Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disruption of endothelial barrier properties with development of noncardiogenic pulmonary edema is a major threat in lung ischemia-reperfusion (I/R) injury that occurs under conditions of lung transplantation. Inhaled nitric oxide (NO) reduced vascular leakage in lung I/R models, but the efficacy of this agent may be limited. We coadministered NO and zaprinast, a cGMP-specific phosphodiesterase inhibitor, to further augment the NO-cGMP axis. Isolated, buffer-perfused rabbit lungs were exposed to 4.5 h of warm ischemia. Reperfusion provoked a transient elevation in pulmonary arterial pressure and a negligible rise in microvascular pressure followed by a massive increase in the capillary filtration coefficient and severe lung edema formation. Inhalation of 10 parts/million of NO or intravascular application of 100 microM zaprinast on reperfusion both reduced pressor response and moderately attenuated vascular leakage. Combined administration of both agents induced no additional vasodilation at constant microvascular pressures, but additively protected against capillary leakage paralleled by a severalfold increase in perfusate cGMP levels. In conclusion, combining low-dose NO inhalation and phosphodiesterase inhibition may be suitable for the maintenance of graft function in lung transplantation by amplifying the beneficial effect of the NO-cGMP axis and avoiding toxic effects of high NO doses.
 ...
PMID:The PDE inhibitor zaprinast enhances NO-mediated protection against vascular leakage in reperfused lungs. 1095 24

1. The effects of ozone inhalation (90 min, 2.15+/-0.05 p.p.m.) and their modification by dexamethasone (20 mg kg(-1)) or the phosphodiesterase-4 inhibitor, rolipram (1 mg kg(-1)), administered (i.p.) 24 and 0.5 h before and 24 h after ozone exposure were examined in conscious guinea-pigs. 2. Ozone caused an early-phase bronchoconstriction (EPB) as a fall in specific airways conductance (sG(aw)) measured by whole body plethysmography, followed at 5 h by a late-phase bronchoconstriction (LPB) and increased respiratory rate. Rolipram did not alter this profile but dexamethasone inhibited the EPB. 3. Airway hyperreactivity to inhaled histamine (1 mM, 20 s) occurred at 0.5, 2, 12, 24 and 48 h after ozone inhalation, the 2 h change being abolished by rolipram and dexamethasone. 4. Bronchoalveolar lavage fluid (BALF) macrophages, eosinophils and neutrophils were significantly (P<0.05) elevated at 12, 24 and 48 h after ozone exposure, the 48 h influx being significantly attenuated (P<0.05) by rolipram and dexamethasone. 5. BALF nitric oxide (NO) metabolites decreased 0.5 h after ozone exposure by 52%, recovered at 2 h and significantly increased at 12 (101%) and 24 h (127%). The elevated NO was unaffected by rolipram or dexamethasone. 6. Lung oedema, measured from wet/dry weight differences, was significant 12, 24 and 48 h after ozone exposure, the latter being significantly attenuated (P<0.05) by rolipram and dexamethasone. 7. Ozone exposure of guinea-pigs produced features common to COPD. Although rolipram and dexamethasone did not affect the airway function changes, they inhibited the inflammation, airway hyperreactivity and oedema.
 ...
PMID:Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone-exposed guinea-pigs: effects of dexamethasone and rolipram. 1208 83

High-altitude pulmonary edema reflects a potentially life-threatening condition affecting susceptible persons in the second night after ascent to altitudes above 2500 m. Currently, nifedipine is the only pharmacological intervention approved for both, prevention and treatment of high-altitude pulmonary edema. We evaluated the application of the phosphodiesterase-V inhibitor sildenafil combined with the non-selective phosphodiesterase-inhibitor theophylline as preventive agents. In theory, the proposed regimen can impede the two main pathophysiological features of high-altitude pulmonary edema: the deleteriously high pulmonary artery pressure (sildenafil's task) on the one hand, and the activation of an inflammatory cascade (theophylline's task) on the other hand. We suggest that these orally applicable phosphodiesterase inhibitors might be useful in the prevention of high-altitude pulmonary edema.
 ...
PMID:Are sildenafil and theophylline effective in the prevention of high-altitude pulmonary edema? 1220 14

