PubMed Health⌕ Search

Biomedical subjects

Alan B Lumsden

Publications and source records attributed to Alan B Lumsden.

At least 55 records · Page 3Linked to original sources
PubMed2005

Effects of progesterone and estrogen on endothelial dysfunction in porcine coronary arteries.

BACKGROUND: The effects of hormone replacement therapy (HRT) on the vascular endothelium have been controversial. In this study, we determined the effects of HRT on endothelium-dependent relaxation in a porcine coronary artery model. METHODS: Coronary artery rings harvested from female swine were incubated as controls or with estrogen (10(-9), 10(-8), 10(-7) g/L), progesterone (1 x 10(-6), 1 x 10(-5), 5 x 10(-5) g/L), or a combination of the two (10(-8)g/L estrogen, 1 x 10(-5)g/L progesterone). After 24 h in tissue culture, the rings were tested on a myograph system to measure contraction and endothelium-dependent relaxation. Myograph analysis was performed with the thromboxane A2 analogue U46619 for contraction and bradykinin or sodium nitroprusside for relaxation. Nitric oxide synthase (eNOS) levels were determined by immunohistochemistry. Levels of superoxide anion in the progesterone or estrogen treated tissues were assessed by lucigenin-enhanced chemiluminescence analysis. RESULTS: In response to 10(-7)M bradykinin, porcine coronary artery rings treated with 1 x 10(-6), 1 x 10(-5) and 5 x 10(-5) g/L of progesterone showed a significant reduction in endothelium-dependent vasorelaxation by 36%, 45%, and 68%, respectively, as compared to controls (P <0.05). However, rings treated with estrogen showed no significant difference as compared to controls. Furthermore, estrogen treatment with progesterone reversed the effect of progesterone, showing no difference in vessel relaxation as compared to controls. There were no differences in endothelium-independent vasorelaxation (sodium nitroprusside) or in smooth muscle contractility (U46619) between the control and the hormone-treated groups. The eNOS immunoreactivity was reduced in progesterone-treated coronary artery rings. Furthermore, coronary endothelium exposed to progesterone showed a 59% increase in superoxide anion production, while estrogen produced a 67% decrease when compared to controls (P <0.05 for both). CONCLUSION: This data suggests that the progesterone component of HRT has a detrimental influence on endothelium-dependent relaxation. This effect appears to be related to decreased eNOS levels, as well as increased consumption of NO by superoxide anion in the endothelium of tissues exposed to progesterone. Estrogen can block progesterone-induced endothelial dysfunction and superoxide anion production in the pig coronary artery model.

Animals↗
PubMed2005

Adipocyte-derived cytokine resistin causes endothelial dysfunction of porcine coronary arteries.

OBJECTIVE: Resistin, a novel adipocyte-derived cytokine, is involved in the development of insulin resistance and diabetes mellitus. In this study, we determined whether resistin could affect vasomotor function, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in porcine coronary arteries. METHODS: Porcine coronary arteries were treated with resistin or antioxidant seleno-L-methionine (SeMet). Vasomotor function was studied by using a myograph system. Levels of superoxide anion (O 2 - ) were detected by the lucigenin-enhanced chemiluminescence method. The eNOS mRNA and protein levels were determined by real-time polymerase chain reaction and immunohistochemistry, respectively. Culture of isolated porcine coronary artery endothelial cells (PCAECs) was also included. RESULTS: Endothelium-dependent relaxation in response to bradykinin was reduced by 15% and 30% for the rings treated with 10 and 40 ng/mL of resistin, respectively, as compared with controls ( P < .05). Endothelium-independent relaxation in response to sodium nitroprusside (SNP) was also reduced by 11% after treatment with 40 ng/mL of resistin ( P < .05). The O 2 - level was increased in the 40 ng/mL resistin-treated vessels by 88% as compared with controls ( P < .05). SeMet reversed these effects. The eNOS mRNA levels in PCAEC cultures treated with resistin (10 and 40 ng/mL) were decreased by 27% and 55%, respectively ( P < .05) and by 39% in the endothelial cells purified from porcine coronary artery rings after treatment with 40 ng/mL of resistin ( P < .05). Immunoreactivity of eNOS in the resistin-treated vessel rings was also substantially reduced. CONCLUSIONS: Resistin reduces the endothelium-dependent and endothelium-independent vasorelaxation. This effect is associated with increased superoxide radical production, decreased eNOS expression, and is effectively reversed by the antioxidant SeMet. CLINICAL RELEVANCE: Obesity has been considered to be an independent risk factor for coronary artery disease and other vascular lesions. Resistin is a newly discovered adipocyte-derived cytokine, and its plasma levels are increased in obese individuals. However, it is not clear whether resistin could directly contribute to vascular disease formation. This study showed that resistin can cause endothelial dysfunction in porcine coronary arteries through oxidative stress and down-regulation of eNOS. Thus, this study may suggest a new mechanism of obesity-associated vascular disease and that antioxidants may effectively prevent vascular disease in obese individuals.

