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Biomedical subjects

Valentin Fuster

Publications and source records attributed to Valentin Fuster.

At least 73 records · Page 4Linked to original sources
PubMed2005

A canine model to study the significance and hemodynamics of type II endoleaks.

OBJECTIVE: The clinical significance of Type 2 endoleak after endovascular repair of abdominal aortic aneurysms (AAA) remains incompletely delineated. This study describes the development of a novel canine model that allows for continuous monitoring of intraaneurysmal pressure in the setting of Type 2 endoleak. METHODS: Infrarenal AAA were created in 10 mongrel dogs by implanting a prosthetic aneurysm containing an intraluminal, solid-state, strain gauge pressure transducer which is able to measure pressures in both solid and liquid media. A segment of native aorta with two or more patent side branch vessels was reimplanted into the prosthetic aneurysm using a Carrel patch. Four animals had two lumbar vessels implanted; two had two lumbar vessels and the caudal mesenteric artery implanted, and four control animals had no vessels reimplanted. Retrograde flow in the aneurysmal side branches caused a Type 2 endoleak after the aneurysm was excluded from antegrade flow by deploying a stent graft. Both systemic and intra-sac pressures were measured daily for up to 90 days after endovascular exclusion and indexed to systemic pressure. Endoleak patency and flow were assessed with digital subtraction angiography, duplex ultrasound, and cine-magnetic resonance angiography (MRA). Histological characterization of the intraaneurysmal contents was performed. RESULTS: Before endovascular exclusion, the systolic, mean arterial, and pulse pressure within the aneurysmal sac closely matched that of the systemic circulation (systolic, 0.96 +/- 0.22; mean, 0.94 +/- 0.21; pulse pressure, 0.97 +/- 0.22) (R value, 0.97). Endovascular exclusion in animals with no collateral side branch vessels resulted in no endoleak and significantly reduced intraaneurysmal pressure when compared to systemic pressure, with systolic, mean arterial, and pulse pressure 0.172 +/- 0.05, 0.137 +/- 0.05, and 0.098 +/- 0.02, respectively (P < 0.001). In animals with Type 2 endoleaks, the pressures were lower than systemic pressure, but statistically significant in their difference from the control group. The systolic pressure of those with Type 2 endoleaks was 0.702 +/- 0.048; mean arterial pressure was 0.784 +/- 0.028, and pulse pressure was 0.406 +/- 0.031 when indexed to systemic pressure (P < 0.001). Cine-MRA and Duplex ultrasound documented persistent patency of the Type 2 endoleaks throughout the study period in animals with multiple side branches. CONCLUSION: Intraaneurysmal pressure in the setting of Type 2 endoleaks may be accurately determined using this canine model. Intraaneurysmal pressure is maintained at a significant level in the context of this retrograde collateral perfusion, suggesting that persistent Type 2 endoleaks are of clinical significance. This model may serve to allow further evaluation and characterization of Type 2 endoleaks.

Angiography, Digital Subtraction↗
PubMed2005

Treatment of type II endoleaks with a novel polyurethane thrombogenic foam: induction of endoleak thrombosis and elimination of intra-aneurysmal pressure in the canine model.