Patients with acute congestive heart failure generally present with profound fluid retention states and dyspnea due to pulmonary edema. If the condition is not aggressively and appropriately treated, irreversible cardiac decompensation may ensue, leading to cardiogenic shock, multiorgan failure, and death. Intravenous inotropic, vasopressor, and vasodilator therapies have proved effective in initial stabilization of acute heart failure decompensation, but these agents, particularly the traditionally used ones, are generally limited by side effects that can be egregious and include substantive ventricular arrhythmias. Dobutamine has largely replaced agents with rather profound toxicity, such as isoproterenol and epinephrine. The phosphodiesterase-inhibiting agent milrinone, having both vasodilator and inotropic properties, can produce tachycardia and significant ventricular arrhythmias, but has proven quite useful for seriously ill patients. Clinical trials of levosimendan have found a positive inotropic response when the drug is given parenterally; vasodilating properties are also evident. Clinical trials are under way to evaluate the potential benefits of endothelin receptor antagonists when given intravenously. Intravenous administration of nesiritide, a recombinant human B-type natriuretic peptide, has been shown to produce favorable hemodynamic effects, including balanced vasodilation associated with a rapid improvement in clinical symptoms.
 ...
PMID:New therapeutic choices in the management of acute congestive heart failure. 1243 58

The standard treatment for acute heart failure (synonymous with pulmonary edema) is an upright posture, oxygen, morphine (often accompanied by an antiemetic), and intravenous diuretics. This treatment has remained unchanged for many years, and the precise mechanism by which each of these methods alleviates symptoms in patients is unclear. Nitrates, oral or intravenous, are also used with benefit, and have some hemodynamic advantages over intravenous diuretics. Recently, three new forms of treatment have been investigated. The use of milrinone, a phosphodiesterase inhibitor, for exacerbation of heart failure in patients with a background of chronic heart failure was not advantageous. The trials of levosimendan, a calcium sensitizer, in patients with pulmonary edema hinted at benefit. Nesiritide, a formulation of brain natriuretic peptide, does bring about hemodynamic improvement in acute heart failure, and is at least as effective as nitroglycerin, easier to prescribe, but prone to cause hypotension. These are small but important advances that increase our knowledge of the pathophysiology of acute heart failure, and also provide an indication of which drugs are preferable for the treatment of this distressing condition.
 ...
PMID:New therapies for the management of acute heart failure. 1269 42

Hand, foot, and mouth disease and herpangina are the major clinical manifestations of enterovirus 71 (EV71) infections. Brain-stem encephalitis and pulmonary edema are severe complications that can lead to death. This study was designed to evaluate the potential therapeutic effect of milrinone, a phosphodiesterase (PDE) inhibitor, in the treatment of patients with EV71-induced pulmonary edema. We conducted a historically controlled trial of 24 children with severe EV71-induced pulmonary edema from April 1998-June 2003 in southern Taiwan. Patients were divided into groups treated before and after the introduction of milrinone therapy. Etiological diagnosis was established by viral cultures and confirmed by specific immunofluorescence and neutralization tests. All 24 patients were below 5 years of age. The mortality was lower in the milrinone-treated vs. nontreated group (36.4% vs. 92.3%, P=0.005). Sympathetic tachycardia was decreased in patients treated with milrinone compared to controls (144 +/- 17/min vs. 206 +/- 26/min, P=0.004). A marked decrease in IL-13 (77 +/- 9 pg/ml vs. 162 +/- 88 pg/ml, P=0.001) was observed in milrinone-treated patients compared to controls. There was a significant reduction in white blood cell (10,838 +/- 4,537/mm3 vs. 19,475 +/- 7,798/mm3, P=0.009) and platelet (257 +/- 45 x 10(3)/mm3 vs. 400 +/- 87 x 10(3)/mm3, P=0.001) counts in milrinone-treated patients compared to controls. These results were associated with improvement in sympathetic regulation and decrease in IL-13 production. Milrinone therapy may provide a useful therapeutic approach for this highly lethal disorder.
 ...
PMID:Therapeutic efficacy of milrinone in the management of enterovirus 71-induced pulmonary edema. 1563 19

