Endovascular stent graft repair for a Salmonella-infected aneurysm of thoracic aorta.

Thoracic endovascular aneurysm repair using stent graft has been reported as a feasible and effective treatment for aortic aneurysm. However, its application for treating infected aortic aneurysms is still controversial and less reported. We report a 74-year-old male diabetic patient diagnosed with Salmonella-infected aortic aneurysm, who was successfully treated with endovascular stent graft repair followed by a 2-month course of intravenous antibiotics and long-term oral antibiotic therapy. Sequential computed tomography scans demonstrated the shrinkage of the aneurysm and no evidence of relapse 11 months later.

Aneurysm of an aberrant right subclavian artery: treatment with thoracic aortic stent graft.

Aberrant right subclavian artery aneurysms are rare but carry a high risk of spontaneous rupture without any treatment. Aggressive early elective treatment is warranted. We present a hybrid endovascular treatment that was used to treat a 77-year-old woman with aberrant right subclavian artery aneurysm for whom surgical treatment would have been associated with high risk. A thoracic stent graft was used to cover the origin of aberrant right subclavian artery at the proximal descending aorta. To prevent any retrograde flow, an Amplatzer septal occluder was deployed at the distal subclavian artery. Axillo-axillary bypass with an 8-mm polytetrafluoroethylene graft was performed due to atherosclerosis change of the common carotid artery to restore the right arm perfusion and prevent vertebrobasilar insufficiency.

Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-beta1 in cultured cardiac fibroblasts.

AIMS: Transforming growth factor-beta1 (TGF-beta1) and endoglin play a causal role in promoting cardiac fibrosis. Atorvastatin has been shown to have an inhibitory effect on cardiac fibroblasts in vitro. However, the effects of statins on TGF-beta1 and endoglin are poorly understood. We therefore sought to investigate the molecular mechanisms of atorvastatin on endoglin expression after TGF-beta1 stimulation in cardiac fibroblasts. METHODS AND RESULTS: Cultured cardiac fibroblasts were obtained from adult male Sprague-Dawley rat hearts. TGF-beta1 stimulation increased endoglin and collagen I expression and atorvastatin inhibited the induction of endoglin and collagen I by TGF-beta1. Phosphatidylinositol-3 kinase (PI-3) and Akt inhibitors (wortmannin and Akt inhibitor X) completely attenuated the endoglin protein expression induced by TGF-beta1. TGF-beta1 induced phosphorylation of PI-3 kinase and Akt, while atorvastatin and wortmannin and Akt inhibitor X inhibited the phosphorylation of PI-3 kinase and Akt induced by TGF-beta1. The gel shift and promoter activity assay showed that TGF-beta1 increased Smad3/4-binding activity and endoglin promoter activity, while wortmannin and atorvastatin inhibited the Smad3/4-binding activity and endoglin promoter activity induced by TGF-beta1. TGF-beta1 increased collagen I protein expression, while endoglin siRNA attenuated collagen I protein expression induced by TGF-beta1. Atorvastatin decreased left ventricular TGF-beta1, endoglin, and collagen I protein expression and fibrotic area in a rat model of volume overload heart failure. CONCLUSION: Atorvastatin inhibits endoglin expression through the inhibition of PI-3 kinase, Akt, and Smad3 phosphorylation, and reduced Smad3/4 binding activity and endoglin promoter activity in cardiac fibroblasts.

Spontaneous rupture of left ventricular true aneurysm.

The rupture of left ventricular true aneurysm is a rare event. We report the case of a 52-year-old man who presented to the emergency department with cardiac tamponade that was due to a ruptured left ventricular true aneurysm. An emergency operation was successfully performed to address this rare event.

A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity.