Animals↗
PubMed2005

Ginsenoside Rb1 blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries.

OBJECTIVE: Homocysteine (Hcy) is an independent risk factor for atherosclerosis. This study investigates the effects of ginsenoside Rb1, a major constituent of ginseng, on Hcy-induced endothelial dysfunction and molecular changes in porcine coronary arteries. METHODS: The coronary arteries were harvested from pig hearts and cut into 5-mm ring segments, which were then divided into six groups, including control, Hcy alone (50 microM), low-dose (1 microM) or high-dose (10 microM) Rb1 alone, and Hcy plus low-dose or high-dose Rb1. After 24-hour incubation, the rings were analyzed for vasomotor function in response to thromboxane A2 analog U46619, bradykinin, and sodium nitroprusside (SNP), respectively. In addition, superoxide anion was assessed by lucigenin-enhanced chemiluminescence analysis. Endothelial nitric oxide synthase (eNOS) was studied using real-time polymerase chain reaction and Western blot. RESULTS: Endothelium-dependent relaxation (bradykinin) was significantly reduced in rings treated with Hcy alone as compared with the control (49.80% vs 71.77%, n = 8, P < .05), whereas neither high-dose nor low-dose Rb1 alone affected the endothelium-dependent relaxation. The low-dose Rb1-Hcy combined group had a partially improved endothelium-dependent relaxation (54.44%), whereas the high-dose Rb1-Hcy combined group showed a complete recovery of endothelium-dependent relaxation (72.89%). There was no substantial difference in maximal contraction induced by U46619 or endothelium-independent relaxation by SNP among all groups (P > .05). Furthermore, superoxide anion was markedly increased by 137% in the Hcy-treated group as compared with the control, but there were no statistically significant changes from the control in all other groups (P > .05). Lastly, eNOS mRNA and protein levels were substantially reduced in the Hcy-treated group, but not in the Rb1-Hcy combined groups. CONCLUSIONS: This is the first study to show that ginsenoside Rb1 can effectively block Hcy-induced endothelial dysfunction and superoxide anion production as well as eNOS downregulation in porcine coronary arteries. This study suggests that ginseng and its active constituents may have potential clinical applications in controlling Hcy-associated vascular injuries. CLINICAL RELEVANCE: Homocysteine (Hcy) is an independent risk factor for atherosclerosis and other vascular lesions. It causes endothelial dysfunction and oxidative stress. Ginseng compounds have effects of vasorelaxation and antioxidation. The purpose of this study was to determine the effect of ginsenoside Rb1, a major constituent of ginseng, on Hcy-induced endothelial dysfunction and molecular changes in porcine coronary arteries. Our results showed that ginsenoside Rb1 can effectively block Hcy-induced dysfunction of endothelium-dependent vasorelaxation as well as superoxide anion production and eNOS downregulation. This study suggests that ginseng compounds may have potential clinical applications in controlling Hcy-associated vascular diseases and other vascular lesions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2005

C-reactive protein decreases expression of thrombomodulin and endothelial protein C receptor in human endothelial cells.

