CLINICAL STUDIES
Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction
Hiroshi Ito, MD*,
Yoshiaki Taniyama, MD*,
Katsuomi Iwakura, MD*,
Nagahiro Nishikawa, MD*,
Tohru Masuyama, MD ,
Tsunehiko Kuzuya,
Masatsugu Hori, MD,
Yorihiko Higashino, MD*,
Kenshi Fujii, MD* and
Takazo Minamino, MD*
* Division of Cardiology, Sakurabashi Watanabe Hospital, Osaka, Japan
First Department of Medicine, Osaka University School of Medicine, Osaka, Japan
Manuscript received July 21, 1998;
revised manuscript received September 17, 1998,
accepted November 5, 1998.
Reprint requests and correspondence: Dr. Hiroshi Ito, The Division of Cardiology, Sakurabashi Watanabe Hospital, 2-4-32 Umeda, Kita-ku, Osaka 530-0001, Japan
itomd{at}osk4.3web.ne.jp
OBJECTIVES
We assessed whether the intravenous administration of nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts beneficial effect on microvascular function and functional and clinical outcomes in patients with acute myocardial infarction (AMI).
BACKGROUND
Experimental studies documented that ATP-sensitive K+ channel opener exerts cardioprotection after prolonged ischemia.
METHODS
We randomly divided 81 patients with a first anterior AMI into two groups, nicorandil (n = 40) and control groups (n = 41). All patients received successful coronary angioplasty within 12 h after the symptom onset and underwent myocardial contrast echcardiography (MCE) with the intracoronary injection of sonicated microbubbles. In the nicorandil group, we injected 4 mg of nicorandil followed by the infusion at 6 mg/h for 24 h and by oral nicorandil (15 mg/day).
RESULTS
The improvement in regional left ventricular function, wall motion score and regional wall motion was significantly better in the nicorandil group then in the control group. Intractable congestive heart failure, malignant ventricular arrhythmia and pericardial effusion were more frequently found in the control group than in the nicorandil group (15% vs. 37%, 5% vs. 20% and 8% vs. 37%, p < 0.05, respectively). The frequency of sizable MCE no reflow phenomenon was significantly lower in the nicorandil group than in the control group (15% vs. 33%, p < 0.05).
CONCLUSIONS
Intravenous nicorandil in conjunction with coronary angioplasty is associated with better functional and clinical outcomes compared to angioplasty alone in patients with an anterior AMI. Myocardial contrast echocardiography findings imply that an improvement in microvascular function with nicorandil may be attributable to this better outcome.
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Abbreviations and Acronyms
| | AMI | = acute myocardial infarction | | ANOVA | = analysis of variance | | ATP | = adenosine triphosphate | | CHF | = congestive heart failure | | ECG | = electrocardiography | | LV | = left ventricular | | LVEDVI | = left ventricular end-diastolic volume index | | MCE | = myocardial contrast echocardiography | | TIMI | = Thrombolysis in Myocardial Infarction |
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2(3):
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|
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H. Ishii, T. Amano, T. Matsubara, and T. Murohara
Pharmacological Intervention for Prevention of Left Ventricular Remodeling and Improving Prognosis in Myocardial Infarction
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118(25):
2710 - 2718.
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J. Am. Coll. Cardiol. Intv.,
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1(3):
268 - 276.
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|
|
|
|
|
|
|
P. A. Grayburn and J. W. Choi
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J. Am. Coll. Cardiol.,
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51(5):
566 - 568.
[Full Text]
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|
|
|
|
|
|
|
S. A. Hayat and R. Senior
Myocardial contrast echocardiography in ST elevation myocardial infarction: ready for prime time?
Eur. Heart J.,
February 1, 2008;
29(3):
299 - 314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kasama, T. Toyama, H. Sumino, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi
Long-Term Nicorandil Therapy Improves Cardiac Sympathetic Nerve Activity After Reperfusion Therapy in Patients with First Acute Myocardial Infarction
J. Nucl. Med.,
October 1, 2007;
48(10):
1676 - 1682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Dirksen, G. J. Laarman, M. L. Simoons, and D. J.G.M. Duncker
Reperfusion injury in humans: A review of clinical trials on reperfusion injury inhibitory strategies
Cardiovasc Res,
June 1, 2007;
74(3):
343 - 355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J. Terkelsen, B. L. Norgaard, J. F. Lassen, S. H. Poulsen, J. C. Gerdes, E. Sloth, L. B.-H. Gotzsche, F. K. Romer, L. Thuesen, T. T. Nielsen, et al.
