PubMed Health⌕ Search

Biomedical subjects

Robert T Eberhardt

Publications and source records attributed to Robert T Eberhardt.

11 recordsLinked to original sources
PubMed2005

Differences in risk factors for lower extremity arterial occlusive disease.

BACKGROUND: Patients undergoing lower extremity revascularization have associated cardiovascular risks: smoking, hypertension, dyslipidemia, and diabetes. This study evaluated the impact of cardiovascular risk factors on proximal versus distal arterial occlusive disease in patients undergoing lower extremity revascularization as adjusted to a control group without vascular disease. STUDY DESIGN: We performed a retrospective, case-control study that included 151 patients undergoing lower extremity revascularization and 229 patients undergoing knee and hip replacement (controls). Risk factors were determined for each of three separate groups undergoing revascularization for different levels of occlusive disease: aortoiliac, superficial femoral, and popliteal-tibial. Comparisons to controls were tested using t-tests or chi-square tests and multiple logistic regression. RESULTS: Dyslipidemia was associated with a significant risk of aortoiliac (odds ratio [OR]=3.4; p=0.0006) and superficial femoral occlusion (OR=2.8; p=0.01) but was less strongly associated with popliteal-tibial occlusion (OR=2.1; p=0.09). Smoking was strongly associated with aortoiliac (OR=4.5; p=0.004) and superficial femoral disease (OR=4.6; p=0.0007) but not popliteal-tibial disease (OR=1.3; p=0.53). In contrast, diabetes mellitus and chronic renal insufficiency were strong risk factors for popliteal-tibial occlusion (OR=5.4, p=0.0002; OR=3.9, p=0.01, respectively), but were not significant risk factors for aortoiliac or superficial femoral occlusion. CONCLUSIONS: These data, which use revascularization level as a surrogate marker for lower extremity arterial disease, suggest that the risk factor profile for proximal disease differs from that of distal disease. These findings may reflect differences in the biology of disease and indicate that different risk factors have various anatomic influences on arterial disease formation.

Arterial Occlusive Diseases↗
PubMed2005

Low-renin hypertension with relative aldosterone excess is associated with impaired NO-mediated vasodilation.

Recent studies suggest that hypertension associated with low renin status and hyperaldosteronism is associated with increased risk for end-organ damage and cardiovascular events compared with other forms of hypertension. Additionally, experimental studies have demonstrated impaired nitric oxide-mediated bioactivity in these states. To investigate the relation between renin/aldosterone status and resistance vessel function, we examined plasma renin activity, serum aldosterone level, and forearm blood flow responses to the endothelium-dependent vasodilator methacholine and the endothelium-independent vasodilators sodium nitroprusside and verapamil using venous occlusion plethysmography in 130 volunteers (43 hypertensive, 87 normotensive). Low renin status was associated with impaired responses to methacholine and nitroprusside in patients with hypertension. Peak methacholine response was 8.7+/-5.6 mL/min per dL in the lowest renin quartile (0.1 to 0.3 ng/mL per hour) versus 14.3+/-7.3 mL/min per dL in the highest 3 renin quartiles combined (0.4 to 4.6 ng/mL per hour; P<0.001). Peak nitroprusside response was 5.6+/-2.3 mL/min per dL in the lowest renin quartile versus 13.3+/-4.1 mL/min per dL in the highest 3 renin quartiles combined (P<0.001). Blood pressure and other clinical characteristics were similar in all 4 quartiles. Vasodilator responses to verapamil did not relate to renin activity. Methacholine and nitroprusside responses did not relate to renin status in normotensive controls (P=0.34). Importantly, hypertensive patients with a high aldosterone/renin ratio also had impaired responses to methacholine. This study demonstrates that low-renin hypertension is associated with marked impairment of nitric oxide-mediated vasodilation of resistance vessels in the forearm vasculature of humans. This impairment could contribute to adverse outcomes in patients with low-renin hypertension and relative aldosterone excess.

