Skip to main content
Top
Published in: Cardiovascular Ultrasound 1/2015

Open Access 01-12-2015 | Research

The effects of nicorandil on microvascular function in patients with ST segment elevation myocardial infarction undergoing primary PCI

Authors: Jelena Kostic, Ana Djordjevic-Dikic, Milan Dobric, Dejan Milasinovic, Milan Nedeljkovic, Sinisa Stojkovic, Jelena Stepanovic, Milorad Tesic, Zoran Trifunovic, Danijela Zamaklar-Tifunovic, Mina Radosavljevic-Radovanovic, Miodrag Ostojic, Branko Beleslin

Published in: Cardiovascular Ultrasound | Issue 1/2015

Login to get access

Abstract

Background

Nicorandil, as a selective potassium channel opener, has dual action including coronary and peripheral vasodilatation and cardioprotective effect through ischemic preconditioning. Considering those characteristics, nicorandil was suggested to reduce the degree of microvascular dysfunction.

Methods

Thirty-two patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI) were included in the study. Index of microvascular resistance (IMR) was measured in all patients immediatelly after pPCI before the after administration of Nicorandil. ST segment resolution was monitored before intervention and 60 min after terminating the procedure. Echocardiographic evaluation of myocardial function and transthoracic Doppler derived Coronary flow reserve (CFR) of infarct related artery (IRA) was performed during hospitalization and 3 months later.

Results

IMR was significantly lower after administration of Nicorandil (9.9 ± 3.7 vs. 14.1 ± 5.1, p < 0.001). There was significant difference in ST segment elevation before and after primary PCI with administration of Nicorandil (6.9 ± 3.7 mm vs. 1.6 ± 1.6 mm, p < 0.001). Transthoracic Doppler CFR measurement improved after 3 months (2.69 ± 0.38 vs. 2.92 ± 0.54, p = 0.021), as well as WMSI (1.14 ± 0.17 vs. 1.07 ± 0.09, p = 0.004).

