Skip to main content
Log in

Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Ischaemic preconditioning (PC) is a cardioprotective phenomenon in which short periods of myocardial ischaemia result in resistance to decreased contractile dysfunction during a subsequent period of sustained ischaemia. Nicorandil, an ATP-sensitive potassium channel opener, can induce PC effects on sympathetic nerves during myocardial ischaemia. However, its effects on cardiac sympathetic nerve activity (CSNA) and left ventricular remodelling have not been determined. In this study, we sought to determine whether nicorandil administration improves CSNA in patients with acute myocardial infarction (AMI).

Methods

We studied 58 patients with first anterior AMI, who were randomly assigned to receive nicorandil (group A) or isosorbide dinitrate (group B) after primary coronary angioplasty. The nicorandil or isosorbide dinitrate was continuously infused for >48 h. The extent score (ES) was determined from 99mTc-pyrophosphate scintigraphy, and the total defect score (TDS) was determined from 201Tl scintigraphy 3–5 days after primary angioplasty. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed TDS and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine (MIBG) images 3 weeks later. The left ventriculography results were re-examined 6 months after treatment.

Results

Fifty patients originally enrolled in the trial completed the entire protocol. After treatment, no significant differences were observed in ES or left ventricular parameters between the two groups. However, in group A (n=25), the TDSs determined from 201Tl and 123I-MIBG were significantly lower (26±6 vs 30±5, P<0.01, and 32±8 vs 40±6, P<0.0001, respectively), the H/M ratio significantly higher (1.99±0.16 vs 1.77±0.30, P<0.005) and the WR significantly lower (36%±8% vs 44%±12%, P<0.005) than in group B (n=25). Moreover, 6 months after treatment, LVEDV and LVEF were better in group A than in group B.

Conclusion

These findings indicate that nicorandil can have beneficial effects on CSNA and left ventricular remodelling in patients with first anterior AMI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Sheehan FH, Braunwald E, Canner P, Dodge HT, Gore J, Van Natta P, et al. The effect of intravenous thrombolytic therapy on left ventricular function: a report on tissue-type plasminogen activator and streptokinase from the thrombolysis in myocardial infarction (TIMI Phase I) trial. Circulation 1987;75:817–29.

    CAS  PubMed  Google Scholar 

  2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349–60.

    Google Scholar 

  3. Kloner RA. Does reperfusion injury exist in humans? J Am Coll Cardiol 1993;21:537–45.

    CAS  PubMed  Google Scholar 

  4. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124–36.

    CAS  PubMed  Google Scholar 

  5. Ramasamy R, Liu H, Anderson S, Lundmark J, Schaefer S. Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts. J Clin Invest 1995;96:1464–72.

    CAS  PubMed  Google Scholar 

  6. Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators. Am J Cardiol 1989;63:18J–24J.

    Article  CAS  PubMed  Google Scholar 

  7. Miura T, Kawamura S, Tatsuno H, Ikeda Y, Mikami S, Iwamoto H, et al. Ischemic preconditioning attenuates cardiac sympathetic nerve injury via ATP-sensitive potassium channels during myocardial ischemia. Circulation 2001;104:1053–8.

    CAS  PubMed  Google Scholar 

  8. Fukuzawa S, Ozawa S, Inagaki M, Shimada K, Sugioka J, Tateno K, Ueda M. Nicorandil affords cardioprotection in patients with acute myocardial infarction treated with primary percutaneous transluminal coronary angioplasty: assessment with thallium-201/iodine-123 BMIPP dual SPECT. J Nucl Cardiol 2000;7:447–53.

    Article  CAS  PubMed  Google Scholar 

  9. Yamazaki J, Ohsawa H, Uchi T, Iida M, Nakano H, Hosoi H, et al. Study of the efficacy of nicorandil in patients with ischaemic heart disease using exercise-Tl-201 myocardial tomography. Eur J Clin Pharmacol 1993;44:211–7.

    CAS  PubMed  Google Scholar 

  10. Sakata K, Mochizuki M, Yoshida H, Nawada R, Ohbayashi K, Ishikawa J, Tamekiyo H. Cardiac sympathetic dysfunction contributes to left ventricular remodeling after acute myocardial infarction. Eur J Nucl Med 2000;27:1641–9.

    Google Scholar 

  11. Matsunari I, Schricke U, Bengel FM, Haase HU, Barthel P, Schmidt G, et al. Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes. Circulation 2000;101:2579–85.

    CAS  PubMed  Google Scholar 

  12. Kasama S, Toyama T, Hoshizaki H, Oshima S, Taniguchi K, Suzuki T, Kurabayashi M. Dobutamine gated blood pool scintigraphy predicts the improvement of cardiac sympathetic nerve activity, cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy. Chest 2002;122:542–8.

