Short-term Endothelin A Receptor Blockade in Patients With On-pump CABG
Status:
Unknown status
Trial end date:
2016-12-01
Target enrollment:
Participant gender:
Summary
Background: Although selected cardiac surgery can be performed off-pump, the vast majority of
cardiac surgical procedures today are performed with the support of cardiopulmonary bypass
(CPB). Blood cardioplegia is used to protect the heart during aortic cross-clamping. However,
negative effects of myocardial hypoxia during surgery are often aggravated by
ischemia/reperfusion injury. In addition, cardiopulmonary bypass leads to an inflammatory
response including endothelial cell activation.
Comparable to the reperfusion injury following acute myocardial infarction resolved by
percutaneous coronary intervention, the microcirculatory impairment observed after cardiac
surgery may be caused by endothelin 1 (ET-1). ET-1 is a potent vasoconstrictor peptide
upregulated in myocardial ischemia-reperfusion injury. Short-term administration of the
selective ETA receptor blocker BQ-123 was found safe in a pilot study including patients with
acute myocardial infarction.
Hypothesis: Acute local ETA receptor blockade by intracoronary administered BQ-123 reduces
myocardial injury.
Methods: BQ-123 will be administered in patients undergoing on-pump aorto-coronary bypass
grafting to the left anterior descending coronary artery with the use a left inner mammary
artery graft and at least one vein graft. Subjects will be randomized to receive the
endothelin-A receptor blocker BQ-123 or placebo administered intracoronarily in combination
with cardioplegia in a double-blind manner. The primary endpoint will be enzymatic infarct
size.
Clinical perspective: The implementation of BQ-123 as an add-on pharmacologic therapy in
cardiac surgery performed with the use of cardiopulmonary bypass could lead to improved
tissue reperfusion and reduced ischemia/reperfusion injury, potentially impacting clinical
long-term outcome.