BACKGROUND: C-reactive protein (CRP) is associated with atherosclerosis and thrombosis. However, it is unclear whether CRP has direct effects on the antithrombogenic properties of endothelial cells. The objective of the present study was to determine the effect of CRP on the expression of thrombomodulin (TM) and the endothelial protein C receptor (EPCR) in human endothelial cells. METHODS: Human coronary artery endothelial cells (HCAECs) were treated with CRP in a dose- and time-dependent manner. The messenger RNA levels of TM and EPCR were determined by real-time polymerase chain reaction. Anti-CD32 antibody and curcumin were used to block the potential effects of CRP. RESULTS: In HCAECs, CRP (10 and 25 microg/mL) significantly reduced TM messenger RNA levels by 18 and 30%, respectively, compared with controls (P < .05). This effect was also confirmed in other types of human endothelial cells from umbilical veins and skin microvessels. The cells treated with CRP (10 and 25 microg/mL) showed significant reductions of EPCR mRNA levels by 34% and 33%, respectively (P < .05). Anti-CD32 antibody partially blocked CRP-induced downregulation of TM and EPCR in HCAECs. Furthermore, curcumin (5 and 10 microM) in combination with CRP (10 microg/mL) significantly increased TM mRNA levels by 45 and 100%, respectively, and increased EPCR mRNA levels by 24 and 45%, respectively, compared with those in CRP-treated cells (P < .05). CONCLUSIONS: CRP significantly decreases the expression of TM and EPCR in human endothelial cells, thereby promoting thrombogenic conditions. This effect is partially mediated by CD32. Curcumin completely blocks CRP-induced downregulation of TM and EPCR in HCAECs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

The case for thrombolysis for iliofemoral venous thrombosis.

Deep venous thrombosis and its consequences remain a significant clinical challenge despite advances in the current healthcare system. The use of thrombolytic therapy has played an important role in the management of both arterial and venous thrombotic conditions. In this article, relevant clinical evidence and rationale in support of thrombolytic therapy in ileofemoral deep venous thrombosis are discussed.

Angioplasty↗
PubMed2005

What is the learning curve for carotid artery stenting with neuroprotection? Analysis of 200 consecutive cases at an academic institution.

Carotid artery stenting (CAS) has emerged as an acceptable treatment alternative in high-risk patients with carotid stenosis. This study assessed the effect of the learning curve on treatment complications and clinical outcome of CAS. Clinical variables and treatment outcomes of 200 consecutive CAS procedures in 182 patients (mean age, 72 years) with carotid stenosis of 70% or greater during a 40-month period were analyzed. Technical success, periprocedural complications, and treatment outcomes were compared in four sequential groups (group I, II, III, and IV) of 50 consecutive interventions. Treatment indications and relevant risk factors were similar among the four groups. The overall technical success was 98%, and the combined 30-day stroke and death rates was 2.5%. An increase in the technical success rate was noted in the latter three groups compared with group I (P < .05). Total procedural time and contrast volume were significantly higher in group I compared with the latter three groups (P < .05). The intraoperative anticoagulation regimen was changed from an intravenous heparin combination to bivalirudin after the first 54 cases, resulting in reduced bleeding complications in groups III and IV (P = .03) compared with group I. The 30-day stroke and death rate in groups I and II was 8% and 2%, which was reduced significantly to 0% in groups III and IV (P < .05). A Cox regression model identified procedural volume (P = .03) as a predictor of a reduced complication rate. Carotid artery stenting with neuroprotection can provide excellent treatment outcome. Our experience demonstrates a procedural-associated learning curve, as evidenced by the reduced procedural-related complications, fluoroscopic time, and contrast volume that occurred with an increase in physician experience. The procedural success is also enhanced partly by endovascular device refinement and improved anticoagulation regimen. Successful outcome of CAS can be achieved once physicians overcome the initial procedural-related learning curve.

Aged↗
PubMed2005

Absorbable cyanoacrylate as a vascular hemostatic sealant: a preliminary trial.