    Article  PubMed  Google Scholar 

  13. Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. Spironolactone improves cardiac sympathetic nerve activity and symptoms in patients with congestive heart failure. J Nucl Med 2002;43:1279–85.

    CAS  PubMed  Google Scholar 

  14. Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. Effect of spironolactone on cardiac sympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy. J Am Coll Cardiol 2003;41:574–81.

    Article  CAS  PubMed  Google Scholar 

  15. Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. Addition of valsartan to an angiotensin-converting enzyme inhibitor improves cardiac sympathetic nerve activity and left ventricular function in patients with congestive heart failure. J Nucl Med 2003;44:884–90.

    CAS  PubMed  Google Scholar 

  16. Kasama S, Toyama T, Kumakura H, Takayama Y, Ishikawa T, Ichikawa S, et al. Effects of intravenous atrial natriuretic peptide on cardiac sympathetic nerve activity in patients with decompensated congestive heart failure. J Nucl Med 2004;45:1108–13.

    CAS  PubMed  Google Scholar 

  17. Opie LH. Reperfusion injury and its pharmacologic modification. Circulation 1989;80:1049–62.

    CAS  PubMed  Google Scholar 

  18. Bajaj AK, Cobb MA, Virmani R, Gay JC, Light RT, Forman MB. Limitation of myocardial reperfusion injury by intravenous perfluorochemicals. Role of neutrophil activation. Circulation 1989;79:645–56.

    CAS  PubMed  Google Scholar 

  19. Hori M, Kitakaze M, Sato H, Takashima S, Iwakura K, Inoue M, et al. Staged reperfusion attenuates myocardial stunning in dogs. Role of transient acidosis during early reperfusion. Circulation 1991;84:2135–45.

    CAS  PubMed  Google Scholar 

  20. Kitakaze M, Weisfeldt ML, Marban E. Acidosis during early reperfusion prevents myocardial stunning in perfused ferret hearts. J Clin Invest 1988;82:920–7.

    CAS  PubMed  Google Scholar 

  21. Westlin W, Mullane K. Does captopril attenuate reperfusion-induced myocardial dysfunction by scavenging free radicals? Circulation 1988;77:I30–9.

    CAS  PubMed  Google Scholar 

  22. Farber NE, Pieper GM, Thomas JP, Gross GJ. Beneficial effects of iloprost in the stunned canine myocardium. Circ Res 1988;62:204–15.

    CAS  PubMed  Google Scholar 

  23. Pitarys CJ II, Virmani R, Vildibill HD Jr, Jackson EK, Forman MB. Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period. Circulation 1991;83:237–47

    PubMed  Google Scholar 

  24. Nabel EG, Topol EJ, Galeana A, Ellis SG, Bates ER, Werns SW, et al. A randomized placebo-controlled trial of combined early intravenous captopril and recombinant tissue-type plasminogen activator therapy in acute myocardial infarction. J Am Coll Cardiol 1991;17:467–73.

    CAS  PubMed  Google Scholar 

  25. Topol EJ, Ellis SG, Califf RM, George BS, Stump DC, Bates ER, et al. Combined tissue-type plasminogen activator and prostacyclin therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 4 Study Group. J Am Coll Cardiol 1989;14:877–84.

    CAS  PubMed  Google Scholar 

  26. Flaherty JT, Pitt B, Gruber JW, Heuser RR, Rothbaum DA, Burwell LR, et al. Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction. Circulation 1994;89:1982–91.

    CAS  PubMed  Google Scholar 

  27. Gross GJ, Auchampach JA. Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs. Circ Res 1992;70:223–33.

    CAS  PubMed  Google Scholar 

  28. Das B, Sarkar C, Karanth KS. Selective mitochondrial K(ATP) channel activation results in antiarrhythmic effect during experimental myocardial ischemia/reperfusion in anesthetized rabbits. Eur J Pharmacol 2002;437:165–71.

    Article  CAS  PubMed  Google Scholar 

  29. Stokely EM, Buja LM, Lewis SE, Parkey RW, Bonte FJ, Harris RA Jr, Willerson JT. Measurement of acute myocardial infarcts in dogs with 99mTc-stannous pyrophosphate scintigrams. J Nucl Med 1976;17:1–5.

    CAS  PubMed  Google Scholar 

  30. Holman BL, Chisholm RJ, Braunwald E. The prognostic implications of acute myocardial infarct scintigraphy with 99mTc-pyrophosphate. Circulation 1978;57:320–66.

    CAS  PubMed  Google Scholar 

  31. Koyanagi S, Eastham CL, Harrison DG, Marcus ML. Transmural variation in the relationship between myocardial infarct size and risk area. Am J Physiol 1982;242:H867–74.