Conclusion

Intracoronary Nicorandil administration after primary PCI significantly decreases IMR, resulting in improved CFR and ventricular function in patients with STEMI undergoing primary PCI.
Literature
1.
go back to reference Resnic F, Wainstein M, Lee M, Behrendt D, Wainstein R, Ohno-Machado L, et al. No-reflow is an independent predictor of death and myocardial infarction after percutaneous coronary intervention. Am Heart J. 2003;145:42–6.CrossRefPubMed Resnic F, Wainstein M, Lee M, Behrendt D, Wainstein R, Ohno-Machado L, et al. No-reflow is an independent predictor of death and myocardial infarction after percutaneous coronary intervention. Am Heart J. 2003;145:42–6.CrossRefPubMed
2.
go back to reference Porto I, Ashar V, Mitchell A. Pharmacological management of no reflow during percutaneous coronary intervention. Curr Vasc Pharmacol. 2006;4:95–100.CrossRefPubMed Porto I, Ashar V, Mitchell A. Pharmacological management of no reflow during percutaneous coronary intervention. Curr Vasc Pharmacol. 2006;4:95–100.CrossRefPubMed
4.
go back to reference Marzilli M, Orsini E, Marraccini P, Testa R. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation. 2000;101:2154–9.CrossRefPubMed Marzilli M, Orsini E, Marraccini P, Testa R. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation. 2000;101:2154–9.CrossRefPubMed
5.
go back to reference Niccoli G, Rigaztieri S, De Vita MR, Valgimigli M, Corvo P, Fabbiocchi F, et al. Open-label, randomized, placebo controlled evaluation of intracoronary adenosine or nitroprusside after thrombus aspiration during primary percutaneous intervention for the prevention of microvascular obstruction in acute myocardial infarction. J Am Coll Cardiol. 2013;6:580–9.CrossRef Niccoli G, Rigaztieri S, De Vita MR, Valgimigli M, Corvo P, Fabbiocchi F, et al. Open-label, randomized, placebo controlled evaluation of intracoronary adenosine or nitroprusside after thrombus aspiration during primary percutaneous intervention for the prevention of microvascular obstruction in acute myocardial infarction. J Am Coll Cardiol. 2013;6:580–9.CrossRef
6.
go back to reference Mahaffey K, Puma J, Barbagelata A, DiCArli M, Leesar M, Brown K, et al. Granger and for the AMISTAD Investigators. J Am Coll Cardiol. 1999;34:1711–20.CrossRefPubMed Mahaffey K, Puma J, Barbagelata A, DiCArli M, Leesar M, Brown K, et al. Granger and for the AMISTAD Investigators. J Am Coll Cardiol. 1999;34:1711–20.CrossRefPubMed
7.
go back to reference Babbitt D, Virmani R, Vildibill H, Daughtry Norton E, Forman M. Intracoronary adenosine administration during reperfusion following 3 hours of ishemia: effects on infarct size, ventricular function, and regional myocardial blood flow. Am Heart J. 1990;120:808–18.CrossRefPubMed Babbitt D, Virmani R, Vildibill H, Daughtry Norton E, Forman M. Intracoronary adenosine administration during reperfusion following 3 hours of ishemia: effects on infarct size, ventricular function, and regional myocardial blood flow. Am Heart J. 1990;120:808–18.CrossRefPubMed
8.
go back to reference Taniyama Y, Ito H, Iwakura K, Masuyama T, Hori M, Takiuchi S, et al. Beneficial effects of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. J Am Coll Cardiol. 1997;30:1193–9.CrossRefPubMed Taniyama Y, Ito H, Iwakura K, Masuyama T, Hori M, Takiuchi S, et al. Beneficial effects of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. J Am Coll Cardiol. 1997;30:1193–9.CrossRefPubMed
9.
go back to reference Grover G, Garlid K. ATP-Sensitive potassium channels: a review of their cardioprotective pharmacology. J Mol Cell Cardiol. 2000;32:677–95.CrossRefPubMed Grover G, Garlid K. ATP-Sensitive potassium channels: a review of their cardioprotective pharmacology. J Mol Cell Cardiol. 2000;32:677–95.CrossRefPubMed
10.
go back to reference Morin D, Assaly R, Paradis S, Berdaux A. Inhibition of mitochondrial membrane permeability as a putative pharmacological target for cardioprotection. Curr Med Chem. 2009;16:4382–98.CrossRefPubMedPubMedCentral Morin D, Assaly R, Paradis S, Berdaux A. Inhibition of mitochondrial membrane permeability as a putative pharmacological target for cardioprotection. Curr Med Chem. 2009;16:4382–98.CrossRefPubMedPubMedCentral
