Keri A. Seymour

Basic Science Review Section: Statin Therapy—Part II: Clinical Considerations for Cardiovascular Disease

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly known as statins, are the medical treatment of choice for hypercholesterolemia. In addition to achieving a therapeutic decrease in serum cholesterol levels, statin therapy appears to promote pleiotropic effects that are independent of changes in serum cholesterol. These cholesterol lowering and pleiotropic effects are beneficial not only for the coronary circulation, but for the myocardium and peripheral arterial system as well. Patients receiving statin therapy must be carefully monitored, however, as statins potentially have harmful side effects and drug interactions. This article is part II of a 2-part review, and it focuses on the clinical aspects of statin therapy in cardiovascular disease.

Is body mass index a risk factor for isolated off-pump coronary revascularization?

Abstract  Objective: The influence of body mass index (BMI) as a risk factor for isolated off‐pump coronary artery bypass (OPCAB) surgery is unknown. We postulated that BMI ≥ 30 kg/m2 would adversely affect outcomes following OPCAB at our institution.

Differential effect of nitric oxide on thrombospondin-1-, PDGF- and fibronectin-induced migration of vascular smooth muscle cells

BACKGROUND Neointimal hyperplasia involves the migration of medial vascular smooth muscle cells (VSMCs) in response to arterial injury. Thrombospondin-1 (TSP1), platelet-derived growth factor (PDGF), and fibronectin (Fn) induce VSMC migration. Nitric oxide (NO) limits VSMC migration. The hypothesis of this study is that NO would dose dependently inhibit TSP1-induced, PDGF-induced, and Fn-induced VSMC chemotaxis. METHODS VSMCs were pretreated with serum free media or the NO donors diethylenetriamine NONOate or S-nitroso-N-acetyl-D,L-penicillamine. Chemotaxis to TSP1, PDGF, or Fn was determined. Analysis of variance with post hoc testing was done. P values < .05 were considered significant. RESULTS PDGF, TSP1, and Fn induced VSMC chemotaxis. NO donors inhibited chemotaxis of VSMCs to PDGF in a concentration-dependent manner. NO donors had a variable effect on TSP1-induced chemotaxis. NO donors did not inhibit Fn-induced chemotaxis. CONCLUSION The complex interactions of these proteins in vivo will need to be considered when developing NO-dependent therapies for neointimal hyperplasia.

Transabdominal Duplex Ultrasonography for Bedside Inferior Vena Cava Filter Placement: Examples, Technique, and Review

Pulmonary embolism remains an endemic challenge for public health care. The first line of treatment for venous thromboembolic disorder has been anticoagulation; however, in the absence of appropriate pharmacologic treatment, because of failure or contraindication, caval filter placement has been widely performed in the prevention of pulmonary embolism. Initially an open surgical procedure, technological advancements have allowed filter placement to be done percutaneously. Bedside filter placement in the intensive care unit with ultrasonographic imaging has been reported to be safe, effective, and reliable. In this report, we present an example, discuss our technique, and review the literature.

Outcome of lower extremity revascularization for peripheral artery occlusive disease: is there a difference between men and women?

The incidence of peripheral arterial occlusive disease (PAD) increases with age. Women represent a growing percentage of the elderly population who present with PAD. While speculation exists that gender affects outcome after revascularization procedures, the literature is confusing and often conflicting. This review compares outcomes by gender after open surgical and endovascular lower extremity revascularization (LER) procedures including: demographic differences, patency rates, limb salvage rates, long-term survival, perioperative complications and 30-day mortality. This review summarizes the existing data and discusses current influences on outcome after LER.

The effects of nicotine on vascular smooth muscle cell chemotaxis induced by thrombospondin-1 and fibronectin

BACKGROUND Vascular smooth muscle cell (VSMC) migration is an important process in many vascular disorders. Nicotine, thrombospondin-1 (TSP-1) and fibronectin (Fn) separately induce VSMC migration. The hypothesis of this study was that nicotine treatment of vascular cells would augment TSP-1-induced and Fn-induced VSMC migration. METHODS VSMCs or endothelial cells (ECs) were treated with serum-free medium or nicotine. Migration of VSMCs was assessed using a modified Boyden chemotaxis chamber to serum-free medium, TSP-1, Fn, EC basal medium, and conditioned EC medium or nicotine-treated conditioned EC medium alone or with supplemented TSP-1 or Fn. RESULTS Nicotine treatment increased VSMC chemotaxis to serum-free medium, but TSP-1 or Fn had no further effect on chemotaxis. Conditioned EC and nicotine-treated conditioned EC enhanced VSMC chemotaxis, which was further augmented by Fn supplementation. CONCLUSIONS Nicotine-stimulated EC derived factors induce VSMC migration, which is augmented by the addition of Fn.

