Ann Thorac Surg 2005;80:2249
© 2005 The Society of Thoracic Surgeons
Original article: Cardiovascular
Invited commentary
John Kern, MD
Department of Surgery, University of Virginia Health Sciences Center, Box 181-95, Charlottesville, VA 22908
(Email: jak3r{at}virginia.edu).
Kaplan and colleagues [1] have found another pharmacologic intervention to protect the fragile spinal cord against ischemia reperfusion (IR) injury in a laboratory model. During the past 2 decades many drugs have been discovered to protect against such injury in animal studies, but time and again these agents have not been translated into clinical efficacy for humans. As much as we know about the pathophysiology of IR injury in numerous organ systems, an effective treatment for spinal cord IR injury eludes us. There is no doubt that the mechanisms discussed by the authors (ie, free oxygen radical formation and subsequent inflammation) play major roles in this particular IR injury. Resveratrol, a natural constituent of red wine, appears ideally suited to impact both of these major and interrelated phathophysiologic IR pathways as documented in this simple but elegant study. But will resveratrol ever make it to a clinical trial?
Although the results of this study are very remarkable, there is much we do not know about resveratrol. What is the optimal dose in humans, let alone in this animal model? What is the optimal duration of treatment? Are the protective effects of resveratrol maintained beyond 24 hours? We all are aware of the toxicity of too much red wine. What is the toxicity profile of resveratrol? Studies such as this one by Kaplan and colleagues give us reason for hope, but we must temper that hope with the fact that many drugs have been here before. With respect to spinal cord IR injury, many drugs have shown promise in pre-clinical laboratory studies, only to never make it to clinical trials. Or if clinical trials have been done, the results have been marginal at best. The fact is that no pharmacologic agent has been deemed the gold standard for significantly protecting the human spinal cord from IR injury.
Although the rabbit is a well known and accepted model for spinal cord IR injury, perhaps the mechanism of human spinal cord IR injury is more complex. Impacting the oxidative stress and inflammation pathways may not be enough. Targeting other pathways of cell death (or repair and regeneration) may be equally or more important. Nevertheless, based on the amazing results of this investigation, resveratrol deserves more study. Should it prove effective, what a palatable new pre-medication selection we may have for our patients with thoracic aortic disease.
 |
References
|
|---|
- Kaplan S, Bisleri G, Morgan JA, Cheema FH, Oz MC. Resveratrol, a natural red wine polyphenol, reduces ischemia-reperfusion-induced spinal cord injury Ann Thorac Surg 2005;80:2242-2249.[Abstract/Free Full Text]
Top
References