Research Interests: Endocrinology, Medicine, Pulmonary Hypertension, Biological Sciences, Internal Medicine, and 15 moreHemodynamics, Applied, Animals, Male, Applied Physiology, Lung, Rats, Poisons, Endothelin Receptor, Pulmonary circulation, Cardiac output, Sulfonamides, Antihypertensive agents, Medical and Health Sciences, and monocrotaline
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Research Interests: Cardiology, Medicine, Humans, Internal Medicine, Hemodynamics, and 15 moreBlood Pressure, Nitric oxide, Female, Male, Clinical Sciences, Phosphodiesterase Inhibitors, Aged, Middle Aged, Adult, Chest, Brain Natriuretic Peptide, Pulmonary Artery, epoprostenol, Pulmonary artery hypertension, and Drug synergism
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Research Interests: Endocrinology, Medicine, Pulmonary Hypertension, Humans, Internal Medicine, and 13 moreAnoxia, Animals, Phosphodiesterase Inhibitors, Experimental, Rats, Sildenafil, cyclic GMP, Atrial Natriuretic Factor, Acute Disease, Drug synergism, purines, Medical and Health Sciences, and right ventricular hypertrophy
Mechanisms that regulate atrial natriuretic peptide (ANP) expression during hypoxia are not well defined. We hypothesized that plasma immunoreactive ANP (irANP) and right heart irANP and ANP mRNA levels would be greater in a strain of... more
Mechanisms that regulate atrial natriuretic peptide (ANP) expression during hypoxia are not well defined. We hypothesized that plasma immunoreactive ANP (irANP) and right heart irANP and ANP mRNA levels would be greater in a strain of Sprague-Dawley rats that develops more severe hypoxic pulmonary hypertension (H rats) than another strain (M rats). After 3 wk of hypoxia (0.5 atm), right ventricular systolic pressure (RVSP) and the right ventricle (RV) weight-to-left ventricle plus septum (LV (+) S) weight ratio [RV/(LV+S)] were greater in H rats than in M rats (70 +/- 4 vs. 40 +/- 2 mmHg and 0.59 +/- 0.02 vs. 0.50 +/- 0.02, respectively; P < 0.05 for both), but plasma ANP increased twofold and RV irANP and ANP mRNA increased fivefold in both rat strains. After 3 days of normoxic recovery from chronic hypoxia, RVSP, RV/(LV+S), and RV irANP and ANP mRNA levels decreased in M rats but not in H rats. Plasma irANP decreased to baseline levels in both rat strains. We conclude that, in addition to changes in RV pressure and hypertrophy, hypoxia acts through other mechanisms to modulate RV ANP synthesis and circulating ANP levels in hypoxia-adapted rats.
Research Interests: Endocrinology, Physiology, Medicine, Pulmonary Hypertension, Internal Medicine, and 15 moreAnoxia, Animals, Male, Heart, Medical Physiology, Rats, Myocardium, Time Factors, Body Weight, Species Specificity, Heart Ventricles, Atrial Natriuretic Factor, systole, right ventricular hypertrophy, and Heart atria
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Atrial and brain natriuretic peptides (ANP and BNP, respectively) are potent pulmonary vasodilators that are upregulated in hypoxia-adapted rats and may protect against hypoxic pulmonary hypertension. To test the hypothesis that C-type... more
Atrial and brain natriuretic peptides (ANP and BNP, respectively) are potent pulmonary vasodilators that are upregulated in hypoxia-adapted rats and may protect against hypoxic pulmonary hypertension. To test the hypothesis that C-type natriuretic peptide (CNP) also modulates pulmonary vascular responses to hypoxia, we compared the vasodilator effect of CNP with that of ANP on pulmonary arterial rings, thoracic aortic rings, and isolated perfused lungs obtained from normoxic and hypoxia-adapted rats. We also measured CNP and ANP levels in heart, lung, brain, and plasma in normoxic and hypoxia-adapted rats. Steady-state CNP mRNA levels were quantified in the same organs by relative RT-PCR. CNP was a less potent vasodilator than ANP in preconstricted thoracic aortic and pulmonary arterial rings and in isolated lungs from normoxic and hypoxia-adapted rats. Chronic hypoxia increased plasma CNP (15 ± 2 vs. 6 ± 1 pg/ml; P < 0.05) and decreased CNP in the right atrium (35 ± 14 vs. 65 ± ...
