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In Response

Thiele, Robert H. MD

doi: 10.1213/ANE.0000000000002477
Letters to the Editor: Letter to the Editor

Department of Anesthesiology, University of Virginia, Charlottesville, Virginia,

Funding: Departmental.

I appreciate the thoughtful remarks provided by Drs Jakob and Takala, their interest in my article, and most importantly, their joint contributions to the field.1 The purpose of my review (and its companion) was, as stated, “to explore the ability of cells (eg, cancer) and organisms (eg, preimplantation embryos) to survive, and in some cases thrive, in ostensibly hostile environments, and identify common themes that suggest therapeutic applications for humans subjected to hypoxic or oxidative stress” with an overall goal of drawing parallels between ostensibly disparate phenomena.

As a critical care anesthesiologist, the impact of sepsis on the mitochondria is certainly of great interest to me, and in fact is the focus of 2 of my mentors, Drs Claude Piantadosi and Raquel Bartz. In addition to the body of work described by Drs Jakob and Takala, their work on mitochondrial biogenesis2 and mitochondrial antioxidant defense systems3 is also of great interest to critical care anesthesiologists and intensivists. It is also worth pointing out that Drs Jakob and Takala have conducted their own important work on the subject that, in an exercise in restraint and humility, they did not describe in their letter.4,5

Unfortunately, it was not possible to include all the relevant literature on sepsis and its impact on subcellular energetics and the mitochondria without exceeding the size requirements for a review article in Anesthesia & Analgesia. In reality, a full discussion on sepsis and the mitochondria likely deserves a stand-alone article dedicated to the subject—I would certainly enjoy reading it!

Robert H. Thiele, MDDepartment of AnesthesiologyUniversity of VirginiaCharlottesville,

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1. Jakob SM, Takala JSubcellular energetics and metabolism: A cross-species framework. Anesth Analg. 2017;125:2160.
2. Bartz RR, Fu P, Suliman HB, et al.Staphylococcus aureus sepsis induces early renal mitochondrial DNA repair and mitochondrial biogenesis in mice. PLoS One. 2014;9:e100912.
3. Cherry AD, Suliman HB, Bartz RR, Piantadosi CAPeroxisome proliferator-activated receptor γ co-activator 1-α as a critical co-activator of the murine hepatic oxidative stress response and mitochondrial biogenesis in Staphylococcus aureus sepsis. J Biol Chem. 2014;289:41–52.
4. Porta F, Takala J, Weikert C, et al.Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function. Crit Care. 2006;10:R118.
5. Regueira T, Djafarzadeh S, Brandt S, et al.Oxygen transport and mitochondrial function in porcine septic shock, cardiogenic shock, and hypoxaemia. Acta Anaesthesiol Scand. 2012;56:846–859.
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