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Systemic changes of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), neutrophil elastase (ELT) and myeloperoxidase (MPO) during mechanical ventilation (MV) in horses anaesthetized for surgery are evaluated. Thirty-four client-owned ASA I-II horses randomly received mechanical ventilation (MV) with either a peak inspiratory pressure (PIP) of 30 cm H2O and tidal volume (VT)>10 mL kg-1 (high pressure-volume MV) or PIP of 15 cm H2O and VT ≤ 10 mL kg-1 (low pressure-volume MV) in dorsal or lateral recumbency. Horses were premedicated with acepromazine (0.1 mg kg-1 IM) and xylazine (0.6 mg kg-1 IV), induced with midazolam (0.06 mg kg-1 IV) and ketamine (2.2 mg kg-1 IV) and maintained with isoflurane in oxygen 70% plus ketamine-midazolam infusion (1 and 0.02 mg kg-1 h-1, respectively). Anti-inflammatory drug and antibiotics were administered before surgery. Plasmatic proinflammatory mediator concentrations were estimated by ELISA at the beginning (T0) and after 60 minutes (T1) of MV. Mean plasmatic TNF-α, MPO, and ELT concentrations at T1 were significantly (p<0.05) lower than T0. Mean plasmatic concentration of IL-6 did not significantly change with time. The reduction in plasmatic concentration of proinflammatory mediators at T1 was not linked to ventilation strategy or recumbency. None of the ventilation protocols enhanced systemic inflammatory response during surgery after 1 hour of MV. The anti-inflammatory properties of drugs included in the anaesthesia protocol may have contributed to the overall decreased systemic inflammatory mediator concentrations, despite MV and surgery.