Research Interests: Endocrinology, Physiology, Medicine, Pulmonary Hypertension, Brain, and 15 moreInternal Medicine, Anoxia, Hemodynamics, Blood Pressure, Animals, Male, American, Medical Physiology, Lung, Body Weight, Brain Natriuretic Peptide, Atrial Natriuretic Factor, Pulmonary circulation, Pulmonary Artery, and In Vitro Techniques
Pulmonary arteries from the Madison (M) strain relax more in response to acetylcholine (ACh) than those from the Hilltop (H) strain of Sprague-Dawley rats. We hypothesized that differences in endothelial nitric oxide (NO) synthase (eNOS)... more
Pulmonary arteries from the Madison (M) strain relax more in response to acetylcholine (ACh) than those from the Hilltop (H) strain of Sprague-Dawley rats. We hypothesized that differences in endothelial nitric oxide (NO) synthase (eNOS) expression and function, metabolism of ACh by cholinesterases, release of prostacyclin, or endothelium-derived hyperpolarizing factor(s) (EDHF) from the endothelium would explain the differences in the relaxation response to ACh in isolated pulmonary arteries. eNOS mRNA and protein levels as well as the NO-dependent relaxation responses to thapsigargin in phenylephrine (10−6 M)-precontracted pulmonary arteries from the M and H strains were identical. The greater relaxation response to ACh in M compared with H rats was also observed with carbachol, a cholinesterase-resistant analog of ACh, a response that was not modified by pretreatment with meclofenamate (10−5M). N ω-nitro-l-arginine (10−4 M) completely abolished carbachol-induced relaxation in H r...
Research Interests: Endocrinology, Physiology, Chemistry, Cardiology, Enzyme Inhibitors, and 15 moreMedicine, Internal Medicine, Animals, Male, Acetylcholine, Medical Physiology, Rats, Nitric Oxide Synthase, Species Specificity, Biological Factors, Phenylephrine, Potassium Chloride, Pulmonary Artery, Prostacyclin, and In Vitro Techniques
We hypothesized that a downregulation in pulmonary atrial natriuretic peptide (ANP) receptors helps raise plasma ANP levels during chronic hypoxia. We measured in vivo pulmonary uptake and plasma clearance of 125I-ANP and in vitro... more
We hypothesized that a downregulation in pulmonary atrial natriuretic peptide (ANP) receptors helps raise plasma ANP levels during chronic hypoxia. We measured in vivo pulmonary uptake and plasma clearance of 125I-ANP and in vitro pulmonary binding kinetics of 125I-ANP in normoxic and chronically hypoxic rats. Exposure to 21 days of hypobaric (0.5 atm) hypoxia did not decrease specific binding of 125I-ANP in the kidney, but pulmonary binding decreased 35 and 75% after 1 and 3 days of hypoxia, respectively, and increased 200% after 3 days of normoxic recovery from 21 days of hypoxia. The total binding capacity for ANP to lung membrane fractions from normoxic rats, chronically hypoxic rats, and rats that had recovered from hypoxia was 488 +/- 59, 109 +/- 17, and 338 +/- 48 fmol/mg, respectively (P < 0.05 for hypoxic vs. normoxic or recovered lung membranes). The area under the 125I-ANP plasma concentration curve for normoxic and hypoxic rats and normoxic rats that were infused with...
