous origin of the left coronary artery in others, or in the simultaneous occurrence of these two cardiac abnormalities.

Congenital quadricuspid aortic valve is a rare anomaly, the morphogenesis of which remains unclear. In this study we report the case of a Syrian hamster embryo that presented an aortic valve with four valve cushions instead of three. The embryo, aged 12 days and 2 hours postcoitum, was at an early stage of valvulogenesis. It was examined using semithin sections of the heart. Two of the four valve cushions were located, one in the dorsal and the other in the left-ventral position, corresponding, respectively, to the dorsal and left valve cushions of a normal aortic valve. The remaining two cushions were situated in the right-ventral position. They were joined at the level of their basal portions and were less developed in size than the other cushions. This report seems to be the first embryological evidence for the formation of a quadricuspid aortic valve. The present findings strongly suggest that the anomalous valve originated from three mesenchymal anlagen and that the supernumerary valve cushion resulted from the division of the anlagen that normally gives rise to the right valve cushion., (Copyright © 1994. Published by Elsevier Inc.)

A histological study was made of the aortic valves of 141 Syrian hamsters aged between 35 and 657 days, belonging to an inbred laboratory colony with a high incidence of congenital bicuspid aortic valves. A tricuspid aortic valve was found in 81 specimens, whereas the remaining 60 possessed a bicuspid aortic valve. In all bicuspid valves there were two aortic sinuses, a ventral and a dorsal, each supporting one cusp. Thirty-three (23.4%) of the 141 specimens showed mucoid dysplasia of the aortic valve. The defect was characterized by thickening of the valve cusps and disruption of the fibrosa layer accompanied by an increased amount of glycosaminoglycans. Ten (12.3%) of the 81 tricuspid aortic valves and 23 (38.3%) of the 60 bicuspid aortic valves were dysplastic. This difference was statistically significant (P < 0.001). The findings indicate that, in the Syrian hamster, the simultaneous occurrence of bicuspid aortic valve and aortic valve dysplasia is not a random event. However, the fact that these valve defects also occur independently suggests that there is no primary morphogenetic dependence between them, but that some other cause predisposes to their concurrence.

We conducted a light-microscopic histologic study of the aortic valves of 224 Syrian hamsters aged between 1 and 771 days. Most of the hamsters examined belonged to a single laboratory-inbred family with a high incidence of bicuspid aortic valves (BAVs). In 146 specimens the aortic valve was tricuspid, and in 107 of them the ventral commissure was more or less fused. The remaining 78 specimens showed a BAV with the aortic sinuses oriented ventrodorsally. In 33 BAVs a raphe was located in the ventral aortic sinus. Cartilaginous foci were present in the aortic valves of 86 specimens, 40-771 days old. The foci were located at two different sites, namely in the ventral wall of the valve and/or in the dorsal aortic sinus. Statistical analyses substantiate that (1) chondrogenesis begins earlier in BAVs, and especially in those having a raphe, than in tricuspid aortic valves and (2) the location of the cartilaginous foci is significantly associated with the morphology of the aortic valve. The present findings support the hypothesis that, in the Syrian hamster, cartilage forms in the aortic valve as a response to locally intense mechanical stimulation.

Bearing in mind that the Syrian hamster provides an animal model for the study of congenital coronary artery anomalies, we decided to undertake a definition of its normal coronary artery pattern. The sample examined consisted of 1204 specimens. They were studied both histologically and by means of a corrosion-cast technique. The course of the coronary arteries in this species is intramyocardial. The right coronary artery has two principal branches: the right circumflex branch and the dorsal interventricular branch. The conal branch usually originates from the main trunk of the right coronary artery. The main branches of the left coronary artery are the obtuse marginal branch, the left circumflex branch, and usually a dorsal ventricular branch as well. The ventral interventricular branch is often absent. When it is present, it always originates from the left coronary artery and seldom reaches the apex of the heart. The interventricular septum is principally supplied by one, or rarely two, septal arteries arising from the right and/or left coronary arteries. According to the number and origin of these vessels, three septal coronary artery patterns were established; namely, the right, the left, and the right-left septal patterns. In the Syrian hamster, the left septal pattern is the most frequent (70.4%). The right septal pattern occurred in 28.1% of the specimens studied, whereas the right-left septal pattern was only found in 1.5% of them.

The present study focused on exploring the relationship between a number of personality measures (Sensation Seeking Scale, SSS; State-Trait Anxiety Inventory, STAI; and Susceptibility to Punishment Scale, SP) and some parameters of the pituitary-gonadal axis (FSH, LH and 17 beta-estradiol). The study was carried out with a group of 37 female volunteers. The subjects were physically and mentally fit. None of them had a personal history of psychiatric or endocrine illness. All subjects were studied at the beginning of the follicular phase. The most relevant results showed an 'inverted U shape' relationship between sensation seeking and plasma FSH levels. Lower Thrill and Adventure Seeking (TAS) scores were also found in subjects with higher levels of 17 beta-estradiol.

A coronary artery that arises from the nonfacing (posterior or dorsal) aortic sinus is regarded as having an anomalous origin. We studied 34 Syrian hamsters in which the left coronary artery originated from the nonfacing aortic sinus. All hamsters belonged to a single family subjected to high endogamous pressure in our laboratory. Twenty-four specimens were examined using a corrosion-cast technique and scanning electron microscopy, whereas the remaining 10 were studied histologically. The aortic valve was normal in 15 cases, whereas it was bicuspid in the other 19 cases. In each specimen of our series, the left coronary artery arose with an acute angle with respect to the aortic valve. Moreover, when the coronary ostium was located in the center of the nonfacing aortic sinus, the proximal coronary artery had an intramural aortic course. These left coronary artery arrangements might underlie an unfavorable coronary circulation physiology. Our morphologic findings agree with the morphogenetic hypothesis that each aortic sinus has the potential to develop coronary artery buds, which hollow out from the aorta to become coronary artery trunks., (Copyright © 1993. Published by Elsevier Inc.)

