Administration of the Mitochondrial Permeability Transition Pore Inhibitor, TRO40303, prior to Primary Percutaneous Coronary Intervention, Does Not Affect the Levels of Pro-Inflammatory Cytokines or Acute-Phase Proteins

Cardiology. 2017;138(2):122-132. doi: 10.1159/000475460. Epub 2017 Jun 27.

Abstract

Objectives: In the MITOCARE study, reperfusion injury was not prevented after administration of the mitochondrial permeability transition pore (mPTP) opening inhibitor, TRO40303, in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). The effects of TRO40303 on pro-inflammatory cytokines and acute-phase proteins were assessed.

Methods: STEMI patients (n = 163, mean age 62 years) with chest pain within 6 h before admission for pPCI were randomized to intravenous bolus of TRO40303 (n = 83) or placebo (n = 80) prior to reperfusion. We tested whether the groups differed in levels of IL-1β, IL-6, IL-10, TNF, and high-sensitive C-reactive protein at various time points (0, 12, and 72 h) after PCI. Further, potential differences between groups in the change of biomarker levels between 0 and 72 h, 0 and 12 h, and 12 and 72 h were tested.

Results: There were no statistically significant differences between the two groups, neither in levels of pro-inflammatory cytokines nor in levels of acute-phase proteins, and there were no statistically significant differences in the change of biomarker levels between the groups considering the time intervals from 0 to 72 h, from 0 to 12 h, and from 12 to 72 h.

Conclusion: The administration of the mPTP, TRO40303, prior to reperfusion does not alter the pharmacokinetics of pro-inflammatory cytokines or acute-phase proteins during the first 72 h after PCI.

Keywords: Cytokines; Mitochondrial permeability transition pore; Primary percutaneous coronary intervention; Reperfusion injury; STEMI.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute-Phase Proteins / metabolism*
  • Aged
  • Biomarkers / metabolism
  • Cytokines / metabolism*
  • Double-Blind Method
  • Europe
  • Female
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Mitochondrial Membrane Transport Proteins / antagonists & inhibitors
  • Mitochondrial Permeability Transition Pore
  • Myocardial Reperfusion Injury / prevention & control
  • Oximes / administration & dosage*
  • Percutaneous Coronary Intervention*
  • ST Elevation Myocardial Infarction / therapy*
  • Secosteroids / administration & dosage*
  • Treatment Outcome

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Cytokines
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Oximes
  • Secosteroids
  • 3,5-seco-4-norcholestan-5-one oxime-3-ol