Endogenous angiotensin II in the regulation of hypoxic pulmonary vasoconstriction in anaesthetized dogs

INTRODUCTION: The role played by several vasoactive mediators that are synthesized and released by the pulmonary vascular endothelium in the regulation of hypoxic pulmonary vasoconstriction (HPV) remains unclear. As a potent vasoconstrictor, angiotensin II could be involved. We tested the hypothesis that angiotensin-converting enzyme inhibition by enalaprilat and type 1 angiotensin II receptor blockade by candesartan would inhibit HPV. METHODS: HPV was evaluated in anaesthetized dogs, with an intact pulmonary circulation, by examining the increase in the Ppa–Ppao gradient (mean pulmonary artery pressure minus occluded pulmonary artery pressure) that occurred in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Plasma renin activity and angiotensin II immunoreactivity were measured to determine whether activation or inhibition of the renin–angiotensin system was present. RESULTS: Administration of enalaprilat and candesartan did not affect the Ppa–Ppao gradient at baseline or during hypoxia. Plasma renin activity and angiotensin II immunoreactivity increased during hypoxia, and subsequent measurements were consistent with effective angiotensin-converting enzyme inhibition after administration of enalaprilat, and with angiotensin receptor blockade after administration of candesartan. CONCLUSION: These results suggest that, although the renin–angiotensin system was activated in hypoxia, angiotensin II is not normally involved in mediating acute HPV

Myocardial infarction stabilization by cell-based expression of controlled Vascular Endothelial Growth Factor levels

Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)‐based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell‐based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF‐expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS‐ purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia

Humoral mediation of pulmonary hypertension in a congenital model of systemo-to-pulmonary shunt in piglet

No abstractDoctorat en Sciences médicalesinfo:eu-repo/semantics/nonPublishe

Humoral mediation of pulmonary hypertension in a congenital model of systemo-to-pulmonary shunt in piglet

No abstractDoctorat en Sciences médicalesinfo:eu-repo/semantics/nonPublishe

Pathobiology of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a syndrome of dyspnea, fatigue, chest pain and syncope defined by an increase in pulmonary vascular resistance (PVR) of unknown cause. The pathobiology of PAH remains incompletely understood. The gene of the idiopathic form of PAH (IPAH) has been located on chromosome 2, and shown to present mutations of a sequence that encodes for a transforming growth factor receptor, bone morphogenenetic protein receptor 2 (BMPR2). Severe pulmonary hypertension is associated with an increased expression of the angiogenic factor, angiopoietin-1, which shuts off the expression of BMPR1A, a transmembrane protein necessary for BMPR2 signalling, and thereby causes pulmonary artery smooth muscle cell proliferation. Additional biological abnormalities have been identified at all pulmonary arterial wall compartments of PAH patients. The endothelium produces an excess of endo-thelin, a potent vasoconstrictor and mitogenic mediator, while synthesis and release of antagonistic prostacyclin and nitric oxide is decreased. Pulmonary vascular smooth muscle cells present with an increased expression of a serotonin transporter, allowing for vasoconstrictive and mitogenic effects of increased circulating serotonin, and also show an increased expression of voltage-dependent potassium channels, which also promotes vasoreactivity and proliferation. The adventitial matrix bound metalloprotases appear to be activated in relation to increased serine elastase, leading to increased production of tenascin, a potent mitogen. While none of these abnormalities isolately explains PAH, their identification has already led to efficient therapeutic interventions, including the administration of prostacyclin derivatives and anti-endothelin compounds.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Pathobiology of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a syndrome of dyspnea, fatigue, chest pain and syncope defined by an increase in pulmonary vascular resistance (PVR) of unknown cause. The pathobiology of PAH remains incompletely understood. The gene of the idiopathic form of PAH (IPAH) has been located on chromosome 2, and shown to present mutations of a sequence that encodes for a transforming growth factor receptor, bone morphogenenetic protein receptor 2 (BMPR2). Severe pulmonary hypertension is associated with an increased expression of the angiogenic factor, angiopoietin-1, which shuts off the expression of BMPR1A, a transmembrane protein necessary for BMPR2 signalling, and thereby causes pulmonary artery smooth muscle cell proliferation. Additional biological abnormalities have been identified at all pulmonary arterial wall compartments of PAH patients. The endothelium produces an excess of endo-thelin, a potent vasoconstrictor and mitogenic mediator, while synthesis and release of antagonistic prostacyclin and nitric oxide is decreased. Pulmonary vascular smooth muscle cells present with an increased expression of a serotonin transporter, allowing for vasoconstrictive and mitogenic effects of increased circulating serotonin, and also show an increased expression of voltage-dependent potassium channels, which also promotes vasoreactivity and proliferation. The adventitial matrix bound metalloprotases appear to be activated in relation to increased serine elastase, leading to increased production of tenascin, a potent mitogen. While none of these abnormalities isolately explains PAH, their identification has already led to efficient therapeutic interventions, including the administration of prostacyclin derivatives and anti-endothelin compounds

Giant true aneurysm of superficial femoral artery in patient with multiple atherosclerotic aneurysms: A case report.

