Project description:BackgroundThe cardioprotective properties of sevoflurane have been reported in studies of the left ventricle. However, whether this volatile anesthetic would also be beneficial for pulmonary vascular remodeling and associated right ventricular hypertrophy (RVH) remained to be explored. Here, we investigated the potential benefit of sevoflurane to right heart function in experimental pulmonary arterial hypertension (PAH).MethodsAdult Wistar rats received one dose peritoneal injection of monocrotaline (MCT, 60 mg/kg) or the equal volume of normal saline. Two weeks later, rats were treated with sevoflurane or sham exposure. PAH status and cardiac function were assessed by echocardiography weekly, and the body weight (BW) was monitored every week. After 6 weeks of exercise, Fulton's index calculation, histological observation, IL-6 and TNF-α immunohistochemical analyses, evaluation of MDA, SOD and GSH-Px levels and NF-κB and MAPK active determination were performed in lung and RV tissue samples.ResultsMCT induced pulmonary vascular remodeling, RVH, increased Fulton's index (P<0.01), and right ventricular failure (RVF) in rats. Animals inhaled sevoflurane had an increased cardiac output (P<0.05) and lower incidence of RVF (P<0.05). Also, these animals had a reduced RVEDD, RVWTd and PAID (P<0.05), increased PV (P<0.05), reduced wall thickness and vascular wall area of pulmonary small vascular (vascular external diameter 50-150 um) (P<0.01), reduced RV fibrosis, and increased RV cardiomyocyte area (P<0.01). Furthermore, sevoflurane reduced IL-6 and TNF-α expression in lungs and heart (P<0.01), decreased level of MDA (P<0.01) and increased activity of SOD and GSH-Px (P<0.01). In addition, it decreased the activities of NF-κB and MAPK pathways (P<0.01).ConclusionSevoflurane reduces pulmonary vascular remodeling and RVH in PAH induced by MCT in rats. This effect is likely due to down-regulation of inflammatory factors IL-6 and TNF-α, reduced level of oxidative stress and the inhibition of NF-κB and MAPK pathways.

Project description:BackgroundIn acute pulmonary embolism, chest computed tomography angiography derived metrics, such as the right ventricle (RV): left ventricle ratio are routinely used for risk stratification. Paucity of intraparenchymal blood vessels has previously been described, but their association with clinical biomarkers and outcomes has not been studied. We sought to determine if small vascular volumes measured on computed tomography scans were associated with an abnormal RV on echocardiography and mortality. We hypothesized that decreased small venous volume would be associated with greater RV dysfunction and increased mortality.MethodsA retrospective cohort of patients with intermediate risk pulmonary embolism admitted to Brigham and Women's Hospital between 2009 and 2017 was assembled, and clinical and radiographic data were obtained. We performed 3-dimensional reconstructions of vasculature to assess intraparenchymal vascular volumes. Statistical analyses were performed using multivariable regression and cox proportional hazards models, adjusting for age, sex, lung volume, and small arterial volume.ResultsSeven hundred twenty-two subjects were identified of whom 573 had documented echocardiography. A 50% reduction in small venous volume was associated with an increased risk of RV dilation (relative risk: 1.38 [95% CI, 1.18-1.63], P<0.001), RV dysfunction (relative risk: 1.62 [95% CI, 1.36-1.95], P<0.001), and RV strain (relative risk: 1.67 [95% CI, 1.37-2.04], P<0.001); increased cardiac biomarkers, and higher 30-day and 90-day mortality (hazard ratio: 2.50 [95% CI, 1.33-4.67], P=0.004 and hazard ratio: 1.84 [95% CI, 1.11-3.04], P=0.019, respectively).ConclusionsLoss of small venous volume quantified from computed tomography angiography is associated with increased risk of abnormal RV on echocardiography, abnormal cardiac biomarkers, and higher risk of 30- and 90-day mortality. Small venous volume may be a useful marker for assessing disease severity in acute pulmonary embolism.

Project description:BACKGROUND:Pulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements. OBJECTIVES:This study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction. METHODS:We measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30). RESULTS:In the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [?PQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine-nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and ?PQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension. CONCLUSIONS:Metabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization.

Project description:IntroductionPulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care.MethodsA systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method.ResultsClinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy.ConclusionsThis systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.

Project description:BackgroundGroup 3 pulmonary hypertension (PH) is a common complication in patients with lung diseases but there are currently no FDA-approved therapies. The data is conflicting, but a few small studies suggest potential benefits in using Group 1 PH therapies in these patients, particularly in severe PH with right ventricular (RV) dysfunction.MethodsA retrospective cohort study of patients with severe Group 3 PH with RV dysfunction who received parenteral prostanoids from 2007-2018 at our institution was undertaken. Severe PH was defined as mean pulmonary arterial pressure (mPAP) ≥35 mmHg or mPAP 25-34 with cardiac index (CI) <2.4 L/min/m2. Routine prognostic studies including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), WHO Functional Class assessment, oxygen requirement, arterial oxygen saturation, right ventricular systolic pressure (RVSP) and right heart catheterization (RHC) pressures, were obtained before initiation of parenteral therapy and at first clinical follow-up.ResultsNine patients were included. Five were female (55.6%) with a median [interquartile range (IQR)] of 69 [54-71] years. Median CI was 1.8 (1.6-2.4) L/min/m2 and median pulmonary vascular resistance (PVR) was 14.7 (10.7-17.1) Wood units (WU). We found no statistically significant improvement in NT-proBNP levels, exercise capacity, or functional class. Resting oxygen requirement worsened from 4 to 6 L/min (P=0.04) and exertional oxygen saturation nadir worsened from 90% to 83% (P=0.01) despite the increase in FiO2 with exertion. Overall results were heterogenous: several patients demonstrated clinical stabilization, with two undergoing lung transplantation and one showing long-term stability with medical therapy. Symptoms remained severe for most: three patients discontinued prostanoid therapy, choosing to pursue hospice care.ConclusionsWe found no statistically significant improvement in NT-proBNP levels, exercise capacity, or functional class, while oxygen requirement at rest and oxygen saturation during exertion significantly worsened. Our results suggest that parenteral prostanoids should not generally be considered in the treatment of Group 3 PH patients.

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Update in Pulmonary Vascular Diseases and Right Ventricular Dysfunction 2019.

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