We studied the conditions of the aortic and pulmonary valves of 153 Syrian hamsters belonging to a single family subjected to high endogamous pressure. Semilunar valves of 143 specimens were examined using a stereomicroscope, and in 5 of these cases a histologic study was also performed. The remaining 10 specimens were studied by means of scanning electron microscopy. In 77 specimens both semilunar valves were normal. The aortic valve was bicuspid and the pulmonary valve was normal in 46 animals, while a normal aortic valve and a bicuspid pulmonary valve occurred in 24. In the remaining 6 specimens both semilunar valves were bicuspid. All bicuspid semilunar valves detected herein showed the same morphotype, namely with the leaflets oriented ventrodorsally. The incidence of these anomalous valves did not significantly differ between sexes. Results of a chi 2-test substantiate that conditions of both outflow tract semilunar valves are independent traits. Thus, concurrence of a bicuspid aortic valve and a bicuspid pulmonary valve in an individual is a random event. The present findings support the assumption that bicuspid aortic and pulmonary valves have different morphogenetic origin, although factors producing a bicuspid aortic valve and those leading to a bicuspid pulmonary valve are not mutually exclusive.

The present study explores the relationships among a number of personality measures (the Sensation-Seeking Scale, SSS; the State-Trait Anxiety Inventory, and the Susceptibility to Punishment Scale) and some parameters of the pituitary-thyroid axis. The study was carried out on a group of 37 physically and mentally fit female volunteers, none of whom had a personal history of psychiatric or endocrinologic illness. The subjects were controlled for the menstrual cycle. The most relevant result was a significant negative relationship between the SSS score and plasma basal levels of thyroxine (T4) and thyroid-stimulating hormone (TSH). Interaction between T4 and TSH levels with trait anxiety was also observed.

We present 4 cases of dissection of the coronary arteries during coronary radiography, which required emergency surgery. The right coronary was dissected in 2 cases and the left coronary in the remaining cases. Coronary artery bypass was carried out using saphenous vein. Although one patient suffered myocardial infarction, all patients had successful recovery and evolution.

A comparative study performed in psychosomatic patients (PG) and healthy subjects (HG) reveals several correlations between personality measurements (Minnesota Multiphasic Personality Inventory, Sensation Seeking Scale, Susceptibility to Punishment), and biochemical variables (in serum: MHPG, acetylcholinesterase, calcium, melatonin; and in platelets: monoamine oxidase B, serotonin, calcium proteins). The relationship between some Sensation Seeking subscales and the enzymatic activities evaluated (negative with MAO and positive with AChase) and the opposite sign relationship between serotonin and some scales of MMPI in both groups studied (negative in the PG and positive in the HG) are noteworthy.

The origin and course of the coronary arteries were studied in 1,436 Syrian hamsters belonging to 10 breeding colonies subjected to high endogamous pressure by mating either animals of the same litter or first cousins. The study was carried out using a corrosion casting technique. A left coronary artery originating from the pulmonary trunk was found in 48 specimens of the series. In all cases anastomoses had developed between the right and left coronary systems. Moreover, five types of minor primary anomalies of the coronary arteries occurred in 144 hamsters. These findings agree with the morphogenetic hypothesis that each of the aortic and pulmonary sinuses has the potential to develop coronary arteries. Familial recurrence risks for coronary arterial anomalies were estimated taking into account the sex and the inbreeding coefficient of the probands carrying a left coronary artery from the pulmonary trunk. The recurrence risks increase as the inbreeding level increases, this suggesting that the whole primary coronary anomalies are a phenotypic set subordinated to a complex mode of inheritance. Therefore, an echocardiographic study of the first degree relatives of patients with coronary arterial anomalies is advisable to diagnose clinically silent coronary malformations.

Individual 5-hydroxyindoles and 5-methoxyindoles were simultaneously isolated and quantified, after o-phthaldehyde condensation in different concentrations of HCl, followed by separation on silica gel plates. The 5-hydroxyindoleamines and 5-methoxyindoleamines were differentiated by intense orange and blue fluorescences, respectively. Distinct Rf values with new phase composition and optimal HCl concentrations in the condensation reaction were established for each of the nine indoleamines tested. Minimal detectable doses ranged from 0.2 ng for 5-methoxytryptophol to 4 ng for 5-hydroxyindole acetic acid. The above methodology was applied in order to determine platelet serotonin. Preliminary results suggest that this method could be adapted to other selected biological samples.

A comparative study performed in psychosomatic patients and healthy subjects reveals different profiles of thyroxine (T4) and thyroid-stimulating hormone (TSH) correlations with personality measurements (Minnesota Multiphasic Personality Inventory (MMPI); Sensation-Seeking Scale (SSS), and Susceptibility to Punishment Scale (SP). Three distinct sets of results may be enumerated, namely: (1) a negative correlation between sensation-seeking and TSH; (2) a positive correlation between the most indicative scales predisposing to depression-anxiety (hypochondriasis, depression, social introversion, susceptibility to punishment) and T4, and (3) the Hypomania Scale (Ma) showed a significant negative correlation with T4 in the patient group and a positive but nonsignificant relationship in the healthy group.