Back to science, which is what this blog is supposed to be partly about. We've been fiddling around, trying to get a working rat hypothermia model that's clinically relevant. We think we've got it now, and yesterday we tried our new system, the Arctic Rat (TM) suit, while monitoring both rectal temperature (body core temperature) and temporal muscle temperature ( a surrogate for brain temperature) in a rat under general anesthesia. Here are the results.
A couple of notes. The temperature is reported, obviously, in deg C. The x-axis time points are every five minutes, so the experiment went from 0 to 90 minutes. Target temp was 32 deg C, which is as far as we intend to go with the current study. That's equivalent to 89.6 deg F, or 9 degrees F lower than body temp. The top two curves are core temp and temporal muscle temp, and they correlate very nicely. The third curve down is the ambient temp (yeah, it's hot down here). The next curve is tank temperature; this is the temperature of coolant we used. The bottom curve is the difference between the two temps, which got tighter quickly and stayed that way; it was always under our max acceptable diff of 2 deg C.
What I'm happiest about is that we were able to get to our target temp quickly and then keep it pretty much on target with minimal adjustments of tank temperature. This model is almost ready for prime time. We have to tweak our sedation method and make sure the core and temporalis temperatures correlate with brain temperature, but once all that's done we're In Like Flynn. Hypothermia for brain ischemia is hot, and we're eager to explore not only its therapeutic benefit but also just exactly what it does at the molecular level.
It's been a crazy month, but a good one--long hours in the lab, and lots of kerfluffle to take care of.
In the lab, it's been eventful. We've ditched our implantable "Refrig-a-RAT-or" and developed a "Cool Suit" for our hypothermia model. Our focal ischemia model is coming together in preparation for the ISIS-funded investigation of our combination therapy approach.
And...we had another paper accepted! More on this later.
I've been off the blog for a few weeks--a very busy time indeed. I got funded for a project to investigate combination therapy for stroke (yes! at last!), and I'm working with my colleagues to launch it. And I'm busy trying to get a fellowship grant out the door, along with a new animal research protocol. Excuses, excuses, yes I know. But at least you can't say I'm not using my time well.
What to say about Obama's cruise through the Old World? This shot puts him in the CiC chair, next to Petraeus, looking like buddies.
Oh, and while he was doing photo-ops with the troops, Maliki endorsed his withdrawl plan, which led one political operative with ties to the McCain campaign to surmise: "we're fucked."
And this article, which must be giving McCain a bit of dyspepsia right now, just appeared in Time, which means it will be read in dens, kitchens, lavatories and waiting rooms from now to November.
Over at fivethirtyeight, the model has narrowed Obama's lead, although the polls are volatile and the simulation still shows him winning 58% of the time with 292 EVs. But I would look for a bounce after Obama's world tour. If it materializes, Obama can take some assurance that he's gone a long way to clearing the CiC bar for the presidency, which means he can probably walk right into the White House. If no post-world-tour bounce materializes, I think that's big trouble for Barack.
As good a way as any to get this going: announce the publication of my most recent scientific paper. It is, I hope, the end of a fairly fallow period for our lab, the Emergency Medicine Cerebral Resuscitation Laboratory at Wayne State University in Detroit. The paper has to do with the use of insulin in stroke, which is a subject I've been involved with since 1999. In that year, I published work showing that a very high dose of insulin administered to animals after 10 minutes of cardiac arrest could rescue protein synthesis in vulnerable brain cells. But we suspected that wasn't the only good thing insulin did for brains after ischemia. (Ischemia is the condition created when blood flow to an organ is interrupted, as in stroke, cardiac arrest, and heart attack.)Since that first paper, the stroke research community has learned that one of the key events occuring in vulnerable brain cells during stroke is the release of a protein called cytochrome c from mitochondria. Mitochondria are the powerplants of every cell. And, as is the case elsewhere in life, it's just no good when your powerplant leaks. When mitochondria leak cytochrome c into the rest of cell, it's harmful to their ability to generate power, and leads to the production of free radicals. But more importantly, the leaking of cytochrome c is a self-destruct signal, causing the cell to off itself in a process called apoptosis.
In the new paper, my colleagues and I demonstrate that high-dose insulin administered to animals with brain ischemia prevents the release of cytochrome c and preserves brain cells after transient global brain ischemia, the kind of brain ischemia that can devastate patients resuscitated from even very brief periods of cardiac arrest. We are guessing that this approach has value in stroke and head trauma as well, although that remains to be proven.
You can see the abstract of the paper here.