Vascular smooth muscle cell migration induced by domains of thrombospondin-1 is differentially regulated

BACKGROUND Thrombospondin-1 (TSP-1) stimulates vascular smooth muscle cell (VSMC) migration via defined intracellular signaling pathways. The aim of this study was to examine the signaling pathways whereby TSP-1 folded domains (amino-terminal [NH(2)], procollagen homology [PCH], all 3 type 1 repeats [3TSR], and a single recombinant protein containing the 3rd type 2 repeat, the type 3 repeats, and the carboxyl-terminal [E3T3C1]) induce VSMC migration. METHODS Quiescent VSMCs were pretreated with serum-free media or inhibitors: PP2 (c-Src), LY294002 (phosphatidylinositol 3-kinase), FPT (Ras), Y27632 (Rho kinase), SB202190 (p38 kinase), and PD98059 (extracellular signal-regulated kinase). Migration induced by serum-free media, TSP-1, NH(2), PCH, 3TSR, and E3T3C1 was assessed using a modified Boyden chamber. RESULTS TSP-1, NH(2), 3TSR, and E3T3C1 induced VSMC chemotaxis (P < .05), but PCH did not (P > .05). PP2, FPT, SB202190, and PD98059 attenuated chemotaxis stimulated by TSP-1, NH(2), 3TSR, and E3T3C1 (P < .05). LY294002 inhibited TSP-1-induced and E3T3C1-induced (P < .05) but not NH(2)-induced or 3TSR-induced (P > .05) chemotaxis. Y27632 inhibited NH(2)-induced, 3TSR-induced, and E3T3C1-induced (P < .05) but not TSP-1-induced (P > .05) induced chemotaxis. CONCLUSIONS TSP-1 folded domains are differentially dependent on intracellular signaling pathways to induce migration.

Lung hernia following robotic-assisted mitral valve repair.

Abstract  Lung hernia is an uncommon diagnosis characterized by lung tissue protruding through a chest wall defect. It may occur spontaneously, as a congenital defect, as a result of trauma, or as a postsurgical complication. We describe the occurrence of lung hernia and subsequent successful herniorraphy in two patients following robotic‐assisted mitral valve repair. (J Card Surg 2012;27:460‐463)

Statins and Nitric Oxide Donors Affect Thrombospondin 1-Induced Chemotaxis

Background: Thrombospondin 1 (TSP-1) induces vascular smooth muscle cell (VSMC) migration and intimal hyperplasia. Statins and nitric oxide (NO) donors decrease intimal hyperplasia. We previously showed that statins (long-term exposure) and NO donors inhibit TSP-1-induced VSMC chemotaxis. Hypotheses: (1) Pretreatment with short-term statin will inhibit TSP-1-induced VSMC chemotaxis and (2) NO donors will enhance statin inhibition of TSP-1-induced or platelet-derived growth factor (PDGF)-induced VSMC chemotaxis. Methods: We examined these treatment effects on TSP-1-induced VSMC chemotaxis: (1) long-term (20 hours) versus short-term (20 minutes) pravastatin, (2) diethylenetriamine NONOate (DETA/NO) or S-nitroso-N-acetylpenicillamine (SNAP) in combination with pravastatin, and (3) comparison of TSP-1 to PDGF as a chemoattractant. Results: Pravastatin (long term or short term) inhibited TSP-1-induced chemotaxis. Diethylenetriamine NONOate and SNAP impeded statin inhibition of TSP-1-induced chemotaxis. Platelet-derived growth factor and TSP-1 had opposite effects on DETA/NO-pravastatin treatment. Conclusion: Short-term statin pretreatment inhibited TSP-1-induced VSMC chemotaxis, suggesting a pleiotropic effect. High-dose NO reversed statin inhibition of TSP-1-induced chemotaxis, suggesting NO and statin combination therapies warrant further study.

Ultrasound accelerated catheter directed thrombolysis for pulmonary embolus and right heart thrombus secondary to transvenous pacing wires.

Acute pulmonary embolism is associated with a significant number of deaths each year, which are commonly attributed to deep venous thrombosis of the lower extremity. Pulmonary embolism due to right-sided cardiac thrombus associated with transvenous wires is a rare occurrence. Treatment considerations have been systemic anticoagulation with heparin or systemic thrombolytic therapy. A unique case of a patient with symptomatic PE and extensive atrial and ventricle thrombus formation associated with transvenous pacing wires treated with ultrasound accelerated catheter directed thrombolysis is presented.