Effects of Intraoperative Infusion of Esmolol on Systemic and Pulmonary Inflammation in a Porcine Experimental Model of Lung Resection Surgery.

BACKGROUND: Lung resection surgery (LRS) is associated with systemic and pulmonary inflammation, which can affect postoperative outcomes. Activation of ß-adrenergic receptors increases the expression of proinflammatory and anti-inflammatory mediators, and their blockade may attenuate the systemic inflammatory response. The aim of this study was to analyze the effect of a continuous perioperative intravenous perfusion of esmolol on postoperative pulmonary edema in an experimental model of LRS requiring periods of one-lung ventilation (OLV). METHODS: Twenty-four large white pigs were randomly assigned to 3 groups: control (CON), esmolol (ESM), and sham. The ESM group received an intravenous esmolol bolus (0.5 mg/kg) and then an esmolol infusion (0.05 mg·kg·minute) throughout the procedure. The CON group received the same volume of 0.9% saline solution as the ESM group plus a continual infusion of saline. The sham group underwent a left thoracotomy without LRS or OLV. At the end of the LRS, the animals were awakened, and after 24 hours, they underwent general anesthesia again. Lung biopsies and plasma samples were obtained to analyze the levels and expression of inflammatory mediators, and the animals also received a bronchoalveolar lavage. RESULTS: At 24 hours after the operation, the ESM group had less lung edema and lower expression of the proinflammatory biomarkers tumor necrosis factor (TNF) and interleukin (IL)-1 compared to the CON group for both lung lobes. For the mediastinal lobe biopsies, the mean difference and 95% confidence interval (CI) between the groups for edema, TNF, and IL-1 were 14.3 (95% CI, 5.6-23.1), P = .002; 0.19 (95% CI, 0.07-0.32), P = .002; and 0.13 (95% CI, 0.04-0.22), P = .006, respectively. In the left upper lobe, the mean differences for edema, TNF, and IL-1 were 12.4 (95% CI, 4.2-20.6), P = .003; 0.25 (95% CI, 0.12-0.37), P < .001; and 0.3 (95% CI, 0.08-0.53), P = .009. CONCLUSIONS: Our results suggest that esmolol reduces lung edema and inflammatory responses in the intraoperative and postoperative periods in animals that underwent LRS with OLV.

Sevoflurane anesthetic preconditioning protects the lung endothelial glycocalyx from ischemia reperfusion injury in an experimental lung autotransplant model.

PURPOSE: The glycocalyx is a glycoprotein-polysaccaride layer covering the endothelium luminal surface, and plays a key regulatory role in several endothelial functions. Lung ischemia reperfusion (IR) is a clinical entity that occurs in everyday thoracic surgery and causes glycocalix destruction and a florid local and systemic immune response. Moreover, sevoflurane is able to modulate the inflammatory response triggered by IR lung injury. In this study, we evaluated the protective effects of sevoflurane on the pulmonary endothelial glycocalyx in an in-vivo lung autotransplant model in pigs. METHODS: Sixteen Large White pigs underwent pneumonectomy plus lung autotransplant. They were divided into two groups depending on the hypnotic agent received (propofol or anesthetic preconditioning with sevoflurane). Glycocalyx components (syndecan-1 and heparan sulphate), cathepsin B, chemokines (MCP-1, MIP-1, and MIP-2) and adhesion molecules (VCAM and ICAM-1) were measured at four different timepoints using porcine-specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: There were no differences between groups in weight or in surgical and one-lung ventilation time. Greater glycocalyx destruction and higher chemokine and adhesion molecule expression were observed in the group that did not receive sevoflurane. Heparan sulphate and serum syndecan levels were higher in the propofol group (P < 0.0001) after reperfusion, as was cathepsin B activity (P < 0.015). MCP-1, MIP-1, MIP-2, VCAM, and ICAM-1 levels were also higher in the propofol group (P < 0.006). CONCLUSION: Sevoflurane preconditioning protects pulmonary glycocalyx and reduces expression of leukocyte chemokines in an in-vivo model of pulmonary IR.