Background: Recent studies suggest that beta-adrenergic blockers attenuate systemic inflammation and improve survival in sepsis. We investigated whether esmolol can reduce lung injury and modulate inflammatory response in a rat model of severe acute pancreatitis (SAP).
Methods: A taurocholate-induced SAP was used, with or without continuously intravenous pumping of esmolol (15 mg/kg/h). Heart rate and arterial pressure were monitored. Nine hrs after esmolol administration, blood was drawn for blood gas analyses and cytokine (interleukin(IL)-6, tumor necrosis factor (TNF)-α) detections, lungs and pancreata were isolated for measurements of myeloperoxidase (MPO) activity and histological damage. In an additional 20 animals, rats were randomized into SAP or SAP + esmolol groups to assess effects of esmolol on survival time.
Results: Treatment with esmolol was associated with improved survival time (11.1 ± 1.6 h vs. 9.2 ± 2.0 h, p = 0.044) and less severe disease, as assessed by lung and pancreas histology. Blood gas analyses were ameliorated in esmolol group. Arterial PO2 increased (109.7 ± 12.4 mmHg vs 93.9 ± 4.1 mmHg, p = 0.008) while lactate levels (2.1 ± 0.5 vs 3.1 ± 0.7 mmol/L, p = 0.001) decreased in SAP + esmolol group as compared with SAP group. Esmolol treatment also abated the increase in bronchoalveolar lavage fluid protein and proinflammatory cytokines. Furthermore, esmolol reduced SAP-induced plasma amylase activity (p = 0.02), blunted the expression of TNF-α (p = 0.003) and IL-6 (p < 0.001), and decreased pancreas/lung MPO activities.
Conclusions: Continuous infusion of esmolol, a selective beta-1 adrenergic blocker, improves outcome, reduces inflammatory responses and also offers lung and pancreas protective effects in SAP rats. This may offer novel therapeutic strategies in treating patients suffering from SAP.
Keywords: Acute lung injury; Beta-1 adrenergic blocker; Inflammatory response; Pancreatitis.
Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.