Postoperative Dexmedetomidine Infusion and Chronic Postsurgical Pain in Thoracoscopic Pulmonary Nodule Surgery: A Retrospective Study with Propensity-Score-Matched Analysis.

INTRODUCTION: Patients frequently suffer from debilitating chronic postsurgical pain (CPSP) subsequent to thoracoscopic surgery. The impact of postoperative dexmedetomidine infusion on CPSP remains elusive. This study aimed to scrutinize the effect of dexmedetomidine on both 1-year incidence of CPSP and the quality of recovery after thoracoscopic pulmonary nodule surgery. METHODS: This retrospective analysis encompassed clinical and follow-up data from 1148 patients undergoing thoracoscopic pulmonary nodule surgery at our institution between September 2021 and August 2022. Depending on whether dexmedetomidine was infused intravenously or not on the first night after surgery, patients were stratified into the dexmedetomidine group or the control group, with propensity score matching applied to harmonize baseline characteristics. Comparative analysis sought to delineate distinctions of CPSP and recovery quality 1 year after surgery. RESULTS: Following propensity score matching, a cohort of 258 patients in each group underwent analysis. Comparisons after matching revealed no statistically significant disparities in 1-year CPSP incidence [76/258 (29.5%) versus 78/258 (30.2%), P = 0.847], moderate-to-severe pain occurrence [17/76 (22.4%) versus 22/78 (28.2%), P = 0.405], neuropathic pain occurrence [11/76 (14.5%) versus 11/78 (14.1%), P = 0.948], and postoperative recovery quality assessed by 12-Item Short Form Health Survey (SF-12) score (113.1 [107.2, 116.0] versus 113.0 [107.4, 116.0], P = 0.328). Multivariate logistic regression analysis encompassing the entire cohort identified being female [odds ratio (OR) 2.10, 95% confidence interval (CI) 1.59-2.79, P < 0.001) and postoperative rescue analgesia (OR 1.47, 95% CI 1.09-1.96, P = 0.010) as risk factors for CPSP, while intraoperative fentanyl dosage (OR 0.92, 95% CI 0.87-0.98, P = 0.006) emerged as a protective factor. CONCLUSION: The prolonged administration of dexmedetomidine did not yield discernible amelioration in either 1-year CPSP or the recovery quality after thoracoscopic surgery. Noteworthy risk factors for CPSP encompassed female sex, postoperative rescue analgesia, and diminished fentanyl dosage intraoperatively.

[Effects of aerosolized earthworm fibrinolytic enzyme on bleomycin induced pulmonary fibrosis in rats].

OBJECTIVE: To explore the effects of aerosolized earthworm fibrinolytic enzyme (EFE) on bleomycin-induced pulmonary fibrosis in rats. METHODS: A total of 72 male SD rats were divided randomly into 3 groups of bleomycin (BLM) group with intratracheal BLM (5 mg/kg), control group with the same dose of normal saline, then after both receiving aerosolization of normal saline once daily instead of EFE, EFE group with EFE (2500 U/kg) by aerosolization once daily after BLM instillation. Lung histopathology, immunohistochemistry for transforming growth factor ß(1) (TGF-ß(1)), lung hydroxyproline contents, levels of urokinase PA (uPA), tissue plasminogen activator (tPA) and PA inhibitor 1 (PAI-1) in lung and blood were observed at Days 7, 14 and 28 of experiment, respectively. RESULTS: Compared with BLM group, pulmonary fibrosis improved and the TGF-ß(1) expression of lung tissue decreased (P < 0.01). Hydroxyproline content of lung tissue decreased in EFE group compared with BLM group ((5.8 ± 2.5) vs (9.6 ± 1.3), (6.7 ± 1.4) vs (9.7 ± 1.5), (7.5 ± 1.2) vs (9.7 ± 1.4) mg/L, P < 0.01). Compared with BLM group, the uPA levels of lung were elevated in EFE group at Days 7 and 14 ((1.04 ± 0.36) vs (0.72 ± 0.11), (0.90 ± 0.09) vs (0.75 ± 0.08) µg/L, P < 0.05). Moreover, the plasma levels uPA of increased at Days 14 and 28 ((0.32 ± 0.04) vs (0.25 ± 0.02), (0.36 ± 0.05) vs (0.28 ± 0.04) µg/L, P < 0.05). Consistently, compared with BLM group, the tPA levels of lung increased in EFE group ((4.70 ± 0.87) vs (3.01 ± 0.62), (5.72 ± 0.37) vs (3.00 ± 0.51), (6.73 ± 1.12) vs (3.18 ± 0.38) µg/L, P < 0.01) and the plasma levels of tPA also increased ((3.40 ± 0.36) vs (1.79 ± 0.38), (3.17 ± 0.37) vs (2.18 ± 0.17), (3.85 ± 0.56) vs (2.80 ± 1.06) µg/L, P < 0.01). However, compared with BLM group, the PAI-1 levels of lung decreased in EFE group ((6.04 ± 0.81) vs (8.52 ± 1.01), (6.78 ± 0.81) vs (9.81 ± 1.73), (7.63 + 0.99) vs (11.44 ± 2.54), P < 0.05) and the plasma levels of PAI-1 also decreased in EFE group ((4.82 ± 0.42) vs (6.89 ± 0.84), (5.73 ± 0.40) vs (7.30 ± 1.09), (5.64 ± 0.87) vs (7.98 ± 1.10) µg/L, P < 0.05). CONCLUSIONS: Earthworm fibrinolytic enzyme may decrease bleomycin-induced pulmonary fibrosis and TGF-ß(1) expression while increasing fibrinolytic activation. And fibrinolytic strategies are probably useful for the therapy of fibrotic lung diseases.

