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Beneficial Effects of Intracoronary Nicorandil on Microvascular Dysfunction After Primary Percutaneous Coronary Intervention: Demonstration of Its Superiority to Nitroglycerin in a Cross-Over Study

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Abstract

Purpose

In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study wasto clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI.

Methods

We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 μg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time.

Results

As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2–20.7] U vs. 2.1[1.0–6.0] U, p = 0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3–12.7] U vs. −1.4[−2.6 to 1.3] U, p < 0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level.

Conclusion

Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.

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Acknowledgments

We are greatly indebted to all of Osaka Saiseikai Senri Hospital personnel.

Conflict of Interest Statement

All authors declare no conflicts of interest.

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Authors and Affiliations

  1. Senri Critical Care Medical Center, Osaka Saiseikai Senri Hospital, 1-1-6, Tsukumodai, Suita, Osaka, 565-0862, Japan

    Noritoshi Ito, Yuma Kurozumi, Tomoaki Natsukawa, Masaya Morita, Atsushi Kawata, Ayumu Tsuruoka, Hirotaka Sawano & Tatsuro Kai

  2. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Shinsuke Nanto & Yasuhiko Sakata

  3. Division of Cardiovascular Medicine, Osaka SaiseikaiSenri Hospital, Suita, Osaka, Japan

    Yasuji Doi, Hiroyuki Shibata, Ken-ichiro Okada & Toru Hayashi

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  1. Noritoshi Ito
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  2. Shinsuke Nanto
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Correspondence to Noritoshi Ito.

Electronic supplementary material

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10557_2013_6456_MOESM1_ESM.jpg

Supplement Figure Contributor of improving IMR. (Figure A) From Baseline to P1 (Figure B) From P1 to P2.IMR measurement was performed following PCI (baseline), after administration of nitroglycerin (P1), and after administration of nicorandil (P2). Nic group: IMR measurement was performed following PCI (Baseline), after administration of nicorandil (P1), and after administration of nitroglycerin (P2). Open boxes are NTG group and black boxes are Nic group. Spearman correlation analysis was performed to assess correlations. IMR = index of microcirculatory resistance; MBP = mean blood pressure; Tmn = hyperemic mean transit time (JPEG 64 kb)

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Ito, N., Nanto, S., Doi, Y. et al. Beneficial Effects of Intracoronary Nicorandil on Microvascular Dysfunction After Primary Percutaneous Coronary Intervention: Demonstration of Its Superiority to Nitroglycerin in a Cross-Over Study. Cardiovasc Drugs Ther 27, 279–287 (2013). https://doi.org/10.1007/s10557-013-6456-y

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