Evaluation of the inflammatory response in a two-hit acute lung injury model using [18F]FDG microPET

Abstract

The aim of this study was to investigate whether a two-hit acute lung injury (ALI) model is better than a one-hit model in simulating ALI, and to evaluate the inflammatory response in the lungs in these two models using micro-positron emission tomography (microPET) with [18F]fluorodeoxyglucose (FDG). Sprague Dawley rats were divided into four groups; rats in the lipopolysaccharide (LPS; n=10) and LPS-HCl (n=10) groups were challenged by the intraperitoneal administration of 5 mg/kg LPS, while rats in the normal saline (NS; n=3) and HCl (n=10) groups received the same volume of normal saline solution. Sixteen hours following the administration, the rats in the HCl and LPS-HCl groups received an acid instillation (IT) of 0.5 ml/kg HCl (pH=1.2), while the rats in the remaining two groups received the same volume of normal saline solution. The mean arterial blood pressure (MAP) and blood gas concentrations were measured in all four groups. MicroPET was performed 4 h following HCl IT and the lungs were excised for histopathological examination. The rats in the LPS-HCl group exhibited a higher arterial PaO2 and a lower arterial PaCO2 compared with the rats in the remaining groups. The MAP decreased markedly in the LPS-HCl group, but remained stable in the LPS, HCl and NS groups. MicroPET results identified that the region of interest ratio in the LPS-HCl group (9.00±1.41) was significantly higher compared with those in the LPS (4.01±0.60) and HCl (3.33±0.55) groups (P<0.01). In addition, histological examination showed that the mean lung injury score in the LPS-HCl group (12.70±0.95) was significantly higher compared with those in the HCl (8.40±1.26) and LPS (7.00±0.82) groups (P<0.01). The present study demonstrates that LPS pretreatment significantly magnifies and prolongs the inflammatory response to subsequent acid IT in the lungs. Moreover, it is simpler to induce ALI using the two-hit model than with the one-hit model, and [18F]FDG microPET is a useful tool for evaluating the inflammatory reaction during ALI.

Comparison of direct and indirect models of early induced acute lung injury

“…In a comprehensive mouse model, ALI induced by orotracheal HCL instillation monitored over 10 days, it was observed an early acute neutrophil infiltration matched by a marked increase in BAL neutrophils over 2 days [ 24 ]. These findings were reproduced previously in other models of HCL tracheal instillation as early as 4 h [ 25 ].…”

“…In a comprehensive mouse model, ALI induced by orotracheal HCL instillation monitored over 10 days, it was observed an early acute neutrophil infiltration matched by a marked increase in BAL neutrophils over 2 days [24]. These findings were reproduced previously in other models of HCL tracheal instillation as early as 4 h [25]. Although our HCl model was based in previous methods [26], we did not observe lung injury at 24 h. In previous studies performed by our group, we observed with a lower concentration of 300 μl of HCl (1.2 μl/g, 0.1 mol/l pH = 1.4) higher protein levels in the bronchoalveolar lavage and raised lung weight at 2 h, but no damage at 24 h [27,28].…”

JNK inhibitor SP600125 protects against lipopolysaccharide-induced acute lung injury via upregulation of claudin-4

“…ALI has a high mortality rate and 40–50% of patients succumb to multiple organ failure (3). In the present study, the effect of SP600125, a JNK selective inhibitor, in LPS-induced ALI and its underlying mechanism was investigated.…”

“…Despite significant advances in antimicrobial supportive care and therapy to improve the survival rate of patients with ALI, the mortality rate remains high (~40%) (3). Therefore, the development of novel and effective measures against ALI is required.…”

Use of micro-positron emission tomography with 18F-fallypride to measure the levels of dopamine receptor-D2 and 18F-FDG as molecular imaging tracer in the pituitary glands and prolactinomas of&nbsp;Fischer-344 rats

“…The PET tracers, 18 F-fallypride and 18 F-FDG, were prepared by the reaction of 18 F with precursors, according to published methods. 13 , 14 The decay corrected radiochemical yield was ~24%; the specific radioactivity was greater than 100 TBq/mmol at the moment of injection, and the radiochemical purity was greater than 98%. The 18 F-fallypride and 18 F-FDG solutions had a pH of 6.0–7.0.…”