R.I. aka Reperfusion injury
Let’s talk about Re-perfusion Injury or commonly referred to as ischemic re-perfusion injury (IRI). This concept is pretty much paradoxical and poorly understood (which is why we should talk about it). Also a bridge to post-resus brain stuff, which I’ve been recently intrigued by.
Organs and tissues need oxygen to function and survive. When this oxygen is cut off, aerobic respiration slows down, stops, and anaerobic respiration takes over (which is why you get lactic acid). After that, cellular processes stop and cells and tissues start to die. Restoring perfusion and in turn oxygen is good but sometimes it’s also bad! Interesting…
When you have a heart attack through plaque rupture, thrombotic occlusions, or vasospasm in the coronary arteries, myocytes start to die, that’s why your door-to-balloon time is so important. Remember, ACC/AHA D2B is 90 min from symptom start. (Can also happen after CABG).Those heart cells are still viable. But sometimes, re-establishing the oxygen supply to cells that were deprived of it can actually cause a cascade of events that lead to more injury.
What happens during ischemia:
Glycogen breaks down into ATP and lactic acid. Your pH drops, negative feedback occurs and you have less ATP (less ATP leads to ATP-dependent cellular pump failure. Remember your Na+, K+, Ca2+ pumps?). Na rush into the cell and swells with water. Ca leaves the mitochondria/cell and become extracellular. When Ca does that, an enzyme in the cell called xanthine dehydrogenase becomes xanthine oxidase.
ATP breaks down to ADP, AMP, and IMP (inosine-mono-phosphate). IMP breaks down to adenosine, inosine, hypoxanthine and xanthine.
During reperfusion:
Now when you restore oxygen to the cells, the re-introduction of oxygen becomes a catalyst for the xanthine oxidase to break hypoxanthine (look at the italics above!) into uric acid and superoxide (O2-), a highly reactive thing. This superoxide becomes hydrogen peroxide (H2O2) and hydroxyl radical (OH). This OH causes peroxidation (degradation) of lipid structures and release systemic proinflammatory things that causes “badness” (thank you Dr. Massera). Proinflammatory things lead to hyperinflammation/cytokines (you know, the TNF-a, IL-6, IL-1, PAF, etc) SIRS, and thus, injury. And there you go, full circle. Re-perfusion or re-bringing-oxygen -back injury.
Sorry this post is a lot longer than I anticipated it to be. Here’s a quick break.
Okay, one of the things that are now created are prostaglandins that are actually protective (we like the vasodilatory effect it causes). But our likable prostaglandins are quickly depleted, leading to unregulated vasoconstriction, reduced blood flow and thus more ischemia. Nitric oxide and ENOS (endothelial NO) can play a role in more damage due to free radicals but lets not confuse ourselves further.
Now let’s bring it back to the heart.
Ok, this all happens and now the myocytes are getting more damage due to reperfusion. You can get post re-perfusion arrhythmias like accelerated idioventricular rhythms or VT/VF. You can also get myocardial stunning due to the oxidative stress and calcium influx on our poor heart cells. And then then sometimes, we’ll just see more myocyte death (apoptosis anyone??). Hopefully, we can save these stunned cells and get them through this “stressful period”…haha get it. Hm, maybe this is why we still trend cTn at certain hospitals post-PCI..
This can happen to most organs. Like the brain. Oh, and brain IRI is a real thing. We can talk about this another time when I talk more about post-resus medicine and TTM. And maybe when I finish reading Dr. Parnia’s book. And note to self, I need to read more about mag and brain arteries before I prescribe >4 grams of Mag Sulfate.
Leave a comment if I wrote something wrong or want to give feedback.
Dk
