Professor Bernard Gersh from Mayo Clinic in Rochester, USA, speaks to Cardio Debate & Radcliffe Cardiology about pathophysiology and management of reperfusion injury, during the ESC2016 Congress held in Rome, Italy earlier this year.

TRANSCRIPT

Why, despite so much research and promising animal trial data, have we seen no major breakthroughs regarding the management of perfusion injury?
It’s a good question, and I’m not sure I can think of an area where there has been such a huge gap between the experimental evidence and the clinical evidence. Reperfusion injury is complex. It’s a very complex pathophysiology, there are a lot of processes and there are lot of potential targets.

There are a lot of people who have disputed whether reperfusion injury is actually clinically relevant. I think it is. And after a wealth of animal studies that are all positive, basically none of the clinical trials have reached their primary end point. It’s been a big agenda with disappointing results, and I think the big question is why.

The most correct answer is we don’t really know. But I think there are a number of explanations. I think we have to accept that dogs and cats are not the same as humans. The species differences are very different. Differences in collaterals in-between species may have a effect.

The other reason why there is a big difference is, in the animal experimental model you create an infarction by putting a ligature on a virgin artery and then you release it. Myocardial infarction in the patient is very different because it is an atherosclerotic coronary artery, there is thrombus there, thrombus dissolves, reforms – it’s a very different model, a different process.

I think differences in collaterals play a role, I think species differences are a major factor, and I think it’s a different pathological process so we probably need a better animal model that we don’t have at the moment. And that would be an animal model of an atherosclerotic artery that is subject to myocardial infarction.

The bottom line is big agenda, unimpressive results.

Is there anything new on the horizon that has potential?
Yes there are a number of ongoing trials and a number of different compounds. The one I still think carries a great deal of promise is the phenomenon of ischaemic preconditioning –and particularly remote ischaemic preconditioning.

Now, there have been some trials of ischaemic conditioning that turned out to be neutral. But I think there are some technical explanations in the design of the trials that account for the fact that they are neutral. So I think that’s an area that is alive. I won’t say it’s alive and well, but it is alive and interesting and needs to be developed further. And personally I think is probably the most interesting approach to modifying reperfusion injury.

If we really could modify it, it could have a big impact – on the size of the infarction and the prognosis.