Adult↗
PubMed2004

Vertebral artery dissection following intravascular catheter placement: a case report and review of the literature.

Vertebral artery dissections (VAD) are known to occur as a result of mechanical manipulations of the cervical region, traumatic injury, iatrogenic injury and are also known to arise spontaneously. We report a case of vertebral artery dissection following vertebral artery cannulation during a central line placement and review the literature. The patient underwent intravascular catheter placement that subsequently demonstrated arterial blood. Duplex ultrasound and computed tomographic (CT) scan confirmed vertebral artery cannulation. The catheter was removed at the bedside with pressure, and a subsequent duplex ultrasound scan revealed a vertebral artery dissection. There were no neurological sequelae. The patient was successfully anticoagulated with warfarin but died from unrelated complications. This case report describes the rare iatrogenic event of VAD and reviews its etiology, diagnosis, complications, and management.

Catheterization, Central Venous↗
PubMed2004

Cardiovascular morbidity and mortality in peripheral arterial disease.

The term peripheral arterial disease (PAD) is often used to describe atherosclerosis involving the arteries supplying the lower extremities. Potentially modifiable factors that predispose to the development and progression of both symptomatic and asymptomatic PAD include smoking, diabetes mellitus, hyperlipidemia, and hypertension. Since the same risk factors for PAD predispose to the development of systemic atherosclerosis, identification of PAD increases the likelihood of coexistent coronary heart and cerebrovascular disease. Even after adjustment for risk factors, PAD appears to increase the risk for ischemic manifestations involving these other vascular territories with about a 2-fold increase in myocardial infarction and perhaps stroke. The most dramatic consequence of PAD is impaired survival with a 2- to 3-fold increased risk of 5- to 10-year mortality. While the adverse cardiovascular and cerebrovascular complications are highest for persons with more severe PAD, there is still a significant risk in persons with mild and even asymptomatic disease. The focus in the management of PAD should be on early diagnosis and efforts to reduce the risk of adverse events including risk factor modification and antiplatelet therapy.

Arteriosclerosis↗
PubMed2003

Short- and long-term COX-2 inhibition reverses endothelial dysfunction in patients with hypertension.

Hypertension is associated with endothelial dysfunction that is attributable to oxidative stress and a proinflammatory state. Under these conditions, enhanced expression of cyclooxygenase-2 might lead to increased production of vasoconstrictor prostanoids and reactive oxygen species that reduce the bioavailability of endothelium-derived nitric oxide. To investigate the contribution of cyclooxygenase-2 activity to endothelial dysfunction in human hypertension, we evaluated brachial artery vasodilator function by ultrasound in 29 hypertensive patients before and after treatment with the selective cyclooxygenase-2 inhibitor celecoxib or placebo in a randomized, double-blind study. Brachial artery flow-mediated dilation improved from a baseline of 7.9+/-4.5% to 9.9+/-5.1% (P=0.005) 3 hours after the first dose and to 10.1+/-6.1% (P=0.006) after 1 week of treatment with celecoxib. In contrast, placebo treatment had no significant effect on flow-mediated dilation (8.1+/-4.4%, 8.3+/-3.5%, and 8.0+/-3.2%, respectively). Neither treatment altered nitroglycerin-mediated dilation, extent of reactive hyperemia, or baseline arterial diameter. Celecoxib treatment had no significant effect on the urinary concentrations of F2 isoprostane or thromboxane metabolites. However, urinary concentrations of the prostacyclin metabolite 2,3-dinor-6-ketoprostglandin F1alpha were significantly lower after 1 week of celecoxib treatment. Thus, cyclooxygenase-2 products contribute to endothelial dysfunction in hypertension, and treatment with a cyclooxygenase-2 inhibitor could have a beneficial effect in this setting. However, cyclooxygenase-2 inhibition also has an adverse effect on prostacyclin production that could promote thrombosis, and the net clinical consequences of improved endothelial function versus loss of prostacyclin merits further investigation.

