Yuan-Teh Lee

Treatment of iatrogenic femoral artery pseudoaneurysm with percutaneous thrombin injection

PURPOSE Local compression has been advocated for the treatment of femoral artery pseudoaneurysms. Although it is effective and has a high success rate, this method bears some limitations; among them are prolonged procedure time, discomfort for patients, and recurrence. As a potent thrombosis-inducing agent, thrombin has been used topically, and occasionally intravascularly, for hemostasis. Pseudoaneurysms with a narrow connecting tract to the native artery may be suitable for treatment with thrombin injection to induce intracavitary coagulation. METHODS Patients with pseudoaneurysms of the femoral artery were evaluated by ultrasonography. Under ultrasound guidance, an intravenous catheter was introduced percutaneously into the pseudoaneurysm, with the catheter position confirmed by contrast ultrasonography. One thousand units of thrombin dissolved in normal saline solution was then injected slowly into the pseudoaneurysm through the catheter to induce thrombosis. The patients were monitored closely for any adverse effects after thrombin injection. RESULTS A total of five patients with femoral artery pseudoaneurysms were treated with direct percutaneous thrombin injection under ultrasound guidance. Within seconds of thrombin injection thrombus formation was evident, and blood flow in the pseudoaneurysm soon ceased when the thrombosis extended to the connecting tract. All procedures were uneventful and successful. No recurrence was noted during follow-up periods of 1 to 28 months. CONCLUSION Our initial experience with the small number of patients demonstrates the simplicity, lack of morbidity, and high success rate for ultrasound-guided percutaneous thrombin injection for the treatment of femoral artery pseudoaneurysms.

Effects of Methionine-Induced Hyperhomocysteinemia on Endothelium-Dependent Vasodilation and Oxidative Status in Healthy Adults

BACKGROUND Homocysteine-mediated endothelial dysfunction has been proposed to occur via oxidative stress mechanisms in humans. However, there is controversy regarding the effects of homocysteine on endothelial function and oxidative status, which may in part result from age discrepancy across the studies. The present study was designed to investigate the aging effect on the relationship between endothelium-dependent vasodilation and oxidative status in methionine-induced hyperhomocysteinemia. METHODS AND RESULTS Plasma homocysteine, phosphatidylcholine hydroperoxide (PCOOH), P-selectin levels, and brachial artery flow-mediated vasodilation were measured at baseline and 4 hours after an oral methionine load (0.1 g/kg) in 15 younger (21 to 40 years) and 15 older (55 to 70 years) healthy adults. Homocysteine increased from 7.3+/-1.3 micromol/L at baseline to 22.7+/-5.2 micromol/L at 4 hours in younger (P<0.001) and from 7. 4+/-1.4 to 24.3+/-4.5 micromol/L in older adults (P<0.001). PCOOH levels were not significantly different between baseline and 4 hours in both groups (P=0.10 in young; P=0.14 in old). P-selectin, which is expected to increase during oxidative stress, was not changed in older (P=0.08) but decreased in younger adults (P=0.037) at 4 hours. Flow-mediated vasodilation was preserved from 13.1+/-2.1% at baseline to 13.5+/-2.8% at 4 hours in younger (P=0.49) and decreased from 12.8+/-2.4% to 8.5+/-2.8% in older adults (P<0.001). CONCLUSIONS The present study demonstrates that endothelial dysfunction caused by methionine-induced hyperhomocysteinemia is age-related and is mediated through impaired nitric oxide activity without change of oxidative status. Our data do not support previous hypotheses that endothelial damage by homocysteine is via oxidative stress mechanism in humans.

Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles

Given that combination therapy with statin plus fibrate confers a risk of myopathy, it is worthwhile to determine whether statin or fibrate monotherapy is associated with greater clinical benefit in individuals with combined hyperlipidemia. In this randomized double-blind study, we compared the efficacy of simvastatin and fenofibrate on indexes of endothelial function (flow-mediated dilation (FMD) of the brachial artery) and inflammatory markers (plasma high-sensitivity C-reactive protein (CRP), interleukin-1 beta (IL-1 beta), soluble CD40, and soluble CD40 ligand (sCD40L) levels), as surrogate indicators of future coronary heart disease (CHD), in patients with combined hyperlipidemia. A total of 70 patients with plasma triglyceride levels between 200 and 500 mg/dl and total cholesterol levels of >200 mg/dl were randomly assigned to receive either simvastatin (20 mg/day) (n=35) or micronized fenofibrate (200 mg/day) (n=35) for 8 weeks. Treatment with simvastatin was associated with significantly greater reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), while the decrease in triglycerides was significantly greater in patients receiving fenofibrate. Both fenofibrate and simvastatin markedly reduced plasma levels of high-sensitivity CRP, IL-1 beta, and sCD40L, and improved endothelium-dependent FMD without mutual differences. The changes in plasma inflammatory markers did not correlate with baseline clinical characteristics in both groups. However, the improvement in FMD with fenofibrate treatment correlated inversely with baseline high-density lipoprotein cholesterol (HDL-C) levels, whereas the improvement in FMD with simvastatin treatment was positively related to HDL-C levels. Accordingly, in the subgroup with a baseline HDL-C of < or =40 mg/dl, only fenofibrate significantly improved the endothelium-dependent FMD. On the other hand, in the subgroup with HDL-C >40 mg/dl, only treatment with simvastatin achieved significant improvement in FMD. The data here indicate that in patients with combined hyperlipidemia, both fenofibrate and simvastatin have comparative beneficial effects on various inflammatory markers and differential beneficial effects on endothelial function according to baseline HDL-C levels. These findings should be validated by additional prospective studies, in which patients are stratified by baseline HDL-C prior to randomization.

Sympathetic Nerve Sprouting, Electrical Remodeling, and Increased Vulnerability to Ventricular Fibrillation in Hypercholesterolemic Rabbits

Abstract— Whether hypercholesterolemia (HC) can induce proarrhythmic neural and electrophysiological remodeling is unclear. We fed rabbits with either high cholesterol (HC, n=10) or standard (S, n=10) chows for 12 weeks (protocol 1), and with HC (n=12) or S (n=10) chows for 8 weeks (protocol 2). In protocol 3, 10 rabbits were fed with various protocols to observe the effects of different serum cholesterol levels. Results showed that the serum cholesterol levels were 2097±288 mg/dL in HC group and 59±9 mg/dL in S group for protocol 1 and were 1889±577 mg/dL in HC group and 50±21 mg/dL in S group for protocol 2. Density of growth-associated protein 43– (GAP43) and tyrosine hydroxylase– (TH) positive nerves in the heart was significantly higher in HC than S in protocol 1. Compared with S, HC rabbits had longer QTc intervals, more QTc dispersion, longer action potential duration, increased heterogeneity of repolarization and higher peak calcium current (ICa) density (14.0±3.1 versus 9.1±3.4 pA/pF;P <0.01) in protocol 1 and 2. Ventricular fibrillation was either induced or occurred spontaneously in 9/12 of hearts of HC group and 2/10 of hearts in S group in protocol 2. Protocol 3 showed a strong correlation between serum cholesterol level and nerve density for GAP43 (R2=0.94;P <0.001) and TH (R2=0.91;P <0.001). We conclude that HC resulted in nerve sprouting, sympathetic hyperinnervation, and increased ICa. The neural and electrophysiological remodeling was associated with prolonged action potential duration, longer QTc intervals, increased repolarization dispersion, and increased ventricular vulnerability to fibrillation.

An Intelligent Telecardiology System Using a Wearable and Wireless ECG to Detect Atrial Fibrillation

This study presents a novel wireless, ambulatory, real-time, and autoalarm intelligent telecardiology system to improve healthcare for cardiovascular disease, which is one of the most prevalent and costly health problems in the world. This system consists of a lightweight and power-saving wireless ECG device equipped with a built-in automatic warning expert system. This device is connected to a mobile and ubiquitous real-time display platform. The acquired ECG signals are instantaneously transmitted to mobile devices, such as netbooks or mobile phones through Bluetooth, and then, processed by the expert system. An alert signal is sent to the remote database server, which can be accessed by an Internet browser, once an abnormal ECG is detected. The current version of the expert system can identify five types of abnormal cardiac rhythms in real-time, including sinus tachycardia, sinus bradycardia, wide QRS complex, atrial fibrillation (AF), and cardiac asystole, which is very important for both the subjects who are being monitored and the healthcare personnel tracking cardiac-rhythm disorders. The proposed system also activates an emergency medical alarm system when problems occur. Clinical testing reveals that the proposed system is approximately 94% accurate, with high sensitivity, specificity, and positive prediction rates for ten normal subjects and 20 AF patients. We believe that in the future a business-card-like ECG device, accompanied with a mobile phone, can make universal cardiac protection service possible.

