Diazoxide Attenuates Ischemic Myocardial Injury in a Porcine Model

Authors

  • Henna Elisa Sarja Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu, Finland
  • Tuomas Anttila Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu, Finland
  • Caius Mustonen Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu, Finland
  • Hannu-Pekka Honkanen Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu, Finland
  • Johanna Herajärvi Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu, Finland
  • Henri Haapanen Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu and Medical Research Center, Oulu, Finland
  • Hannu Tuominen Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Finland
  • Ilkka Miinalainen Medical Research Center Oulu, Research Unit of Biomedicine, University of Oulu and University Hospital Oulu, Oulu, Finland
  • Tatu Juvonen Department of Cardiac Surgery, Heart and Lung Center, Helsinki University Central Hospital, Helsinki University Hospital, Helsinki, Finland
  • Vesa Anttila Heart Center, University of Turku and Turku University Hospital, Turku, Finland

DOI:

https://doi.org/10.1532/hsf.1790

Abstract

Background: We hypothesized that diazoxide, a mitochondrial ATP-sensitive potassium channel opener, has cardioprotective effects during acute myocardial ischemia. Diazoxide is suggested to act through protein kinase Cε (PKCε) activation.

Methods: Twelve piglets were randomly assigned to receive intravenous infusion of diazoxide (3.5 mg/kg) with solvent or only solvent (6 animals per group) before cardiac ischemia. Myocardial ischemia was induced by occluding the left circumflex artery (LCX) for 40 minutes. The reperfusion and follow-up period lasted for three hours. Throughout the experiment hemodynamic measurements and blood samples were collected, and after the follow-up period the hearts were harvested for transmission electron microscopy (TEM) as well as histopathological and immunohistochemical analyses.

Results: TEM showed less ischemic damage on a cellular level in the diazoxide group (P = .004) than in the control group. Creatinine kinase MB levels (Pt*g = .030) were lower, and oxygen consumption (Pt*g = .037) and delivery
(Pg = .038) were higher in the diazoxide group compared to the controls.

Conclusion: Diazoxide preserves myocardial cellular structure and cellular function, and thus it may have benefits in treating ischemic myocardial injury.

References

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Published

2017-08-25

How to Cite

Sarja, H. E., Anttila, T., Mustonen, C., Honkanen, H.-P., Herajärvi, J., Haapanen, H., Tuominen, H., Miinalainen, I., Juvonen, T., & Anttila, V. (2017). Diazoxide Attenuates Ischemic Myocardial Injury in a Porcine Model. The Heart Surgery Forum, 20(4), E153-E161. https://doi.org/10.1532/hsf.1790

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