Proteolytic Enzyme Induction Within the Human Myocardial Interstitium
Summary
A robust release of endothelin-1-1 (ET) with subsequent ETA subtype receptor (ET-AR) activation occurs in patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Increased ET-AR activation has been identified in patients with poor left ventricular (LV) function (reduced ejection fraction; EF). Accordingly, this study tested the hypothesis that a selective ET-AR antagonist (ET-ARA) administered peri-operatively would favorably affect post-CPB hemodynamic profiles in patients with a pre-existing poor LVEF.
Timeline
- Start
- 2008-07
- Primary completion
- 2011-06
- Completion
- 2013-04
Outcome
Met primary endpoint
paper a significant endothelin-A subtype receptor antagonist effect was observed for pulmonary vascular resistance (analysis of variance; P < .05). PMID 20074751 ↗
registry analysis (superiority or other test); Vehicle vs 1mg/kg ET-ARA vs 2mg/kg ET-ARA; p <0.05; ANOVA NCT00744211 ↗
Publications
- Results Spinale FG, Koval CN, Deschamps AM, Stroud RE, Ikonomidis JS. Dynamic changes in matrix metalloprotienase activity within the human myocardial interstitium during myocardial arrest and reperfusion. Circulation. 2008 Sep 30;118(14 Suppl):S16-23. doi: 10.1161/CIRCULATIONAHA.108.786640.
- Results Ford RL, Mains IM, Hilton EJ, Reeves ST, Stroud RE, Crawford FA Jr, Ikonomidis JS, Spinale FG. Endothelin-A receptor inhibition after cardiopulmonary bypass: cytokines and receptor activation. Ann Thorac Surg. 2008 Nov;86(5):1576-83. doi: 10.1016/j.athoracsur.2008.06.076.
- Results Toole JM, Ikonomidis JS, Szeto WY, Zellner JL, Mulcahy J, Deardorff RL, Spinale FG. Selective endothelin-1 receptor type A inhibition in subjects undergoing cardiac surgery with preexisting left ventricular dysfunction: Influence on early postoperative hemodynamics. J Thorac Cardiovasc Surg. 2010 Mar;139(3):646-54. doi: 10.1016/j.jtcvs.2009.11.046. Epub 2010 Jan 13.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Sitaxentan | Small molecule | 1 mg/kg | Intravenous |
| Subject | Sitaxentan | Small molecule | 2 mg/kg | Intravenous |