Oxidized Low-Density Lipoproteins Inhibit Endothelial Cell Proliferation by Suppressing Basic Fibroblast Growth Factor Expression

BACKGROUND Hyperlipidemia inhibits proliferation of endothelial cells (ECs) in culture and angiogenesis in vivo and in arterial explants. Elucidation of the mechanisms may suggest novel therapies against atherosclerosis. METHODS AND RESULTS Basic fibroblast growth factor (bFGF) expression and mitogenic effects were assessed in bovine aortic ECs incubated with oxidized LDL (ox-LDL). Compared with native LDL and lipoprotein-free controls, ox-LDL reduced bFGF mRNA levels in a time- and concentration-dependent manner, 100 microg/mL producing a maximum reduction of 40% to 50% within 24 to 48 hours. There were commensurate reductions in intracellular and extracellular bFGF concentrations, DNA and total RNA syntheses, and cell replication. FGF receptor 1 and beta-actin mRNA levels were unchanged. Ox-LDL accelerated bFGF mRNA degradation in actinomycin D-treated cells. However, inhibition of bFGF expression by ox-LDL was attenuated by cyclohexamide, indicating a requirement for continuous new protein synthesis for posttranscriptional destabilization. Reduced syntheses of DNA and total RNA were completely restored by bFGF but not by vascular endothelial growth factor. Inhibition of total RNA synthesis achieved by exposing cells to a bFGF-neutralizing antibody was similar in magnitude to that induced by ox-LDL. CONCLUSIONS Cytotoxic effects of ox-LDL on ECs are attributable in part to suppression of bFGF expression.

Cyclosporine A regulate oxidative stress‐induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70

Previous study suggested that cyclosporine A (CsA) could partially reduce ischaemia/reperfusion‐induced injury in isolated heart, but the mechanism was still unclear. In this study, the possible mechanisms of cyclosporine A in regulating oxidative stress‐induced cardiomyocyte apoptosis were examined. Morphological (cell shrinkage, apoptotic body formation, and DNA fragmentation) and biochemical (annexin‐V staining for exposed phosphatidylserine residues) evidences showed that both hydrogen peroxide (H2O2) and hypoxia/reoxygenation could induce apoptotic change in the embryonal rat heart myoblast‐derived cells (H9c2). These effects were inhibited by pre‐treatment with CsA at concentration of 0.01–1.0 μM for 24 h, but were increased with 10.0 μM CsA. While examining the mechanisms of CsA in protecting cardiomyocyte apoptosis, we found that the collapse of mitochondria membrane potential (ΔΨm) induced by oxidative stress was partially reversed by CsA (0.01–1.0 μM). Compared to the control, CSA at the concentration of 0.1 and 10.0 μM significantly increased the level of intracellular reactive oxygen species (ROS) to 117.2±12.4% and 234.4±9.3%, respectively. Co‐incubating with the antioxidant, ascorbic acid (10.0 μM), could partially reduce the protective effect of CsA (0.01–1.0 μM) and the toxic effect of 10.0 μM CsA. Pre‐treatment with CsA at concentration of 0.01–1.0 μM for 24 h produced up‐regulation of heat shock protein 70 (Hsp 70), inducible nitric oxide synthase (iNOS) and also induced NO production, indicating that these factors might be associated with the cell protective effects of CsA. These results suggest that CsA could protect the oxidative stress‐induced cardiomyocyte apoptosis not only by preventing the loss of ΔΨm in mitochondria, but also through ROS generation, Hsp70, and iNOS up‐regulation.

Chin-Shan Community Cardiovascular Cohort in Taiwan–baseline data and five-year follow-up morbidity and mortality

