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

Pulmonary edema which develops during acute myocardial infarction is generally believed to result solely from pulmonary microvascular hypertension. However, patient with myocardial infarction and pulmonary edema occasionally are found to have normal pulmonary wedge pressure. We report data indicating that pulmonary edema develops after coronary artery ligation despite stable microvascular pressure. Four groups of open-chest dogs were studied: (1) nine dogs with left anterior descending coronary artery ligation, (2) seven dogs with sham coronary ligation, (3) seven dogs ligated after beginning an infusion of indomethacin (5 mg/kg per hr), and (4) five dogs ligated after an infusion of the drug's vehicle was begun. Extravascular lung water and pulmonary blood volume were measured at hourly intervals during the 2 hours before and after coronary ligation or sham ligation. Gravimetric lung water was measured immediately thereafter. Changes of net pulmonary intravascular driving force (the difference of microvascular hydrostatic and oncotic pressure) after ligation or sham ligation were small and comparable in all groups. Pulmonary blood volume did not change in any group. Pulmonary extravascular water volume remained constant in the sham group but rose significantly in the ligated group. Gravimetric lung water also was significantly higher in the latter group. We interpret these results to indicate that factors other than microvascular pressure can mediate the formation of these results to indicated that factors other than microvascular pressure can mediate the formation of edema during acute myocardial infarction; increased pulmonary microvascular permeability may be responsible. Indomethacin infusion blocked the formation of edema after coronary ligation, even though net microvascular driving force was highest in this group. Infusion of the vehicle alone did not prevent edema. The mechanism by which indomethacin exerts this protective effect is unclear but is probably a result of its inhibition of cyclo-oxygenase or cyclic nucleotide phosphodiesterase.
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PMID:Non-hydrostatic pulmonary edema after coronary artery ligation in dogs. Protective effect of indomethacin. 705 61

There is a need for pharmacological agents for the treatment of pulmonary edema associated with the adult respiratory distress syndrome. Therefore, we examined the effects of isozyme-selective cyclic AMP phosphodiesterase (cAMP PDE) inhibitors, as well as aminophylline and dexamethasone, on the pulmonary edema, protein leakage into the airways and airway neutrophilia induced by aerosolized lipopolysaccharide (LPS) in intact guinea pigs. Twenty-four hours after LPS exposure lung wet/dry weight ratios increased from 4.9 +/- 0.004 to 5.8 +/- 0.02. Rolipram (PDE4 selective), CI-930 (PDE3 selective), aminophylline and dexamethasone (given p.o. 1 hr before and 4 hr after LPS exposure) inhibited pulmonary edema formation with ED50 values of 1.7, 0.5, 31 and 2.8 mg/kg, respectively. Maximum inhibition occurred with rolipram at 10 mg/kg (70 +/- 17%), CI-930 at 10 mg/kg (101 +/- 4%), aminophylline at 50 mg/kg (88 +/- 14%) and dexamethasone at 3 mg/kg (64 +/- 6%). Denbufylline and milrinone also inhibited pulmonary edema formation at 10 mg/kg i.p., supporting the inhibition of PDE4 and PDE3 as the mechanisms of action of rolipram and CI-930, respectively. Rolipram, CI-930, aminophylline and dexamethasone (at maximum doses for inhibiting pulmonary edema) inhibited the 3-fold increase in bronchoalveolar lavage albumin concentration 24 hr after LPS exposure (42 +/- 14%, 98 +/- 2%, 70 +/- 9% and 53 +/- 13%, respectively). However, none of these compounds (at maximum doses for inhibiting pulmonary edema) inhibited the corresponding 400-fold increase in lavage neutrophil counts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of lipopolysaccharide-induced pulmonary edema by isozyme-selective phosphodiesterase inhibitors in guinea pigs. 747 57

Severe congestive heart failure and cardiogenic shock don't resemble a homogeneous clinical picture, but a syndrome that is based on very different etiologies. What all the etiologies have in common is the inadequate peripheral O2-supply to essential organs with or without signs of severe pulmonary congestion up to pulmonary edema. For prognosis and therapy is a fast diagnostical clarification of the causes crucial. The therapeutical procedure for the various etiologies may be diametrically opposed. For the therapy is it also dicisive to distinguish between acute myocardial failure, e.g. acute myocardial infarction, and the development of myocardial failure from a longer existing consistent congestive heart failure (cardiomyopathy). Whenever possible, next to symptomatically therapy of cardiogenic shock the basic conditions of the disease should be cured (e.g., PTCA, lysis with acute myocardial infarction, lysis in acute pulmonary embolism). In myogenic cardiogenic shock the use of positive-inotropic substances with and without simultaneous vasodilatory effects, if necessary in combination with other vasodilators, may be life-saving. Up until now there still doesn't exist an alternative to the catecholamines in the acute phase, initially they should be used as a first-line-therapy to stabilize the hemodynamics. The insertion of a Swan-Ganz-catheter for invasive therapy-monitoring, especially for the regulation of the therapy is a "condition sine qua non" for every patient with unstable hemodynamics. Because of the prompt beta-receptor-down-regulation during shock, caused by endogenous catecholamines, successful therapy with exogenous catecholamines is limited (adrenaline, dopamine, dobutamine), on account of the acceleration and intensification of the beta-receptor-down-regulation process. Possible beta-receptor independent alternatives are beta 2-agonists (dopexamine), PDE-III-inhibitors (amrinone, milrinone, enoximone) as well as H2-receptor agonists (impromidine, arpromidine) and finally the calcium-sensitisers (pimobendane). First results give rise to optimism to effectively reduce the mortality of congestive heart failure. The combination of these new pharmacological possibilities with interventional transcutaneous applicable assist-systems (aortic counterpulsationpump IABP, hemopump, transcutaneous heart-lung-machine) as well as the transitory application of an artificial heart (Novacor) can possibly increase the success of these therapeutic strategies. So far there are no convincing results shown in the world literature.
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PMID:[Pharmacotherapy of severe heart failure with inodilators--new approaches]. 902 10

