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Effects of Hyperoxia During Resuscitation From Hemorrhagic Shock in Swine With Preexisting Coronary Artery Disease

Hartmann, Clair MD1,2; Loconte, Maurizio MD3; Antonucci, Elena MD3,4; Holzhauser, Michael1; Hölle, Tobias1; Katzsch, David1; Merz, Tamara MSc1; McCook, Oscar BSc1; Wachter, Ulrich MSc1; Vogt, Josef A. PhD1; Hoffmann, Andrea VMD1; Wepler, Martin MD1,2; Gröger, Michael PhD1; Matejovic, Martin MD, PhD5; Calzia, Enrico MD, PhD1; Georgieff, Michael MD, PhD2; Asfar, Pierre MD, PhD6,7; Radermacher, Peter MD, PhD1; Nussbaum, Benedikt L. MD1,2

doi: 10.1097/CCM.0000000000002767
Online Laboratory Investigations

Objectives: Investigation of the effects of hyperoxia during resuscitation from hemorrhagic shock in swine with preexisting coronary artery disease.

Design: Prospective, controlled, randomized trial.

Setting: University animal research laboratory.

Subjects: Nineteen hypercholesterolemic pigs with preexisting coronary artery disease.

Interventions: Anesthetized, mechanically ventilated, and surgically instrumented pigs underwent 3 hours of hemorrhagic shock (removal of 30% of the calculated blood volume and subsequent titration of mean arterial blood pressure ≈40 mm Hg). Postshock resuscitation (48 hr) comprised retransfusion of shed blood, crystalloids (balanced electrolyte solution), and norepinephrine support. Pigs were randomly assigned to “control” (Fio2 0.3, adjusted for arterial oxygen saturation ≥ 90%) and “hyperoxia” (Fio2 1.0 for 24 hr) groups.

Measurements and Main Results: Before, at the end of shock and every 12 hours of resuscitation, datasets comprising hemodynamics, calorimetry, blood gases, cytokines, and cardiac and renal function were recorded. Postmortem, organs were sampled for immunohistochemistry, western blotting, and mitochondrial high-resolution respirometry. Survival rates were 50% and 89% in the control and hyperoxia groups, respectively (p = 0.077). Apart from higher relaxation constant τ at 24 hours, hyperoxia did not affect cardiac function. However, troponin values were lower (2.2 [0.9–6.2] vs 6.9 [4.8–9.8] ng/mL; p < 0.05) at the end of the experiment. Furthermore, hyperoxia decreased cardiac 3-nitrotyrosine formation and increased inducible nitric oxide synthase expression. Plasma creatinine values were lower in the hyperoxia group during resuscitation coinciding with significantly improved renal mitochondrial respiratory capacity and lower 3-nitrotyrosine formation.

Conclusions: Hyperoxia during resuscitation from hemorrhagic shock in swine with preexisting coronary artery disease reduced renal dysfunction and cardiac injury, potentially resulting in improved survival, most likely due to increased mitochondrial respiratory capacity and decreased oxidative and nitrosative stress. Compared with our previous study, the present results suggest a higher benefit of hyperoxia in comorbid swine due to an increased susceptibility to hemorrhagic shock.

1Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm, Ulm, Germany.

2Klinik für Anästhesiologie, Universitätsklinikum Ulm, Ulm, Germany.

3Department of Surgical Sciences and Integrated Diagnostics, AOU IRCCS San Martino IST, University of Genoa, Genoa, Italy.

4Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.

51st Medical Department, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.

6CNRS UMR 6214, INSERM U1083, Université Angers, Angers, France.

7Département de Réanimation Médicale et de Médecine Hyperbare, Centre Hospitalier Universitaire, Angers, France.

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Supported, in part, by a research grant from the Deutsche Forschungsgemeinschaft, Bonn, Germany (SFB 1149, Teilprojekt B03).

Mr. Holzhauser’s, Mr. Wachter’s, and Drs. Vogt, Gröger, Radermacher, and Nusbaum’s institutions received funding from Deutsche Forschungsgemeinschaft. Mr. Holzhauser and Dr. Nusbaum received support for article research from Deutsche Forschungsgemeinschaft CRC1149. Dr. Radermacher’s institution received funding from the German Ministry of Defense. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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