[Expression of intercellular cell adhesion molecule-1, interleukin-10 and the activation of activator protein-1 in ventilator-induced lung injury in rabbits].

OBJECTIVE: To study the expression of intercellular cell adhesion molecule-1 (ICAM-1), Interleukin-10 (IL-10) and the activation of transcription factor activator protein-1 (AP-1) in a rabbit model of ventilator-induced lung injury (VILI) and therefore to explore their possible role in VILI. METHODS: The VILI model was established by mechanical ventilation with a large tide volum (V(T)) of 40 ml/kg. Forty healthy male New Zealand rabbits were randomly divided into 5 groups: a control group without mechanical ventilation, a conventional ventilation group, and injurious ventilation with large V(T) for 1 h group, 2 h group and 4 h group. The concentrations of soluble ICAM-1 (sICAM-1) and IL-10 in lung homogenates were measured by enzyme-linked immunosorbent assay (ELISA). The level of mRNA was measured by semiquantitative transcription-polymerase chain reaction (RT-PCR). The DNA-binding activity of AP-1 was measured by electrophoretic mobility shift assay (EMSA). The partial arterial blood pressure of oxygen (PaO2), myeloperoxidase (MPO) in lung homogenate, wet lung weight to dry lung weight ratio (W/D) were observed. RESULTS: (1) The concentrations of sICAM-1 in large V(T) for 2 h group (23 ± 5) ng/L and 4 h group (35 ± 5) ng/L were higher than that in the conventional ventilation group (16 ± 4) ng/L (P all < 0.05), and that in the Large V(T) for 4 h group were higher than that in 1 h group (19 ± 4) ng/L and 2 h group (P all < 0.01). The concentrations of IL-10 in the large V(T) for 2 h group (24 ± 4) ng/L and 4 h group (26 ± 5) ng/L were higher than that in the conventional ventilation group (15 ± 2) ng/L (P all < 0.05), and that in the Large V(T) for 4 h group was higher than that in the 1h group (19 ± 4) ng/L(P < 0.05). The level of ICAM-1 mRNA in the large V(T) for 2 h group (1.18 ± 0.19) and 4 h group (1.29 ± 0.19) were higher than that in the conventional ventilation group (0.84 ± 0.13) (P all < 0.05), and that in Large V(T) for 4 h group was higher than that in 1 h group (0.96 ± 0.24) (P < 0.05). The level of IL-10 mRNA in the large V(T) for 4 h group (1.13 ± 0.17) was higher than that in the conventional ventilation group (0.84 ± 0.20) and Large V(T) for 1 h group (0.86 ± 0.12) (P all < 0.05). (2) The DNA-binding activity of AP-1 in the large V(T) for 2 h group (33.77 ± 8.23) and 4 h group (38 ± 9) were higher than that in the conventional ventilation group (23 ± 9) (P all < 0.01), and that in Large V(T) for 4 h group was higher than that in 1h group (25 ± 9) (P < 0.01). (3) Histopathological findings demonstrated that diffused alveolar damage induced by mechanical ventilation was worse with time, and after mechanical ventilation with large V(T) for 2 h, the level of MPO began to increase, and for 4 h the PaO2 reduced and the W/D increased. CONCLUSIONS: ICAM-1 and IL-10 took part in the inflammatory responses of VILI, and their up-regulation maybe due to the increase of their mRNA. Nuclear transcription factor AP-1 maybe involved in the transcriptional regulation mechanisms of these inflammatory mediators.

