True pregnancy toxemia (preeclampsia) in the guinea pig (Cavia porcellus)

In this study, normal nonpregnant, normal full-term pregnant, fasting ketotic and spontaneous pregnancy toxemic guinea pigs were compared to define the mechanism of this disease. In addition to conventional clinical, laboratory and pathologic studies, arterial blood pressure (thoracic and abdominal aortic) measurements and angiography were used. The results showed that in spontaneous cases of pregnancy toxemia, there is an aortic compression just caudal to the renal arteries. This compression reduced the aortic diameter by 22% of prerenal level as compared to 10% for fasting ketotic and normal pregnant guinea pigs. The aortic compression also resulted in a 30% postcompression reduction in blood pressure. No pressure differences were seen in the other groups. The postulated etiology for true toxemia of pregnancy in guinea pigs is, therefore, similar to that of man where aortic compression produces uterine ischemia and the resultant syndrome.     

Diagnosing moyamoya syndrome using ultrasound - a case report

Background

Moyamoya syndrome is a vasculopathy characterised by progressive occlusion of the cerebral arteries resulting in the development of abnormal collateral circulation. To diagnose this syndrome, imaging of the cerebral arteries is required including CT- or MR-angiography and conventional angiography. We present a case of moyamoya disease with typical findings detected in the sonography. The diagnosis was suspected after reviewing the initial ultrasound images of the cerebral arteries with evidence for obliterated intracranial arteries and the detection of an existing collateral circulation network.

Case presentation

A 62 years old male patient presented in the hospital’s emergency department with symptoms indicating a subacute cerebrovascular event. Immediate sonographic studies showed a right-sided pulsatile Doppler-signal in the common and internal carotid arteries, suggestive of distal stenoses. In addition, the transcranial examination indicated obliteration of both middle cerebral arteries. Numerous arterial vessels suggestive of leptomeningeal collateral arteries revealed a strong arterial leptomeningeal flow. At this stage of the diagnostic work-up, the collateral circulation network, characteristic of moyamoya disease, was indicated by sonography. Moyamoya syndrome was verified by conventional angiography. The aetiological work remained empty, so the diagnosis of moyamoya disease was established.

Conclusion

Our case report indicates that sonography can be a useful tool for detecting the vaculopathy in moyamoya syndrome. In case routine procedures, such as the CT- or MR-angiography, with evidence for obliterated intracerebral arteries, ultrasound studies might provide important information regarding an existing collateral network in the scope of a moyamoya syndrome.

     

Accumulation of elements in the arteries and cardiac valves of Thai with aging

To elucidate whether the extent of element accumulation in the arteries and cardiac valves with aging was different between different races, the authors investigated the accumulation of elements in the arteries and cardiac valves of the Thai with aging and the relationships among elements in the cardiac valves. After ordinary dissection at Chiang Mai University was finished, 16 arteries and 4 cardiac valves were resected and element contents were determined by inductively coupled plasma-atomic emission spectrometry. In the 16 arteries, the average content of calcium was the highest in the site of the abdominal aorta ramifying into the common iliac arteries, and it decreased in the order internal iliac, coronary, abdominal aorta, common iliac, external iliac, superior mesenteric, inferior mesenteric, thoracic aorta, brachial, radial, common carotid, subclavian, ulnar, axillary, renal, and internal thoracic arteries. The average contents of phosphorus and magnesium in respective arteries were parallel with the average contents of calcium, except for the coronary artery. In comparison with the arteries of the Japanese, the trend of calcium accumulation in the arteries of the Thai was almost similar to that in the arteries of the Japanese, except for the coronary artery and thoracic aorta. The calcium accumulation in the coronary artery was much higher in the Thai than in the Japanese, whereas that in the thoracic aorta was lower in the Thai than in the Japanese. Regarding elements in the cardiac valves, the calcium content increased remarkably in the seventies in the aortic valve and in the nineties in the pulmonary valve, but it hardly increased in both the mitral and tricuspid valves with aging. The average content of calcium was the highest in the aortic valve, and it decreased in the order pulmonary, tricuspid, and mitral valves. Regarding the relationship among elements in the aortic valves, it was found that there were extremely significant direct correlations among the contents of calcium, phosphorus, and magnesium, whereas there were significant direct correlations between zinc and either calcium or phosphorus contents. Although significant correlations were found between sulfur and the other element contents in the aortic valves of the Japanese, no significant correlations were found between them in the aortic valves of the Thai. In the mitral valves, extremely or very significant direct correlations were found among the contents of calcium, phosphorus, magnesium, and sulfur, with some exceptions that there were no significant correlations between phosphorus and either magnesium or sulfur contents. In addition, no significant correlation was found in the calcium content between the aortic valve and coronary artery in the same individuals.     