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Recent studies have focused on the role of female sex and estradiol (E2) in pulmonary arterial hypertension (PAH), but it is not known whether sex hormones are risk factors for PAH in men. We performed a case-control study to determine... more
Recent studies have focused on the role of female sex and estradiol (E2) in pulmonary arterial hypertension (PAH), but it is not known whether sex hormones are risk factors for PAH in men. We performed a case-control study to determine whether hormone levels (E2, dehydroepiandrosterone-sulfate [DHEA-S], and testosterone) are associated with PAH in men. Plasma sex hormone levels in men with idiopathic, heritable, or connective tissue disease-associated PAH were compared to those from age- and body mass index-matched men without clinical cardiovascular disease. There were 23 cases with PAH (70% had idiopathic PAH, 65% were functional class III/IV) and 67 controls. Higher E2 and E2:testosterone levels were associated with the risk of PAH (OR per 1 ln[E2:testosterone] = 6.0, 95% CI 2.2 - 16.4, p = 0.001) while higher levels of DHEA-S were associated with a reduced risk (OR per 1 ln[DHEA-S] = 0.1, 95% CI 0.0 - 0.3, p = 0.001). E2 and DHEA-S levels were strong predictors of case status (c...
Research Interests: Endocrinology, Medicine, Pulmonary Hypertension, Humans, Internal Medicine, and 14 moreMale, Body Mass Index, Risk factors, Aged, Middle Aged, Odds ratio, Dehydroepiandrosterone, Risk Factors, Sex hormone-binding globulin, Estradiol, Confidence Interval, Case Control Studies, Medical and Health Sciences, and dehydroepiandrosterone sulfate
Research Interests: Medicine, Pulmonary Hypertension, Prospective studies, Humans, Nitric oxide, and 15 moreFemale, Male, Lung, Clinical Sciences, Middle Aged, Analysis of Variance, Cardiac Output Monitoring, Combination drug therapy, Exercise Test, Pulmonary Artery, epoprostenol, Cardiac output, Pulmonary artery hypertension, purines, and Cardiovascular medicine and haematology
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Targeted disruption of the gene for natriuretic peptide receptor-A (NPR-A) worsens pulmonary hypertension and right ventricular hypertrophy during hypoxia, but its effect on left ventricular mass and systemic pressures is not known. We... more
Targeted disruption of the gene for natriuretic peptide receptor-A (NPR-A) worsens pulmonary hypertension and right ventricular hypertrophy during hypoxia, but its effect on left ventricular mass and systemic pressures is not known. We examined the effect of 3 wk of hypobaric hypoxia (0.5 atm) on right and left ventricular pressure and mass in mice with 2 (wild type), 1, or 0 copies of Npr1, the gene that encodes for NPR-A in mice. Under normoxic conditions, right ventricular peak pressure (RVPP) was greater in 0 than in 2 copy mice, but there were no genotype-related differences in carotid artery PP (CAPP). The left ventricular free wall weight-to-body weight (LV/body wt) ratio was greater in 0 than in 2 copy mice and there was a trend toward a greater right ventricular weight-to-body weight (RV/body wt) ratio. Three weeks of hypoxia increased RVPP and RV/body wt in all genotypes. The increase in RVPP was similar in all genotypes (11-14 mmHg), but the hypoxia-induced increase in RV...
Research Interests: Endocrinology, Physiology, Biology, Medicine, Internal Medicine, and 15 moreAnoxia, Mice, Animals, American, Medical Physiology, Lung, Disease Progression, Muscle hypertrophy, Hydroxyproline, Guanylate Cyclase, Atrial Natriuretic Factor, Pulmonary circulation, Carotid Arteries, Cardiomegaly, and right ventricular hypertrophy
Nitric oxide is an endogenous pulmonary vasodilator that is synthesized from L-arginine in pulmonary vascular endothelial cells by nitric oxide synthase and diffuses to adjacent vascular smooth muscle cells where it activates soluble... more
Nitric oxide is an endogenous pulmonary vasodilator that is synthesized from L-arginine in pulmonary vascular endothelial cells by nitric oxide synthase and diffuses to adjacent vascular smooth muscle cells where it activates soluble guanylyl cyclase. This enzyme converts GTP to cGMP which activates cGMP dependent protein kinase leading to a series of events that decrease intracellular calcium and reduce vascular muscle tone. Nitric oxide is an important mediator of pulmonary vascular tone and vascular remodeling. A number of studies suggest that the bioavailability of nitric oxide is reduced in patients with pulmonary vascular disease and that augmentation of the nitric oxide/cGMP pathway may be an effective strategy for treatment. Several medications that target nitric oxide/cGMP signaling are now available for the treatment of pulmonary hypertension. This review explores the history of nitiric oxide research, describes the major NO synthetic and signaling pathways and discusses a...
