Diazoxide Attenuates Ischemic Myocardial Injury in a Porcine Model

Heart Surg Forum. 2017 Aug 25;20(4):E153-E161. doi: 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.

MeSH terms

  • Animals
  • Diazoxide / administration & dosage*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Infusions, Intra-Arterial
  • Microscopy, Electron, Transmission
  • Myocardial Reperfusion Injury / diagnosis
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / ultrastructure
  • Swine
  • Vasodilator Agents / administration & dosage

Substances

  • Vasodilator Agents
  • Diazoxide