Potential significance of spontaneous and interventional ST-changes in patients transferred for primary percutaneous coronary intervention: observations from the ST-MONitoring in Acute Myocardial Infarction study (The MONAMI study)
Eur. Heart J.,
February 1, 2006;
27(3):
267 - 275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ishii, S. Ichimiya, M. Kanashiro, T. Amano, T. Matsubara, and T. Murohara
Effects of Intravenous Nicorandil Before Reperfusion for Acute Myocardial Infarction in Patients With Stress Hyperglycemia
Diabetes Care,
February 1, 2006;
29(2):
202 - 206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ishii, S. Ichimiya, M. Kanashiro, T. Amano, K. Imai, T. Murohara, and T. Matsubara
Impact of a Single Intravenous Administration of Nicorandil Before Reperfusion in Patients With ST-Segment-Elevation Myocardial Infarction
Circulation,
August 30, 2005;
112(9):
1284 - 1288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. A. Krombach, C. B. Higgins, M. Chujo, and M. Saeed
Gadomer-enhanced MR Imaging in the Detection of Microvascular Obstruction: Alleviation with Nicorandil Therapy
Radiology,
August 1, 2005;
236(2):
510 - 518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. P. Bouki, G. Pavlakis, and E. Papasteriadis
Management of Cardiogenic Shock Due to Acute Coronary Syndromes
Angiology,
March 1, 2005;
56(2):
123 - 130.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. Bolli, L. Becker, G. Gross, R. Mentzer Jr, D. Balshaw, and D. A. Lathrop
Myocardial Protection at a Crossroads: The Need for Translation Into Clinical Therapy
Circ. Res.,
July 23, 2004;
95(2):
125 - 134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ueda, T. Hayashi, K. Tsumura, K. Yoshimaru, Y. Nakayama, and J. Yoshikawa
Intravenous Nicorandil Can Reduce QT Dispersion and Prevent Bradyarrhythmia During Percutaneous Transluminal Coronary Angioplasty of the Right Coronary Artery
Journal of Cardiovascular Pharmacology and Therapeutics,
July 1, 2004;
9(3):
179 - 184.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Schalla, C. B. Higgins, M. Chujo, and M. Saeed
Effect of Potassium-Channel Opener Therapy on Reperfused Infarction in Hypertrophied Hearts: Demonstration of Preconditioning by Using Functional and Contrast-Enhanced Magnetic Resonance Imaging
Journal of Cardiovascular Pharmacology and Therapeutics,
July 1, 2004;
9(3):
193 - 202.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Sakuma, J. Sklenar, H. Leong-Poi, N. C. Goodman, D. K. Glover, and S. Kaul
Molecular Imaging Identifies Regions with Microthromboemboli During Primary Angioplasty in Acute Coronary Thrombosis
J. Nucl. Med.,
July 1, 2004;
45(7):
1194 - 1200.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Greaves, S. R Dixon, I. O. Coker, A. I Mallet, M. Vkiran, M. J Shattock, M. J Fejka, W. W O'Neill, R. Senior, S. Redwood, et al.