11.
go back to reference Lim S, Bae E, Jeong M, Kang D, Lee Y, Kim K, et al. Effect of combined intracoronary adenosine and nicorandil on no-reflow phenomenon during percutaneous coronary intervention. Circulation. 2004;68:928–32.CrossRef Lim S, Bae E, Jeong M, Kang D, Lee Y, Kim K, et al. Effect of combined intracoronary adenosine and nicorandil on no-reflow phenomenon during percutaneous coronary intervention. Circulation. 2004;68:928–32.CrossRef
12.
go back to reference Ishii H, Ichimiya S, Kanashiro M, Amano T, Imai K, Murohara T, et al. Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment elevation myocardial infarction. Circulation. 2005;112:1284–8.CrossRefPubMed Ishii H, Ichimiya S, Kanashiro M, Amano T, Imai K, Murohara T, et al. Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment elevation myocardial infarction. Circulation. 2005;112:1284–8.CrossRefPubMed
13.
go back to reference Kushner G, Hand M, Smith Jr C, King 3rd B, Anderson L, Antman M, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009;54:2205–41.CrossRefPubMed Kushner G, Hand M, Smith Jr C, King 3rd B, Anderson L, Antman M, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009;54:2205–41.CrossRefPubMed
14.
go back to reference Brodie BR, Stuckey TD, Hansen C, VerSteeg DS, Muncy DB, Moore S, et al. Relation between electrocardiographic ST-segment resolution and early and late outcomes after primary percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol. 2005;95:343–8.CrossRefPubMed Brodie BR, Stuckey TD, Hansen C, VerSteeg DS, Muncy DB, Moore S, et al. Relation between electrocardiographic ST-segment resolution and early and late outcomes after primary percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol. 2005;95:343–8.CrossRefPubMed
15.
go back to reference Cannon P, Braunwald E. Time to reperfusion: the critical modulator in thrombolysis and primary angioplasty. J Thromb Thrombolysis. 1996;3:117–25.PubMed Cannon P, Braunwald E. Time to reperfusion: the critical modulator in thrombolysis and primary angioplasty. J Thromb Thrombolysis. 1996;3:117–25.PubMed
16.
go back to reference Henriques J, Zijlstra F, WJ van’Hof A, Jan de Boer M, Dambrink JH, Gosselink M, et al. Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade. Circulation. 2003;107:2115–9.CrossRefPubMed Henriques J, Zijlstra F, WJ van’Hof A, Jan de Boer M, Dambrink JH, Gosselink M, et al. Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade. Circulation. 2003;107:2115–9.CrossRefPubMed
17.
go back to reference Schiller B, Shah M, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr. 1989;2:358–67.CrossRefPubMed Schiller B, Shah M, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr. 1989;2:358–67.CrossRefPubMed
18.
go back to reference Tesic M, Djordjevic-Dikic A, Beleslin B, Trifunovic D, Giga V, Marinkovic J, et al. Regional difference of microcirculation in patients with asymmetric hypertrophic cardiomyopathy: transthoracic Doppler coronary flow velocity reserve analysis. J Am Soc Echocardiogr. 2013;26:775–82.CrossRefPubMed Tesic M, Djordjevic-Dikic A, Beleslin B, Trifunovic D, Giga V, Marinkovic J, et al. Regional difference of microcirculation in patients with asymmetric hypertrophic cardiomyopathy: transthoracic Doppler coronary flow velocity reserve analysis. J Am Soc Echocardiogr. 2013;26:775–82.CrossRefPubMed
19.
go back to reference Djordjevic-Dikic A, Beleslin B, Stepanovic J, Giga V, Tesic M, Dobric M, et al. Prediction of myocardial functional recovery by noninvasive evaluation of basal and hyperemic coronary flow in patients with previous myocardial infarction. J Am Soc Echocardiogr. 2011;24:573–81.CrossRefPubMed Djordjevic-Dikic A, Beleslin B, Stepanovic J, Giga V, Tesic M, Dobric M, et al. Prediction of myocardial functional recovery by noninvasive evaluation of basal and hyperemic coronary flow in patients with previous myocardial infarction. J Am Soc Echocardiogr. 2011;24:573–81.CrossRefPubMed
