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Lidocaine reduces reperfusion injury and neutrophil migration in canine lung allografts
R A Schmid1, M Yamashita, K Ando
1Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, Barnes Hospital, St. Louis 63110, USA.
Background:
Depletion of neutrophils (PMNs) and inhibition of PMN endothelial adhesion ameliorate post-ischemic lung reperfusion injury. Lidocaine reduces PMN adhesion to endothelial surfaces in vivo, and inhibits upregulation of PMN-CD11b/CD18 (Mac-1) in vitro. We evaluated the effect of lidocaine on reperfusion injury, PMN adhesion, and PMN migration in preserved lung allografts.
Methods:
Donor lungs were flushed with modified Euro-Collins solution (4 degrees C) after prostaglandin E1 administration (250 micrograms), inflated with 550 mL (inspired oxygen fraction = 1.0), and stored for 24 hours at 1 degree C. Left lung allotransplantation was performed in 13 mongrel dogs. Immediately after reperfusion the recipient right pulmonary artery and bronchus were ligated to permit assessment of allograft function during a 6-hour postreperfusion period. Allograft gas exchange (every 15 minutes) and hemodynamics (every 60 minutes) were assessed. Peripheral blood PMN CD11b expression was determined by flow cytometry. After sacrifice allograft bronchoalveolar lavage fluid PMN count and allograft tissue myeloperoxidase activity were measured. Two groups were studied: In group I (n = 8) lidocaine hydrochloride was added to the donor flush (20 mg/L) solution. In addition lidocaine was given to the recipient at the time of thoracotomy (intravenous bolus of 4 mg/kg) followed by a continuous infusion of 4 mg/kg/h during implantation and the assessment period. Three dogs that did not reach effective lidocaine blood levels at the time of reperfusion (3 to 4 micrograms/mL) were excluded from analysis. Group II animals (n = 5) received no lidocaine.
Results:
Gas exchange in group I was superior throughout the assessment period (p < 0.05). Bronchoalveolar lavage fluid PMN count in group I was reduced (0.36 x 10(6)PMN/mL versus 6.2 x 10(6) PML/mL; p < 0.03). Group I allograft myeloperoxidase activity was 0.17 U/mg/min compared with 0.28 U/mg/min in group II (p < 0.01). In lidocaine-treated animals PMN CD11b expression was maintained at basal levels 2 hours after reperfusion, compared with group II, in which upregulation of CD11b was observed. Lower lobe wet/dry ratio was not different in the two groups.
Conclusions:
Our observations indicate that lidocaine reduces reperfusion injury and inhibits PMN adhesion and subsequent migration to the lung allograft.
Insights
Lidocaine treatment significantly reduced lung reperfusion injury by inhibiting neutrophil (PMN) adhesion and migration in lung allografts. This study demonstrates lidocaine
Area of Science:
- Transplantation immunology
- Ischemia-reperfusion injury research
- Pharmacological interventions in organ preservation
Background:
- Neutrophil (PMN) depletion and inhibition of PMN endothelial adhesion are known to ameliorate post-ischemic lung reperfusion injury.
- Lidocaine has demonstrated the ability to reduce PMN adhesion to endothelial surfaces in vivo and inhibit PMN-CD11b/CD18 (Mac-1) upregulation in vitro.
Purpose of the Study:
- To evaluate the therapeutic effect of lidocaine on lung allograft reperfusion injury.
- To assess lidocaine's impact on neutrophil adhesion and migration within preserved lung allografts.
Main Methods:
- Donor lungs were preserved using modified Euro-Collins solution and stored for 24 hours.
- Left lung allotransplantation was performed in mongrel dogs, with assessment of allograft function over a 6-hour postreperfusion period.
- Lidocaine was administered to the donor flush solution and recipient intravenously in the treatment group (Group I), compared to a control group (Group II).
Main Results:
- Lidocaine treatment (Group I) resulted in superior allograft gas exchange compared to the control group (Group II).
- Bronchoalveolar lavage fluid PMN counts and allograft myeloperoxidase activity were significantly reduced in the lidocaine-treated group.
- PMN CD11b expression remained at basal levels in lidocaine-treated animals post-reperfusion, unlike the upregulation observed in the control group.
Conclusions:
- Lidocaine effectively reduces lung allograft reperfusion injury.
- The findings indicate lidocaine inhibits neutrophil adhesion and subsequent migration to the lung allograft.