We explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI) funded trials has increased over time.
Increased intestinal permeability and translocation of gut microbiota from the intestinal lumen to the systemic circulation predispose patients to various diseases and may be one of the main triggers thereof. The role of microbiota in increased intestinal permeability is under intensive investigation. Here, we studied alterations in the host and increased intestinal permeability as a direct effect of treatment with a bacteriophage cocktail. After 10 days of challenge, the rats showed weight loss, messy hair, and decreased activity. Additionally, they displayed a significantly elevated lactulose:mannitol ratio and the level of circulating immune complexes. To our knowledge, this study demonstrates for the first time that increased intestinal permeability may be induced by bacteriophages that affect the microbiota.
Slow deep breathing improves blood oxygenation (Sp(O2)) and affects hemodynamics in hypoxic patients. We investigated the ventilatory and hemodynamic effects of slow deep breathing in normal subjects at high altitude. We collected data in healthy lowlanders staying either at 4559 m for 2-3 days (Study A; N = 39) or at 5400 m for 12-16 days (Study B; N = 28). Study variables, including Sp(O2) and systemic and pulmonary arterial pressure, were assessed before, during and after 15 minutes of breathing at 6 breaths/min. At the end of slow breathing, an increase in Sp(O2) (Study A: from 80.2±7.7% to 89.5±8.2%; Study B: from 81.0±4.2% to 88.6±4.5; both p<0.001) and significant reductions in systemic and pulmonary arterial pressure occurred. This was associated with increased tidal volume and no changes in minute ventilation or pulmonary CO diffusion. Slow deep breathing improves ventilation efficiency for oxygen as shown by blood oxygenation increase, and it reduces systemic and pulmonary blood pressure at high altitude but does not change pulmonary gas diffusion.
During embryonic development, vascular networks remodel to meet the increasing demand of growing tissues for oxygen and nutrients. This is achieved by the pruning of redundant blood vessel segments, which then allows more efficient blood flow patterns. Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail. Here, we present the subintestinal vein (SIV) plexus of the zebrafish embryo as a novel model to study pruning at the cellular level. We show that blood vessel regression is a coordinated process of cell rearrangements involving lumen collapse and cell-cell contact resolution. Interestingly, the cellular rearrangements during pruning resemble endothelial cell behavior during vessel fusion in a reversed order. In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection. Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion. In a second step, the unicellular connection is resolved unilaterally, and the pruning cell rejoins the opposing branch. Thus, we show for the first time that various cellular activities are coordinated to achieve blood vessel pruning and define two different morphogenetic pathways, which are selected by the flow environment.
Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP) causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15 µg/animal) every 2(nd) day for 6 days (a total of 4 exposures), and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric) on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α) in the bronchoalveolar lavage (BAL) fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP) and TNF α concentrations, systolic blood pressure (SBP) as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1). Pretreatment with curcumin by oral gavage (45 mg/kg) 1 h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNFα release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNFα and protects against the pulmonary and cardiovascular effects of DEP.
The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains: Do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease? In complementary clinical and experimental studies, we used gold nanoparticles to evaluate particle translocation, permitting detection by high-resolution inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min to 24 h after exposure, and was still present 3 months after exposure. Levels were greater following inhalation of 5 nm (primary diameter) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2-200 nm primary diameter), with translocation markedly greater for particles <10 nm diameter. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease and has major implications for risk management in the use of engineered nanomaterials.
Effective treatment of venous thromboembolism (VTE) strikes a balance between prevention of recurrence and bleeding complications. The current standard of care is heparin followed by a vitamin K antagonist such as warfarin. However, this option is not without its limitations, as the anticoagulant effect of warfarin is associated with high inter- and intra-patient variability and patients must be regularly monitored to ensure that anticoagulation is within the narrow target therapeutic range. Several novel oral anticoagulant agents are in the advanced stages of development for VTE treatment, some of which are given after an initial period of heparin treatment, in line with current practice, while others switch from high to low doses after the initial phase of treatment. In this review we assess the critical considerations for treating VTE in light of emerging clinical data for new oral agents and discuss the merits of novel treatment regimens for patients who have experienced an episode of deep vein thrombosis or pulmonary embolism.
To synthesise current evidence for the effects of exenatide and liraglutide on heart rate, blood pressure and body weight.
Abstract Objective. We studied the relationship between systolic blood pressure and hemodynamics using impedance cardiography in elderly Han residents in order to evaluate how different hemodynamic variables are altered with normal aging and with hypertension superimposed on aging. Methods. A total of 670 subjects, aged 60-93 years, were evaluated with impedance cardiography for non-invasive hemodynamic variables. The subjects were categorized as hypertensives or normotensives, and then they were also divided into six subgroups according to actual systolic blood pressure values. Results. Hypertensive patients had significantly lower values of cardiac output (4.4 ± 1.5 L/min) and cardiac index (2.6 ± 1.0 L/min/m(2)) than those in the normotensive group (4.7 ± 1.5 L/min, and 2.8 ± 0.8 L/min/m(2), respectively; P < 0.05 for both). Compared to the normotensive group, stroke volume and stroke index values were also lower and systemic vascular resistance and systemic vascular resistance index were higher in the hypertensive group. There were no significant differences in left ventricular stroke work and left ventricular stroke work index between the two groups. When all 670 subjects were stratified to actual blood pressure, cardiac output of group 6 patients (systolic blood pressure ≥180 mmHg) was 19% lower than that of group 1 subjects (SBP <140 mmHg; P < 0.05). Similarly, systemic vascular resistance of group 6 patients was 56% higher than that of group 1 subjects (P < 0.05). Conclusion. With aging, arterial systolic blood pressure is elevated as a result of increased arterial stiffness and increased systemic vascular resistance. With hypertension, these values are further elevated. Non-invasive impedance cardiography helps to characterize the hemodynamic mechanisms, which can improve hypertension management.
Percutaneous transsplenic portal vein catheterization: technical procedures, safety, and clinical applications
- Journal of vascular and interventional radiology : JVIR
- Published about 6 years ago
To evaluate the safety and feasibility of percutaneous transsplenic portal vein catheterization (PTSPC) by retrospective review of its use in patients with portal vein (PV) occlusion.