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Scavenging free radicals improves endothelial dysfunction in human coronary arteries in vivo
Jun-ichi Oyama1, Shinji Satoh, Nobuhiro Suematsu
1Department of Cardiovascular, Respiratory, and Geriatric Medicine, Kyushu University Hospital at Beppu and Medical Institute of Bioregulation, Kyushu University, Oita, Japan. joyama@tsurumi.beppu.kyushu-u.ac.jp
Insights
Edaravone, a free radical scavenger, improved coronary endothelial dysfunction in patients with attenuated blood flow responses to acetylcholine. This suggests that scavenging free radicals benefits patients with coronary endothelial dysfunction.
Area of Science:
- Cardiology
- Pharmacology
- Free Radical Biology
Background:
- Coronary endothelial dysfunction plays a role in cardiovascular disease.
- Free radicals are implicated in endothelial dysfunction.
- Edaravone is a novel free radical scavenger.
Purpose of the Study:
- To investigate the effect of edaravone on coronary endothelial dysfunction.
- To elucidate the role of free radicals in coronary endothelial dysfunction.
- To assess the impact of edaravone on coronary blood flow (CBF) responses to acetylcholine (ACh).
Main Methods:
- Quantitative coronary arteriography and intracoronary Doppler technique were used to measure CBF responses to ACh.
- Twenty-four patients with no significant coronary stenosis were divided into "attenuated" and "normal" flow response groups based on ACh challenge.
- Edaravone was administered intracoronary before and after ACh infusion.
Main Results:
- Edaravone significantly improved ACh-induced CBF increases in patients with attenuated flow responses (36.8% +/- 7.3%, P < 0.01).
- Edaravone had no significant effect in patients with normal flow responses (0.0% +/- 5.1%).
- Patients with attenuated responses had lower nitric oxide compounds (NOx) and higher oxidative stress markers (malondialdehyde, 4-hydroxynonenal) compared to the normal group.
Conclusions:
- Free radical scavenging with edaravone demonstrates a beneficial effect on coronary endothelial dysfunction in vivo.
- The findings suggest that targeting free radicals may be a therapeutic strategy for patients with coronary endothelial dysfunction.
- Lower NOx levels and higher oxidative stress correlate with improved CBF response to edaravone.
Abstract:
The effect of a novel free radical scavenger, edaravone, on coronary endothelial dysfunction was examined in patients who had no significant stenosis of coronary arteries, to elucidate the role of free radicals on coronary endothelial dysfunction. The coronary blood flow (CBF) responses to acetylcholine (ACh) were measured by quantitative coronary arteriography and the intracoronary Doppler technique before and after the administration of edaravone. Twenty-four patients were divided into two groups on the basis of CBF responses to ACh; those with "attenuated" (%Delta CBF < 300%, n = 12) and "normal" (%Delta CBF > 300%, n = 12) flow responses. An intracoronary infusion of edaravone significantly improved ACh-induced increases in CBF in patients with attenuated flow responses; however, edaravone had no effect in those with normal flow responses (36.8% +/- 7.3% vs 0.0% +/- 5.1%, P < 0.01). The plasma levels of nitric oxide compounds (NOx) in the attenuated response group were lower than those in the normal group (35.7 +/- 2.3 vs 49.4 +/- 6.2 muM, P < 0.01) and correlated with the magnitude of CBF improvement by edaravone (r = 0.566, P < 0.01). The plasma level of malondialdehyde and 4-hydroxynonenal, which indicates the level of oxidative stress, in the attenuated group was higher than that in the normal group (6.9 +/- 0.9 vs 3.3 +/- 0.5 muM, P < 0.01) and correlated with the magnitude of CBF improvement by edaravone (r = 0.854, P < 0.01). A free radical scavenger improved the ACh-induced CBF response in patients with coronary atherosclerosis in vivo. Therefore, the current results suggest that scavenging free radicals has a beneficial effect for patients with coronary endothelial dysfunction.