No absorbable cyanoacrylate tissue adhesive for safe internal surgical use is available. This prospective multicenter preliminary study was designed to evaluate the safety and effectiveness of an investigational absorbable cyanoacrylate (IAC) as an adjunct to hemostasis in arteriovenous shunt (AVS) procedures for dialysis access. Consenting adults (10) underwent placement of expanded polytetrafluoroethylene (ePTFE) upper extremity vascular grafts for AVS access using continuous 5-0 or 6-0 polypropylene after heparinization (> or =3000 units i.v.). Arterial anastomoses were evaluated after sealing with IAC followed by 120 seconds of polymerization time. After vascular clamp removal, the mean time to hemostasis was 9.1 +/- 28.8 seconds. Additionally, 90 per cent (9/10) and 100 per cent (10/10) achieved hemostasis by 1 and 5 minutes, respectively. No patients required further adjunctive hemostatic measures. Adverse event safety data analysis through 12 weeks revealed occlusion of graft or vessel in four patients and graft thrombosis in one patient, all thought unrelated to sealant use. Other unrelated adverse events (bleeding, death, deep venous thrombosis, edema, erythema, hematoma, infection, and rash) occurred in single patients. Thus, IAC could be a useful sealant for vascular procedures with a potentially satisfactory safety profile. Larger, randomized, multicenter, prospective trials to further evaluate the use of this material are indicated and appropriate.

Adult↗
PubMed2004

Effects of TNF-alpha and curcumin on the expression of thrombomodulin and endothelial protein C receptor in human endothelial cells.

The objective of this study was to elucidate the effects of tumor necrosis factor-alpha (TNF-alpha) on the expression of thrombomodulin (TM) and endothelial protein C receptor (EPCR) in human endothelial cells as well as the effect of curcumin, a spice and coloring food compound, as a potential therapeutic agent. Human umbilical vein endothelial cells (HUVECs) treated with TNF-alpha (2.0 ng/ml) showed reduced TM mRNA levels by 80%, 97%, 94%, and 97% at 3, 6, 12, and 24 h, respectively (P<0.05), by real-time PCR analysis. Dose-dependent study showed that TM mRNA levels of HUVECs were decreased by 86%, 89%, 91%, and 94% after treatment of TNF-alpha (0, 0.25, 0.5, 1, and 2 ng/ml) for 6 h, respectively (P<0.05). TM protein levels in HUVECs were significantly reduced by 69% in TNF-alpha-treated cells as compared to controls (P<0.05) by Western blot analysis. Secreted protein and activity of TM of HUVEC cultures were also significantly reduced in TNF-alpha-treated cells. In addition, EPCR mRNA levels of HUVECs were significantly reduced in TNF-alpha-treated group as compared to controls (P<0.05). Furthermore, these effects were observed in other types of endothelial cells from human coronary arteries, lung, and skin. Curcumin effectively blocked these effects of TNF-alpha on downregulation of TM and EPCR. These data demonstrate that TNF-alpha significantly decreases expression of TM and EPCR at both mRNA and protein levels in several human endothelial cells. Curcumin can effectively block TNF-alpha-induced endothelial dysfunction. This study suggests a new molecular mechanism of inflammation-induced thrombosis and a new therapeutic strategy to prevent this clinical problem.

Antigens, CD↗
PubMed2004

Molecular mechanisms and clinical applications of ginseng root for cardiovascular disease.

Ginseng root is used extensively in traditional Chinese medicine for its alleged tonic effect and possible curative and restorative properties. There are increasing evidences in the literature on the potential role of ginseng in treating cardiovascular diseases. We herein examine the history of ginseng usage and review the current literature on a myriad pharmacological function of ginseng on the cardiovascular system. From the published studies involving cell cultures and animal models, ginseng is shown to have potential benefits on the cardiovascular system through diverse mechanisms, including antioxidant, modifying vasomotor function, reducing platelet adhesion, influencing ion channels, altering autonomic neurotransmitters release, improving lipid profiles, and involving in glucose metabolism and glycemic control. In addition, the relevant clinical trials regarding the effects of ginseng on the cardiovascular disease are summarized, particularly in managing hypertension and improving cardiovascular function. Finally, the controversies in the literature and the possible adverse interactions between ginseng and other drugs are discussed. This review underscores the potential benefit effects of ginseng on cardiovascular diseases, highlights the gaps in our current research, and emphasizes the necessity for more rigorous systemic investigation.

