1. Novel Synthesized Radical-Containing Nanoparticles Limit Infarct Size Following Ischemia and Reperfusion in Canine Hearts
- Author
-
Madoka Ihara, Seiji Takashima, Yoshihiro Asano, Hideyuki Sasaki, Shoji Sanada, Hidezo Mori, Masafumi Kitakaze, Masaru Sugimachi, Yukio Nagasaki, Toru Yoshitomi, Hiroyuki Takahama, Hiroshi Asanuma, Yoshiro Shinozaki, Tetsuo Minamino, Hiroko Takahama, Atsushi Nakano, and Masanori Asakura
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Cardiotonic Agents ,Ischemia ,Myocardial Infarction ,Myocardial Reperfusion Injury ,030204 cardiovascular system & hematology ,Nitric Oxide ,Nitric oxide ,Cyclic N-Oxides ,03 medical and health sciences ,chemistry.chemical_compound ,Coronary circulation ,0302 clinical medicine ,Dogs ,Internal medicine ,Coronary Circulation ,medicine ,Animals ,Pharmacology (medical) ,Myocardial infarction ,Pharmacology ,Cardioprotection ,Drug Carriers ,business.industry ,General Medicine ,Venous blood ,medicine.disease ,Coronary arteries ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Injections, Intravenous ,Cardiology ,Nanoparticles ,Spin Labels ,Cardiology and Cardiovascular Medicine ,business ,Reperfusion injury - Abstract
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. 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. 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. 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.
- Published
- 2017