Esmolol attenuates lung injury and inflammation in severe acute pancreatitis rats.

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.