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Research Interests: Adolescent, Medicine, Prospective studies, Humans, Internal Medicine, and 15 moreEurope, Respite Care, Female, Male, Pulmonary arterial hypertension, North America, Phosphodiesterase Inhibitors, Aged, Middle Aged, Adult, Pyrazoles, Adverse effect, Riociguat, Antihypertensive agents, and Medical and Health Sciences
BackgroundBreathlessness is the most common symptom reported by patients with pulmonary arterial hypertension (PAH). The Modified Borg Dyspnea Scale (MBS) is routinely obtained during the six‐minute walk test in the assessment of PAH... more
BackgroundBreathlessness is the most common symptom reported by patients with pulmonary arterial hypertension (PAH). The Modified Borg Dyspnea Scale (MBS) is routinely obtained during the six‐minute walk test in the assessment of PAH patients, but it is not known whether the MBS predicts clinical outcomes such as hospitalizations in PAH.MethodsWe performed a retrospective study of World Health Organization (WHO) Group 1 PAH patients followed at our center. The dates of the first three MBS and hospitalizations that occurred within three months of a documented MBS were collected. Marginal Cox hazard regression modeling was used to assess for a relationship between MBS and all‐cause as well as PAH‐related hospitalization.ResultsA total of 50 patients were included; most (92%) were functional class III/IV, 44% and 65% were treatment‐naïve prior to their first MBS and hospitalization, respectively. The first recorded MBS was inversely correlated with the first recorded six‐minute walk di...
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The aromatase inhibitor anastrozole blocks the conversion of androgens to estrogen and blunts pulmonary hypertension in animals, but its efficacy in treating patients with pulmonary arterial hypertension (PAH) is unknown. We aimed to... more
The aromatase inhibitor anastrozole blocks the conversion of androgens to estrogen and blunts pulmonary hypertension in animals, but its efficacy in treating patients with pulmonary arterial hypertension (PAH) is unknown. We aimed to determine the safety and efficacy of anastrozole in PAH. We performed a randomized, double-blind, placebo-controlled trial of anastrozole in patients with PAH receiving background therapy at two centers. A total of 18 patients with PAH were randomized to anastrozole 1 mg or matching placebo in a 2:1 ratio. The two co-primary outcomes were percent change from baseline in 17β-estradiol levels (E2) and tricuspid annular plane systolic excursion (TAPSE) at three months. Anastrozole significantly reduced E2 levels compared to placebo (% change, -40% [IQR, -61 to -26%] vs -4% [IQR, -14 to +4%], p = 0.003), but there was no difference in TAPSE. Anastrozole significantly increased the six-minute walk distance (6MWD) (median change = +26 m) compared to placebo (...
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Atrial natriuretic peptide (ANP) inhibits agonist-induced pulmonary edema formation, but the signaling pathway responsible is not well defined. To investigate the role of the particulate guanylate cyclase-linked receptor, natriuretic... more
Atrial natriuretic peptide (ANP) inhibits agonist-induced pulmonary edema formation, but the signaling pathway responsible is not well defined. To investigate the role of the particulate guanylate cyclase-linked receptor, natriuretic peptide receptor-A (NPR-A), we measured acute lung injury responses in intact mice and pulmonary microvascular endothelial cells (PMVEC) with normal and disrupted expression of NPR-A. NPR-A wild-type (NPR-A+/+), heterozygous (NPR-A+/−), and knockout (NPR-A−/−) mice were anesthetized and treated with thrombin receptor agonist peptide (TRAP) or lipopolysaccharide (LPS). Lung injury was assessed by lung wet-to-dry (W/D) weight and by protein and cell concentration of bronchoalveolar lavage (BAL) fluid. No difference in pulmonary edema formation was seen between NPR-A genotypes under baseline conditions. TRAP and LPS increased lung W/D weight and BAL fluid cell counts more in NPR-A−/− mice than in NPR-A+/− or NPR-A+/+ mice, but no genotype-related differenc...