20.
go back to reference Wu M, Huang Z, Xie H, Zhou Z. Nicorandil in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis. PLoS ONE. 2013;8:e78231.CrossRefPubMedPubMedCentral Wu M, Huang Z, Xie H, Zhou Z. Nicorandil in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis. PLoS ONE. 2013;8:e78231.CrossRefPubMedPubMedCentral
22.
go back to reference Eeckhout E. Nicorandil: a drug for many purposes: too good to be true? Eur Heart J. 2003;24:1282–4.CrossRefPubMed Eeckhout E. Nicorandil: a drug for many purposes: too good to be true? Eur Heart J. 2003;24:1282–4.CrossRefPubMed
23.
go back to reference Kloner R, Rezkalla S. Cardiac protection during acute myocardial infarction: where do we stand in 2004? J Am Coll Cardiol. 2004;44:276–86.CrossRefPubMed Kloner R, Rezkalla S. Cardiac protection during acute myocardial infarction: where do we stand in 2004? J Am Coll Cardiol. 2004;44:276–86.CrossRefPubMed
24.
go back to reference Hirohata A, Yamamoto K, Hirose E, Kobayashi Y, Takafuyi H, Sano F, et al. Nicorandil prevents microvascular dysfunction resulting from PCI in patients with stable angina pectoris: a randomized trial. Eurointervention. 2014;9:1050–6.CrossRefPubMed Hirohata A, Yamamoto K, Hirose E, Kobayashi Y, Takafuyi H, Sano F, et al. Nicorandil prevents microvascular dysfunction resulting from PCI in patients with stable angina pectoris: a randomized trial. Eurointervention. 2014;9:1050–6.CrossRefPubMed
25.
go back to reference Fearon W, Aarnousde W, Pijls N, de Bruyne B, Balsam L, Cooke D, et al. Microvascular resistance is not influenced by epicardial coronary artery stenosis severity. Experimental validation. Circulation. 2004;109:2269–72.CrossRefPubMed Fearon W, Aarnousde W, Pijls N, de Bruyne B, Balsam L, Cooke D, et al. Microvascular resistance is not influenced by epicardial coronary artery stenosis severity. Experimental validation. Circulation. 2004;109:2269–72.CrossRefPubMed
26.
go back to reference Sezer M, Umman B, Okcular I, Nisanci Y, Umman S. Relationship between microvascular resistence and perfusion in patients with reperfused acute myocardial infarction. J Int Cardiol. 2007;20:340–50.CrossRef Sezer M, Umman B, Okcular I, Nisanci Y, Umman S. Relationship between microvascular resistence and perfusion in patients with reperfused acute myocardial infarction. J Int Cardiol. 2007;20:340–50.CrossRef
27.
go back to reference Fearon W, Shah M, Ng M, Brinton T, Wilson A, Tremmel J, et al. Predictive value of index of microvasculatory resistance in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2008;51:560–5.CrossRefPubMed Fearon W, Shah M, Ng M, Brinton T, Wilson A, Tremmel J, et al. Predictive value of index of microvasculatory resistance in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2008;51:560–5.CrossRefPubMed
28.
go back to reference Fearon WF, Low AF, Yong AS, McGeoch R, Berry C, Shah MG, et al. Prognoctis value of the index of microcirculatory resistance measured after primary percutaneous intervention. Circulation. 2013;127:2436–41.CrossRefPubMed Fearon WF, Low AF, Yong AS, McGeoch R, Berry C, Shah MG, et al. Prognoctis value of the index of microcirculatory resistance measured after primary percutaneous intervention. Circulation. 2013;127:2436–41.CrossRefPubMed
29.
go back to reference Iida S, Kinoshita H, Holford N. Population pharmacokinetic and pharmacodynamic modeling of the effects of nicorandil in the treatment of acute heart failure. Br J Clin Pharmacol. 2008;66:352–65.CrossRefPubMedPubMedCentral Iida S, Kinoshita H, Holford N. Population pharmacokinetic and pharmacodynamic modeling of the effects of nicorandil in the treatment of acute heart failure. Br J Clin Pharmacol. 2008;66:352–65.CrossRefPubMedPubMedCentral
30.
go back to reference Ito H, Taniyama Y, Iwakura K, Nishikawa N, Masuyama T, Kuzuya T, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol. 1999;33:654–60.CrossRefPubMed Ito H, Taniyama Y, Iwakura K, Nishikawa N, Masuyama T, Kuzuya T, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol. 1999;33:654–60.CrossRefPubMed
