Caroline E. Gebhard

Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis

BackgroundThe phytosterol guggulsterone is a potent anti-inflammatory mediator with less side effects than classic steroids. This study assesses the impact of guggulsterone on tissue factor (TF) expression and thrombus formation.Methods and resultsGuggulsterone inhibited TNF-α-induced endothelial TF protein expression and surface activity in a concentration-dependent manner; in contrast, dexamethasone did not affect TNF-α-induced TF expression. Guggulsterone enhanced endothelial tissue factor pathway inhibitor and impaired plasminogen activator inhibitor-1 as well as vascular cell adhesion molecule-1 protein. Real-time polymerase chain reaction revealed that guggulsterone inhibited TNF-α-induced TF mRNA expression; moreover, it impaired activation of the MAP kinases JNK and p38, while that of ERK remained unaffected. In vivo, guggulsterone inhibited TF activity and photochemical injury induced thrombotic occlusion of mouse carotid artery. Guggulsterone also inhibited TF expression, proliferation, and migration of vascular smooth muscle cells in a concentration-dependent manner.ConclusionsGuggulsterone inhibits TF expression in vascular cells as well as thrombus formation in vivo; moreover, it impairs vascular smooth muscle cell activation. Hence, this phytosterol offers novel therapeutic options, in particular in inflammatory diseases associated with an increased risk of thrombosis.

Coronary artery stents: influence of adaptive statistical iterative reconstruction on image quality using 64-HDCT

OBJECTIVE The assessment of coronary stents with present-generation 64-detector row computed tomography (HDCT) scanners is limited by image noise and blooming artefacts. We evaluated the performance of adaptive statistical iterative reconstruction (ASIR) for noise reduction in coronary stent imaging with HDCT. METHODS AND RESULTS In 50 stents of 28 patients (mean age 64 ± 10 years) undergoing coronary CT angiography (CCTA) on an HDCT scanner the mean in-stent luminal diameter, stent length, image quality, in-stent contrast attenuation, and image noise were assessed. Studies were reconstructed using filtered back projection (FBP) and ASIR-FBP composites. ASIR resulted in reduced image noise vs. FBP (P < 0.0001). Two readers graded the CCTA stent image quality on a 4-point Likert scale and determined the proportion of interpretable stent segments. The best image quality for all clinical images was obtained with 40 and 60% ASIR with significantly larger luminal area visualization compared with FBP (+42.1 ± 5.4% with 100% ASIR vs. FBP alone; P < 0.0001) while the stent length was decreased (-4.7 ± 0.9%, <P = 0.002) and volume measurements were unaffected. CONCLUSION Reconstruction of CCTA from HDCT using 40 and 60% ASIR incrementally improves intra-stent luminal area, diameter visualization, and image quality compared with FBP reconstruction.

Age- and Gender-Dependent Left Ventricular Remodeling

The effect of age and gender on left ventricular (LV) size, muscle mass, and systolic function as determined by two‐dimensional echocardiography has not yet been investigated in a large population.

Amphetamines induce tissue factor and impair tissue factor pathway inhibitor: role of dopamine receptor type 4

AIMS Amphetamine intake is associated with acute vascular syndromes. Since these events are caused by arterial thrombosis and this in turn is triggered by tissue factor (TF), this study examines whether amphetamines regulate TF in human endothelial cells. METHODS AND RESULTS Amphetamine (10(-7)-10(-4) mol/L) enhanced thrombin- and tumour necrosis factor (TNF)-alpha-induced as well as basal TF expression (P = 0.029, 0.0003, and 0.003 at maximal concentration), and TNF-alpha-induced plasminogen activator inhibitor (PAI)-1 expression (P = 0.003), whereas tissue factor pathway inhibitor expression was impaired (P = 0.008). Similarly, 3,4-methylenedioxymethamphetamine (10(-7)-10(-4) mol/L) enhanced TF expression (P = 0.046). These effects were paralleled by an increased TF activity (P = 0.002); moreover, clotting time of human plasma was accelerated by supernatant from amphetamine-treated cells (P = 0.03). Amphetamine enhanced TF mRNA expression via phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK) and p38 (P = 0.03 and 0.033), but not c-Jun NH(2)-terminal kinase (JNK; P = 0.81). The effect of amphetamine on TF expression was abrogated by the dopamine D4 receptor antagonists L-745,870 and L-750,667, but not D2 or D3 receptor antagonists; furthermore, L-745,870 blunted the amphetamine-induced activation of ERK and p38, but not JNK. CONCLUSION Amphetamines induce endothelial TF expression via stimulation of dopamine D4 receptor and activation of the MAPKs p38 and ERK. These effects occur at clinically relevant amphetamine concentrations and may account for the increased incidence of acute vascular syndromes after amphetamine consumption.

