Randomized Controlled Study of L-Arginine Blood Cardioplegia Administration in Patients with Reduced Left Ventricular Function Undergoing Coronary Artery Bypass Graft Surgery

Aim We aim to detect any significant improvement in myocardial protection when L-arginine is added to standard blood cardioplegia. The study and control populations will consist of patients undergoing coronary artery graft surgery with pre-existing poor myocardial function. This group of individuals often have underlying ischaemia and frequently exhibit low output syndrome (LOS) post-cardiopulmonary bypass. Inadequate myocardial protection resulting in ischaemia-reperfusion injury may be a cause for LOS. As a consequence these patients require a high incidence of pharmacological and mechanical support and frequently experience a protracted stay in the intensive care unit (ICU). L-arginine has been shown to reduce reperfusion injury when added to cardioplegia. Our hypothesis is that effective prevention of ischaemia-reperfusion injury in the jeopardised myocardium leads to an improvement in myocardial preservation and a reduction in the complications that ensue. To prove this, we propose to conduct a randomised, double blind placebo control trial in which L-arginine is added to standard blood cardioplegia. Markers of reperfusion injury, myocyte damage, will be measured. Other markers will include cardiac function, inotrope use and length of ICU stay. Study design A prospective double blind randomised controlled trial of L-arginine cardioplegia administered to patients with known poor myocardial function undergoing coronary artery graft surgery. A minimum of fifty patients in total will be allocated into two groups according to a computer generated random sequence. Once randomization has occurred all participants in the patient’s management will remain blinded to group selection. The control group will receive standard blood cardioplegia technique; while the treatment group will receive L-arginine enriched blood cardioplegia. Endpoints 1. Indicators of cell death – systemic cardiac Troponin I levels pre-cardiopulmonary bypass at 15 min and 12 and 24hrs post aortic clamp removal. Serum Troponin I levels are a measure of myocardial cell death. 2. Markers of myocardial oxidative stress - coronary sinus concentrations of xanthine oxidase, superoxide dismutase and malondialdehyde pre-cardiopulmonary bypass at 5 and 15 minutes post removal of cross clamp. These are a measure of reperfusion injury. 3. Lactic Acid flux at 1 and 5 and 15 minutes post removal of cross clamp as a measure of myocardial aerobic reserve capacity. 3. Effect upon myocardial function - myocardial systolic and diastolic function as measured by intraoperative transoesophageal echocardiography.