[Effects of bone marrow mesenchymal stem cells on bleomycin induced pulmonary fibrosis in rats].

OBJECTIVE: To study the effects of bone marrow mesenchymal stem cells (MSC) on pulmonary fibrosis. METHODS: Bone marrow MSC were harvested from 6 week old male SD rats. Forty-eight female SD rats were randomly divided into six groups. The pulmonary fibrosis models were made by intratracheal instillation of bleomycin (5 mg/kg in 0.3 ml normal saline). The normal controls received intratracheal instillation of NS instead of bleomycin. On the 1st and 7th day after bleomycin administration, the rats received MSC infusion or a same amount of phosphate buffer solution (PBS) as controls via the tail vein, respectively. The rats were sacrificed by the 28 day of experiment, and the pathologic changes and hydroxyproline contents of the lung tissues were investigated. The sry gene of Y chromosome was detected by polymerase chain reaction (PCR). RESULTS: For rats receiving MSC on the 1st and 7th day after bleomycin administration, the lung fibrotic scores were 1.0 +/- 0.2 and 1.6 +/- 0.5, respectively, significantly decreased as compared with rats receiving no MSC (2.5 +/- 0.5 & 2.3 +/- 0.8, respectively). The hydroxyproline contents of lung tissue were (83 +/- 17) microg/mg and (96 +/- 20) microg/mg, also significantly decreased as compared with rats receiving no MSCs [(123 +/- 32) microg/mg & (127 +/- 34) microg/mg, respectively]. Earlier administration of MSCs resulted in more significant improvement of lung injury. The sry gene (322 bp) was detected in lungs of female rats receiving MSC on the first day of bleomycin induced lung injury. CONCLUSIONS: MSC may be involved in the repair of lung injury, especially in the early stage. MSCs are effective in preventing bleomycin induced lung injury and fibrosis.

Beta-carotene protects rats against bronchitis induced by cigarette smoking.

OBJECTIVE: To investigate the protective effects of beta-carotene in rats against the development of chronic bronchitis induced by cigarette smoking. METHODS: Forty-two Male Wistar rats were randomly divided into three study groups: (1) control (n = 15), animals underwent no treatment; (2) cigarette smoking (n = 15), animals developed chronic bronchitis through long-term cigarette smoking twice a day for 75 d; (3) beta-carotene plus cigarette smoking animals (n = 12) were given 1 ml or 15 mg/kg beta-carotene orally every day just before cigarette smoking. The levels of IL-6, IL-8, NO, superoxide dismutase (SOD) and lipoperoxide (LPO) in serum, bronchoalveolar lavage fluid (BALF) and lung tissue were measured and the pathological changes to lung tissue were analyzed using light microscopy. RESULTS: Long-term cigarette smoking caused an obvious increase in the amount of IL-6, IL-8 and LPO and a sharp decrease in the levels of NO and SOD in smoking animals compared to controls. beta-carotene intake reversed all the changes induced by smoking and alleviated the pathological changes caused by chronic bronchitis. CONCLUSIONS: Quantitative oral intake of beta-carotene had protective effects against chronic bronchitis induced by long-term cigarette smoking, which was associated with the increased production of NO, the clearance of some oxidative free radicals (OFR) and the alleviation of chronic inflammation.

[Expression of matrix metalloproteinases in lung tissue and levels of some cytokines in bronchoalveolar lavage fluid in the obstructive emphysema rat models].

