Ischemia-reperfusion Injury

00:02 One last topic in this topic, of kind of cell injury and mechanisms there of is Ischemia and Reperfusion.

00:11 So, in the typical clinical setting where this occurs, a patient comes in there having crushing substernal chest pain.

00:18 They're having a heart attack.

00:20 We know that most commonly this is due to a plaque rupture in the coronary artery with a blood clot on top of it.

00:27 So we rushed them into the angiography suite, and we inject tissue plasminogen activator, a clot buster, and we break up the clot.

00:35 Except that the heart has been ischemic for a certain period of time.

00:39 Now we're restoring blood flow into tissues that have had partial injury.

00:45 So when that happens, we have a high concentration of extra cellular calcium that's coming into a potentially compromise cell.

00:54 We already talked about cells.

00:56 If they see a spike of calcium, we'll start down that calpain activation pathway, and we'll end up with some cell death.

01:03 So that's one part of ischemia reperfusion.

01:07 When we reperfuse ischemic tissue, we also get increased recruitment of inflammatory cells.

01:13 And recall the inflammatory cells have a rich resource of for generating reactive oxygen species.

01:21 So as a result of that, we will get more damage because we recruit more inflammatory cells into this area of reperfusion.

01:30 The damage mitochondria in that tissue.

01:32 So the mitochondria been scheming for a certain period of time to, and they are not firing on all cylinders.

01:38 They are not working as well as they should.

01:41 The electron transport chain is not quite up to par yet, and so as a result, those damaged but still working mitochondria will pump out more of the reactive oxygen species because they're getting incomplete oxygen reduction down the electron transport chain.

01:59 It turns out that injured endothelium in a hypoxic or ischemic tissue will lead to the not specific deposition of certain forms of antibodies that will lead to complement activation, so there will be damaged there too.

02:12 So ischemia, and then reperfusion, even when it's saving the life of the patient can have secondary consequences in terms of injury to the tissue.

02:24 That's important to understand, because there is clearly a therapeutic intervention that we need to do.

02:31 We want to save patients lives, so we will do the reperfusion.

02:36 But we don't want to have any more damage.

02:38 So, we all, you and I need to be more clever about preventing that reperfusion damage.

02:46 And with that, we've covered the biochemical mechanisms by which cells get injured.