Accumulation of calcium in human common iliac artery, aortic valve, xiphoid process, costal cartilage, posterior longitudinal ligament, trigeminal nerve, and rib accompanied by increase of magnesium

To examine whether an accumulation of Ca in the tissues was accompanied by an increase of Mg, the authros investigated the relationships between Ca and Mg contents in the common iliac arteries, aortic valves, xiphoid processes, costal cartilages, posterior longitudinal ligaments, trigeminal nerves, and ribs by inductively coupled plasma-atomic emission spectrometry. After the ordinary dissections by medical students were finished, the common iliac arteries, aortic valves, xiphoid processes, bilateral the fourth costal cartilages, posterior longitudinal ligaments between the fourth and fifth cervical vertebrae, trigeminal nerves, and bilateral the sixth ribs were resected from the subjects and elements were determined. It was found that there were extremely significant direct correlations between Ca and Mg contents in all of the common iliac arteries, aortic valves, costal cartilages, posterior longitudinal ligaments, and trigeminal nerves, whereas there were significant direct correlations in both the xiphoid processes and ribs. As for the tissues containing Ca higher than 20 mg/g, the average mass ratios of Mg/Ca were similar among the seven tissues. As Ca increased in all of the common iliac arteries, aortic valves, xiphoid processes, costal cartilages, posterior longitudinal ligaments, trigeminal nerves, and ribs, Mg increased simultaneously in the seven tissues.     

Chromosome 22q11 deletions in patients with selected outflow tract malformations

The incidence of 22q11 deletions and its effect on the phenotype were established in 170 patients with selected outflow tract malformations and transposition of the great arteries (conotruncal defects). Cases were seen both prospectively and retrospectively. All patients had a dysmorphological evaluation by the clinical geneticist and a cytogenetic analysis including FISH analysis for 22q11 deletions. A chromosomal abnormality was present in 29 patients, including a 22q11 deletion in 22/170 patients (13%). The 22q11 deletion was found in 11% of tetralogy of Fallot, in 11% of pulmonary atresia and VSD, in 44% of pulmonary atresia. VSD and collateral arteries, in 20% of truncus arteriosus, in 60% of interrupted aortic arch and in 25% patients with aberrant subclavian artery. They were absent in double outlet right ventricle or in transposition of the great arteries. No parental deletion was found. All patients had clinical characteristics of the velocardiofacial syndrome. This study confirms a high incidence of chromosome 22q11 deletions in patients with selected outflow tract malformations, with great clinical impact for further management and genetic counseling.     

