Kang Hsu

Fructose-1,6-diphosphate attenuates acute lung injury induced by ischemia-reperfusion in rats.

Objective To determine whether fructose-1,6-diphosphate (FDP) pretreatment can attenuate acute lung injury induced by ischemia-reperfusion in our isolated lung model in rats. Design Randomized, controlled study. Setting Animal care facility procedure room. Subjects Twenty-four adult male Sprague-Dawley rats each weighing 250–350 g. Interventions Typical acute lung injury in rats was induced successfully by 10 mins of hypoxia followed by 75 mins of ischemia and 50 mins of reperfusion. Ischemia-reper-fusion significantly increased microvascular permeability as measured by the capillary filtration coefficient, lung weight gain, lung weight to body weight ratio, pulmonary arterial pressure, and protein concentration of bronchoalveolar lav-age fluid. Measurements and Main Results Pretreatment with FDP significantly attenuated the acute lung injury induced by ischemia-reperfusion as shown by a significant decrease in all of the assessed variables (p < .05 p < .001). The protective effect of FDP was nearly undetectable when promazine (an ecto-adenosine 5-triphosphatase inhibitor) was added before FDP pretreatment. Conclusions Pretreatment with FDP significantly ameliorates acute lung injury induced by ischemia-reperfusion in rats.

Protective effect of lipophilic antioxidants on phorbol-induced acute lung injury in rats.

ObjectiveTo determine whether the lipophilic antioxidant U-74389G can ameliorate the acute lung injury induced by phorbol myristate acetate (PMA) in our isolated lung model in rats, and to compare its activity with the intracellular enzymes superoxide dismutase (SOD) or catalase. DesignRandomized, controlled study. SettingAnimal-care facility procedure room. SubjectsForty-two adult male Sprague-Dawley rats each weighing 250–350 g. InterventionsTypical acute lung injury was induced successfully by PMA during 60 mins of observation. PMA (2 &mgr;g/kg) elicited a significant increase in microvascular permeability (measured by using the capillary filtration coefficient Kfc), lung weight gain, the lung weight/body weight ratio, pulmonary arterial pressure, and the protein concentration of the bronchoalveolar lavage fluid. Measurements and Main Results Pretreatment with 1 mg of U-74389G significantly attenuated the acute lung injury induced by PMA, all parameters having decreased significantly (p < .001). The protective effect of U-74389G was dose dependent, but SOD (6,000 U/kg) or catalase (50,000 U/kg) exhibited no protective effect. ConclusionsU-74389G significantly ameliorates acute lung injury induced by PMA in rats.

PULMONARY EDEMA INDUCED BY PHORBOL MYRISTATE ACETATE IS ATTENUATED BY COMPOUNDS THAT INCREASE INTRACELLULAR CAMP

We have investigated the effect of terbutaline, aminophylline and dibutyryl cyclic AMP (DBcAMP) on phorbol myristate acetate (PMA)-induced acute lung injury in isolated, blood-perfused rabbit lungs. Pulmonary arterial pressure and lung weight were measured for 30 min after a bolus injection of PMA (10 μg/kg). In the group exposed to PMA alone, the mean pulmonary arterial pressure (PAP) increased from 16.33±1.28 to 77.30±6.40 mmHg (P<0.001), and lung weight increased by 70.69±10.94 g during the 30 min after PMA challenge (P<0.001). Pretreatment with terbutaline, aminophylline or DBcAMP prevented the increases in both PAP and lung weight (P<0.001). Each of the three drugs also prevented the increase in pulmonary vascular permeability induced by PMA: terbutaline, aminophylline, and DBcAMP all significantly reduced the pulmonary capillary filtration coefficient (Kfc) as well as the albumin concentration in the lung, lavage fluid after PMA exposure. Post-treatment with terbutaline 5 min after PMA administration also had a protective effect. The mechanisms responsible for these protective effects may all involve an increase in intracellular cAMP, since all three drugs increase cAMP in the lung (though by different mechanisms). Our data further indicate that the inhibition of tumor necrosis factor production may likewise play an important role in the protective effect exerted by these drugs.

Effects of an endogenous nitric oxide synthase inhibitor on phorbol myristate acetate-induced acute lung injury in rats

1. In the present study, we determined whether the endogenous nitric oxide (NO) synthase (NOS) inhibitor Nω‐nitro‐l‐arginine methyl ester (l‐NAME) could ameliorate the acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in rat isolated lung.

Dimethylthiourea ameliorates acute lung injury induced by phorbol myristate acetate in dogs

Background and Methods:The protective effects of dimethylthiourea, a potent scavenger of hydroxy radical (·OH) and hydrogen peroxide, in experimental lung injury in large animals remain controversial. The present study was designed to determine whether dimethylthiourea can ameliorate the acute lung injury produced in dogs by phorbol myristate acetate. Six dogs were infused with dimethylthiourea (0.75 μg/kg in saline) for 1.5 hrs, beginning 1 hr before an iv bolus injection of phorbol myristate acetate (17 μg/kg); six dogs received phorbol myristate acetate (17 μg/kg) alone; and six dogs were infused with saline alone. Hemodynamic changes, arterial oxygenation, and the development of lung edema were monitored for 4 hrs after phorbol myristate acetate injection to assess the extent of lung damage. Results:As compared with the dogs that received phorbol myristate acetate alone, the edematous lung damage was significantly reduced in those dogs that received dimethylthiourea as well as phorbol myristate acetate. In the dimethylthiourea-treated dogs, the lung wet/dry weight ratios were smaller (p < .01); protein concentrations in lung lavage fluid were lower (p < .01); the decrease in Pao2 was significantly reduced (p < .01); and there were significant reductions in the alveolar-arterial oxygen tension difference (P[A-a]o2) (p < .01) and shunt (Qsp/Qt) (p < .05). Also, dimethylthiourea significantly lowered the increased mean pulmonary arterial pressure levels during the second half of the experiment. Conclusions:These experimental data suggest that dimethylthiourea is capable of reducing the neutrophil-mediated lung injury produced by the release of hydroxy radical and/or hydrogen peroxide in dogs exposed to phorbol myristate acetate.

Protective effect of U74500A on phorbol myristate acetate-induced acute lung injury.

1. The present study was designed to determine whether U74500A could ameliorate acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in our rat isolated lung model compared with any amelioration induced by dimethylthiourea (DMTU), superoxide dismutase (SOD) and catalase.

Pentoxifylline attenuates acute lung injury induced by microemboli

Pentoxifylline (PTX), a methylxanthine derivative, effectively prevents acute lung injury in different animal models. To investigate whether PTX would attenuate acute lung injury induced by microemboli resulting from treatment with calcium chloride (CaCl2) suspension, an isolated blood-perfused rat lung model was used. Pretreatment with PTX prevented the increase in pulmonary arterial pressure (PAP), lung weight gain and protein concentration in the lavage fluid after CaCl2 treatment.