HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Jay G. Shake Eric A. Peck Vincent L. Gott Michael V. Johnston William A. Baumgartner Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shake, J. G. Articles by Baumgartner, W. A. Search for Related Content PubMed Articles by Shake, J. G. Articles by Baumgartner, W. A. Related Collections Mediastinum

Ann Thorac Surg 2002;74:632-633
© 2002 The Society of Thoracic Surgeons

---

Correspondence

Reply

^a Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, 600 N Wolfe St, Blalock 618, Baltimore, MD 21287-4618, USA

e-mail: wbaumgar{at}csurg.jhmi.jhu.edu

To the Editor

We thank Dr Lang-Lazdunski and associates for their interest in our work and congratulate them on their outstanding contributions toward understanding neuronal injury and cerebral ischemic preconditioning. Their comments address two specific issues: (1) whether or not the animals were sacrificed too early, and (2) the safety of diazoxide as an agent to initiate "pharmacologic preconditioning."

Regarding the first point, indeed we have witnessed examples of temporary neuronal protection in preparations investigating brain injury secondary to hypothermic circulatory arrest and ischemia-induced spinal cord injury. In fact, our interest in preconditioning stemmed from the hypothesis that apoptosis, not cellular necrosis, is the cause of delayed injury. It followed then that amelioration of neuronal death would occur only if pharmacologic manipulation were early in the destructive cascade, prior to the initiation of programmed cell death. From our experience, delayed neuronal death occurs by 48 hours, thus our 72-hour sacrifice time was beyond this window. We have used immunohistochemical studies (TUNEL method, caspase) in prior investigations to identify those neurons undergoing apoptosis, though in our experience the microscopic changes described in our article have been a better indicator of cell survivability.

Regarding the use of diazoxide, we see the diazoxide experiments more as a proof of concept rather than identifying diazoxide as "the" drug to use. Having said that, we believe a lot has been learned about intraoperative management since the 1970s and that, if we are aware of the hypotensive and hyperglycemic effects of diazoxide, the abnormalities can be readily countered by conventional therapy. Moreover, the drugs half-life is short so any ill effects would be self limited. Ultimately, we anticipate more pharmacologically specific drugs in the near future.

Though not specifically addressed in the article the blood glucose levels of the animals were followed. The values of the experimental group significantly increased in the first hour of rewarming versus pre-CPB (246 ± 38.0 mg/dl vs 123.5 ± 12.21 mg/dl) though it had nearly returned to baseline by 120 minutes (157 ± 32.4 mg/dl). These values were only slightly higher than both the control and 5-HD groups.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Jay G. Shake Eric A. Peck Vincent L. Gott Michael V. Johnston William A. Baumgartner Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shake, J. G. Articles by Baumgartner, W. A. Search for Related Content PubMed Articles by Shake, J. G. Articles by Baumgartner, W. A. Related Collections Mediastinum