A study on reducing the absorption of lidocaine from the airway in cats.

PURPOSE:: To determine if the combination of lidocaine with epinephrine or gamma globulin would decrease the rate or reduce the amount of local absorption of lidocaine through the airway. METHODS:: Twenty adult male cats were randomly and evenly distributed into four groups: 1) Group LG: lidocaine administered with gamma globulin; 2) Group LS: lidocaine administered with physiological saline); 3) Group LE: lidocaine administered with epinephrine; 4) Group C: control group. Invasive blood pressure, heart rate, and concentration of lidocaine were recorded before and after administration. RESULTS:: The peak of plasma concentrations appeared difference (Group LG: 1.39 ± 0.23 mg/L; Group LS: 1.47 ± 0.29 mg/L and Group LE: 0.99 ± 0.08 mg/L). Compared to Group C, there were significant differences in the average heart rate of Groups LG, LS, and LE (P < 0.05). The average systolic blood pressures were significantly different when each group was compared to Group C (P < 0.05). The biological half-life, AUC0-120, peak time, and half-life of absorption among the three groups have not presented statistically significant differences (P > 0.05). CONCLUSION:: Administering lidocaine in combination with gamma globulin through airway causes significant decrease the rate and reduce the amount of local absorption of lidocaine in cats.

A study on reducing the absorption of lidocaine from the airway in cats

Abstract Purpose: To determine if the combination of lidocaine with epinephrine or gamma globulin would decrease the rate or reduce the amount of local absorption of lidocaine through the airway. Methods: Twenty adult male cats were randomly and evenly distributed into four groups: 1) Group LG: lidocaine administered with gamma globulin; 2) Group LS: lidocaine administered with physiological saline); 3) Group LE: lidocaine administered with epinephrine; 4) Group C: control group. Invasive blood pressure, heart rate, and concentration of lidocaine were recorded before and after administration. Results: The peak of plasma concentrations appeared difference (Group LG: 1.39 ± 0.23 mg/L; Group LS: 1.47 ± 0.29 mg/L and Group LE: 0.99 ± 0.08 mg/L). Compared to Group C, there were significant differences in the average heart rate of Groups LG, LS, and LE (P < 0.05). The average systolic blood pressures were significantly different when each group was compared to Group C (P < 0.05). The biological half-life, AUC0-120, peak time, and half-life of absorption among the three groups have not presented statistically significant differences (P > 0.05). Conclusion: Administering lidocaine in combination with gamma globulin through airway causes significant decrease the rate and reduce the amount of local absorption of lidocaine in cats.

Hydrogen sulfide decreases ß-adrenergic agonist-stimulated lung liquid clearance by inhibiting ENaC-mediated transepithelial sodium absorption.

In pulmonary epithelia, ß-adrenergic agonists regulate the membrane abundance of the epithelial sodium channel (ENaC) and, thereby, control the rate of transepithelial electrolyte absorption. This is a crucial regulatory mechanism for lung liquid clearance at birth and thereafter. This study investigated the influence of the gaseous signaling molecule hydrogen sulfide (H2S) on ß-adrenergic agonist-regulated pulmonary sodium and liquid absorption. Application of the H2S-liberating molecule Na2S (50 µM) to the alveolar compartment of rat lungs in situ decreased baseline liquid absorption and abrogated the stimulation of liquid absorption by the ß-adrenergic agonist terbutaline. There was no additional effect of Na2S over that of the ENaC inhibitor amiloride. In electrophysiological Ussing chamber experiments with native lung epithelia (Xenopus laevis), Na2S inhibited the stimulation of amiloride-sensitive current by terbutaline. ß-adrenergic agonists generally increase ENaC abundance by cAMP formation and activation of PKA. Activation of this pathway by forskolin and 3-isobutyl-1-methylxanthine increased amiloride-sensitive currents in H441 pulmonary epithelial cells. This effect was inhibited by Na2S in a dose-dependent manner (5-50 µM). Na2S had no effect on cellular ATP concentration, cAMP formation, and activation of PKA. By contrast, Na2S prevented the cAMP-induced increase in ENaC activity in the apical membrane of H441 cells. H441 cells expressed the H2S-generating enzymes cystathionine-ß-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, and they produced H2S amounts within the employed concentration range. These data demonstrate that H2S prevents the stimulation of ENaC by cAMP/PKA and, thereby, inhibits the proabsorptive effect of ß-adrenergic agonists on lung liquid clearance.

