Proteolytic Enzyme Induction Within the Human Myocardial Interstitium
| Status: | Completed |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 60 - Any |
| Updated: | 11/11/2017 |
| Start Date: | July 2008 |
| End Date: | April 2013 |
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.
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.
Patients with a reduced LVEF were prospectively randomized, in a blinded fashion, at the time
of elective coronary revascularization and/or valve replacement requiring CPB, to infusion of
the highly-selective and potent ET-ARA, sitaxsentan at 1 or 2 mg/kg (IV bolus) or vehicle
(saline). Infusion of the ET-ARA/vehicle was performed immediately prior to separation from
CPB and again at 12 hrs post-CPB. ET and hemodynamic measurements were performed at baseline,
at separation from CPB (Time 0) and at 0.5, 6, 12, 24 hrs post-CPB.
of elective coronary revascularization and/or valve replacement requiring CPB, to infusion of
the highly-selective and potent ET-ARA, sitaxsentan at 1 or 2 mg/kg (IV bolus) or vehicle
(saline). Infusion of the ET-ARA/vehicle was performed immediately prior to separation from
CPB and again at 12 hrs post-CPB. ET and hemodynamic measurements were performed at baseline,
at separation from CPB (Time 0) and at 0.5, 6, 12, 24 hrs post-CPB.
Inclusion Criteria:
- >60 years of age
- Body mass index <40 kg/m2
- Left ventricular ejection fraction less than or equal to 50% documented by a
pre-operative echocardiogram
- Patients undergoing coronary artery bypass (CABG), aortic and/or mitral valve
replacement or combined CABG and valve procedures requiring CPB.
- If diabetic, be under proper control, (fasting glucose <350 mg/dL or recent hemoglobin
A1c [HgbA1c] <9%).
- If hypertensive, be on a stable medical regimen with no significant changes over the
past 30 days.
- Female of child bearing potential with a negative pregnancy test, or post-menopausal
for at least 2 years
- The patient is an appropriate study candidate as determined by the Investigator on the
basis of medical history and physical examination
Exclusion Criteria:
- Emergent revascularization
- Previous stroke or thrombo-embolic event in the 3 months prior to study entry
- A previous myocardial infarction within the last 7 days
- Documented coagulopathy
- Hepatic dysfunction as defined by aspartate transaminase (AST) or alanine transaminase
(ALT) > 1.5 times the upper limit of normal
- Patient is pregnant or breastfeeding
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