Research Interests: Endocrinology, Medicine, Signal Transduction, Biological Sciences, Thrombin, and 15 moreInternal Medicine, Endothelial Cells, Mice, Animals, Vascular endothelium, Applied Physiology, Lipopolysaccharides, Receptors, Receptor, Lung Injury, Pulmonary Edema, Agonist, Bronchoalveolar lavage, Atrial Natriuretic Factor, and Medical and Health Sciences
Research Interests: Medicine, Pulmonary Hypertension, Multivariate Analysis, Humans, Internal Medicine, and 14 moreHemodynamics, Blood Pressure, Female, Male, Risk factors, Aged, Middle Aged, Adult, Sex Factors, Risk Factors, Vascular Resistance, Randomized Controlled Trials as Topic, Cardiac output, and Medical and Health Sciences
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In the present study, we assessed the effects of chemical inhibitors shown to be selective for protein kinase C (PKC) isoforms on lung barrier function both in vitro and in vivo. Rottlerin, a purported inhibitor of PKCdelta, but not other... more
In the present study, we assessed the effects of chemical inhibitors shown to be selective for protein kinase C (PKC) isoforms on lung barrier function both in vitro and in vivo. Rottlerin, a purported inhibitor of PKCdelta, but not other chemical inhibitors, dose dependently promoted barrier dysfunction in lung endothelial cells in vitro. This barrier dysfunction correlated with structural changes in focal adhesions and stress fibers, which were consistent with functional changes in cell stiffness. To determine whether the effects noted in vitro correlated with changes in intact lungs, we tested the effects of rottlerin in the formation of pulmonary edema in rats using both ex vivo and in vivo models. Isolated, perfused lungs demonstrated a significant increase in filtration coefficients on exposure to rottlerin, compared with vehicle-treated lungs, an effect that correlated with increased extravasation of Evan&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s blue dye (EBD)-conjugated albumin. Additionally, compared with vehicle, the ratio of the wet lung weights to dry lung weights was significantly greater on exposure of animals to rottlerin; rottlerin also produced a dose-dependent increase in EBD extravasation into the lungs. These effects on lung edema occurred without any increase in right ventricular pressures. Microscopic assessment of edema in the ex vivo lungs demonstrated perivascular cuffing, with no evidence of septal capillary leak, in rottlerin-exposed lungs. Taken together, rottlerin increases barrier dysfunction in pulmonary endothelial cell monolayers and causes pulmonary edema in rats; results suggestive of an important role for PKCdelta in maintaining lung endothelial barrier function.
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To compare the ease and efficacy of two commonly used methods for choosing optimal positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome: a static pressure-volume curve to determine the lower... more
To compare the ease and efficacy of two commonly used methods for choosing optimal positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome: a static pressure-volume curve to determine the lower inflection point (P(flex)) and the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;best PEEP&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (PEEP(best)) as determined by the maximal compliance curve. Prospective study. Medical and respiratory intensive care units of university-associated tertiary care hospital. Twenty-eight patients on mechanical ventilation with acute respiratory distress syndrome. A critical care attending physician or fellow and an experienced respiratory therapist attempted to obtain both static pressure-volume curves and maximal compliance curves on 28 patients with acute respiratory distress syndrome by using established methods that were practical to everyday use. The curves then were used to determine both P(flex) and PEEP(best), and the results were compared. Our results showed at least one value for optimal PEEP was obtained in 26 of 28 patients (93%). P(flex) was determined in 19 (68%), a PEEP(best) in 24 (86%), and both values in 17 (61%). In patients who had both P(flex) and PEEP(best) determined, there was a close concordance (+/-3 cm H2O) in 60%. When the values of P(flex) and PEEP(best) were interpreted by two additional investigators, there was unanimous agreement on the P(flex) (+/-3) only 64% of the time. There was agreement on the value of PEEP(best) 93% of the time. Our data show that optimal PEEP, as determined by a pressure-volume curve and a maximal compliance curve, are sometimes unobtainable by practical means but, when obtained, often correspond. A maximal compliance is more often identified, has less interobserver variability, and poses less risk to the patient. We conclude that determining optimal PEEP by maximal static compliance may be easier to measure and more frequently obtained at the bedside than by using a static pressure-volume curve.
