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Correspondence  |   February 2004
Alpha-stat Induced Alkalosis: Cause of Neuronal Apoptosis after Deep Hypothermic Perfusion: In Reply
Author Affiliations & Notes
  • Andreas W. Loepke, M.D., Ph.D.
    *
  • *Cincinnati Children’s Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio. andreas.
Article Information
Correspondence
Correspondence   |   February 2004
Alpha-stat Induced Alkalosis: Cause of Neuronal Apoptosis after Deep Hypothermic Perfusion: In Reply
Anesthesiology 2 2004, Vol.100, 457. doi:
Anesthesiology 2 2004, Vol.100, 457. doi:
We thank Dr. Tadaomi A. Miyamoto and Dr. Koho J. Miyamoto for their interest in our work. We share their perception that the use of pH-stat management during cardiopulmonary bypass (CPB) for cardiovascular surgery in neonates confers neurologic protection compared with the use of α-stat management during CPB. 1–3 However, we do not agree with their theory that α-stat management during CPB cooling “primes the system” for neuronal apoptosis after deep hypothermic circulatory arrest. This theory is based on their selective interpretation of caspase-8 data in our study and altered brain bioenergetics data in other studies. 4,5 
First, we cannot conclude that caspase-8 was elevated following α-stat CPB cooling. Although caspase-8 was elevated in Western blot analysis, as the authors point out, we did not find increased caspase-8 by immunohistochemistry or enzyme assays in the same brain specimens. Thus, the evidence for caspase-8 elevation was not conclusive. Moreover, we observed no functional impairment, histopathologic damage, or caspase-3 activation following deep hypothermic CPB using α-stat management.
Second, the experimental evidence for brain energetic failure during α-stat CPB cooling is conflicting. During α-stat CPB cooling, adenosine triphospate is preserved and cerebral hemoglobin oxygenation increases. 6 Whereas early work suggested cytochrome aa3reduction during α-stat CPB cooling (supporting the idea of bioenergetic failure), recent work refutes the validity of these cytochrome aa3measurements. 2,7,8 
In summary, our interpretation of the literature is that pH-stat management for CPB provides neurologic protection for neonates through multiple mechanisms, but α-stat management does not, in and of itself, induce neurologic injury.
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