Abstract 172: Increased Cardiac Contractility by Endothelial ?1-Adrenoceptors in the Early Phase of Endotoxemic Shock
The septic shock is associated with an alteration of the sympathetic regulation of the cardiovascular system but also with an endothelial dysfunction contributing to cardiovascular failure. Several studies report that endocardial endothelium (EE) regulated the cardiac contractility through several mediators (NO, endothelin, ¼). As the β-adrenergic receptors (β-AR) are the major therapeutic targets in the septic shock and located both in cardiomyocytes and endothelial cells, the aims of our project were, first to determine the role of the three β-AR subtypes, β1, β2 and β3-AR in the cardiac dysfunction in an endotoxemic rat model and secondly to evaluate the implication of the EE in those β-adrenergic responses.
Males Sprague Dawley rats received either lipopolysaccharide (LPS, 5mg.kg-1) or saline intravenously (C). 3h later, cardiac parameters were studied in vivo by echocardiography. The cardiac contractility in response to selective β-AR agonists was studied on papillary muscle with or without a functional EE. EE removal was performed with Triton X-100 and validated by electronic microscopy and functional studies.
In vivo, LPS rats presented altered systolic (shortening fraction -21±4% vs C p<0.05) and diastolic (E wave -47±4% vs C p<0.05) functions. In papillary muscles, contractility induced by isoproterenol (non selective β-AR agonist) was surprisingly increased in LPS (+102±19% vs C; p<0.05). In LPS papillary muscles, albeit β1-AR expression was decreased (-66±5% vs C; p<0.05), β1-AR-induced contractility was increased (+90±25% vs C; p<0.05). Conversely, β2-AR and β3-AR expression were decreased by 47±7% (p<0.05 vs C) and 20±4% (p<0.05 vs C) respectively without alteration of their effects on cardiac contractility. In C muscles without EE, neither β1-AR nor β2-AR responses were modified whereas the EE removal of LPS papillary muscle abolished the increased β1-AR-induced contractility without effect on β2-AR response.
In conclusion, we demonstrated for the first time an endothelium-dependant increased of β1-AR-induced contractility in papillary muscle at early phase of endotoxemic shock. This work suggests that it is necessary to take into account endothelial β1-AR in the septic shock.
- © 2012 by American Heart Association, Inc.