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Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our... more
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... From the Division of Pulmonary and ...
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Nitric oxide is an endothelial relaxing factor. When given as an inhalational agent in the acute respiratory distress syndrome (ARDS), it vasodilates well ventilated areas of lung and improves oxygenation. Nitric oxide is a highly... more
Nitric oxide is an endothelial relaxing factor. When given as an inhalational agent in the acute respiratory distress syndrome (ARDS), it vasodilates well ventilated areas of lung and improves oxygenation. Nitric oxide is a highly reactive molecule with myriad biologic effects, both potentially beneficial and toxic; its use as an inhalational agent in ARDS is experimental. This article reviews the available studies of inhaled nitric oxide.
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Right ventricular dysfunction is common in sepsis and septic shock because of decreased myocardial contractility and elevated pulmonary vascular resistance despite a concomitant decrease in systemic vascular resistance. The mainstay of... more
Right ventricular dysfunction is common in sepsis and septic shock because of decreased myocardial contractility and elevated pulmonary vascular resistance despite a concomitant decrease in systemic vascular resistance. The mainstay of treatment for acute right heart failure includes treating the underlying cause of sepsis and reversing circulatory shock to maintain tissue perfusion and oxygen delivery. Decreasing pulmonary vascular resistance with selective pulmonary vasodilators is a reasonable approach to improving cardiac output in septic patients with right ventricular dysfunction. Treatment for right ventricular dysfunction in the setting of sepsis should concentrate on fluid repletion, monitoring for signs of RV overload, and correction of reversible causes of elevated pulmonary vascular resistance, such as hypoxia, acidosis, and lung hyperinflation.
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Research Interests: Quality of life, Treatment Outcome, Pulmonary Hypertension, Activities of Daily Living, Humans, and 18 moreFemale, Male, Statistical Significance, Exercise, Follow-up studies, Placebos, STEM (short form), Dyspnea, Clinical Sciences, Aged, Middle Aged, Public health systems and services research, Circulation, World Health Organization, Low Risk, PHARMACY TECHNOLOGY, Health Survey, and Treatment Effect
A 27-year-old woman presented with cough, fever, and pulmonary infiltrates after heavy cocaine smoking. Large amounts of carbonaceous material and pigment-laden macrophages were recovered by bronchoalveolar lavage. Alveolar deposition of... more
A 27-year-old woman presented with cough, fever, and pulmonary infiltrates after heavy cocaine smoking. Large amounts of carbonaceous material and pigment-laden macrophages were recovered by bronchoalveolar lavage. Alveolar deposition of particulate matter from heavy cocaine smoking has not been previously reported and may have been the cause of this patient&#39;s symptoms and abnormal findings on chest radiograph.
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Nitric oxide (NO) signaling plays a major role in modulating vascular tone and remodeling in the pulmonary circulation, but its role in the pathogenesis of pulmonary vascular diseases is still not completely understood. Numerous... more
Nitric oxide (NO) signaling plays a major role in modulating vascular tone and remodeling in the pulmonary circulation, but its role in the pathogenesis of pulmonary vascular diseases is still not completely understood. Numerous abnormalities of NO synthesis and signaling have been identified in animal models of pulmonary vascular disease and in humans with pulmonary hypertension. Many of these abnormalities have become targets of new therapies for the treatment of pulmonary hypertension. However, it is unclear to what extent alterations in NO signaling contribute to pulmonary hypertensive responses or merely reflect abnormalities induced by the underlying disease. This perspective examines the current understanding of altered NO signaling in pulmonary hypertensive diseases and discusses how these alterations may contribute to the pathogenesis of pulmonary hypertension. The efficacy and limitations of presently available therapies for pulmonary hypertension that target NO signaling are reviewed along with an update on investigational therapies that use this pathway to reverse pulmonary hypertensive changes.
