In vivo detection of hyperoxia-induced pulmonary endothelial cell death using (99m)Tc-duramycin.

Introduction: (99m)Tc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury.

Methods: Rats were exposed to room air (normoxic) or >98% O2 for 48 or 60 hours.

Differential lung uptake of 99mTc-hexamethylpropyleneamine oxime and 99mTc-duramycin in the chronic hyperoxia rat model.

Unlabelled: Noninvasive radionuclide imaging has the potential to identify and assess mechanisms involved in particular stages of lung injury that occur with acute respiratory distress syndrome, for example. Lung uptake of (99m)Tc-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue whereas (99m)Tc-duramycin, a new marker of cell injury, senses cell death via apoptosis or necrosis. Thus, we investigated changes in lung uptake of these agents in rats exposed to hyperoxia for prolonged periods, a common model of acute lung injury.

Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury.

Rat exposure to 60% oxygen (O(2)) for 7 days (hyper-60) or to >95% O(2) for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O(2). The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function.

Precursors and inhibitors of hydrogen sulfide synthesis affect acute hypoxic pulmonary vasoconstriction in the intact lung.

The effects of hydrogen sulfide (H(2)S) and acute hypoxia are similar in isolated pulmonary arteries from various species. However, the involvement of H(2)S in hypoxic pulmonary vasoconstriction (HPV) has not been studied in the intact lung. The present study used an intact, isolated, perfused rat lung preparation to examine whether adding compounds essential to H(2)S synthesis or to its inhibition would result in a corresponding increase or decrease in the magnitude of HPV.

Differential responses of targeted lung redox enzymes to rat exposure to 60 or 85% oxygen.

Rat exposure to 60% O(2) (hyper-60) or 85% O(2) (hyper-85) for 7 days confers susceptibility or tolerance, respectively, of the otherwise lethal effects of exposure to 100% O(2). The objective of this study was to determine whether activities of the antioxidant cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III are differentially altered in hyper-60 and hyper-85 lungs. Duroquinone (DQ), an NQO1 substrate, or its hydroquinone (DQH(2)), a complex III substrate, was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of DQH(2) and DQ were measured.

Distribution of capillary transit times in isolated lungs of oxygen-tolerant rats.

Rats pre-exposed to 85% O₂ for 5-7 days tolerate the otherwise lethal effects of 100% O₂. The objective was to evaluate the effect of rat exposure to 85% O₂ for 7 days on lung capillary mean transit time t(c) and distribution of capillary transit times (h(c)(t)). This information is important for subsequent evaluation of the effect of this hyperoxia model on the redox metabolic functions of the pulmonary capillary endothelium.

Coenzyme Q1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia.

The objective was to evaluate the pulmonary disposition of the ubiquinone homolog coenzyme Q(1) (CoQ(1)) on passage through lungs of normoxic (exposed to room air) and hyperoxic (exposed to 85% O(2) for 48 h) rats. CoQ(1) or its hydroquinone (CoQ(1)H(2)) was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of CoQ(1)H(2) and CoQ(1) were measured. CoQ(1)H(2) appeared in the venous effluent when CoQ(1) was infused, and CoQ(1) appeared when CoQ(1)H(2) was infused.

Bronchial circulation angiogenesis in the rat quantified with SPECT and micro-CT.

Introduction: As pulmonary artery obstruction results in proliferation of the bronchial circulation in a variety of species, we investigated this angiogenic response using single photon emission computed tomography (SPECT) and micro-CT.

Materials And Methods: After surgical ligation of the left pulmonary artery of rats, they were imaged at 10, 20, or 40 days post-ligation. Before imaging, technetium-labeled macroaggregated albumin ((99m)Tc MAA) was injected into the aortic arch (IA) labeling the systemic circulation.

Airway responses to esophageal acidification.

The effects of esophageal acidification on airway function are unclear. Some have found that the esophageal acidification causes a small increase in airway resistance, but this change is too small to cause significant symptoms. The aims of this study were to investigate the effects of esophageal acidification on multiple measures of airway function in chloralose-anesthetized cats.

Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs.

NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to 85% O2 for > or =7 days stimulates adaptation to the otherwise lethal effects of >95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung.

Kinetic characterization of P-glycoprotein-mediated efflux of rhodamine 6G in the intact rabbit lung.

P-Glycoprotein (P-gp) is an ATP-dependent drug efflux transporter involved in multidrug resistance and drug disposition in many organ systems. A majority of P-gp substrates are lipophilic amine drugs which also exhibit rapid extensive accumulation in lung tissue. P-gp is expressed in lung tissue, and the very nature of this drug efflux mechanism suggests a moderating role in pulmonary drug disposition.

Duroquinone reduction during passage through the pulmonary circulation.

The lungs can substantially influence the redox status of redox-active plasma constituents. Our objective was to examine aspects of the kinetics and mechanisms that determine pulmonary disposition of redox-active compounds during passage through the pulmonary circulation. Experiments were carried out on rat and mouse lungs with 2,3,5,6-tetramethyl-1,4-benzoquinone [duroquinone (DQ)] as a model amphipathic quinone reductase substrate.

Influence of gravity on radiographic contrast material-based measurements of regional blood flow distribution.

Rationale And Objectives: Radiographic measurement of regional blood flow distribution in the lungs is potentially biased because the contrast material used to track flow is denser than blood. The authors performed this study to evaluate the effect of gravity on flow estimates by using an experimental test phantom and numeric simulations.

Materials And Methods: Cross-sectionally uniform boluses of radiopaque contrast material were delivered at the upstream end of a horizontal inlet tube connected to a downstream axisymmetric bifuration attached to collecting tubing spirals.