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Ann Thorac Surg 2000;69:1748-1749
© 2000 The Society of Thoracic Surgeons
Dr VINCENT L. GOTT (Baltimore, MD): That was a good presentation of an intriguing approach to spinal cord protection. As you know, several of us working in William Baumgartner’s lab have been looking at retroperfusion in a swine preparation, so we have followed your work with considerable interest.
As Dr Baumgartner mentioned at the Southern Thoracic Surgical Association meeting a year ago in the discussion of a paper from your group, in our swine preparation we use left atrial-caval perfusion with cold blood. In our control group, which underwent 30 minutes of aortic cross-clamping (just beyond the subclavian artery), we found virtually no paralysis; with 45 minutes of cross-clamping, about half of the animals were paralyzed; and with 60 minutes, all of them were paralyzed. Unfortunately, using this hypothermic arterial blood shunted from the left atrium to the cava, we found no protection with 1 hour of cross-clamping, which was, of course, disappointing to us.
I was also intrigued by a paper by Follis and associates in the October 1999 issue of the Journal of Thoracic and Cardiovascular Surgery. They had a swine preparation with a straight shunt (aorta to the azygos and vena cava), and they showed no protection with 1 hour of cross-clamping in the pig. They proposed that, because of the considerable collaterals around the spinal cord, most of the blood was shunted away from it. You say you have shown barium dye in the spinal cord capillaries. John Doty and Mark Redmond in our group have shown a yellow gelatin dye at least in the venules of the spinal cord, which was encouraging to us. I am concerned about your rabbit model in which you clamp below the renal arteries. Is this really a good model for what we are trying to do clinically?
Have you clamped the thoracic aorta in the rabbit model, and then, with reference to your paper at the last American Association of Thoracic Surgeons meeting (and I have only seen the abstract), you used a 30-minute cross-clamp in the swine and you showed protection with retroperfusion of a solution like this. Have you tried an hour of cross-clamping in your swine model?
We were hopeful that this would be a very simple system; it certainly is easy when one uses left atrial-femoral artery bypass to simply open a shunt circuit into the inferior vena cava. We are hopeful that retroperfusion of the spinal cord will be feasible, but I would like to know your thoughts on the rabbit model using a thoracic aorta clamp as well as your experience with the swine model with an hour of cross-clamping.
DR GANGEMI: We have not cross-clamped the thoracic aorta in the rabbit model. We found consistent results with the rabbit, which we applied to the pig model. In our swine model we have shown that 30 minutes of cross-clamping consistently shows a Tarlov score of approximately 0.5 to 1, which is consistent with significant neurologic damage. We have used somatosensory evoked potentials in our control swine groups and found that within approximately 8 to 10 minutes, the action potential disappears, and 30 minutes after unclamping and 24 hours later, the action potential is still gone in the controls, again, consistent with significant neurologic damage. So we have seen significant neurologic damage to the 30-minute controls in our swine model. Because of our consistent results at 30 minutes of cross-clamping in the swine model, we have not yet performed experiments using 60 minutes of cross-clamping. However, given the encouraging results using this neuroprotective agent, we are excited about attempting to protect the spinal cord during longer periods of ischemia.
DR JOHN W. HAMMON, JR (Winston-Salem, NC): Dr Gangemi, that was a very nice and very complete presentation of your data. The last couple of slides were shown quickly. Did I notice that the saline group had equal protection with the phenytoin group? If so, what is the mechanism?
DR GANGEMI: The retrograde saline group had an average Tarlov scale of approximately 1.5. The retrograde phenytoin group was statistically significantly more improved than the saline group; however, the retrograde saline group had a better Tarlov scale (not statistically significant, however) than the control cross-clamping group. One of the reasons is that during retrograde perfusion, the saline is at a consistent rate of 1 mL/kg per minute. I think that we might be washing out some of the neutrophils, platelets, and other inflammatory agents that could cause subsequent reperfusion injury. That might be providing a bit of neurologic protection but not nearly the amount of protection as in the phenytoin group.
DR J. ALEX HALLER (Baltimore, MD): I also want to congratulate you on a beautifully presented paper, particularly because I do not do this kind of surgery yet I could follow it easily. I would like to ask you one question about the delivery of the solution intravenously.
If I understood your model correctly, you are depending on the retrograde perfusion up and down the inferior vena cava without anything driving it into that particular area. Have you considered using a balloon catheter that would block above thereby increasing the venous pressure at that point and therefore possibly delivering a higher concentration of your solution into the immediate area of ischemia?
DR GANGEMI: No, we have not, and I think at this point because of our consistent model that we have had over the years, we have been just going with the cross-clamping method. To infuse the drug we use an infusion pump (IVAC, Alaris Medical Systems), so there is constant perfusion, constant flow into the inferior vena cava. A balloon occlusion is something that we can try. We cross-clamp both the aorta and inferior vena cava both proximally (just distal to the left renal artery) and distally at the aortic bifurcation, so there is minimal chance of systemic infusion and a better chance of localized delivery to the spinal cord.
I think in a clinical setting, a balloon occlusion is much more feasible than isolating a hemiazygos vein or an intercostal vein, which may be possible, but certainly a balloon occluder might be more clinically feasible.
DR ALVAN W. ATKINSON (Raleigh, NC): It appears that the mechanism for epidural anesthesia is infusing epidural veins with an anesthetic agent. Have you tried intrathecal administration of these protective agents? I am not sure that it would be technically easy in a rabbit model or a pig model, but I just wondered about that.
DR GANGEMI: No. I know Dr Follis’s group recently used intrathecal administration of this drug. We have not done that.
DR ATKINSON: Or epidural perhaps?
DR GANGEMI: Right, or epidural. We have not done that at this point.
We are very excited about the sodium channel blockers because they are commonly used clinically and they are well tolerated. We would like to apply this to the swine model and use not only somatosensory evoked potentials to determine what happens to the action potential, ie, are we preserving it, does it disappear, and does it come back after the ischemic period? We also would like to use microdialysis probes to measure the glutamate levels, to determine whether we are indeed decreasing the amount of glutamate, which is obviously neurotoxic.
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