Catecholamine-O-Methyl-Transferase(COMT)-Polymorphism in Cardiac Surgery
Although clinical risk factors for postoperative development of vasodilatory shock and acute renal failure have been identified; there is a considerable proportion of patients undergoing cardiac surgery where this syndrome cannot be predicted.
We sought to investigate the impact of Catecholamine-O-Methyltransferase (COMT) polymorphism on the duration of vasodilatory shock and other important clinical outcomes in cardiac surgery patients.
COMT is a key enzyme in the degradation of catechols eg. catecholamines. 25% of the population have a low activity (L/L) of this enzyme. Sustained low COMT activity is associated with an altered metabolic profile of catecholamines and their degradation products.
The process of cardiopulmonary bypass (CPB)over-activates some of the same mechanisms the body uses to defend itself against severe infection. One of the main overactive defence mechanisms is the release of highly toxic compounds derived from oxygen - a process called 'oxidative-stress'. Increased reactive oxygen species (ROS) generation can lead to inactivation of biologic mediators, including catecholamines. It is well established that some radicals autoxidizes catecholamines, including DA, NE, and epinephrine and contribute significantly to vasoplegia.
As part of this study, we will take six 2.7mL samples of blood, collected before, and after the operation, from the arterial catheter routinely inserted in every patient. This blood will be used to measure COMT genotype, the concentration of plasma-catecholamines as well as marker of oxidative stress.
Our plan is to enrol patients undergoing cardiac surgery if the use of the CPB is planned.
|Study Design:||Time Perspective: Prospective|
|Official Title:||Impact of Catecholamine-O-Methyl-Transferase Enzyme Activity on Clinical and Biological Parameters in Patients After Cardiac Surgery.|
- duration of vasoplegia and incidence of acute renal failure following cardiopulmonary bypass
- length of stay in intensive care and in hospital, requirement of renal replacement therapy, mortality
|Study Start Date:||June 2006|
|Estimated Study Completion Date:||November 2006|
|Melbourne, Victoria, Australia, 3084|
|Principal Investigator:||Rinaldo Bellomo, MD, FRACP||Austin Health|
|Principal Investigator:||Duska Dragun, MD||Department of Nephrology, Charite University Hospital, Berlin|