OBJECTIVE: The clinical significance and treatment of retrograde collateral arterial perfusion of abdominal aortic aneurysms after endovascular repair (type II endoleak) have not been completely characterized. A canine abdominal aortic aneurysm model of type II endoleak with an implanted pressure transducer was used to evaluate the use of polyurethane foam to induce thrombosis of type II endoleaks. The effect on endoleak patency, intra-aneurysmal pressure, and thrombus histology was studied. METHODS: Prosthetic aneurysms with an intraluminal, solid-state, strain-gauge pressure transducer were created in the infrarenal aorta of 14 mongrel dogs. Aneurysm side-branch vessels were reimplanted into the prosthetic aneurysm of 10 animals by using a Carrel patch. Type II (retrograde) endoleaks were created by excluding the aneurysm from antegrade perfusion with an impermeable stent graft. Thrombosis of the type II endoleak was induced by implantation of polyurethane foam into the prosthetic aneurysm sac of four animals. Six animals with type II endoleaks were not treated. In four control animals, no collateral side branches were reimplanted, and therefore no endoleak was created. Intra-aneurysmal and systemic pressures were measured daily for 60 to 90 days after the implantation of the stent graft. Endoleak patency and flow were assessed during surgery and at the time of death by using angiographic imaging and duplex ultrasonography. Histologic analysis of the intra-aneurysmal thrombus was also performed. RESULTS: Intra-aneurysmal pressure values are indexed to systemic pressure and are represented as a percentage of the simultaneously obtained systemic pressure, which has a value of 1.0. All six animals with untreated type II endoleaks maintained patency of the endoleak and side-branch arteries throughout the study period. Compared with control aneurysms that had no endoleak, animals with patent type II endoleaks exhibited significantly higher intra-aneurysmal pressurization (systolic pressure: patent type II endoleak, 0.702 +/- 0.283; control, 0.172 +/- 0.091; P < .001; mean pressure: endoleak, 0.784 +/- 0.229; control, 0.137 +/- 0.102; P < .001; pulse pressure: endoleak, 0.406 +/- 0.248; control, 0.098 +/- 0.077; P < .001; P < .001 for comparison for all groups by analysis of variance). Treatment of the type II endoleak with polyurethane foam induced thrombosis of the endoleak and feeding side-branch arteries in all four animals with type II endoleaks. This resulted in intra-aneurysmal pressures statistically indistinguishable from the controls (systolic pressure, 0.183 +/- 0.08; mean pressure, 0.142 +/- 0.09; pulse pressure, 0.054 +/- 0.04; not significant). Angiography and histology documented persistent patency up to the time of death (mean, 64 days) for untreated type II endoleaks and confirmed thrombosis of polyurethane foam-treated endoleaks in all cases. CONCLUSIONS: Untreated type II endoleaks were associated with intra-aneurysmal pressures that were 70% to 80% of systemic pressure. Treatment with polyurethane foam resulted in a reduction of intra-aneurysmal pressure to a level that was indistinguishable from control aneurysms that had no endoleak. CLINICAL RELEVANCE: Endovascular repair of abdominal aortic aneurysms is dependent on the successful exclusion of the aneurysm from arterial circulation. Type II endoleaks originate from retrograde flow into the aneurysm sac. This study demonstrates the use of polyurethane foam to induce thrombosis in a canine model of a type II endoleak, thereby reducing intra-aneurysmal pressure to levels similar to levels in animals without endoleaks. This approach may be a strategy for future treatment of type II endoleaks.

Animals↗
PubMed2005

Drug insight: cyclo-oxygenase 2 inhibitors and cardiovascular risk--where are we now?

Cyclo-oxygenase (COX) 1 mediates the production of thromboxane A2 in platelets, leading to platelet aggregation and vasoconstriction. Conversely, COX2 catalyzes endothelial prostacyclin synthesis, which effectively counteracts thromboxane A2, triggering vasodilation and platelet inhibition. Selective COX2 inhibitors decrease prostacyclin production, potentially disrupting homeostasis and creating a prothrombotic state. The VIGOR study findings of increased cardiovascular risk with rofecoxib were subsequently confirmed by large meta-analyses, observational studies and recent APPROVe trial publication. The APC trial findings of increased cardiovascular risk with Celebrex (celecoxib) conflict with those in the ADAPT trial, the upcoming PreSAP publication, a case-control study by Graham et al. and prior large clinical trials, meta-analyses and observational studies of this drug. Therefore, while an adverse class effect is a possibility for COX2 inhibitors, the published data are inconsistent. Baseline cardiovascular risk in patients might contribute significantly to these findings. In light of the negative Vioxx (rofecoxib) publicity, however, COX2 inhibitors might forever remain underinvestigated. The relative selectivity of these compounds for COX2 is extremely variable, casting significant doubt on the class-effect hypothesis. Improved endothelial function has also been reported with celecoxib, leading to endothelium-dependent vasodilation, and associated decreases in C-reactive protein and LDL cholesterol. The addition of meloxicam to low-dose aspirin and heparin has improved clinical outcomes after acute coronary syndromes. These are the first studies suggesting improvement in endothelial function and reduction of inflammation with COX2 inhibition. Thus, more randomized controlled trials are needed to study the relative cardiovascular effects of different COX2 inhibitors, alone and in combination with aspirin.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Sudden cardiac death: mechanisms, therapies and challenges.