OBJECTIVE: To observe the changes of matrix metalloproteinase-2 (MMP-2), MMP-9 and interleukin-10 (IL-10), tumor necrosis factor-alpha (TNFalpha) in lung tissue of the obstructive emphysema rat models and to evaluate the relationship between these changes and emphysema formation. METHODS: The rat emphysema models were established by exposure to cigarette smoking. Pulmonary function tests were performed to evaluate the forced expiratory volume in 0.3 second (FEV(0.3)), FEV(0.3)/forced vital capacity (FVC) and functional residual capacity (FRC). The morphological indices of emphysema were measured by computer image analyzer. The protein expression and enzymatic activity of MMPs in lung tissue were observed. The contents of IL-10 and TNFalpha in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: Pulmonary function test showed that in model group the FEV(0.3)/FVC was decreased, whereas the FRC was increased significantly than those in control group (P < 0.01, respectively). There was a significant decrease in the relative content of elastin in lung tissue in model group than that in control group. The expression and enzymatic activity of MMP-2 and MMP-9 in lung tissue, the counts of total leukocytes and neutrophils and the level of TNFalpha in BALF were significantly elevated, but the level of IL-10 in BALF was significantly reduced in model group compared with those in control group (P < 0.01, respectively). There were statistically significant positive correlations between the enzymatic activity of MMP-2, MMP-9 and the total leukocyte counts (P < 0.01, respectively), and significant negative correlations between the enzymatic activity of MMP-2, MMP-9 and the content of elastin (P < 0.05, respectively). CONCLUSIONS: MMP-2, MMP-9, IL-10 and TNFalpha may play an important role in the formation of obstructive emphysema in rat models caused by passive smoking.

[Prophylactic effect of retinoic acid on chronic obstructive pulmonary emphysema in rats].

OBJECTIVE: To evaluate the effect and molecular mechanism of retinoic acid (RA) in preventing experimental pulmonary emphysema in rats. METHODS: Thirty-six Wistar rats were randomly divided into three groups, the normal group(A), the model group (B) and the RA treated group (C). Rats in group B group were exposed to cigarette smoke, and group C was treated with RA. Pulmonary function indices and histopathological changes were evaluated. The enzymatic activity of gelatinases was measured by ELISA, and the expression of gelatinases and the proliferating cell nuclear antigen (PCNA) was examined by immunohistochemical method. RESULTS: Compared with group A, group B presented significant differences in FEV(0.3),FEV(0.3)/FVC and FRC [(5.1 +/- 0.4) ml vs (6.0 +/- 0.3) ml, (71 +/- 10) ml/s vs (87 +/- 3) ml/s, (7.2 +/- 2.2) ml vs (2.9 +/- 1.1) ml (P < 0.01)];the enzymatic activity [(1.06 +/- 0.23)ng/ml vs (0.53 +/- 0.17)ng/ml, (0.960 +/- 0.230)ng/ml vs (0.300 +/- 0.090)ng/ml] and the expression of gelatinases were also markedly elevated(P < 0.01). In comparison with group B, the pulmonary function indices in group C [(5.2 +/- 0.4)ml, (81 +/- 5) ml/s, (6.1 +/- 2.7)ml/s] were improved (P < 0.05); the enzymatic activity [(0.83 +/- 0.23)ng/ml, (0.570 +/- 0.010)ng/ml] and the expression of gelatinases were decreased, while the PCNA index staining (93 +/- 4 vs 53 +/- 6) was increased (P < 0.01). CONCLUSION: RA can prevent the development of pulmonary emphysema in rats.

[The pathology of and the cardio-pulmonary functional changes in acute multiple pulmonary microthromboembolism in a canine model].

OBJECTIVE: To evaluate the effect of acute multiple pulmonary microthromboembolism on circulation, ventilation, lung histology, and the coagulatory and fibrinolytic functions. METHODS: Thirteen dogs were studied, 7 in the embolism group and 6 in the control group. 10 ml of blood was withdrawn from each animal. Thrombi were formed and cut into pieces of 1 mm to 2 mm in size. The thrombi were counted, and 300 thrombi were infused at one time back to the same animal. PAP, PAWP, VO(2), DO(2), D-dimer, protein C, protein S were measured before and immediately, 30 min, 1 hour, 2 hour after embolism. RESULTS: PAP was increased immediately after embolisation, and then decreased at 1 hour. The level of D-dimer was elevated at an early stage. Pulmonary hemorrhage, consolidation and microembolism were observed. CONCLUSIONS: Multiple microthromboembolism caused lung injury and thrombosis. PAP was increased at the early stage, but ventilation was not affected. The level of D-dimer changed at the early stage of thromboembolism.