A genetic link between Tbx1 and fibroblast growth factor signaling

Tbx1 haploinsufficiency causes aortic arch abnormalities in mice because of early growth and remodeling defects of the fourth pharyngeal arch arteries. The function of Tbx1 in the development of these arteries is probably cell non-autonomous, as the gene is not expressed in structural components of the artery but in the surrounding pharyngeal endoderm. We hypothesized that Tbx1 may trigger signals from the pharyngeal endoderm directed to the underlying mesenchyme. We show that the expression patterns of Fgf8 and Fgf10, which partially overlap with Tbx1 expression pattern, are altered in Tbx1(-/-) mutants. In particular, Fgf8 expression is abolished in the pharyngeal endoderm. To understand the significance of this finding for the pathogenesis of the mutant Tbx1 phenotype, we crossed Tbx1 and Fgf8 mutants. Double heterozygous Tbx1(+/-);Fgf8(+/-) mutants present with a significantly higher penetrance of aortic arch artery defects than do Tbx1(+/-);Fgf8(+/+) mutants, while Tbx1(+/+);Fgf8(+/-) animals are normal. We found that Fgf8 mutation increases the severity of the primary defect caused by Tbx1 haploinsufficiency, i.e. early hypoplasia of the fourth pharyngeal arch arteries, consistent with the time and location of the shared expression domain of the two genes. Hence, Tbx1 and Fgf8 interact genetically in the development of the aortic arch. Our data provide the first evidence of a genetic link between Tbx1 and FGF signaling, and the first example of a modifier of the Tbx1 haploinsufficiency phenotype. We speculate that the FGF8 locus might affect the penetrance of cardiovascular defects in individuals with chromosome 22q11 deletions involving TBX1.     

Fibulin-1 is required for morphogenesis of neural crest-derived structures

Here we report that mouse embryos homozygous for a gene trap insertion in the fibulin-1 (Fbln1) gene are deficient in Fbln1 and exhibit cardiac ventricular wall thinning and ventricular septal defects with double outlet right ventricle or overriding aorta. Fbln1 nulls also display anomalies of aortic arch arteries, hypoplasia of the thymus and thyroid, underdeveloped skull bones, malformations of cranial nerves and hemorrhagic blood vessels in the head and neck. The spectrum of malformations is consistent with Fbln1 influencing neural crest cell (NCC)-dependent development of these tissues. This is supported by evidence that Fbln1 expression is associated with streams of cranial NCCs migrating adjacent to rhombomeres 2-7 and that Fbln1-deficient embryos display patterning anomalies of NCCs forming cranial nerves IX and X, which derive from rhombomeres 6 and 7. Additionally, Fbln1-deficient embryos show increased apoptosis in areas populated by NCCs derived from rhombomeres 4, 6 and 7. Based on these findings, it is concluded that Fbln1 is required for the directed migration and survival of cranial NCCs contributing to the development of pharyngeal glands, craniofacial skeleton, cranial nerves, aortic arch arteries, cardiac outflow tract and cephalic blood vessels.     

ASCENDING AORTIC ANEURYSM RESECTION EIGHT MONTHS AFTER TRIPLE CORONARY ARTERY BYPASS: CASE REPORT

This report involves the surgical treatment of a patient who underwent saphenous vein triple coronary artery bypass and subsequently developed an ascending aortic aneurysm and aortic insufficiency. Although the implantation of vascular structures into synthetic grafts is commonplace, this case is unique in that it involves the successful implantation of an aortic island containing the origin of the coronary arteries.     

叉头框-c2基因在主动脉弓发育过程中的作用

为了研究叉头框-c2（Forkhead Box c2, Fox c2）基因在心血管发生和发育中的作用, 通过制作小鼠的Fox c2 基因无效突变,解析该基因缺失鼠主动脉弓的异常发育状况.纯合子胎鼠从12.5天胚胎(embryo, E)开始有宫内死亡;即使完成宫内发育过程,新生鼠出生24 h后也全部死亡.这些鼠全部表现出与人的先天性心血管发育缺陷相似的B型或C型主动脉弓离断.杂合子鼠发育正常.E10.5胚胎的原位杂交分析显示,Fox c2 mRNA在第三、第四和第六弓型动脉强烈表达,而第四弓型动脉在E10.5胚胎后逐渐消失.这些结果表明,在主动脉弓形成过程中,Fox c2基因产物是左第四弓形动脉广泛改建所必需.     