Paracetamol and ibuprofen block hydrothorax absorption in mice.

OBJECTIVES: Non-steroidal anti-inflammatory agents (NSAIDs) and paracetamol alter pleural permeability, hindering pleural fluid recycling. The aim of this study was to investigate the effect of different analgesic and anti-inflammatory agents on fluid recycling in an induced hydrothorax model in mice. METHODS: Hydrothorax was induced in C57BL/6 mice by injecting 500 µl phosphate-buffered saline-bovine serum albumin 1% isosmotic in the right hemithorax. Paracetamol (1 g/kg), ibuprofen (250 mg/kg) and parecoxib (2 mg/kg) were administered systematically by intraperitoneal injections. Each drug group included eight mice, which were sacrificed at 2 h and 4 h, respectively, after injections. The remaining hydrothorax volume and total cells contained were determined. RESULTS: Regarding the paracetamol and ibuprofen groups, the remaining hydrothorax volume was greater than in the control group (350 ± 61, 348 ± 62 and 270 ± 51 µl, respectively, P = 0.042) when mice were sacrificed within 2 h. Similar observations were made in groups sacrificed after 4 h (202 ± 45 and 198 ± 44 vs 107 ± 56 µl, respectively, P = 0.002). In the parecoxib group, the remaining hydrothorax volume was 122 ± 53 µl (P = 0.038 versus paracetamol and ibuprofen, P > 0.05 versus control group). At the same time, the absorption rate in the paracetamol and ibuprofen groups was lower than in the parecoxib and control groups (P = 0.033). In the parecoxib group, the absorption rate was lower than that in the control group after 2 h (P = 0.042). In the paracetamol and ibuprofen groups, the total cell count and the macrophage and the neutrophils counts were increased, compared with the control and parecoxib groups (P = 0.025, 0.028 and 0.032, respectively). CONCLUSIONS: Paracetamol and ibuprofen acutely hinder pleural fluid recycling by lowering the fluid absorption rate (higher remaining hydrothorax volume), while they increased total white cell counts. COX-2s presented lower remaining hydrothorax volume without acutely increasing the absorption rate. These findings could present some relevance to the administration of painkillers in patients with pleural effusion after thoracotomy.

Netrin-1 promotes epithelial sodium channel-mediated alveolar fluid clearance via activation of the adenosine 2B receptor in lipopolysaccharide-induced acute lung injury.

BACKGROUND: The epithelial sodium channel (ENaC) is the driving force for pulmonary edema absorption in acute lung injury (ALI). Netrin-1 is a newly found anti-inflammatory factor that works by activating the adenosine 2B receptor (A2BAR). Meanwhile, activated A2BAR has the potential to enhance ENaC-dependent alveolar fluid clearance (AFC). However, whether netrin-1 can increase ENaC-mediated AFC by activating A2BAR remains unclear. OBJECTIVES: To investigate the effect of netrin-1 on AFC in ALI and clarify the pathway via which netrin-1 regulates the expression of ENaC in vivo and in vitro. METHODS: An ALI model was established by intratracheal instillation of lipopolysaccharide (LPS; 5 mg/kg) in C57BL/J mice, followed by netrin-1 with or without pretreatment with PSB1115, via the caudal vein. Twenty-four hours later, the lungs were isolated for determination of the bronchoalveolar lavage fluid, the lung wet/dry weight (W/D) ratio, AFC, the expressions of α-, ß-, and γ-ENaC, and cyclic adenosine monophosphate (cAMP) levels. LPS-stimulated MLE-12 cells were incubated with netrin-1 with or without preincubation with PSB1115. Twenty-four hours later, the expressions of α-, ß-, and γ-ENaC were detected. RESULTS: In vivo, netrin-1 expression was significantly decreased during ALI. Substituted netrin-1 significantly dampened the lung injury, decreased the W/D ratio, and enhanced AFC, the expressions of α-, ß-, and γ-ENaC, and cAMP levels in ALI, which were abolished by specific A2BAR inhibitor PSB1115. In vitro, netrin-1 increased the expressions of α-, ß-, and γ-ENaC, which were prevented by PSB1115. CONCLUSION: These results indicate that netrin-1 dampens pulmonary inflammation and increases ENaC-mediated AFC to alleviate pulmonary edema in LPS-induced ALI by enhancing cAMP levels through the activation of A2BAR.