β1‐Blockers Provide Cardioprotection, Attenuation of Intramyocardial Inflammation and Leukocyte Endothelial Transmigration in Septic Mice

Abstract

Septic cardiac dysfunction is a key feature of severe sepsis and septic shock, contributing to multiorgan dysfunction syndrome and death. Persistent β adrenergic stimulation is detrimental in sepsis, and specific β1 blockade mitigates excessive systemic inflammation and seems to improve myocardial function. The aim of this study was to investigate the effects of the specific β1 blocker atenolol on the septic mouse myocardium. We also evaluated the survival of septic mice and systemic inflammation in response to atenolol treatment.Mice were rendered septic using intraperitoneal injection of lipopolysaccharide (LPS). The effects of atenolol on the myocardium were assessed by a microarray technique and were confirmed by subsequent western blot, elisa protein assays and confocal microscopy. Infusion of atenolol significantly reduced the intramyocardial production of the proinflammatory cytokines tumor necrosis factor α (TNF‐α), interleukin 1β (IL‐1β) and interleukin‐6 (IL‐6) in the septic model. Cell adhesion molecules and local myocardial chemotaxis were down‐regulated, with a significant reduction in the myocardial levels of angiopoietin 2 (Ang‐2), monocyte chemoattractant protein 1 (MCP‐1), macrophage inflammatory protein 1α (MIP‐1α), MIP‐2, E‐selectin, P‐selectin, intracellular adhesion molecule 1 (ICAM‐1) and vascular cell adhesion molecule 1 (VCAM‐1). Furthermore, atenolol significantly improved left ventricular ejection fraction, arterial pressure and aortic blood flow in septic mice. The median survival time was increased by atenolol in septic model, and the plasma levels of lactate, TNF‐α, IL‐1β, IL‐6, MCP‐1 and MIP‐1α were significantly reduced in response to atenolol treatment.In mice with experimentally induced septic shock, the β1 adrenergic blocker atenolol exerts cardioprotective effects through the tempering of both systemic and local inflammation and by reducing intramyocardial chemotaxis and the synthesis of endothelial transmigration proteins.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.