Pharmacological Preconditioning with Diazoxide in the Experimental Hypothermic Circulatory Arrest Model

Authors

  • Henri Johannes Haapanen Department of Cardiothoracic Surgery, Great Ormond Street Hospital for Children, London,
  • Oiva Arvola Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu,
  • Johanna Herajärvi Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu,
  • Tuomas Anttila Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu,
  • Hannu Tuominen Department of Pathology, Medical Research Center, Oulu University Hospital and University of Oulu,
  • Ulla Puistola Department of Obstetrics and Gynecology, Medical Research Center, Oulu University Hospital and University of Oulu,
  • Peeter Karihtala Department of Oncology and Radiotherapy, Medical Research Center, Oulu University Hospital and University of Oulu,
  • Kai Kiviluoma Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu,
  • Tatu Juvonen Department of Cardiac Surgery, Heart and Lung Center HUCH, Helsinki,
  • Vesa Anttila Heart Center, Turku University Hospital, University of Turku, Turku,

DOI:

https://doi.org/10.1532/hsf.1717

Abstract

Background: Hypothermic circulatory arrest includes a remarkable risk for neurological injury. Diazoxide, a mitochondrial adenosine triphosphate–dependent potassium ion (K+ATP) channel opener, is known to have cardioprotective effects. We assessed its efficacy in preventing ischemic injury in a clinically relevant animal model. 

Methods: Eighteen piglets were randomized into a diazoxide group (n = 9) and a control group (n = 9). Animals underwent 60 minutes of hypothermic circulatory arrest at 18°C. Diazoxide (5 mg/kg + 10 mL NaOH + 40 mL NaCl) was infused during the cooling phase. Metabolic and hemodynamic data were collected throughout the experiment. After 24-hour follow-up, whole brain, heart, and kidney biopsy specimens were collected for analysis. 

Results: Cerebellar Cytochrome-C and caspase-3 activation was higher in the control group (P = .02 and
P = .016, respectively). Antioxidant activity tended to be higher in the diazoxide group (P = .099). Throughout the experiment, the oxygen consumption ratio was higher in the control animals (Pg = .04), as were the lactate levels
(Pg = .02). Cardiac function tended to be better in diazoxide-treated animals. 

Conclusion: Diazoxide might confer neuroprotective effect as implied by the immunohistochemical analysis of the brain. Additionally, the circulatory effects of diazoxide were beneficial, supporting its neuroprotective effect. 

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Published

2017-04-30

How to Cite

Haapanen, H. J., Arvola, O., Herajärvi, J., Anttila, T., Tuominen, H., Puistola, U., Karihtala, P., Kiviluoma, K., Juvonen, T., & Anttila, V. (2017). Pharmacological Preconditioning with Diazoxide in the Experimental Hypothermic Circulatory Arrest Model. The Heart Surgery Forum, 20(2), E069-E076. https://doi.org/10.1532/hsf.1717

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