Suri, Ajay; (2017) Factors Affecting The Cardioprotective Response To Remote Ischaemic Preconditioning In Patients Undergoing Cardiac Surgery. Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

Death from ischaemic heart disease (IHD) remains the most common cause of death worldwide, and is also a significant cause of morbidity. Coronary artery bypass graft (CABG) surgery is performed in a significant number of IHD patients that meet certain clinical and angiographic criteria or are unsuitable for percutaneous coronary intervention. Increasingly higher risk surgeries are taking place, as the population survives to become more aged with well-managed co-morbidities. As such, the myocardium is at risk of peri-operative myocardial injury (PMI) during CABG surgery, the presence of which impacts on clinical outcomes. There are a number of strategies already in place to protect the myocardium during CABG surgery including therapeutic hypothermia, and the use of cardioplegic solutions, but there is a need to increase cardioprotection especially in higher-risk patients. In this regard, remote ischaemic conditioning (RIPC) is a promising, yet simple and cheap, non-invasive intervention, which shows huge promise in reducing PMI during CABG surgery. RIPC involves the serial inflations and deflations of a blood pressure cuff to the upper and/or lower limbs to induce brief cycles of ischaemia and reperfusion to the skeletal muscle. Despite the promise, clinical studies have produced variable results RIPC in the setting of CABG surgery, with confounding factors such as co-morbidities (age and diabetes) and comedications (propofol and glyceryl trinitrate) being proposed to interfere with the cardioprotective effect. In two separate clinical studies of adult patients undergoing CABG surgery, we investigated the effect of diabetes and glyceryl trinitrate (GTN) on the cardioprotective effect elicited by RIPC. We used an intensified RIPC protocol comprising 3 cycles of simultaneous inflation and deflation of two cuffs – one placed on the upper arm and the other on the thigh. The primary outcome measures of both clinical studies, was the extent of peri-operative myocardial injury (PMI), as evidenced by the 72 hours serum Troponin T area-under-the-curve. Secondary outcomes measures included the incidence of post-operative atrial fibrillation, acute kidney injury, inotrope score and length of intensive care and hospital stay. In the diabetic study, we found that RIPC significantly reduced the extent of PMI, whereas in the GTN study, RIPC resulted in only a non-significant reduction in PMI, when compared to control. There were no differences in the secondary outcome measurements with RIPC versis control in either study. In conclusion, we have demonstrated that intensifying the RIPC stimulus can overcome the confounding effects of diabetes and GTN on RIPC cardioprotection in patients undergoing CABG surgery.

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