Influence of isoprostane F2{alpha}-III on reflow after myocardial infarction
Eur. Heart J.,
May 2, 2004;
25(10):
847 - 853.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-L. Tang, Y.-T. Xuan, Y. Zhu, G. Shirk, and R. Bolli
Nicorandil induces late preconditioning against myocardial infarction in conscious rabbits
Am J Physiol Heart Circ Physiol,
April 1, 2004;
286(4):
H1273 - H1280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Takeuchi, Y. Nohtomi, H. Yoshitani, C. Miyazaki, K. Sakamoto, and J. Yoshikawa
Enhanced coronary flow velocity during intra-aortic balloon pumping assessed by transthoracic doppler echocardiography
J. Am. Coll. Cardiol.,
February 4, 2004;
43(3):
368 - 376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L Galiuto
Optimal therapeutic strategies in the setting of post-infarct no reflow: the need for a pathogenetic classification
Heart,
February 1, 2004;
90(2):
123 - 125.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N Ikeda, T Yasu, N Kubo, S Hashimoto, Y Tsuruya, M Fujii, M Kawakami, and M Saito
Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon angioplasty in acute myocardial infarction
Heart,
February 1, 2004;
90(2):
181 - 185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kaul and H. Ito
Microvasculature in Acute Myocardial Ischemia: Part II: Evolving Concepts in Pathophysiology, Diagnosis, and Treatment
Circulation,
January 27, 2004;
109(3):
310 - 315.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. T. Ashby, G. Dangas, E. A. Aymong, I. Iakovou, F. Kuepper, R. Mehran, G. W. Stone, M. B. Leon, and J. W. Moses
Effect of percutaneous coronary interventions for in-stent restenosis in degenerated saphenous vein grafts without distal embolic protection
J. Am. Coll. Cardiol.,
March 5, 2003;
41(5):
749 - 752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.S Petronio, D Rovai, G Musumeci, R Baglini, C Nardi, U Limbruno, C Palagi, D Volterrani, and M Mariani
Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplasty
Eur. Heart J.,
January 1, 2003;
24(1):
67 - 76.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Iwakura, H. Ito, M. Ikushima, S. Kawano, A. Okamura, K. Asano, T. Kuroda, K. Tanaka, T. Masuyama, M. Hori, et al.
Association between hyperglycemia and the no-reflow phenomenon inpatients with acute myocardial infarction
J. Am. Coll. Cardiol.,
January 1, 2003;
41(1):
1 - 7.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J P Greenwood, I Malik, P Jennings, and R N Stevenson
Haemodynamic and electrocardiographic consequences of severe nicorandil toxicity
Emerg. Med. J.,
January 1, 2003;
20(1):
98 - 100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K Shimada, Y Sakanoue, Y Kobayashi, S Ehara, M Hirose, Y Nakamura, D Fukuda, H Yamagishi, M Yoshiyama, K Takeuchi, et al.
Assessment of myocardial viability using coronary zero flow pressure after successful angioplasty in patients with acute anterior myocardial infarction
Heart,
January 1, 2003;
89(1):
71 - 76.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tsuchida, T. Miura, M. Tanno, J. Sakamoto, T. Miki, A. Kuno, T. Matsumoto, Y. Ohnuma, Y. Ichikawa, and K. Shimamoto
Infarct size limitation by nicorandil: Roles of mitochondrial KATP channels, sarcolemmal KATP channels, and protein kinase C
J. Am. Coll. Cardiol.,
October 16, 2002;
40(8):
1523 - 1530.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Genda, T. Miura, T. Miki, Y. Ichikawa, and K. Shimamoto
KATP channel opening is an endogenous mechanism of protection against the no-reflow phenomenon but its function is compromised by hypercholesterolemia
J. Am. Coll. Cardiol.,
October 2, 2002;
40(7):
1339 - 1346.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-K. Wong, J.K. French, M.W. Krucoff, W. Gao, P.E. Aylward, and H.D. White
Slowed ST segment recovery despite early infarct artery patency in patients with Q waves at presentation with a first acute myocardial infarction. Implications of initial Q waves on myocyte reperfusion
Eur. Heart J.,
September 2, 2002;
23(18):
1449 - 1455.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Saeed, N. Watzinger, G. A. Krombach, G. K. Lund, M. F. Wendland, M. Chujo, and C. B. Higgins
Left Ventricular Remodeling after Infarction: Sequential MR Imaging with Oral Nicorandil Therapy in Rat Model
Radiology,
September 1, 2002;
224(3):
830 - 837.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Akao, Y. Teshima, and E. Marban
Antiapoptotic effect of nicorandil mediated by mitochondrial atp-sensitive potassium channels in cultured cardiac myocytes
J. Am. Coll. Cardiol.,
August 21, 2002;
40(4):
803 - 810.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Watzinger, G. K. Lund, C. B. Higgins, M. Chujo, and M. Saeed
Noninvasive assessment of the effects of nicorandil on left ventricular volumes and function in reperfused myocardial infarction
Cardiovasc Res,
April 1, 2002;
54(1):
77 - 84.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Rezkalla and R. A. Kloner
No-Reflow Phenomenon
Circulation,
February 5, 2002;
105(5):
656 - 662.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Reffelmann and R. A Kloner
The "no-reflow" phenomenon: basic science and clinical correlates
Heart,
February 1, 2002;
87(2):
162 - 168.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. G. Angeja, M. Gunda, S. A. Murphy, B. E. Sobel, A. C. Rundle, M. Syed, A. Asfour, S. Borzak, S. G. Gourlay, H. V. Barron, et al.