Intratracheal Milrinone Bolus Administration During Acute Right Ventricular Dysfunction After Cardiopulmonary Bypass

OBJECTIVE To evaluate intratracheal milrinone (tMil) administration for rapid treatment of right ventricular (RV) dysfunction as a novel route after cardiopulmonary bypass. DESIGN Retrospective analysis. SETTING Single-center study. PARTICIPANTS The study comprised 7 patients undergoing cardiac surgery who exhibited acute RV dysfunction after cardiopulmonary bypass. INTERVENTIONS After difficult weaning caused by cardiopulmonary bypass-induced acute RV dysfunction, milrinone was administered as a 5-mg bolus inside the endotracheal tube. MEASUREMENTS AND MAIN RESULTS RV function improvement, as indicated by decreasing pulmonary artery pressure and changes of RV waveforms, was observed in all 7 patients. Adverse effects of tMil included dynamic RV outflow tract obstruction (2 patients) and a decrease in systemic mean arterial pressure (1 patient). CONCLUSIONS tMil may be an effective, rapid, and easily applicable therapeutic alternative to inhaled milrinone for the treatment of acute RV failure during cardiac surgery. However, sufficiently powered clinical trials are needed to confirm these findings.

Successful Repair of a Bicuspid Pulmonary Autograft Valve Causing Early Insufficiency After a Ross Procedure

The Ross procedure is an excellent option in terms of long-term outcomes for young patients requiring aortic valve replacement. We report the case of a 49-year-old woman who presented with worsening dyspnea and episodes of presyncope in the context of a patient-prosthesis mismatch, 13 years after mechanical aortic valve replacement. She underwent a Ross procedure despite the pulmonary valve being bicuspid at intraoperative examination. Following implantation, the autograft valve showed an eccentric jet of regurgitation requiring bicuspid valve repair. To our knowledge, this is the first reported case of successful repair of a bicuspid pulmonary autograft valve.

Weather and risk of ST-elevation myocardial infarction revisited: Impact on young women

Background During the last decade, the incidence and mortality rates of ST-elevation myocardial infarction (STEMI) has been steadily increasing in young women but not in men. Environmental variables that contribute to cardiovascular events in women remain ill-defined. Methods and results A total of 2199 consecutive patients presenting with acute ST-elevation myocardial infarction (STEMI, 25.8% women, mean age 62.6±12.4 years) were admitted at the Montreal Heart Institute between June 2010 and December 2014. Snow fall exceeding 2cm/day was identified as a positive predictor for STEMI admission rates in the overall population (RR 1.28, 95% CI 1.07–1.48, p = 0.005), with a significant effect being seen in men (RR 1.30, 95% CI 1.06–1.53, p = 0.01) but not in women (p = NS). An age-specific analysis revealed a significant increase in hospital admission rates for STEMI in younger women ≤55 years, (n = 104) during days with higher outside temperature (p = 0.004 vs men ≤55 years) and longer daylight hours (p = 0.0009 vs men ≤55 years). Accordingly, summer season, increased outside temperature and sunshine hours were identified as strong positive predictors for STEMI occurrence in women ≤55 years (RR 1.66, 95% CI 1.1–2.5, p = 0.012, RR 1.70, 95% CI 1.2–2.5, p = 0.007, and RR 1.67, 95% CI 1.2–2.5, p = 0.011, respectively), while an opposite trend was observed in men ≤55 years (RR for outside temperature 0.8, 95% CI 0.73–0.95, p = 0.01). Conclusion The impact of environmental variables on STEMI is age- and sex-dependent. Higher temperature may play an important role in triggering such acute events in young women.