Glucagon and exenatide improve contractile recovery following ischaemia/reperfusion in the isolated perfused rat heart

Abstract

Abstract The inotropic effects of glucagon have been recognized for many years, but it has remained unclear whether glucagon signaling is beneficial to cardiac function. We evaluated the effects of glucagon alone and in combination with the glucagon‐like peptide 1 (GLP‐1) receptor agonist exenatide in the isolated perfused rat heart. The isolated perfused rat heart was used to investigate the initial inotropic and chronotropic effects of glucagon and exenatide during aerobic perfusion, and recovery of contractile function following ischaemia/reperfusion. Glucagon, but not exenatide, elicited an acute chronotropic and inotropic response during aerobic perfusion of the rat heart. Compared with control, glucagon improved recovery of left ventricular developed pressure (LVDP) by 33% (p < 0.05) and rate‐pressure product (RPP) by 66% (p < 0.001) following ischaemia/reperfusion and amplified the mild recovery enhancement elicited by exenatide in a dose‐dependent manner. Glucagon shows inotropic properties in the isolated perfused rat heart and improves contractile recovery following ischaemia/reperfusion, both alone and when co‐administered with a GLP‐1 receptor agonist. Glucagon and exenatide, a GLP‐1 receptor agonist, combine to stimulate greater recovery of postischaemic contractile function in the Langendorff heart. Glucagon was inotropic and chronotropic, yet this initial effect decreased over time and did not account for the increased contractility observed postischaemia/reperfusion.

Keywords

• cardiac ischaemia/reperfusion
• contractile recovery
• GLP‐1 receptor agonist
• glucagon