Remote Ischaemic Conditioning and Critical Care

Paul Young discusses remote ischaemic preconditioning and along he delves into the pitfalls of clinical research. 2016 was the 30th anniversary of ischaemic preconditioning. Remote ischaemic preconditioning is the magical offspring of ischaemic preconditioning and refers to the phenomenon whereby brief periods of ischaemia in one organ can protect other organs from subsequent prolonged ischaemic insults. Ischaemic preconditioning rose to prominence after a seminal paper in 1986 that demonstrated the protective effects of ischaemic preconditioning in dogs who had coronary ischaemia. This effect had been appreciated in humans. For instance, pre-infarct angina leads to smaller infarcts that in heart attacks without preceding angina. Remote preconditioning is for more magical. Paul takes you through the basics. The idea is simple enough. Blockage to one site leading to ischaemia preconditions another site to subsequent ischaemia. This was first demonstrated by blocking the circumflex artery in the first instance with a series of temporary occlusions. The left anterior descending was then blocked for a prolonged period. This preconditioned the heart to the prolonged ischaemia and decreased deleterious effects. This effect was then repeated with transient renal ischaemia protecting the heart from prolonged cardiac ischaemia. This effect was demonstrated with different organs – with almost any organ being able to protect another organ. The clinical application? Inflate a blood pressure cuff on an arm (to above systolic blood pressure) for five minutes and you will protect the opposite limb… or the heart. Remote ischaemic preconditioning is a reproducible phenomenon. However, as Paul explains, no one knows how it works. In this talk Paul describes his research – a double blind trial on remote ischaemic preconditioning; the first of its kind. He also describes a systematic review and meta-analysis he conducted. He found conflicting results in his trial and heterogeneity across other studies. When considering further research Paul concluded that it nothing was convincing and there were many pitfalls in the papers. What matters? What the patient can do, how they feel, whether they live and to a lesser extent does the intervention save money. In the end it seems that it is the relationship between ischaemia and reperfusion that makes a difference. That is, apply the remote ischaemic preconditioning after the primary ischaemia but before the reperfusion.

This has potential clinical implications for the following:

1. Heart surgery with cardiopulmonary bypass

2. Planned percutaneous coronary interventions

3. Acute myocardial infarction

4. CBA being treated with lysis or clot retrieval

5. Carotid endarterectomy surgery

6. Hypoxic ischaemic encephalopathy

7. Organ transplantation

8. abdominal aortic aneurysm surgery While this technique is not yet ready for clinical application, it remains an exciting potential therapeutic modality for the future. Finally, Paul finished with his top tips. Don't believe single centre studies, consider biological plausibility, be sceptical about secondary endpoints and don't be misled by surrogate endpoints.

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