Administration of the Mitochondria! Permeability Transition Pore Inhibitor, TR040303, prior to Primary Percutaneous Coronary Intervention, Does Not Affect the Levels of Pro-Inflammatory Cytokines or Acute-Phase Proteins

Objectives: In the MITOCARE study, reperfusion injury was not prevented after administration of the mitochondrial permeability transition pore (mPTP) opening inhibitor, TR040303, in patients with ST-segment elevation myocardial infarction (STEN) treated with primary percutaneous coronary intervention (pPCI). The effects of TR040303 on pro-inflammatory cytokines and acute-phase proteins were assessed. Methods: STEN patients (n = 163, mean age 62 years) with chest pain within 6 h before admission for pPCI were randomized to intravenous bolus of TR040303 (n = 83) or placebo (n = 80) prior to reperfusion. We tested whether the groups differed in levels of IL-113, 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, TR040303, prior to reperfusion does not alter the pharmacokinetics of pro-inflammatory cytokines or acute-phase proteins during the first 72 h after PCI. (C) 2017 S. Karger AG, Basel