Adult↗
PubMed2003

Sickle cell anemia is associated with reduced nitric oxide bioactivity in peripheral conduit and resistance vessels.

The purpose of the study was to examine endothelium-dependent and -independent vasodilation of conduit and resistance vessels in sickle cell anemia (HbSS). We measured the effects of intra-arterial infusion of methacholine, sodium nitroprusside, and NG-monomethyl-L-arginine (L-NMMA) on forearm blood flow using venous occlusion plethysmography in eight patients with HbSS and 11 HbAA controls. We assessed vasodilation of the conduit brachial artery using ultrasound in 17 patients with HbSS and 41 nonanemic controls. Forearm blood flow response to methacholine was similar in HbSS and HbAA, while the response to sodium nitroprusside was greater in those with HbSS. Nitric oxide synthase inhibition with L-NMMA attenuated methacholine-induced forearm blood flow to a lesser extent in HbSS compared to HbAA, suggesting diminished nitric oxide (NO) contribution to endothelium-dependent vasodilation. Flow-mediated and nitroglycerin-induced dilation were impaired in HbSS compared to controls and were not affected by the antioxidant vitamin C or the precursor substrate for NO synthesis L-arginine. NO bioactivity is reduced but differs in peripheral conduit and resistance vessels in HbSS. Resistance vessels have preserved response to exogenous NO donors but have diminished contribution of NO to endothelium-dependent vasodilation. Conduit vessels demonstrate impaired vasodilation to endogenous and exogenous NO.

Adult↗
PubMed2002

Heterozygous cellular glutathione peroxidase deficiency in the mouse: abnormalities in vascular and cardiac function and structure.

BACKGROUND: Oxidant stress has been implicated in the pathogenesis of atherothrombosis and other vascular disorders accompanied by endothelial dysfunction. Glutathione peroxidases (GPx) play an important role in the cellular defense against oxidant stress by utilizing glutathione (GSH) to reduce lipid hydroperoxides and hydrogen peroxide to their corresponding alcohols. Cellular GPx (GPx-1) is the principal intracellular isoform of GPx. We hypothesized that GPx-1 deficiency per se induces endothelial dysfunction and structural vascular abnormalities through increased oxidant stress. METHODS AND RESULTS: A murine model of heterozygous deficiency of GPx-1 (GPx(+/-)) was investigated to examine this hypothesis. Mesenteric arterioles in GPx-1(+/-) mice demonstrated vasoconstriction to acetylcholine compared with vasodilation in wild-type mice (maximal change in vessel diameter, -13.0+/-2.8% versus 13.2+/-2.8%, P<0.0001). We also noted an increase in the plasma and aortic levels of the isoprostane iPF(2alpha)-III, a marker of oxidant stress, in GPx-1(+/-) mice compared with wild-type mice (170.4+/-23 pg/mL plasma versus 98.7+/-7.1 pg/mL plasma, P<0.03; 11.7+/-0.87 pg/mg aortic tissue versus 8.2+/-0.55 pg/mg aortic tissue, P<0.01). Histological sections from the coronary vasculature of GPx-1(+/-) mice show increased perivascular matrix deposition, an increase in the number of adventitial fibroblasts, and intimal thickening. These structural abnormalities in the myocardial vasculature were accompanied by diastolic dysfunction after ischemia-reperfusion. CONCLUSIONS: These findings demonstrate that heterozygous deficiency of GPx-1 leads to endothelial dysfunction, possibly associated with increased oxidant stress, and to significant structural vascular and cardiac abnormalities. These data illustrate the importance of this key antioxidant enzyme in functional and structural responses of the mammalian cardiovascular system.

Animals↗
PubMed2002

Factors that predict site of outflow target artery anastomosis in infrainguinal revascularization.

