Infrainguinal occlusive disease: endovascular intervention is the first line therapy.

The preferred treatment of infrainguinal occlusive disease at many centers has undergone a paradigm shift from open bypass to endovascular intervention as the first-line therapeutic modality. Our own experience supports a percutaneous first approach. Though skeptics initially cited lower primary patency rates for angioplasty when compared with bypass, more recent studies have shown favorable secondary patencies nearly challenging that of bypass. The need for repeat endovascular intervention to achieve a higher secondary patency is not a major deterring factor because most procedures are associated with a short hospital stay and a relatively low rate of complication. The risk is low and this complex group of patients can tolerate minimally invasive reinterventions well. The longevity of this patient population is generally short, and consequently less durable outcomes may be acceptable. Patients do require close follow-up with early treatment of restenosis. However, there appears to be a decreased cost of intervention when compared with surgery. Furthermore, the functional outcomes and quality of life appear more optimal with angioplasty. The concern that angioplasty may preclude future surgical intervention by damaging the distal bypass target has not borne true. It is unusual for a percutaneous therapy to eliminate the possibility of a bypass should the endovascular approach not be successful. Finally, advances in techniques and devices may herald improved outcomes because percutaneous therapy in the periphery is still in the early stages of its maturation. Thus, endovascular intervention has become an established, as well as a developed method for treating peripheral arterial occlusive disease and should be considered the first-line therapeutic modality for patients with.lower extremity vascular disease.

Assessing the effectiveness of endografts: clinical and experimental perspectives.

The increasing use of endografts to treat abdominal aortic aneurysms has prompted the need for improved postoperative imaging and surveillance. Although patients benefit from decreased morbidity with endovascular repair compared with open abdominal aortic aneurysm repair, the long-term outcome of stent repair has yet to be fully determined. The persistence of endoleaks highlights the need for close follow-up, particularly because this may lead to aneurysm rupture, even after endograft repair. The current mainstay of assessing the healing of endografts is obtaining serial helical computed tomography angiography (CTA) to identify endoleaks, graft migration, thrombosis, and structural failure. CTA is not completely effective at identifying endoleaks and predicting aneurysm rupture, however. Other modalities have been studied to improve on current imaging methods, including three-dimensional CTA with volumetric analysis, contrast-enhanced duplex ultrasound imaging, cine magnetic resonance angiography, and explant analysis. In vitro and large-animal models of abdominal aortic aneurysm have also been developed to study the pathophysiology and treatment response of aneurysm exclusion. Thus, clinical and experimental models of endograft healing are attempting to define the optimal method of postoperative surveillance of endovascular repair.

Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury.

BACKGROUND: The beneficial effects of reperfusion therapies have been limited by the amount of ischemic damage that occurs before reperfusion. To enable development of interventions to reduce cell injury, our research has focused on understanding mechanisms involved in cardiac cell death after ischemia/reperfusion (I/R) injury. In this context, our laboratory has been investigating the role of the receptor for advanced-glycation end products (RAGE) in myocardial I/R injury. METHODS AND RESULTS: In this study we tested the hypothesis that RAGE is a key modulator of I/R injury in the myocardium. In ischemic rat hearts, expression of RAGE and its ligands was significantly enhanced. Pretreatment of rats with sRAGE, a decoy soluble part of RAGE receptor, reduced ischemic injury and improved functional recovery of myocardium. To specifically dissect the impact of RAGE, hearts from homozygous RAGE-null mice were isolated, perfused, and subjected to I/R. RAGE-null mice were strikingly protected from the adverse impact of I/R injury in the heart, as indicated by decreased release of LDH, improved functional recovery, and increased adenosine triphosphate (ATP). In rats and mice, activation of the RAGE axis was associated with increases in inducible nitric oxide synthase expression and levels of nitric oxide, cyclic guanosine monophosphate (cGMP), and nitrotyrosine. CONCLUSIONS: These findings demonstrate novel and key roles for RAGE in I/R injury in the heart. The findings also demonstrate that the interaction of RAGE with advanced-glycation end products affects myocardial energy metabolism and function during I/R.

RAGE axis: Animal models and novel insights into the vascular complications of diabetes.

Receptor for AGE (RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. Engagement of RAGE by its signal transduction ligands evokes inflammatory cell infiltration and activation in the vessel wall. In diabetes, when fueled by oxidant stress, hyperglycemia, and superimposed stresses such as hyperlipidemia or acute balloon/endothelial denuding arterial injury, the ligand-RAGE axis amplifies vascular stress and accelerates atherosclerosis and neointimal expansion. In this brief synopsis, we review the use of rodent models to test these concepts. Taken together, our findings support the premise that RAGE is an amplification step in vascular inflammation and acceleration of atherosclerosis. Future studies must rigorously test the potential impact of RAGE blockade in human subjects; such trials are on the horizon.

RAGE and its ligands: a lasting memory in diabetic complications?

The complications of diabetes are myriad and represent a rising cause of morbidity and mortality, particularly in the Western world. The update of the Diabetes Control and Clinical Trials Group/Epidemiology of Diabetes Interventions and Complications Research Group (DCCT/EDIC) suggested that previous strict control of hyperglycaemia was associated with reduced carotid atherosclerosis compared to conventional treatment, even after levels of glycosylated haemoglobin between the two treatment groups became indistinguishable. These intriguing findings prompt the key question, why does the blood vessel 'remember'? This review focuses on the hypothesis that the ligand/RAGE axis contributes importantly to glycaemic 'memory'. Studies in rodent models of diabetes suggest that blockade or genetic modification of RAGE suppress diabetes-associated progression of atherosclerosis, exaggerated neointimal expansion consequent to acute arterial injury, and cardiac dysfunction. We propose that therapeutic RAGE blockade will intercept maladaptive diabetes-associated memory in the vessel wall and provide cardiovascular protection in diabetes.