31.
go back to reference Sugimoto K, Ito H, Iwakura K, Ikushima M, Kato A, Kimura R, et al. Intravenous nicorandil in conjuction with coronary repefusion therapy is associated with better clinical outcome and functional outcomes in patients with acute myocardial infarction. Circulation. 2003;67:295–300.CrossRef Sugimoto K, Ito H, Iwakura K, Ikushima M, Kato A, Kimura R, et al. Intravenous nicorandil in conjuction with coronary repefusion therapy is associated with better clinical outcome and functional outcomes in patients with acute myocardial infarction. Circulation. 2003;67:295–300.CrossRef
32.
go back to reference Ishii H, Amano T, Ichimiya S, Matsubara T, Kanashiro M, Murohara T. Effects of intravenous nicorandil before reperfusion for acute myocardial infarction in patients with stress hyperglycemia. Diabetes Care. 2006;29:202–6.CrossRefPubMed Ishii H, Amano T, Ichimiya S, Matsubara T, Kanashiro M, Murohara T. Effects of intravenous nicorandil before reperfusion for acute myocardial infarction in patients with stress hyperglycemia. Diabetes Care. 2006;29:202–6.CrossRefPubMed
33.
go back to reference The IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact of nicorandil in Angina (IONA) randomized trial. Lancet. 2002;359:1269–75.CrossRef The IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact of nicorandil in Angina (IONA) randomized trial. Lancet. 2002;359:1269–75.CrossRef
34.
go back to reference Ono H, Osanai T, Ishizaka H, Hanada H, Kamada T, Onodera H, et al. Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation. Am Heart J. 2004;148:611.CrossRef Ono H, Osanai T, Ishizaka H, Hanada H, Kamada T, Onodera H, et al. Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation. Am Heart J. 2004;148:611.CrossRef
35.
go back to reference Ito N, Nanto S, Doi Y, Kurozumi Y, Natsukawa T, Shibata H, 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. 2013;27:279–87.CrossRefPubMed Ito N, Nanto S, Doi Y, Kurozumi Y, Natsukawa T, Shibata H, 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. 2013;27:279–87.CrossRefPubMed
36.
go back to reference Giga V, Dobric M, Beleslin B, Sobic-Saranovic D, Tesic M, Djordjevic-Dikic A, et al. Estimation of infarct size using transthoracic Doppler echocardiographic measurement of coronary flow reserve in infarct related and reference coronary artery. Int J Cardiol. 2013;168:169–75.CrossRefPubMed Giga V, Dobric M, Beleslin B, Sobic-Saranovic D, Tesic M, Djordjevic-Dikic A, et al. Estimation of infarct size using transthoracic Doppler echocardiographic measurement of coronary flow reserve in infarct related and reference coronary artery. Int J Cardiol. 2013;168:169–75.CrossRefPubMed
37.
go back to reference Trifunovic D, Sobic-Saranovic D, Beleslin B, Stankovic S, Marinkovic J, Orlic D, et al. Coronary flow of the infarct artery assessed by transthoracic Doppler after primary percutaneous coronary intervention predicts final infarct size. Int J Cardiovasc Imaging. 2014;30:1509–18.CrossRefPubMed Trifunovic D, Sobic-Saranovic D, Beleslin B, Stankovic S, Marinkovic J, Orlic D, et al. Coronary flow of the infarct artery assessed by transthoracic Doppler after primary percutaneous coronary intervention predicts final infarct size. Int J Cardiovasc Imaging. 2014;30:1509–18.CrossRefPubMed
Metadata
Title
The effects of nicorandil on microvascular function in patients with ST segment elevation myocardial infarction undergoing primary PCI
Authors
Jelena Kostic
Ana Djordjevic-Dikic
Milan Dobric
Dejan Milasinovic
Milan Nedeljkovic
Sinisa Stojkovic
Jelena Stepanovic
Milorad Tesic
Zoran Trifunovic
Danijela Zamaklar-Tifunovic
Mina Radosavljevic-Radovanovic
Miodrag Ostojic
Branko Beleslin
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Ultrasound / Issue 1/2015
Electronic ISSN: 1476-7120
DOI
https://doi.org/10.1186/s12947-015-0020-9

Other articles of this Issue 1/2015

Cardiovascular Ultrasound 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.