INTRODUCTION: Lower extremity revascularization is indicated for limb salvage and incapacitating leg claudication. Many risk factors (age, hypertension, diabetes, tobacco use, dyslipidemia, etc) have been associated with atherosclerosis and the development of peripheral arterial occlusive disease. However, whether these risk factors or the surgical indication (claudication or limb salvage) influences the extent and location of infrainguinal disease and hence the target artery (distal anastomosis) is unclear. This study examines the risk factors and indication for infrainguinal revascularization with respect to the type of bypass performed. METHODS: Three hundred fifty-two infrainguinal revascularizations in 282 patients were retrospectively reviewed. Patient data, including demographics, cardiovascular risk factors, indications, types of revascularization, and perioperative complications and mortality, were collected. Data were analyzed with t test, chi(2) test, Fisher exact test, and multiple logistic regression. RESULTS: The indication for surgical revascularization was claudication in 70 patients and limb salvage in 282. The likelihood of a popliteal anastomosis (above or below knee) versus a tibial or pedal anastomosis was decreased with increasing age (P =.002) and diabetes (P =.0001), and smoking increased the likelihood (P =.056). However, popliteal bypass also was strongly associated with claudication as the surgical indication (odds ratio [OR], 8.7; P =.0001), and 90% of the claudicant group had undergone popliteal anastomosis. Claudication and popliteal anastomosis were both linked to smoking; 97% of subjects who underwent operation for claudication were smokers compared with 75% of subjects who underwent tibial or pedal anastomosis for limb salvage (P =.001). After adjustment for indication, the likelihood of popliteal anastomosis was still decreased with diabetes (OR, 0.46; P =.002), and age had a borderline significant effect (P =.077). When the analysis was stratified by indication for surgery, the likelihood of popliteal bypass among patients who underwent operation for claudication was not influenced by age, diabetes, or smoking. However, within the subset of patients who underwent operation for limb salvage, the likelihood of any popliteal anastomosis was diminished by diabetes (OR, 0.50; P =.007), age (OR, 0.968 per year; P =.01), and chronic renal insufficiency (OR, 0.476; P =.04). CONCLUSION: Infrainguinal peripheral arterial occlusive disease is not a homogenous disease entity. Claudication and limb salvage are associated with two distinct patterns of vascular disease with different risk factors. Patients who undergo operation for claudication are seen at an earlier age, have a high prevalence of smoking, and have proximal disease and a greater likelihood of a popliteal anastomosis. In contrast, patients for limb salvage are less likely to have a popliteal bypass, favoring a more distal target outflow anastomosis that is strongly influenced by advanced age, diabetes, and chronic renal insufficiency.

Aged↗
PubMed2002

Cellular glutathione peroxidase deficiency and endothelial dysfunction.

Cellular glutathione peroxidase (GPx-1) is the most abundant intracellular isoform of the GPx antioxidant enzyme family. In this study, we hypothesized that GPx-1 deficiency directly induces an increase in vascular oxidant stress, with resulting endothelial dysfunction. We studied vascular function in a murine model of homozygous deficiency of GPx-1 (GPx-1(-/-)). Mesenteric arterioles of GPx-1(-/-) mice demonstrated paradoxical vasoconstriction to beta-methacholine and bradykinin, whereas wild-type (WT) mice showed dose-dependent vasodilation in response to both agonists. One week of treatment of GPx-1(-/-) mice with L-2-oxothiazolidine-4-carboxylic acid (OTC), which increases intracellular thiol pools, resulted in restoration of normal vascular reactivity in the mesenteric bed of GPx-1(-/-) mice. We observed an increase of the isoprostane iPF(2alpha)-III, a marker of oxidant stress, in the plasma and aortas of GPx-1(-/-) mice compared with WT mice, which returned toward normal after OTC treatment. Aortic sections from GPx-1(-/-) mice showed increased binding of an anti-3-nitrotyrosine antibody in the absence of frank vascular lesions. These findings demonstrate that homozygous deficiency of GPx-1 leads to impaired endothelium-dependent vasodilator function presumably due to a decrease in bioavailable nitric oxide and to increased vascular oxidant stress. These vascular abnormalities can be attenuated by increasing bioavailable intracellular thiol pools.

Animals↗