True atherosclerotic aneurysms of superficial femoral artery (SFA) are rare and often associated with other peripheral or aortic aneurysms. We report the case of a 84-year-old patient presenting a giant degenerative ruptured aneurysm of the superficial femoral artery. The patient underwent successful aneurysm resection and bypass grafting, with a satisfying long-term follow-up and patency of the graft. The patient was also operated one year before, for a ruptured aneurysm of the abdominal aorta. This case report is rare, because we described a case of patient with multiple atherosclerotic aneurysms, who present, for the second time, a life threating ruptured aneurysm. In this report, we see extreme and rapid evolution of SFA Aneurysm before being symptomatic. Degenerative aneurysms of the lower extremity most commonly involve the popliteal artery, while they are rarely detected in the femoral region (Leon et al., 2008). In this region, aneurysms most frequently involve the common femoral artery (CFA), whereas true aneurysms of the superficial femoral artery (SFA) represent only 15% to 25% of femoral arterial aneurysms [1-5]. Degenerative aneurysms of the SFA display peculiar characteristics (in terms of clinical onset, diagnostic timing, and clinical behavior) so that they differ from other peripheral aneurysms. Because the relative rarity of this location, our case report can be useful to participate to increase the number of reported cases, and define the therapeutic approach for this rare location

A rare case of aortic endograft infection by Francisella tularensis: A case report.

INTRODUCTION AND IMPORTANCE: endovascular repair is an alternative to open repair for abdominal aortic aneurysms (AAA), which lowers morbidity and mortality but may presents infectious complications. Endograft infection is a rare but serious life-threatening condition with a mortality rate up to 50 %. We reported a case of aortic endograft infection by Francisella tularensis, rare and highly virulent gram-negative coccobacillus known for use in bioterrorism. CASE PRESENTATION: A 79-year-old man presented with asthenia, weight loss, night sweats and one episode of fever. In 2007, he underwent aorto-bi-iliac endograft repair for AAA without any complication. The diagnostic workup showed some signs of inflammation, but negative blood cultures and no sign of infection on CT scan. The combination of positron emission tomography (PET) and white blood cell (WBC) scintigraphy led to the diagnosis of aortic endograft infection. The management was antimicrobial therapy and surgery. Perioperative analysis shows the presence of Francisella Tularensis. DISCUSSION AND CONCLUSIONS: Aortic endograft infection is a serious complication with a high mortality rate. Its diagnosis may be difficult, but the combination of WBC scintigraphy and PET scan may improve identification of the infection, even if blood cultures and CT scan are negative. The gold standard treatment is removal of the endograft, debridement, and in situ reconstruction along with antibacterial therapy

Surgical Resection of Painless Carotid Body Tumour without Preoperative Embolization: A Case Report and Review of Literature

Paragangliomas are rare tumors representing a therapeutic challenge. We present a case report of surgical resection of carotid body tumor without preoperative embolization. Our therapeutic attitude is based on controversial benefits of the embolization for those tumors. The major indication for the preoperative embolization is to reduce intraoperative blood loss, but this benefit is not demonstrated. Also, because the relative rarity of this tumor, the confounding factors relative to the surgeon and radiologist experience, no randomized trial can be performed. So, our case report can be useful to participate to increase the number of reported cases, and define the therapeutic approach for this rare tumor

Complications de la transplantation pulmonaire :Complications péri-opératoires, rejet aigu et chronique

In 2009 lung transplantation is a valuable therapeutic option for a spectrum of end-stage pulmonary diseases. To many patients who are dying, lung transplantation offers a new and normal life for several years. However, lung transplantation is a major surgical intervention associated with a significant early mortality. Moreover, matching according to the major human histocompatibilty antigens is impossible, exposing the recipient to an increased risk of acute and chronic rejection. Chronic rejection and its clinical corollary the bronchiolitis obliterans syndrome, is the main cause of death medium and long term. The immunosuppressive treatment administered in order to prevent or stabilize this complication induces a number of potentially severe complications including infection, malignancies, and cardio-vascular, metabolic and renal complications which not only limit autonomy and quality of life, but also cause death in a number of long term survivors. A better understanding of the precise mechanisms underlying the development of the bronchiolitis obliterans syndrome and the development of specific preventive or therapeutic strategies will be key elements for the improvement of long term survival. The control of this main cause of death will allow individual tailoring of the immunosuppressive therapy and decrease the incidence of infectious and metabolic complications.SCOPUS: re.jinfo:eu-repo/semantics/publishe