The pleiotropic cytokine tumor necrosis factor-alpha (TNF-alpha) and thrombin lead to increased endothelial permeability in sepsis. Numerous studies demonstrated the significance of intracellular cyclic nucleotides for the maintenance of endothelial barrier function. Actions of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are terminated by distinct cyclic nucleotide phosphodiesterases (PDEs). We hypothesized that TNF-alpha could regulate PDE activity in endothelial cells, thereby impairing endothelial barrier function. In cultured human umbilical vein endothelial cells (HUVECs), we found a dramatic increase of PDE2 activity following TNF-alpha stimulation, while PDE3 and PDE4 activities remained unchanged. Significant PDE activities other than PDE2, PDE3, and PDE4 were not detected. TNF-alpha increased PDE2 expression in a p38 mitogen-activated protein kinase (MAPK)-dependent manner. Endothelial barrier function was investigated in HUVECs and in isolated mice lungs. Selective PDE2 up-regulation sensitized HUVECs toward the permeability-increasing agent thrombin. In isolated mice lungs, we demonstrated that PDE2 inhibition was effective in preventing thrombin-induced lung edema, as shown with a reduction in both lung wet-to-dry ratio and albumin flux from the vascular to bronchoalveolar compartment. Our findings suggest that TNF-alpha-mediated up-regulation of PDE2 may destabilize endothelial barrier function in sepsis. Inhibition of PDE2 is therefore of potential therapeutic interest in sepsis and acute respiratory distress syndrome (ARDS).
 ...
PMID:Tumor necrosis factor-alpha-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability. 1565 61

Platelet aggregation is the key process in primary hemostasis. Certain conditions such as hypoxia may induce platelet aggregation and lead to platelet sequestration primarily in the pulmonary microcirculation. We investigated the influence of high-altitude exposure on platelet function as part of a larger study on 30 subjects with a history of high-altitude pulmonary edema (HAPE) and 10 healthy controls. All participants were studied in the evening and the next morning at low altitude (450 m) and after an ascent to high altitude (4,559 m). Platelet count, platelet aggregation (platelet function analyzer PFA100; using epinephrine and ADP as activators), plasma soluble P (sP)-selectin, and the coagulation parameters prothrombin fragments 1+2 and thrombin-antithrombin complex were measured. High-altitude exposure decreased the platelet count, shortened the platelet function analyzer closure time by approximately 20%, indicating increased platelet aggregation, increased sP-selectin levels to approximately 250%, but left plasma coagulation unaffected. The HAPE-susceptible subjects were prophylactically treated with either tadalafil (a phosphodiesterase 5 inhibitor), dexamethasone, or placebo in a double-blind way. Subgroup analyses between these different treatments and comparisons of the seven placebo-treated individuals developing HAPE and controls revealed no differences in platelet count, platelet aggregation, or sP-selectin values. We conclude that exposure to high altitude activates platelets, which leads to platelet aggregation, platelet consumption, and decreased platelet count. These effects are, however, not more pronounced in individuals with a history of HAPE or actually suffering from HAPE than in controls and therefore may not be a pathophysiological mechanism of HAPE.
 ...
PMID:Platelet count and function at high altitude and in high-altitude pulmonary edema. 1642 Dec 78

The combination of a tendency to affect otherwise fit and healthy individuals, and a characteristically rapid progression to death within hours of the first symptoms, renders high altitude pulmonary edema (HAPE) a particularly devastating illness in travelers to high altitudes. The alveolar edema and ventilation:perfusion mismatch initiate a catastrophic downward spiral of worsening alveolar hypoxia. This reviewo discusses the rationale for the use of phosphodiesterase (PDE)5 inhibitors in HAPE, compares the pharmacokinetic properties of the available agents, and appraises the relevant experimental evidence. Although this class of drugs shows promise in high altitude medicine, further research is necessary to determine the efficacy and safety of PDE5 inhibitors as a treatment for established
 ...
PMID:Phosphodiesterase type 5 inhibitors in the treatment and prevention of high altitude pulmonary edema. 1740 18

High altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that can occur in healthy individuals who ascend rapidly to altitudes above 3000-4000m. Excessive pulmonary artery pressure (PAP) is crucial for the development of HAPE, since lowering pulmonary artery pressure by nifedipine or tadalafil (phosphodiesterase-5-inhibitor) will in most cases prevent HAPE. Recent studies using microspheres in swine and magnetic resonance imaging in humans strongly support the concept and primacy of nonuniform hypoxic arteriolar vasoconstriction to explain how hypoxic pulmonary vasoconstriction occurring predominantly at the arteriolar level can cause leakage. Evidence is accumulating that the excessive PAP response in HAPE-susceptible individuals is due to a reduced NO bioavailability. HAPE-susceptible individuals show an endothelial dysfunction in the systemic circulation in hypoxia. Lower levels of exhaled NO in hypoxia before and during HAPE suggest that this abnormality also occurs in the lungs and polymorphisms of the eNOS gene are associated with susceptibility to HAPE in the Indian and Japanese population.
 ...
PMID:High altitude pulmonary edema: a pressure-induced leak. 1760 98


<< Previous 1 2 3 4 5 Next >>