A non-invasive way to protect against the stress of surgery for heart disease

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Lay Summary: Support of the blood circulation during heart surgery using the heart-lung bypass machine is inevitably associated with organ damage and associated reduced function. This is due to reduced blood flow (ischemia), the effects of restoration of flow (reperfusion injury) and the subsequent inflammation that is caused. The body has its own way of protecting itself against reduced blood flow and oxygen by a mechanism known as preconditioning. In essence, brief periods of mild ischemia are protective against a subsequent more severe episode of ischemia. These periods of mild ischemia can be of the organ itself or of another organ in the body. For example ischemia of the leg can protect the heart against ischemia, so called “remote preconditioning”. We have shown in animal and human models that remote preconditioning using a tourniquet (or blood pressure cuff) placed around a thigh for brief periods (similar in duration to when taking blood samples from children) reduces the amount of injury to heart muscle by 50% and also leads to improved heart and lung function. We have shown that remote preconditioning in a similar way protects the organs of a heterogeneous group of children undergoing cardiac surgery, resulting in better function of the heart and lungs and also a reduction of the inflammatory response to the heart-lung machine. This could potentially reduce the problems in looking after children after surgery and also reduce the amount of time spent in the intensive care unit. We will study paediatric patients undergoing heart surgery inorder to identify key protein and metabolic changes that occur within this 'heart-protection' protocol. All interventions will be performed during the period of routine general anaesthesia at the time of surgical repair. We will study the degree of organ injury induced by heart-lung bypass using standard intensive care parameters and equipment for measuring lung function. The degree of plasma and blood cell metabolic function will be assessed by laboratory tests. Blood samples will be taken from indwelling catheters routinely placed at the time of surgery and not require additional venepuncture. Measurements will be made prior to surgery and also at set time intervals in the first 24 hours postoperatively to determine the evolution of effects. Primary Objective: Does remote ischemic preconditioning (RIPC) modify the global plasma proteomic and mitochondrial response in patients undergoing congenital heart surgery? Hypothesis: RIPC induces significant changes to global proteomic response in plasma and the metabolic function in heart muscle and lymphocyte mitochondria of patients undergoing congenital heart surgery. Aims: To assess in blood plasma and lymphocyte/myocardial mitochondria the impact of RIPC on the global proteomic and mitochondrial metabolic function response to heart surgery with cardiopulmonary bypass support. Secondary Objectives: Does RIPC modify clinical markers of injury and cardiopulmonary function post-Cardiopulmonary bypass in patients undergoing congenital heart surgery? Hypothesis: Remote IPC reduces post-cardiopulmonary bypass release of markers of cellular injury and permits recovery of cardiac pump function with less complication including inotrope requirement in patients undergoing congenital heart surgery. Aims: To assess the impact of remote IPC on lactate release, inotrope requirement, and standard clinical cardiopulmonary assessments in response to heart surgery with cardiopulmonary bypass support. This small randomised, blinded, surgical trial of preoperative therapy with highly regulated, brief, non-invasively-induced, localised leg ischaemia and reperfusion, will test for the capacity to invoke remote ischemic preconditioning-related molecular signalling (proteomic and metabolic) changes. The study will recruit 40 paediatric tetralogy of patients to RIPC treatment or SHAM RIPC (Placebo control) treatment groups and is expected to be completed by the end of March 2012.