INSERTION OF AN INTRAAORTIC BALLOON THROUGH A LIMB OF AN AORTOFEMORAL GRAFT AFTER AORTIC VALVE REPLACEMENT, DOUBLE CORONARY ARTERY BYPASS, AND RESECTION OF AN ABDOMINAL AORTIC ANEURYSM

This case report describes a useful and unusual route for insertion of an intraaortic balloon in 63-year-old man who was operated upon for calcific aortic stenosis, coronary atherosclerosis involving the left anterior descending and right coronary arteries, and a large abdominal aortic aneurysm. Aortic valve replacement was accomplished with a porcine heterograft prosthesis. Bypasses to the left anterior descending and right coronary arteries were constructed with reversed saphenous vein grafts, and the abdominal aneurysm was resected and repaired with a bifurcated woven Dacron vascular graft. An electively placed intraaortic balloon was inserted through the right limb of the aortic graft prosthesis and used to assist the patient during the immediate postoperative period. Uneventful recovery ensued.     

TGFβ signaling and congenital heart disease: Insights from mouse studies

Transforming growth factor β (TGFβ) regulates one of the major signaling pathways that control tissue morphogenesis. In vitro experiments using heart explants indicated the importance of this signaling pathway for the generation of cushion mesenchymal cells, which ultimately contribute to the valves and septa of the mature heart. Recent advances in mouse genetics have enabled in vivo investigation into the roles of individual ligands, receptors, and coreceptors of this pathway, including investigation of the tissue specificity of these roles in heart development. This work has revealed that (1) cushion mesenchyme can form in the absence of TGFβ signaling, although mesenchymal cell numbers may be misregulated; (2) TGFβ signaling is essential for correct remodeling of the cushions, particularly those of the outflow tract; (3) TGFβ signaling also has a role in ensuring accurate remodeling of the pharyngeal arch arteries to form the mature aortic arch; and (4) mesenchymal cells derived from the epicardium require TGFβ signaling to promote their differentiation to vascular smooth muscle cells to support the coronary arteries. In addition, a mouse genetics approach has also been used to investigate the disease pathogenesis of Loeys-Dietz syndrome, a familial autosomal dominant human disorder characterized by a dilated aortic root, and associated with mutations in the two TGFβ signaling receptor genes, TGFBR1 and TGFBR2. Further important insights are likely as this exciting work progresses.     

Effect of nifedipine on calcium-induced contractions to potassium in the aorta and mesenteric arteries of spontaneously hypertensive and normotensive rats

Graded contractions to cumulative additions of calcium in the presence of KCl were obtained in strips of aorta and mesenteric arteries of normotensive (WKY) and spontaneously hypertensive (SHR) rats. In calcium-free medium, a maximally effective concentration of KCl produced a response that was larger in the mesenteric arteries (43-51% of control) than in the aorta (12-14% of control). The calcium channel blocker nifedipine (NFD, up to 10(-7) M) did not significantly alter these calcium-insensitive responses. The Ca2+-induced responses were inhibited by NFD, in a concentration-dependent fashion, in both vessel types of WKY and SHR rats. The aortic responses were more sensitive to inhibition by NFD than the responses of mesenteric arteries. Moreover, the aortic responses of WKY were inhibited to a greater extent than those of the SHR. The results suggest: (a) a differential calcium dependence of contractions to KCl in the vessels studied; (b) that aortic responses are dependent on NFD-sensitive voltage-sensitive Ca2+ channels to a greater extent than the responses of mesenteric arteries; and (c) that hypertension results in a decreased sensitivity of the aorta Ca2+ channels to NFD.     