    CAS  Google Scholar 

  32. Schofer J, Mathey DG, Montz R, Bleifeld W, Stritzke P. Use of dual intracoronary scintigraphy with thallium-201 and technetium-99m pyrophosphate to predict improvement in left ventricular wall motion immediately after intracoronary thrombolysis in acute myocardial infarction. J Am Coll Cardiol 1983;2:737–44.

    CAS  PubMed  Google Scholar 

  33. Wieland DM, Wu J, Brown LE, Mangner TJ, Swanson DP, Beierwaltes WH. Radiolabeled adrenergi neuron-blocking agents: adrenomedullary imaging with [131I]iodobenzylguanidine. J Nucl Med 1980;21:349–53.

    CAS  PubMed  Google Scholar 

  34. Schofer J, Spielmann R, Schuchert A, Weber K, Schluter M. Iodine-123 meta-iodobenzylguanidine scintigraphy: a noninvasive method to demonstrate myocardial adrenergic nervous system disintegrity in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 1988;12:1252–8.

    CAS  PubMed  Google Scholar 

  35. Spyrou N, Rosen SD, Fath-Ordoubadi F, Jagathesan R, Foale R, Kooner JS, Camici PG. Myocardial beta-adrenoceptor density one month after acute myocardial infarction predicts left ventricular volumes at six months. J Am Coll Cardiol 2002;40:1216–24.

    Article  CAS  PubMed  Google Scholar 

  36. Ikeda N, Yasu T, Kubo N, Hashimoto S, Tsuruya Y, Fujii M, et al. Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon angioplasty in acute myocardial infarction. Heart 2004;90:181–5.

    Article  CAS  PubMed  Google Scholar 

  37. Galie N, Guarnieri C, Ussia GP, Zimarino M, Traini AM, Parlangeli R, et al. Limitation of myocardial infarct size by nicorandil after sustained ischemia in pigs. J Cardiovasc Pharmacol 1995;26:477–84.

    CAS  PubMed  Google Scholar 

  38. 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.

    Article  CAS  PubMed  Google Scholar 

  39. Nitenberg A, Ledoux S, Valensi P, Sachs R, Attali JR, Antony I. Impairment of coronary microvascular dilation in response to cold pressor-induced sympathetic stimulation in type 2 diabetic patients with abnormal stress thallium imaging. Diabetes 2001;50:1180–5.

    CAS  PubMed  Google Scholar 

  40. Lanza GA, Giordano A, Pristipino C, Calcagni ML, Meduri G, Trani C, et al. Abnormal cardiac adrenergic nerve function in patients with syndrome X detected by [123I]metaiodobenzylguanidine myocardial scintigraphy. Circulation 1997;96:821–6.

    CAS  PubMed  Google Scholar 

  41. Sisson JC, Wieland DM, Sherman P, Mangner TJ, Tobes MC, Jacques S Jr. Metaiodobenzylguanidine as an index of the adrenergic nervous system integrity and function. J Nucl Med 1987;28:1620–4.

    CAS  PubMed  Google Scholar 

  42. Tobes MC, Jaques S Jr, Wieland DM, Sisson JC. Effect of uptake-one inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine. J Nucl Med 1985;26:897–907.

    CAS  PubMed  Google Scholar 

  43. Kline RC, Swanson DP, Wieland DM, Thrall JH, Gross MD, Pitt B, Beierwaltes WH. Myocardial imaging in man with I-123 meta-iodobenzylguanidine. J Nucl Med 1981;22:129–32.

    CAS  PubMed  Google Scholar 

  44. Nakajo M, Shimabukuro K, Yoshimura H, Yonekura R, Nakabeppu Y, Tanoue P, Shinohara S. Iodine-131 metaiodobenzylguanidine intra- and extravesicular accumulation in the rat heart. J Nucl Med 1986;27:84–9.

    Google Scholar 

  45. Maunoury C, Acar P, Sidi D. Use of 123I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy. Eur J Nucl Med Mol Imaging 2003;30:1651–6.

    Article  PubMed  Google Scholar 

  46. Oe K, Sperlagh B, Santha E, Matko I, Nagashima H, Foldes FF, Vizi ES. Modulation of norepinephrine release by ATP-dependent K(+)-channel activators and inhibitors in guinea-pig and human isolated right atrium. Cardiovasc Res 1999;43:125–34.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shu Kasama.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kasama, S., Toyama, T., Kumakura, H. et al. Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction. Eur J Nucl Med Mol Imaging 32, 322–328 (2005). https://doi.org/10.1007/s00259-004-1672-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-004-1672-0

Keywords

Navigation