Extrait

Background and study aims During conventional open-heart surgery, the blood supply is diverted from the heart and lungs, to allow the operation to be carried out in a still and blood-free environment. The heart is carefully protected in order to prevent damage. However, a small degree of damage can occur due to the reduced blood flow. To minimise this, techniques have been used to protect the heart from injury and one such technique is the process of remote ischaemic preconditioning (RIPC). This is the simple application of several cycles of inflating and deflating a blood pressure cuff to the arm before heart surgery. Although some trials have suggested that RIPC protects the heart of child and adult patients undergoing open heart surgery using cardiac arrest (CA), other trials have reported that RIPC is ineffective. Reasons for the differing results may include the use of different surgical and anaesthetic techniques. Understanding the nature of any changes triggered in the heart by RIPC before and after cardiac arrest is a key step in optimising RIPC as an effective intervention to protect the heart. RIPC is assumed to produce triggers that target the heart. These triggers may be neural, hormonal or simply metabolites. If we identify the protein (e.g. enzyme) in the heart that is targeted then it may be possible to use drugs or other interventions to optimise protection through the same mechanism. Additionally, the protection induced by RIPC may be affected by disease and differences in the heart muscle. In the case of the former, the relatively ill heart muscle of a patient who requires coronary revascularisation may already be preconditioned to some extent, whereas this may not be the case for a patient with an enlarged heart who requires aortic valve replacement. In this study we plan to monitor the changes in the heart muscle associated with RIPC in patients having isolated coronary artery bypass grafting (CABG) or aortic valve replacement (AVR) using cardiopulmonary bypass (CPB) and cardiac arrest. Who can participate? Patients having elective or urgent CABG and AVR using the heart lung machine and with the heart stopped. What does the study involve? Patients will be assigned by chance to have one of two treatments after the anaesthesia and before the operation. One group will receive RIPC, where a blood pressure cuff will be inflated for a five-minute period on one of the patient’s limbs (preferably the left upper arm), after which it will be deflated for 5 minutes. This cycle of inflation followed by deflation will be performed four times in total. The other group will receive conventional treatment, which means RIPC will not be applied. The surgery and post-operative management will be carried out in the usual way and be the same for all participants. Changes in the heart muscle will be monitored in samples (left and right ventricular biopsies) collected at two times: (a) after the harvest of the mammary artery and prior to cardiopulmonary bypass and (b) at the end of the cardiac arrest. The biopsies will be analysed to compare ischaemic stress and key markers of survival signalling in the left and right ventricles, with and without RIPC, and before and after CPB and cardiac arrest. Additionally, markers of cardiac injury, inflammatory response and oxidative stress will be measured in blood samples collected at different time points throughout surgery. What are the possible benefits and risks of participating? If we are right in thinking that inflating and deflating a cuff around the patient’s limb is beneficial and protective, patients treated in this way will be less likely to have a heart injury. However, we do not know that this will happen. It is possible that patients treated conventionally may do better. We can only find out which treatment will benefit patients most by doing the study. We do not expect patients to be at higher risk. In particular, we do not expect patients receiving RIPC to have any additional pain, discomfort, distress or changes to lifestyle compared to patients who have conventional treatment. Where is the study run from? The study will be run by doctors and researchers at the Hammersmith Hospital and the Bristol Royal Infirmary where cardiac surgery operations are carried out. When is the study starting and how long is it expected to run for? The study started in February 2013 and is expected to run for 15 months. Who is funding the study? The study is funded by the NIHR Biomedical Research Unit (BRU) at Bristol and a personal award to Prof Gianni Angelini from the British Heart Foundation. Who is the main contact? Dr Francesca Fiorentino [email protected]

Critère d'inclusion

• Topic: Cardiovascular; Subtopic: Cardiovascular (all Subtopics); Disease: Cardiovascular

Liens

• ictrp
• isrctn