Warfarin, a commonly prescribed anticoagulant, exhibited large inter-individual and inter-ethnic differences in the dose required for its anticoagulation effect. Asian populations, including Chinese, require a much lower maintenance dose than Caucasians, for which the mechanisms still remain unknown. We determined DNA sequence variants in CYP2C9 and VKORC1 in 16 Chinese patients having warfarin sensitivity (< or = 1.5 mg/day, n = 11) or resistance (> or = 6.0 mg/day, n = 5), 104 randomly selected Chinese patients receiving warfarin, 95 normal Chinese controls and 92 normal Caucasians. We identified three CYP2C9 variants, CYP2C9*3, T299A and P382L, in four warfarin-sensitive patients. A novel VKORC1 promoter polymorphism (-1639 G > A) presented in the homozygous form (genotype AA) was found in all warfarin-sensitive patients. The resistant patients were either AG or GG. Among the 104 randomly selected Chinese patients receiving warfarin, AA genotype also had lower dose than the AG/GG genotype (P < 0.0001). Frequencies of AA, AG and GG genotypes were comparable in Chinese patients receiving warfarin (79.7, 17.6 and 2.7%) and normal Chinese controls (82, 18 and 0%), but differed significantly from Caucasians (14, 47 and 39%) (P < 0.0001). The promoter polymorphism abolished the E-box consensus sequences and dual luciferase assay revealed that VOKRC1 promoter with the G allele had a 44% increase of activity when compared with the A allele. The differences in allele frequencies of A/G allele and its levels of VKORC1 promoter activity may underscore the inter-individual differences in warfarin dosage as well as inter-ethnic differences between Chinese and Caucasians.

Electrical remodeling of the canine superior vena cava after chronic rapid atrial pacing.

BACKGROUND: The superior vena cava (SVC) might serve as the trigger and/or substrate for paroxysmal atrial fibrillation (AF). However, the electrophysiological properties of the SVC with chronic AF are unknown. The purposes of this study were to investigate the electrophysiological properties of the SVC and the electropharmacological effects of intravenous dl-sotalol on the canine SVC after chronic rapid atrial pacing (RAP). METHODS AND RESULTS: In the control group, the effective refractory period (ERP), conduction velocity, and AF inducibility of the SVC were assessed in 6 normal dogs before and after an infusion of dl-sotalol. In the experimental group, the ERP, conduction velocity, and AF inducibility of the SVC were assessed before and after dl-sotalol administration in 10 dogs after 8 weeks of RAP. The SVC showed a shorter ERP, decreased slope of rate-adaptation of the ERP, increased ERP dispersion, a decreased conduction velocity, and increased inducibility and duration of AF initiated from the SVC in the RAP dogs. In the RAP dogs, intravenous dl-sotalol significantly increased the ERP, but dl-sotalol did not change the slope of rate-adaptation of the ERP, dispersion of the ERP, conduction velocity, inducibility, or duration of AF initiated from the SVC. CONCLUSIONS: The present study demonstrates that the canine SVC shows significant electrical remodeling and increased AF vulnerability after chronic RAP. Intravenous dl-sotalol was unable to decrease the inducibility or duration of AF initiated from the SVC.

Angiotensin II signals mechanical stretch-induced cardiac matrix metalloproteinase expression via JAK-STAT pathway.

BACKGROUND: Mechanical stress induces many pathophysiological effects in cardiomyocytes. The objective of this study was to test the hypothesis that angiotensin II is a potential mediator of stretch-induced activation of matrix metalloproteinases (MMP). METHODS: Neonatal rat cardiomyocytes grown on a flexible membrane were cyclically stretched achieving up to 20% elongation at 60 cycles/min (using a vacuum). We explored the signaling pathways involved in cyclical stretch-induced expression of MMP-14 and MMP-2. RESULTS: Cyclical mechanical stretch significantly increased mRNA expression and protein synthesis for MMP-14 and MMP-2 from the 6(th) to 24(th) h. The increase in MMP-14 and -2 proteins after stretch was completely blocked after the pretreatment with losartan (an angiotensin II AT1 receptor antagonist, 200 nM) and AG-490 (a Janus kinase 2 tyrosine kinase inhibitor, 100 nM) but not with PD 98059 (an inhibitor of p42/p44 mitogen-activated protein kinase, 50 microM) or wortmannin (a phosphatidylinositol 3-kinase, 30 nM). By zymography, MMP-2 activity was increased by cyclical stretch that was significantly attenuated by losartan and AG-490. The mechanical strain also increased the immunohistochemical labeling of MMP-14 and -2 that was attenuated by adding losartan. Cyclical stretch increased the expression of STAT-1 that was abolished by pretreating with losartan or AG-490 (50 microM and 100 microM). CONCLUSION: These findings indicate that cyclical stretch induces MMP-14 and -2 expression in neonatal rat cardiomyocytes and that the induction is mediated by the angiotensin II-JAK-STAT1 pathway.

Role of tissue oxygen saturation monitoring in diagnosing necrotizing fasciitis of the lower limbs.

