Effect of Intravenous Lidocaine on Inflammatory and Apoptotic Response of Ischemia‐Reperfusion Injury in Pigs Undergoing Lung Resection Surgery

Abstract

Background. Ischemia-reperfusion injury is one of the most critical phenomena in lung transplantation and causes primary graft failure. Its pathophysiology remains incompletely understood, although the inflammatory response and apoptosis play key roles. Lidocaine has anti-inflammatory properties. The aim of this research is to evaluate the effect of intravenous lidocaine on the inflammatory and apoptotic responses in lung ischemia-reperfusion injury. Methods. We studied the histological and immunohistochemical changes in an experimental model of lung transplantation in pigs. Twelve pigs underwent left pneumonectomy, cranial lobectomy, caudal lobe reimplantation, and 60 minutes of graft reperfusion. Six of the pigs made up the control group, while six other pigs received 1.5 mg/kg of intravenous lidocaine after induction and a 1.5 mg/kg/h intravenous lidocaine infusion during surgery. In addition, six more pigs underwent simulated surgery. Lung biopsies were collected from the left caudal lobe 60 minutes after reperfusion. We conducted a double study on these biopsies and assessed the degree of inflammation, predominant cell type (monocyte-macrophage, lymphocytes, or polymorphous), the degree of congestion, and tissue edema by hematoxylin and eosin stain. We also conducted an immunohistochemical analysis with antibodies against CD68 antigens, monocyte chemoattractant protein-1 (MCP-1), Bcl-2, and caspase-9. Results. The lungs subjected to ischemia-reperfusion injury exhibited a higher degree of inflammatory infiltration. The predominant cell type was monocyte-macrophage cells. Both findings were mitigated by intravenous lidocaine administration. Immunohistochemical detection of anti-CD68 and anti-MCP-1 showed higher infiltration in the lungs subjected to ischemia-reperfusion injury, while intravenous lidocaine decreased the expression. Ischemia-reperfusion induced apoptotic changes and decreased Bcl-2 expression. The group treated with lidocaine showed an increased number of Bcl-2-positive cells. No differences were observed in caspase-9 expression. Conclusions. In our animal model, intravenous lidocaine was associated with an attenuation of the histological markers of lung damage in the early stages of reperfusion.

The dose-response relationships of the direct scavenging activity of amide-based local anesthetics against multiple free radicals

“…Moreover, lidocaine pretreatment combined with dexmedetomidine can effectively improve the oxidative stress injury induced by NADPH oxidase, nNOS, and iNOS via decreasing the expression of related proteins. ( 23 ) Lidocaine was also protective against ischemia-reperfusion injury of lung ( 24 ) and brain ( 25 ) in animal models. With regard to anti-inflammatory activity, elevated plasma levels of IL-6, IL-8, complement C3a, and IL-1ra as well as expression of CD11b, L- and P-selectin, and platelet-leukocyte aggregates were significantly attenuated by systemic lidocaine.…”

Pig Sedation and Anesthesia for Medical Research

“…Lidocaine is widely used intravenously in different species to provide analgesia and as an adjunct to general anesthesia. In one experimental model of lung transplantation, intravenous lidocaine was associated with an attenuation of the histological markers of lung damage in the early stages of reperfusion [62]. Administration of lidocaine may help to prevent lung injury during surgery with one lung ventilation, reducing the expression of proinflammatory cytokines and lung apoptosis [63].…”

Lidocaine reinforces the anti-inflammatory action of dexamethasone on myeloid and epithelial cells activated by inflammatory cytokines or SARS-CoV-2 infection

“…Besides the applications as local anesthetic or antiarrhythmic, different studies that evaluated the administration of intravenous lidocaine in a perioperative way showed that it exerts positive effects by attenuating the inflammatory response [ [14] , [15] , [16] ]. Interestingly, it has been shown that intravenous lidocaine administration attenuates inflammation of the lower respiratory tract in an ischemia-reperfusion injury model [ 17 ].…”