The effect of diazepam on myocardial function and coronary vascular tone after endotoxemia in the isolated rat heart model
- William M. L. NeethlingAffiliated withFremantle Heart Institute, Fremantle Hospital, School of Surgery and Pathology, University of Western AustraliaFremantle Heart Institute, Cell Biology Research Unit, Z Block, Fremantle Hospital Email author
- , Andrew J. HodgeAffiliated withDepartment of Cardiothoracic Surgery, Fremantle Hospital
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Objective and design
Tumor necrosis factor alpha (TNF-α) has been implicated in the pathogenesis of cardiovascular disease and sepsis-associated cardiac dysfunction. Although initially described solely as a lipopolysaccharide (LPS)-induced macrophage product, evidence exists that cardiac myocytes themselves produce substantial amounts of TNF-α in response to ischemia as well as LPS. The use of phosphodiesterase inhibitors has been shown to decrease LPS-induced TNF-α elaboration. The aim of the present study was to determine the effect of diazepam (Type IV phosphodiesterase inhibitor) on (1) myocardial function and (2) coronary vascular flow after LPS-induced endotoxic shock in an isolated rat heart model.
Materials and methods
Endotoxemia was induced by intraperitoneal LPS administration in adult male Wistar rats. Hearts were isolated after 6 h and perfused in a working mode with oxygenated Krebs–Henseleit buffer at 37°C. Diazepam was mixed with Krebs–Henseleit buffer and administered (3.0 μg/ml) for 20 min.
LPS-treated hearts showed depressed cardiac function and reduced coronary flow. Myocardial functional parameters (LVDP, +dP/dt, −dP/dt, RPP) and coronary flow (ml/min) were significantly (p < 0.01) improved by diazepam administration.
These findings suggest that diazepam can salvage myocardial function and undo coronary vascular constriction in the endotoxemic rat heart. These findings are clinically relevant to the treatment of cardiovascular depression caused by endotoxic shock.
KeywordsEndotoxemia Diazepam Heart rat model
- The effect of diazepam on myocardial function and coronary vascular tone after endotoxemia in the isolated rat heart model
Volume 59, Issue 11 , pp 907-913
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- SP Birkhäuser Verlag Basel
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- Heart rat model
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- Author Affiliations
- 1. Fremantle Heart Institute, Fremantle Hospital, School of Surgery and Pathology, University of Western Australia, Fremantle, WA, Australia
- 3. Fremantle Heart Institute, Cell Biology Research Unit, Z Block, Fremantle Hospital, Alma Street, Fremantle, WA, 6959, Australia
- 2. Department of Cardiothoracic Surgery, Fremantle Hospital, Fremantle, WA, Australia