TIMI Myocardial Perfusion Grade and ST Segment Resolution: Association With Infarct Size as Assessed by Single Photon Emission Computed Tomography Imaging
Circulation,
January 22, 2002;
105(3):
282 - 285.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Taylor, A. Bobik, M. C. Berndt, D. Ramsay, and G. Jennings
Experimental Rupture of Atherosclerotic Lesions Increases Distal Vascular Resistance: A Limiting Factor to the Success of Infarct Angioplasty
Arterioscler Thromb Vasc Biol,
January 1, 2002;
22(1):
153 - 160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hamada, T. Nishiue, S. Nakamura, T. Sugiura, H. Kamihata, H. Miyoshi, Y. Imuro, and T. Iwasaka
TIMI frame count immediately after primary coronary angioplasty as a predictor of functional recovery in patients with TIMI 3 reperfused acute myocardial infarction
J. Am. Coll. Cardiol.,
September 1, 2001;
38(3):
666 - 671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Iwakura, H. Ito, S. Kawano, Y. Shintani, K. Yamamoto, A. Kato, M. Ikushima, K. Tanaka, M. Kitakaze, M. Hori, et al.
Predictive factors for development of the no-reflow phenomenon in patients with reperfused anterior wall acute myocardial infarction
J. Am. Coll. Cardiol.,
August 1, 2001;
38(2):
472 - 477.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Iglesias-Garriz, F.e. Corral, M. A. Rodriguez, C. Garrote, M. Montes, and E. Sevillano
Pre-infarction angina elicits greater myocardial viability on reperfusion after myocardial infarction: a dobutamine stress echocardiographic study
J. Am. Coll. Cardiol.,
June 1, 2001;
37(7):
1846 - 1850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E Eeckhout and M.J Kern
The coronary no-reflow phenomenon: a review of mechanisms and therapies
Eur. Heart J.,
May 1, 2001;
22(9):
729 - 739.
[PDF]
|
|
|
|
|
|
|
A. Okamura, H. Rakugi, M. Ohishi, Y. Yanagitani, M. Shimizu, T. Nishii, Y. Taniyama, T. Asai, S. Takiuchi, K. Moriguchi, et al.
Additive effects of nicorandil on coronary blood flow during continuous administration of nitroglycerin
J. Am. Coll. Cardiol.,
March 1, 2001;
37(3):
719 - 725.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kaneko, Y. Saito, Y. Hikawa, K. Yasuda, and K. Makita
Dose-dependent prophylactic effect of nicorandil, an ATP-sensitive potassium channel opener, on intra-operative myocardial ischaemia in patients undergoing major abdominal surgery
Br. J. Anaesth.,
March 1, 2001;
86(3):
332 - 337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.H. Davies
Revascularization for cardiogenic shock
QJM,
February 1, 2001;
94(2):
57 - 67.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Roe, E. M. Ohman, A. C. P. Maas, R. H. Christenson, K. W. Mahaffey, C. B. Granger, R. A. Harrington, R. M. Califf, and M. W. Krucoff
Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion
J. Am. Coll. Cardiol.,
January 1, 2001;
37(1):
9 - 18.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Topol and J. S. Yadav
Recognition of the Importance of Embolization in Atherosclerotic Vascular Disease
Circulation,
February 8, 2000;
101(5):
570 - 580.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sato, N. Sasaki, B. O'Rourke, and E. Marban
Nicorandil, a potent cardioprotective agent, acts by opening mitochondrial ATP-dependent potassium channels
J. Am. Coll. Cardiol.,
February 1, 2000;
35(2):
514 - 518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. K. Lund, C. B. Higgins, M. F. Wendland, N. Watzinger, H.-J. Weinmann, and M. Saeed
Assessment of Nicorandil Therapy in Ischemic Myocardial Injury by Using Contrast-enhanced and Functional MR Imaging
Radiology,
December 1, 2001;
221(3):
676 - 682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