The pharmacotherapy of prevention and treatment of acute altitude- related problems - acute mountain sickness, high-altitude cerebral oedema and high-altitude pulmonary oedema - is reviewed. Drug therapy is only part of the answer to the medical problems of high altitude; prevention should include slow ascent and treatment of the more severe illnesses should include appropriate descent. Carbonic anhydrase inhibitors, in particular acetazolamide, remain the most effective drugs in preventing, to a large extent, the symptoms of acute mountain sickness, and can be used in the immediate management of the more severe forms of altitude-related illnesses. Glucocorticoids in relatively large doses are also effective preventative drugs, but at present are largely reserved for the treatment of the more severe acute mountain sickness and acute cerebral oedema. Calcium channel blockers and PDE-5 inhibitors are effective in the management of acute pulmonary oedema. Further work is required to establish the role of antioxidants and anticytokines in these syndromes.
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PMID:High hopes at high altitudes: pharmacotherapy for acute mountain sickness and high-altitude cerebral and pulmonary oedema. 1807 43

In the present study, we investigated the effect of classic PDE4 inhibitor rolipram and novel PDE4 inhibitor ZL-n-91 on LPS-induced acute lung injury (ALI) in mice and its mechanism. ALI was induced in ICR mice by instilling intratracheally with LPS, and mice were divided into seven groups: control (Saline), LPS group, ZL-n-91 (3 microg, 10 microg, and 30 microg kg(-1), ip), Rolipram (1.0 mg kg(-1), ip) and dexamethasone (0.5 mg kg(-1), ip). After the 6h of instilling intratracheally with LPS in mice, total leukocyte number, neutrophil number and protein content in BALF increased rapidly, a large number of neutrophil infiltration around the pulmonary vessel and airway, the lung wet weight/dry weight (w/d)ratio raised significantly. MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate raised significantly. P(a)O(2), P(a)CO(2) and PH value in peripheral arterial blood also changed obviously, P(a)O(2) and PH value dropped slightly and P(a)CO(2) increased significantly in LPS group. ZL-n-91 (3 microg, 10 microg, 30 microg kg(-1)) dose-dependently reduced the total leukocyte number, neutrophil number and total protein content in BALF, MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate, but the effect of ZL-n-91 in pathological changes and lung wet w/d ratio is slight; Rol and Dex significantly reduced lung wet w/d ratio and improved pathological changes, neutrophil around the pulmonary vessel and airway significantly reduced, symptoms of lung edema relieved; The PH value, P(a)O(2) and P(a)CO(2) in ZL-n-91 high dosage group and Rol group had changes, but there was no significant difference compared with LPS group or saline group; After the administration, the righting reflex recovery time significantly shorten in every group of ZL-n-91. the righting reflex recovery time of Rol group was similar with ZL-n-91 30 microg kg(-1) group, while Dex group was similar with saline group. The present study confirms that the inhibitory effect of ZL-n-91(30 microg kg(-1)) on the inflammatory reactivity, including inhibition of inflammatory cell and protein exudation, MPO and PDE4 activity, improvement of the blood gas, those effects were equivalent with rolipram 1 mg kg(-1), and suggested that ZL-n-91 was stronger than rolipram in PDE4 inhibition. So we speculated that ZL-n-91 may have stronger therapeutic potential for treatment of inflammatory disease than rolipram, meantime have stronger nervous system effect than rolipram.
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PMID:Action of a Novel PDE4 inhibitor ZL-n-91 on lipopolysaccharide-induced acute lung injury. 2007 67

Coronavirus Disease 2019 (COVID-19) has had a devastating impact on the ability of highly trained healthcare providers to render sufficient care, due to both the significant demand on resources and the unique nature of this disease that make it resistant to traditional therapies. This review sought to determine the potential role of phosphodiesterase-5 inhibitors (PDE-5) in the management of COVID-19 by extrapolating relevant data and clinical studies from other related disease states, including acute respiratory distress syndrome, acute lung injury, and high altitude pulmonary edema. Following a literature search, 4 reports were analyzed and included in this review. While the heterogenicity of data and the small number of trials included limit the interpretation and applicability, it was consistently demonstrated that PDE-5 inhibitors lowered pulmonary arterial pressures. The overall benefit of these agents is seemingly dependent upon the etiology of the respiratory failure, which warrants expanded clinical investigation for COVID-19.
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PMID:The Role of Phosphodiesterase-5 Inhibitors in COVID-19: An Exploration of Literature From Similar Pathologies. 3290 98