STUDY OBJECTIVE: We determine the utility of tissue oxygen saturation monitoring in diagnosing necrotizing fasciitis of the lower extremities. METHODS: We prospectively studied patients who met the criteria of soft tissue infection throughout the lower extremities by tissue oxygen saturation monitoring (with near-infrared spectroscopy) over the middle third of possible involved areas. Cases with evidence of chronic venous stasis, peripheral vascular disease, shock, and systemic hypoxia were excluded. Biceps and contralateral unaffected leg areas were measured as references. The tissue oxygen saturation reading for each area was compared with those finally diagnosed as necrotizing fasciitis and those with only simple soft tissue infection. The tissue oxygen saturation reading was presented as mean+/-SD. Receiver operating characteristic (ROC) curves were used to determine a cutoff value of tissue oxygen saturation reading for early diagnosis of necrotizing fasciitis. RESULTS: Two hundred thirty-four consecutive patients were enrolled. Nineteen patients (group N) were confirmed to have necrotizing fasciitis, whereas the remaining 215 patients (group C) had only cellulitis. The tissue oxygen saturation reading measured over the biceps muscle was 86%+/-11% in group N and 85%+/-12% in group C. In group N, the leg with necrotizing fasciitis had a tissue oxygen saturation reading of 52%+/-18% throughout the involved site, whereas the tissue oxygen saturation reading measured in the comparative values found in group C was 84%+/-7% (difference 95% confidence interval [CI] 22% to 29%). After fasciotomy, the tissue oxygen saturation reading of the leg with necrotizing fasciitis returned to 82%+/-17% (95% CI 23% to 28% compared with prefasciotomy value) in group N. At the cutoff value of a tissue oxygen saturation reading less than 70% (area under the curve 0.883; 95% CI 0.817 to 0.949) defined by ROC curve, the test revealed a sensitivity of 100% (95% CI 82% to 100%), a specificity of 97% (95% CI 94% to 99%), and an accuracy of 97% (95% CI 95% to 99%). CONCLUSION: The low tissue oxygen saturation reading values measured by near-infrared spectroscopy throughout the involved areas of the lower extremities are of value in identifying necrotizing fasciitis. This method may offer a reliable noninvasive method of assessing lower extremities at risk for necrotizing fasciitis, at least for a selected patient population.

Evolution of plasma D-dimer and fibrinogen in witnessed onset of paroxysmal atrial fibrillation.

BACKGROUND: Although increased D-dimer and fibrinogen have been proved to be related with atrial fibrillation (AF), their evolution in the course of time remains unclear. METHODS: To elucidate the evolution of plasma D-dimer and fibrinogen in AF of different duration. 56 patients (group A) of 3,524 patients in whom the onset of AF had been witnessed in a chest pain clinic were enrolled for study. Plasma D-dimer and fibrinogen concentrations were checked within 30 min after the onset of AF and followed up as scheduled. Another 50 patients (group B) with chronic AF underwent the same protocol and served as controls. RESULTS: In group A, the D-dimer levels reached a plateau at the 18th hour (382 +/- 52 vs. 840 +/- 280 ng/ml, p < 0.001 by ANOVA) and the fibrinogen level increased gradually from 4.1 +/- 0.6 g/ml at baseline to 6.1 +/- 0.9 g/ml at the 48th hour (p < 0.001). No subjects had evidence of intra-cardiac thrombi by transesophageal echocardiography. There were significant differences in plasma D-dimer and fibrinogen levels between the two groups at each measurement. At the cut- off value of 500 ng/ml, plasma D-dimer had a sensitivity of 100%, a specificity of 93% in defining AF lasting for less than 12 h. The positive and negative predictive values were 52% and 100%, respectively. Plasma D-dimer increased above the normal range prior to the 12th hour after the onset of AF. CONCLUSION: The observations support its use as a screening tool for identifying patients with short duration AF capable of being safely converted.

Spontaneous cardiac rupture.

An 83-year-old woman had a sudden onset of loss of consciousness with no detectable blood pressure. Pulseless electrical activity was present in the electrocardiogram and massive pericardial effusion was found by echocardiography. Emergent subxiphoid pericardiotomy and drainage was immediately performed to release the cardiac tamponade at bedside and was followed by rushing the patient to the operating room for exploration. As a result a ruptured hole was identified on the posterior-lateral wall of the left ventricle and the defect was successfully repaired. The patient had an uneventful postoperative recovery and received postoperative study by cardiac catheterization, which disclosed coronary artery disease.