A cohort consisting of 3602 residents (82.8% of the target population) aged 35 years and older was established in 1990 in the Chin-Shan Community, a suburb 20 miles outside of metropolitan Taipei, Taiwan. The long-term objective was to investigate the prospective impact on cardiovascular health in a society undergoing transition from a developing to a developed nation. This article presents the study design, selected baseline risk factors of cardiovascular diseases (CVD), and CVD events at the 5-year follow-up evaluation with an emphasis on sociodemographic differences. The multivariate logistic regression analyses revealed that white-collar individuals were more likely than blue-collar workers to have dyslipidemia including high-density lipoprotein cholesterol (HDL-C) levels <35 mg/dl [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.2-2.4] and low-density lipoprotein cholesterol (LDL-C) levels >/=160 mg/dl (OR = 1.3, 95% CI = 1.0-1.7). However, they were at slightly lower risk for stroke and CVD/sudden death, and at moderately higher risk for coronary artery disease and diabetes, although both these trends were not significant. Men were more likely than women to have HDL-C levels <35 mg/dl (OR = 1.8, 95% CI = 1.4-2.2), but they were less likely to have LDL-C levels >/=160 mg/dl (OR = 0.7, 95% CI = 0.6-0.8). The risk of CVD/sudden death was higher for men than for women during the follow-up period (OR = 1.9, 95% CI = 1.3-2.9). This could be due to risk factors such as a much higher prevalence of tobacco (61.9% vs. 4.5%) and alcohol (43.7% vs. 6.4%) use in men. In conclusion, individuals of higher socioeconomic status have a higher prevalence of dyslipidemia but slightly lower 5-year incidence of CVD events.

Relations of Epicardial Adipose Tissue Measured by Multidetector Computed Tomography to Components of the Metabolic Syndrome Are Region-Specific and Independent of Anthropometric Indexes and Intraabdominal Visceral Fat

CONTEXT Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot. Its distribution is asymmetrical and primarily concentrated in the grooves. To date, it remains unclear which measurement of EAT best reflects its metabolic risk. OBJECTIVE We aimed to examine the correlations between various multidetector computed tomographic measurements of EAT, metabolic syndrome components, and plasma levels of high-sensitivity C-reactive protein and adipokines. DESIGN, SETTING, AND PARTICIPANTS This study included 148 consecutive patients undergoing multidetector computed tomography prior to diagnostic coronary angiography. Thickness in the grooved segments, cross-sectional areas, and total volume of EAT were measured. The cross-sectional areas of sc and visceral abdominal fat depots were additionally measured in 70 randomly selected patients. RESULTS Thickness of EAT in the left atrioventricular groove was the only EAT measurement significantly correlated with all three metabolic syndrome components (blood pressure, lipid, and glucose components) and plasma levels of resistin and high-sensitivity C-reactive protein after age and gender adjustments. The association between left atrioventricular groove thickness and increasing number of metabolic syndrome components remained significant after additional adjustments for body mass index, waist circumference, and intraabdominal visceral fat area. By using the receiver operating characteristic analysis, the optimal cutoff point for left atrioventricular groove thickness to predict the presence of at least two metabolic syndrome components was 12.4 mm. CONCLUSIONS A simple measurement of EAT thickness in the left atrioventricular groove may provide a more accurate assessment of metabolic risk associated with EAT, which could not be accounted for by anthropometric indexes and intraabdominal visceral fat.

The graded effect of hyperhomocysteinemia on the severity and extent of coronary atherosclerosis

It is not clear to what extent methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia effect the severity and extent of coronary atherosclerosis in Asian populations. We examined the MTHFR genotypes and plasma homocysteine (HCY) concentrations in 192 Taiwanese and investigated their relationship with coronary artery disease (CAD), and the severity and extent of coronary atherosclerosis. The distribution of MTHFR genotypes was similar in 116 CAD patients and 76 non-CAD subjects. Homozygosity was noted in 8% of CAD patients and 13% of non-CAD subjects (P=0.33; 95% CI, 0. 2-1.6). The geometric mean of HCY values was higher in CAD patients (11.10+/-1.51 micromol/l) than in non-CAD subjects (9.21+/-1.55 micromol/l) (P=0.003). HCY levels were higher in patients with multi-vessel disease (P<0.05) or in patients with > or = 90% stenotic lesions (P=0.005), compared with non-CAD subjects. The CAD risks in the top two HCY quartiles (> or = 14.0 and 10.1-13.9 micromol/l) were 4.0 (95% CI, 1.7-9.2) and 3.2 (95% CI, 1.4-7.4) times higher than in the lowest quartile (< or = 7.9 micromol/l) (P=0.001 and 0.007, respectively). Linear regression analysis showed significant correlations between HCY concentrations and the severity and extent of atherosclerosis (P=0.0001 for both). In conclusion, hyperhomocysteinemia appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings do not support the homozygous genotype of MTHFR as a genetic risk factor for CAD in this Taiwanese population. Perhaps a further study including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.