Pitx2c patterns anterior myocardium and aortic arch vessels and is required for local cell movement into atrioventricular cushions

Inactivation of the left-right asymmetry gene Pitx2 has been shown, in mice, to result in right isomerism with associated defects that are similar to that found in humans. We show that the Pitx2c isoform is expressed asymmetrically in a presumptive secondary heart field within the branchial arch and splanchnic mesoderm that contributes to the aortic sac and conotruncal myocardium. Pitx2c was expressed in left aortic sac mesothelium and in left splanchnic and branchial arch mesoderm near the junction of the aortic sac and branchial arch arteries. Mice with an isoform-specific deletion of Pitx2c had defects in asymmetric remodeling of the aortic arch vessels. Fatemapping studies using a Pitx2 cre recombinase knock-in allele showed that daughters of Pitx2-expressing cells populated the right and left ventricles, atrioventricular cushions and valves and pulmonary veins. In Pitx2 mutant embryos, descendents of Pitx2-expressing cells failed to contribute to the atrioventricular cushions and valves and the pulmonary vein, resulting in abnormal morphogenesis of these structures. Our data provide functional evidence that the presumptive secondary heart field, derived from branchial arch and splanchnic mesoderm, patterns the forming outflow tract and reveal a role for Pitx2c in aortic arch remodeling. Moreover, our findings suggest that a major function of the Pitx2-mediated left right asymmetry pathway is to pattern the aortic arches, outflow tract and atrioventricular valves and cushions.     

Relaxing effect of atrial natriuretic factor on endothelin-precontracted vascular strips

Endothelin (ET), a peptide recently isolated from the supernatant of cultured porcine aortic endothelial cells, is a potent vasoconstrictor. On the other hand, atrial natriuretic factor (ANF) is a powerful vasorelaxant found in cardiocytes. Its effect was investigated in ET-precontracted rabbit vascular strips. ANF-induced a dose-dependent relaxation of maximally-precontracted mesenteric, renal and aortic strips. Mesenteric artery strips were more sensitive to ANF than either renal or aortic strips. The relaxant effect of ANF on ET-precontracted arteries was more potent than that of other vasorelaxant agents, such as isoproterenol and sodium nitroprusside. Renal and aortic arteries were more sensitive to the vasoconstrictor effect of ET than mesenteric strips. From these results, we conclude that ANF may play a role as a physiological antagonist of ET. The different sensitivity of vascular segments to ET could be due to varying vascular ET receptor densities.     

In vitro hemodynamic investigation of the embryonic aortic arch at late gestation

This study focuses on the dynamic flow through the fetal aortic arch driven by the concurrent action of right and left ventricles. We created a parametric pulsatile computational fluid dynamics (CFD) model of the fetal aortic junction with physiologic vessel geometries. To gain a better biophysical understanding, an in vitro experimental fetal flow loop for flow visualization was constructed for identical CFD conditions. CFD and in vitro experimental results were comparable. Swirling flow during the acceleration phase of the cardiac cycle and unidirectional flow following mid-deceleration phase were observed in pulmonary arteries (PA), head-neck vessels, and descending aorta. Right-to-left (oxygenated) blood flowed through the ductus arteriosus (DA) posterior relative to the antegrade left ventricular outflow tract (LVOT) stream and resembled jet flow. LVOT and right ventricular outflow tract flow mixing had not completed until approximately 3.5 descending aorta diameters downstream of the DA insertion into the aortic arch. Normal arch model flow patterns were then compared to flow patterns of four common congenital heart malformations that include aortic arch anomalies. Weak oscillatory reversing flow through the DA junction was observed only for the Tetralogy of Fallot configuration. PA and hypoplastic left heart syndrome configurations demonstrated complex, abnormal flow patterns in the PAs and head-neck vessels. Aortic coarctation resulted in large-scale recirculating flow in the aortic arch proximal to the DA. Intravascular flow patterns spatially correlated with abnormal vascular structures consistent with the paradigm that abnormal intravascular flow patterns associated with congenital heart disease influence vascular growth and function.     