Antioxidants↗
PubMed2004

HIV protease inhibitor ritonavir decreases endothelium-dependent vasorelaxation and increases superoxide in porcine arteries.

OBJECTIVE: Although HIV Protease inhibitors significantly reduce the viral load, they are associated with increased risk of cardiovascular disease. The aim of this study was to investigate the effects of HIV protease inhibitor ritonavir on vascular endothelial cell function. METHODS: Porcine carotid arteries were perfusion-cultured for 24 h as controls or with 15 microM of ritonavir. Vessels were precontracted with norepinephrine followed by endothelium-dependent vasorelaxation with acetylcholine. Rings of vessels were cultured as controls or with ritonavir for 24 h and basal and NADPH-stimulated superoxide levels were determined using lucigenin-enhanced chemiluminescence. Superoxide levels in situ were also examined using dihydroethidium (DHE) staining, and nitrotyrosine levels were examined using a nitrotyrosine antibody. RESULTS: Endothelium-dependent vasorelaxation was significantly reduced in ritonavir-treated vessels compared to controls. There were significant increases in basal and NADPH-stimulated superoxide production in vessel rings treated with ritonavir compared to control vessels. Dihydroethidium staining and nitrotyrosine staining were also elevated in endothelial cells of ritonavir-treated vessels, indicating increased superoxide production and increased oxidative stress, respectively, in ritonavir-treated vessels compared to controls. CONCLUSIONS: These data demonstrate that HIV protease inhibitor ritonavir causes a significant reduction in endothelium-dependent vasorelaxation in cultured porcine carotid arteries. Increased oxidative stress may be a possible mechanism of HIV protease inhibitor ritonavir-induced endothelial dysfunction.

Animals↗
PubMed2004

Evaluation of platelet deposition and neointimal hyperplasia of heparin-coated small-caliber ePTFE grafts in a canine femoral artery bypass model.

INTRODUCTION: Bypass graft failure due to acute thrombosis and intimal hyperplasia remains a major challenge in small-diameter vascular prosthetic graft reconstruction. Heparin has been shown to prevent thrombus formation and inhibit intimal antithrombotic in animal studies. In this study, we evaluated the effect of small-caliber heparin-coated expanded polytetrafluoroethylene (ePTFE) grafts on platelet deposition and intimal hyperplasia in a canine model of femoral artery bypass grafting. METHODS: Nine adult greyhound dogs underwent placement of bilateral femorofemoral artery bypass grafts with ePTFE grafts (4 mm diameter and 7 cm long). In each animal, a heparin-coated ePTFE graft was placed on one side while a noncoated graft was placed on the contralateral side which served as the control. Platelet deposition was measured by autologous (111)indium-labeling and scintillation camera imaging analysis in 24 h. The graft patency was assessed at 4 weeks following the bypass. The effect of intimal hyperplasia was assessed with histological and morphometric analysis. RESULTS: Platelet deposition on the heparin-coated grafts at 24 h was significantly reduced by 72% as compared to controls (P = 0.001). The patency rate was 44% in control grafts and 89% in heparin-coated grafts. There was a significant reduction of graft intimal hyperplasia at both proximal (0.38 +/- 0.21 mm(2)) and distal (0.19 +/- 0.06 mm(2)) anastomoses in the heparin-coated grafts as compared with proximal (1.01 +/- 0.28 mm(2)) and distal (0.42 +/- 0.01 mm(2)) anastomoses in the untreated control grafts, respectively (P < 0.05). Heparin coating significantly reduced graft neointimal hyperplasia at patent graft anastomoses by 55-72% as compared to controls. CONCLUSIONS: These data demonstrate that heparin coating of ePTFE significantly reduced early platelet deposition and inhibited anastomotic neointimal hyperplasia. Moreover, small-caliber heparin-coated ePTFE graft significantly increased graft patency in a canine femoral artery bypass model. This may represent a promising treatment strategy for improving the clinical performance of small-caliber prosthetic vascular grafts.

Anastomosis, Surgical↗
PubMed2004

Estrogen blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries(1,2).