Sudden cardiac death (SCD) is the leading cause of cardiac death in the US. In the past few years, intensive efforts have been made to expand public awareness of SCD and to increase our understanding of its pathophysiology, medical treatment options and device therapy. Significant advances have been made in our ability to prevent SCD in both primary and secondary health care. Two critical issues remain, however: the identification of patients who would benefit from such therapies, and how to achieve even greater prevention, especially primary prevention. The goal of this article is to provide a review of the topic of SCD in the setting of abnormal myocardial substrate, to outline the techniques that are useful in identifying patients at risk, and available treatment options.

Anti-Arrhythmia Agents↗
PubMed2005

The importance of end-systole for optimal reconstruction protocol of coronary angiography with 16-slice multidetector computed tomography.

OBJECTIVES: Multidetector-row computed tomography coronary images are usually analyzed in mid-diastole (MD). Because of slow coronary motion also in end-systole (ES), we evaluated the impact on image quality of including ES images and defined an efficient reconstruction protocol. MATERIAL AND METHODS: In 50 coronary multidetector-row computed tomography studies, 9 reconstructions (at 10% increments of the RR interval) were graded for image quality. Multiple combinations of reconstructions were compared. RESULTS: MD (60-70% of the RR interval) offered the best image quality. In 44% patients, the best reconstruction for >or=1 coronary was found in ES (20-30%). Their heart rate was higher (68.2+/-9.9 bpm vs. 59.2+/-8.8 bpm, P=0.0014). Combining ES and MD consistently offered superior image quality and less nonevaluable vessels than even larger numbers of diastolic reconstructions alone. A combination of 2-3 reconstructions was most efficient. Adding more reconstructions did not significantly improve results. CONCLUSIONS: Combining ES and MD reconstructions reduces nonevaluable coronary arteries, particularly with higher heart rates. A protocol including 2-3 reconstructions is the most efficient.

Adolescent↗
PubMed2004

New aspects in the pathogenesis of diabetic atherothrombosis.

Diabetes mellitus is increasing worldwide, resulting from the interaction of obesity, inflammation, and hyperglycemia. Activated immunity and cytokine production lead to insulin resistance and other components of the metabolic syndrome, establishing the link between diabetes and atherosclerosis. Hyperglycemia-induced endothelial dysfunction is mediated by increased oxidative stress, a promoter of adventitial inflammation and vasa vasorum neovascularization in experimental models of diabetic atherosclerosis. Recent studies have documented increased inflammation, neovascularization, and intraplaque hemorrhage in human diabetic atherosclerosis. This inflammatory microangiopathic process is independently associated with plaque rupture, leading to coronary thrombosis. Tissue factor, the most potent trigger of the coagulation cascade, is increased in diabetic patients with poor glycemic control. Circulating tissue factor microparticles are also associated with apoptosis of plaque macrophages, closing the link among inflammation, plaque rupture, and blood thrombogenicity. High-density lipoproteins, responsible for free cholesterol removal, are reduced in patients with insulin resistance and diabetes. High-density lipoprotein therapy leads to a significant decrease in plaque macrophages and increase in smooth-muscle cells. These beneficial effects may be responsible for coronary plaque stabilization in patients treated with recombinant Apolipoprotein A-I Milano/phospholipid complex. Finally, peroxisomal proliferator-activated receptors (PPARs) are now considered the nuclear transcriptional regulators of atherosclerosis. Three subfamilies, including PPAR-alpha, -delta, and -gamma, have been identified with crucial roles in lipid metabolism, plaque inflammation, expression of adhesion molecules and cytokines, and regulation of matrix metalloproteinases. Multiple experimental studies have documented plaque stabilization with PPAR-gamma agonists, a group of medications holding great promise in the treatment of diabetes atherosclerosis.

Arteriosclerosis↗