RGS3 inhibits TGF‐β1/Smad signalling in adventitial fibroblasts

Recent evidence suggests that adventitial fibroblasts (AFs) are crucially implicated in atherosclerosis. However, the mechanisms by which AFs are dysfunctional and contribute to atherosclerosis remain unclear. This study aimed to investigate the role of regulator of G‐protein signalling 3 (RGS3) in the regulation of AFs using apoE knockout mouse as the model. Pathological changes in aortic arteries of apoE knockout mice fed with hyperlipid diet were examined by Movat staining. The expression of RGS3, α‐SMA, TGF‐β1, Smad2, and Smad3 in the adventitia was detected by immunohistochemistry. Adventitial fibroblasts were isolated from aortic arteries of apoE knockout mice and infected with RGS3 overexpression lentivirus or empty lentivirus. The expression of RGS3, α‐SMA, TGF‐β1, Smad2, and Smad3 in AFs was detected by real‐time polymerase chain reaction and Western blot analysis. We found that hyperlipidic diet caused significant aortic intima thickening and atherosclerotic plaques in 15‐week‐old apoE knockout mice. Compared to wild‐type mice, RGS3 expression was lower while α‐SMA, TGF‐β1, Smad2, and Smad3 expression was higher in the adventitia of apoE knockout mice. In addition, lentivirus mediated overexpression of RGS3 caused decreased expression of α‐SMA, TGF‐β1, Smad2, and Smad3 in AFs derived from apoE(?/?) mice. In conclusion, these results suggest that RGS3 may provide protection against pathological changes of AFs and the development of atherosclerosis by inhibiting TGF‐β1/Smad signalling. RGS3 may be a potential therapeutic target for atherosclerosis.     

Loss of Gbx2 results in neural crest cell patterning and pharyngeal arch artery defects in the mouse embryo

Several syndromes characterized by defects in cardiovascular and craniofacial development are associated with a hemizygous deletion of chromosome 22q11 in humans and involve defects in pharyngeal arch and neural crest cell development. Recent efforts have focused on identifying 22q11 deletion syndrome modifying loci. In this study, we show that mouse embryos deficient for Gbx2 display aberrant neural crest cell patterning and defects in pharyngeal arch-derived structures. Gbx2(-/-) embryos exhibit cardiovascular defects associated with aberrant development of the fourth pharyngeal arch arteries including interrupted aortic arch type B, right aortic arch, and retroesophageal right subclavian artery. Other developmental abnormalities include overriding aorta, ventricular septal defects, cranial nerve, and craniofacial skeletal patterning defects. Recently, Fgf8 has been proposed as a candidate modifier for 22q11 deletion syndromes. Here, we demonstrate that Fgf8 and Gbx2 expression overlaps in regions of the developing pharyngeal arches and that they interact genetically during pharyngeal arch and cardiovascular development.     

The origin and pattern of distribution of the posterior intercostal arteries in the baboon (Papio ursinus)

The posterior intercostal arteries of six female and four adult male baboons (Papio ursinus) were investigated by latex injection and subsequent dissection to determine their origin and pattern of distribution. Basic morphological and functional similarities with that of man could provide some base-line data pertinent to future experimental studies in the areas of thoracic aortic aneurysm and aortic atherosclerotic lesion in man. Basic similarities were observed between the baboon and man in the number of intersegmental arteries, the origin of the first two pairs of posterior intercostal arteries, and the anastomosis between the superior intercostal and the third posterior intercostal arteries. However, the baboon showed a craniocaudal sequence of paired orifices giving rise to paired arteries; orifices with incompletely divided septum giving rise to paired arteries; single orifices leading to a common trunk, which finally gives rise to paired arteries; and single orifices opening into single arteries. In addition, there was a craniocaudal decrease in the distance between any given pair of intercostal arteries and an increase in the spacing between adjacent pairs of intercostal arteries. Where a single artery supplied one side of the intercostal space, the contralateral side received a collateral branch, either from the preceding or succeeding intercostal artery. Though the basic organisation of the origin and distribution of the posterior intercostal arteries in the baboon is similar to that of man, the differences observed in the baboon might be attributed to factors such as body size, mode of activity, and even the phylogenetic level of development of the baboon.