BACKGROUND: The objective of this study was to examine the effect of estrogen combined with homocysteine on vasomotor function and endothelial integrity in intact porcine coronary arteries. MATERIALS AND METHODS: Pig coronary artery rings were incubated with estrogen, homocysteine, or estrogen and homocysteine for 24 h. Myographic analysis was performed with thromboxane A2 analog U46619 for contraction and bradykinin or sodium nitroprusside for relaxation. Endothelial nitric oxide synthase (eNOS) levels were determined by immunohistochemistry. Levels of superoxide anion were assessed by lucigenin-enhanced chemiluminescence analysis. RESULTS: Endothelium-dependent vasorelaxation (bradykinin) for the homocysteine alone group was 62% compared with control (P < 0.05), and endothelium-dependent vasorelaxation for the estrogen alone group was 85% compared with control (P > 0.05). Endothelium-dependent vasorelaxation for the estrogen-homocysteine combined group was 79% compared with 89% for control (P > 0.05). There were no differences in endothelium-independent vasorelaxation (sodium nitroprusside) or in smooth muscle contractility (U46619) between all three groups and control. In addition, the eNOS immunoreactivity was declined in the homocysteine group and had no major change in the estrogen or estrogen plus homocysteine-treated group as compared with controls. The superoxide free radical measurement showed a marked increase in the homocysteine group, no major change from controls in the estrogen group, and a much-lessened effect in the combination of estrogen and homocysteine. CONCLUSIONS: These data demonstrate that combining estrogen with homocysteine significantly blocks the effect of homocysteine on impairing endothelium-dependent vasorelaxation as well as on decreasing eNOS expression and increasing oxidative stress in porcine coronary arteries. This study suggests that estrogen may play a role in preventing homocysteine-mediated endothelial dysfunction and may be of benefit in the hyperhomocysteinemic patient.

Animals↗
PubMed2004

Carotid artery stenting with routine cerebral protection in high-risk patients.

BACKGROUND: Carotid artery stenting has emerged as an alternative treatment modality in carotid occlusive disease. This study examined our experience of carotid stenting with routine cerebral embolization protection in high-risk patients. METHODS: Clinical variables and treatment outcome of high-risk patients who underwent carotid stenting with neuroprotection were analyzed during a 26-month period. RESULTS: Sixty-eight high-risk patients with 72 carotid artery stenoses were treated. Procedural success was achieved in 70 cases (97%), and symptomatic lesions existed in 17 (24%) patients. Monorail Wallstents stents were used in all cases. Neuroprotective devices used were PercuSurge (28%) and Filterwire (72%). There was no periprocedural mortality or neuroprotective device-related complications. The 30-day stroke and death rate was 2.7%, and the overall complication rate was 6.9%. All stented vessels remained patent during the follow-up period (mean 15.3 +/- 4.2, range 1 to 23 months). Two asymptomatic in-stent restenosis (3%) occurred at 6 and 8 months, which were both successfully treated with balloon angioplasty. CONCLUSIONS: Our study showed that percutaneous carotid stenting with routine use of a cerebral protection device is a feasible and effective treatment in high-risk patients with carotid occlusive disease.

Aged↗
PubMed2004

The impact of anesthetic modality on the outcome of carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with high-grade carotid artery stenosis. This study evaluates the clinical outcome of CEA performed under local anesthesia (LA) versus general anesthesia (GA). METHODS: Clinical variables and treatment outcomes were analyzed in 548 CEAs performed under either LA or GA during a 30-month period. Factors associated with morbidity were also analyzed. RESULTS: A total of 263 CEAs under LA and 285 CEA under GA were analyzed. The LA group was associated with a lower incidence of shunt placement, operative time, and perioperative hemodynamic instability compared to the GA group. No differences in neurologic complications or mortality were found between the 2 groups. Hyperlipidemia was a risk factor for postoperative morbidity in both the LA and GA groups, while age greater than 75 years was associated with increased overall morbidity in the GA group but not the LA group. CONCLUSIONS: This study demonstrates that increased age is associated with increased morbidity in CEA under GA, while hyperlipidemia is associated with increased morbidity in CEA regardless of the anesthetic choice.

Age Distribution↗