Novel Synthesized Radical-Containing Nanoparticles Limit Infarct Size Following Ischemia and Reperfusion in Canine Hearts

Hiroshi Asanuma, Shoji Sanada, Toru Yoshitomi, Hideyuki Sasaki, Hiroyuki Takahama, Madoka Ihara, Hiroko Takahama, Yoshiro Shinozaki, Hidezo Mori, Masanori Asakura, Atsushi Nakano, Masaru Sugimachi, Yoshihiro Asano, Tetsuo Minamino, Seiji Takashima, Yukio Nagasaki, Masafumi Kitakaze

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Purpose: Although nitroxyl radicals such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) scavenge free radicals, their short half-life and considerable side effects such as systemic hypotension and bradycardia have limited their clinical application. Since a radical-containing nanoparticle (RNP) delivers nitroxyl radicals with a prolonged half-life specific to ischemic hearts, we investigated whether RNPs reduce infarct size without the occurrence of substantial side effects and whether nitric oxide (NO) contributes to the cardioprotective effects of RNPs. Methods: The left anterior descending coronary arteries of dogs were occluded for 90 min, followed by reperfusion for 6 h. Either RNPs, micelles (not containing TEMPO) (control), or 4-hydroxy-TEMPO (TEMPOL) was injected into a systemic vein for 5 min before reperfusion. We evaluated the infarct size, myocardial apoptosis, plasma NO levels in coronary venous blood, and the RNP spectra using an electron paramagnetic resonance assay. Results: RNPs reduced infarct size compared with the control group and TEMPOL group (19.5 ± 3.3 vs. 42.2 ± 3.7 vs. 30.2 ± 3.4%). RNPs also reduced myocardial apoptosis compared with the control and TEMPOL group. Coronary venous NO levels increased in the RNP group. Conclusions: In conclusion, the administration of 2,2,6,6-tetramethylpiperidine-1-oxyl as a RNP exerted cardioprotective effects against ischemia and reperfusion injury in canine hearts without exerting unfavorable hemodynamic effects. RNPs may represent a promising new therapy for patients with acute myocardial infarction.

Original languageEnglish
Pages (from-to)501-510
Number of pages10
JournalCardiovascular Drugs and Therapy
Volume31
Issue number5-6
DOIs
Publication statusPublished - 2017 Dec 1
Externally publishedYes

Keywords

  • Cardioprotection
  • Ischemia-reperfusion
  • Myocardial infarction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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