Ischemia is not required for arteriogenesis in zebrafish embryos.

OBJECTIVE: The role of ischemia in collateral vessel development (arteriogenesis) is a contentious issue that cannot be addressed using mammalian models. To investigate this, we developed models of arteriogenesis using the zebrafish embryo, which gains sufficient oxygenation via diffusion to prevent ischemia in response to arterial occlusion. METHODS AND RESULTS: We studied gridlock mutant embryos that suffer a permanently occluded aorta and show that these restore aortic blood flow by collateral vessels. We phenocopied gridlock mutants by laser-induced proximal aortic occlusion in transgenic Fli1:eGFP/GATA1:dsRED embryos. Serial imaging showed these restore aortic blood flow via collateral vessels by recruitment of preexisting endothelium in a manner similar to gridlocks. Collateral aortic blood flow in gridlock mutants was dependent on both nitric oxide and myeloid cells. Confocal microscopy of transgenic gridlock/Fli1:eGFP mutants demonstrated no aberrant angiogenic response to the aortic occlusion. qPCR of HIF1alpha expression confirmed the absence of hypoxia in this model system. CONCLUSIONS: We conclude that NO and myeloid cell-dependent collateral vessel development is an evolutionarily ancient response to arterial occlusion and is able to proceed in the absence of ischemia.

Hemodynamic changes during complete umbilical cord occlusion in fetal sheep related to hippocampal neuronal damage.

OBJECTIVES: The purpose of our study was to examine the physiologic changes caused by 10 minutes of umbilical cord occlusion in fetal sheep and to determine the correlation between fetal acidemia or cerebral ischemia and hippocampal neuronal damage. STUDY DESIGN: Thirteen fetal sheep were instrumented and catheterized. Carotid artery blood flow (CaF), fetal mean arterial blood pressure (FMABP), pH, PCO (2), base excess, oxygen saturation (SatO(2)), and PO (2) were monitored throughout the occlusion study. Brain sections were examined for the hippocampal neuronal damage. RESULTS: Our data showed severe ischemia (CaF: 10 +/- 7 mL/min; FMABP: 29 +/- 8 mm Hg) and acidemia (pH: 7.0 +/- 0.05; base excess: -9.9 +/- 2.4 mEq/L) at the end of occlusion. The neuronal damage score had significant correlations with ischemia and also with reperfusion, but not with the acidemic or hypoxic parameters. CONCLUSION: We demonstrated that the degree of hippocampal damage was correlated with the degree of ischemia and reperfusion.

Elastin is an essential determinant of arterial morphogenesis.

Elastin, the main component of the extracellular matrix of arteries, was thought to have a purely structural role. Disruption of elastin was believed to lead to dissection of arteries, but we showed that mutations in one allele encoding elastin cause a human disease in which arteries are blocked, namely, supravalvular aortic stenosis. Here we define the role of elastin in arterial development and disease by generating mice that lack elastin. These mice die of an obstructive arterial disease, which results from subendothelial cell proliferation and reorganization of smooth muscle. These cellular changes are similar to those seen in atherosclerosis. However, lack of elastin is not associated with endothelial damage, thrombosis or inflammation, which occur in models of atherosclerosis. Haemodynamic stress is not associated with arterial obstruction in these mice either, as the disease still occurred in arteries that were isolated in organ culture and therefore not subject to haemodynamic stress. Disruption of elastin is enough to induce subendothelial proliferation of smooth muscle and may contribute to obstructive arterial disease. Thus, elastin has an unanticipated regulatory function during arterial development, controlling proliferation of smooth muscle and stabilizing arterial structure.

Fetoscopic and open transumbilical fetal cardiac catheterization in sheep. Potential approaches for human fetal cardiac intervention.

BACKGROUND: Shortening the prenatal disease course of severe aortic and pulmonary stenoses by balloon valvuloplasty may diminish their postnatal expression. The purpose of this study in fetal sheep was to assess the feasibility of fetoscopic and open transumbilical fetal cardiac catheterization guided by fetal transesophageal echocardiography to provide alternative approaches for human fetal cardiac intervention. METHODS AND RESULTS: We studied a total of nine fetal sheep (95 to 103 days of gestation; term = 145 to 150 days) and performed transumbilical fetal cardiac catheterization by a minimally invasive fetoscopic (n = 6) or an open fetal surgical approach (n = 3). Monitored by fetal transesophageal echocardiography, with an 8F or 10F, 10-MHz intravascular ultrasound catheter we placed guidewires and interventional catheters via the umbilical arterial route into the fetal heart. In three of the fetuses, we created supravalvar pulmonary artery stenosis by open fetal cardiac surgery After fetal and maternal recovery, we exteriorized these fetuses and performed open transumbilical fetal cardiac catheterization with successful pulmonary arterial angioplasty in two. Three fetuses survived fetoscopic transumbilical catheterization for 1 or 2 days and died most likely of blood loss after sheath dislodgment (n = 1) or removal (n = 2). By securing the sheath insertion site with a suture, we prevented sheath dislodgment and minimized bleeding during sheath removal in three fetuses. These fetuses then survived fetoscopic transumbilical fetal cardiac catheterization for 1 to 2 weeks before being killed. CONCLUSIONS: This study in fetal sheep demonstrates that fetoscopic and open transumbilical fetal cardiac catheterization are feasible and, guided by fetal transesophageal echocardiography, provide potential alternative approaches for human fetal cardiac intervention.

Entrapment of the popliteal artery.

Although entrapment of the popliteal artery is uncommon, it is an important cause of arterial insufficiency in younger patients. Accurate diagnosis depends on a high index of suspicion combined with dynamic noninvasive testing and "stress angiography." Although angiographic demonstration of medial deviation of the artery is diagnostic, absence of this finding does not exclude the diagnosis of entrapment of the popliteal artery. Positional angiography may be necessary in these instances. Surgical exploration should be performed by a posterior approach, since this facilitates identification of the precise anatomic variant while allowing easy arterial repair, if necessary. The condition of the popliteal popliteal artery must dictate the extent of the surgical procedure. If the popliteal artery is normal, then relief of the constricting lesion alone will suffice. If the artery appears diseased or is thrombosed, then myotomy and arterial reconstruction must be performed. This is best accomplished by bypass grafting using autogenous vein or artery. If thromboendarterectomy is used, the clinician can expect a higher percentage of acute postoperative thromboses.

The carotid web: a developmental anomaly of the brachiocephalic system.

A case of a congenital carotid web is reported. This lesion is believed to be a very rare anomaly of carotid development. The embryologic development of the brachiocephalic arteries is discussed. Anomalies of the brachiocephalic arteries including anomalies of origin from the aortic arch, atresia, and persistent communications between the carotid and vertebral system are reviewed.

[Idiopathic arterial occlusive disease (moyamoya); report of 4 cases]. / Doença arterial obstrutiva idiopatica (moyamoya); estudo de quatro casos.

Four cases of the occlusive arterial disease "moyamoya" type, are reported with comments on the clinical, roentgenological and embriological aspects. The clinical onset in all four cases was of isquemic type, in spite of different ages (2 adult male, one young adult female, 1 child female). Some particular symptoms are analysed, mainly the constant complaint of episodes in which the patient is, suddendly, extremely tired. The causes of this episodes are thought to be due to suddendly lowering of the cerebral perfusion in the disease. The importance of the radiological appearance is emphasyzed. The plain roentgenographic films, the site of the occlusion, the associated vascular malformations, the collateral circulation and the site of the vascular nest, are discussed. Some embriologic aspects of the etiology including the variable time onset of the pathologic process are also discussed.