The paradox at the centre of surgery
Here is something that surprises most people. When tissue is starved of blood, the damage does not end when the blood comes back. A lot of it starts then.
That sounds backwards. Surely restoring blood flow is the cure? It is, and it is essential. But the moment oxygen floods back into tissue that has been without it, a burst of harmful reactions follows. Cells that survived the starvation can be killed by the rescue.
This is called ischaemia-reperfusion injury. Ischaemia means a lack of blood supply. Reperfusion means the blood returning. The injury is the damage caused by the combination, and especially by the return.
Why surgeons care so much
Ischaemia-reperfusion is not a rare event. It happens every day in hospitals, often on purpose.
- During many operations, surgeons clamp blood vessels to control bleeding, then release them.
- In organ transplants, the donor organ is without blood for hours before being connected in its new home.
- When tissue is moved from one part of the body to another in reconstructive surgery, it is briefly cut off from its blood supply before being reconnected.
- After a heart attack, opening the blocked artery restores blood to muscle that has been starved.
In each case, the return of blood is necessary. And in each case, it can cause additional damage. Finding ways to reduce that damage is one of the long-running goals of surgical research.
The study behind this series
This series is built on a short piece of research presented at the American College of Surgeons Surgical Forum, and published as an abstract in the Journal of the American College of Surgeons in September 2011.
It came from Weill Cornell Medical College in New York, by Alyssa Reiffel, Justin Perez, Natalia Jimenez, Hazel Szeto and Jason Spector.
One name on that list is worth noting. Hazel Szeto is one of the scientists behind the SS family of peptides. The "SS" in SS-31 comes from Szeto and Schiller. So this is research with one of the people who developed the compound.
What they wanted to know
The team was interested in two very different molecules that had each shown protective effects in the heart:
- Hydrogen sulfide, a gas the body makes in small amounts as a signalling molecule. The abstract notes it gives significant protection against ischaemia-reperfusion injury in the heart.
- SS-31, which the abstract describes as a novel cell-permeable four-part peptide that had been shown to protect heart muscle cells from oxidative stress.
The question was whether these two could also protect skeletal muscle, the muscle in your limbs, from ischaemia-reperfusion injury. And, more specifically, what they do inside the cell to offer that protection.
The approach in one line
They grew mouse muscle cells in a dish, treated some with hydrogen sulfide or SS-31 beforehand, cut off their oxygen for three hours, then gave the oxygen back for 24 hours and measured two protective signals inside the cells.
The headline finding: both compounds strongly raised a protective protein called HSP70, and hydrogen sulfide also switched off a pro-death protein called Bad.
Why the word "before" matters
The key word in the study title is pre-conditioning. The compounds were given before the injury, not after.
That might sound like a technicality. It is actually one of the most interesting ideas in this series, because in surgery, unlike in a stroke or heart attack, doctors often know exactly when the injury is going to happen. They schedule it. That opens a door that is closed in most emergencies. We look at that properly in Part 2.
What this series will cover
Over the next parts we will look at:
- The idea of pre-conditioning and why surgery is the perfect place for it
- Hydrogen sulfide and SS-31, a very odd pair
- Exactly how the experiment in the dish was done
- HSP70, the cell's repair crew
- Bad, a death protein, and what it means to switch it off
- How little SS-31 was needed
- And finally, what a one-page abstract can and cannot tell us
One thing to keep in mind throughout: this is an abstract, a short summary of early lab work in cells. It is a starting point, not a finished body of evidence, and it says nothing about what SS-31 does in people.
This series discusses a published conference abstract describing a laboratory study in cultured mouse cells. The results have not been shown in people. Nothing here is medical advice, and SS-31 is discussed for research purposes only.