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Research Interests: Humans, Male, Lung Diseases, Aged, Middle Aged, and 3 moreBullous Pemphigoid, Hemorrhage, and Hemoptysis
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Research Interests: Psychology, Gastroenterology, Magnetic Resonance Imaging, Pulmonary Hypertension, Biopsy, and 23 moreHumans, Postgraduate medical education, Female, Thorax, Multiple Myeloma, Male, Young Adult, Differential Diagnosis, Lung, Clinical Sciences, Aged, Middle Aged, Gastrointestinal Endoscopy, Adult, Public health systems and services research, Sternum, BMJ, Chest, Pleural Effusion, X ray Computed Tomography, Abscess, Chest Pain, and Neurosciences
Rationale Mesenchymal stem cell extracellular vesicles (MSC EVs) reverse pulmonary hypertension, but little information is available regarding what dose is effective and how often it needs to be given. This study examined the effects of... more
Rationale Mesenchymal stem cell extracellular vesicles (MSC EVs) reverse pulmonary hypertension, but little information is available regarding what dose is effective and how often it needs to be given. This study examined the effects of dose reduction and use of longer dosing intervals and the effect of hypoxic stress of MSC prior to EV collection. Methods Adult male rats with pulmonary hypertension induced by Sugen 5416 and three weeks of hypoxia (SuHx-pulmonary hypertension) were injected with MSC EV or phosphate buffered saline the day of removal from hypoxia using one of the following protocols: (1) Once daily for three days at doses of 0.2, 1, 5, 20, and 100 µg/kg, (2) Once weekly (100 µg/kg) for five weeks, (3) Once every other week (100 µg/kg) for 10 weeks, (4) Once daily (20 µg/kg) for three days using EV obtained from MSC exposed to 48 h of hypoxia (HxEV) or MSC kept in normoxic conditions (NxEV). Main results MSC EV reversed increases in right ventricular systolic pressure...
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Colice, Gene L., Nicholas Hill, Yan-Jie Lee, Hongkai Du, James Klinger, James C. Leiter, and Lo-Chang Ou. Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness. J. Appl. Physiol. 83(1):... more
Colice, Gene L., Nicholas Hill, Yan-Jie Lee, Hongkai Du, James Klinger, James C. Leiter, and Lo-Chang Ou. Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness. J. Appl. Physiol. 83(1): 25–31, 1997.—Hilltop (H) strain Sprague-Dawley rats are more susceptible to chronic mountain sickness than are the Madison (M) strain rats. It is unclear what role pulmonary vascular remodeling, polycythemia, and hypoxia-induced vasoconstriction play in mediating the more severe pulmonary hypertension that develops in the H rats during chronic hypoxia. It is also unclear whether the increased sensitivity of the H rats to chronic mountain sickness is specific for a hypoxia effect or, instead, reflects a general propensity toward the development of pulmonary hypertension. Monocrotaline (MCT) causes pulmonary vascular remodeling and pulmonary hypertension. We hypothesized that the difference in the pulmonary vascular response to chronic hypoxia between H ...
Research Interests: Medicine, Pulmonary Hypertension, Biological Sciences, Internal Medicine, Blood Pressure, and 15 moreApplied, Animals, Male, Applied Physiology, Lung, Vasoconstriction, Rats, Altitude Sickness, Poisons, Altitude, Blood gas analysis, Heart Ventricles, Respiratory Mechanics, Medical and Health Sciences, and monocrotaline
High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown.Post-menopausal women aged... more
High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown.Post-menopausal women aged ≥55 years with PAH were matched by age and body mass index to women without cardiovascular disease. Plasma sex hormone levels were measured by immunoassay.Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02) were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were associated with worse haemodynamics (all p<0.01) and more right ventricular dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class (p=0.004). Each Ln(1 µg·dL) decrease in DHEA-S was associated with a doubling in the risk of death (hazard ratio 2.0, 95% CI 1.5-2.7; p<0.001). Higher levels of E2 were associated with shorter 6MWD (p=0.03) and worse functiona...