Skip to main content
Top
Published in: Journal of Nuclear Cardiology 3/2011

01-05-2011 | Original Article

The effect of ranolazine on the vasodilator-induced myocardial perfusion abnormality

Authors: Rajesh Venkataraman, MD, MPH, Wael Aljaroudi, MD, Luiz Belardinelli, MD, Jaekyeong Heo, MD, Ami E. Iskandrian, MD, MACC

Published in: Journal of Nuclear Cardiology | Issue 3/2011

Login to get access

Abstract

Background

We previously reported that ranolazine improved myocardial ischemia during exercise myocardial perfusion imaging (MPI). Since the mechanism of reversible perfusion defects is different in exercise than vasodilator MPI, and based on the mechanism of action of ranolazine, we hypothesized that vasodilator stress MPI may fail to show improvement in myocardial perfusion pattern.

Methods

Patients (n = 18) with known coronary artery disease and with reversible perfusion defects on a clinically indicated vasodilator stress MPI were re-studied 4 weeks after ranolazine (500-1000 mg PO BID) was added to their conventional treatment in an open-label trial. Perfusion pattern was assessed using automated methods.

Results

The baseline left ventricular ejection fraction was 59% ± 14%. The total perfusion defect (measured by polar maps) was 22% ± 13% before and 21% ± 16% of LV myocardium after treatment (P = NS). The reversible defect size was 14% ± 10% before and 14% ± 11% of LV myocardium after treatment (P = NS). The automated-derived summed stress score was 12 ± 8 before and 12 ± 10 after treatment (P = NS) and the automated-derived summed difference score was 6 ± 5 before and 6 ± 5 after treatment (P = NS). Only 3 patients showed a decrease in reversible perfusion defect size with treatment.

Conclusion

Vasodilator stress MPI failed to show improvement in perfusion pattern after ranolazine treatment in most patients with baseline reversible defects. This is consistent with the unique anti-ischemic mechanism of ranolazine, which acts on the late I Na channel.
Literature
1.
go back to reference Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics—2008 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008;117:e25-146.PubMedCrossRef Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics—2008 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008;117:e25-146.PubMedCrossRef
2.
go back to reference Zoghbi GJ, Dorfman TA, Iskandrian AE. The effects of medications on myocardial perfusion. J Am Coll Cardiol 2008;52:401-16.PubMedCrossRef Zoghbi GJ, Dorfman TA, Iskandrian AE. The effects of medications on myocardial perfusion. J Am Coll Cardiol 2008;52:401-16.PubMedCrossRef
3.
go back to reference Allely MC, Alps BJ. Prevention of myocardial enzyme release by ranolazine in a primate model of ischaemia with reperfusion. Br J Pharmacol 1990;99:5-6.PubMed Allely MC, Alps BJ. Prevention of myocardial enzyme release by ranolazine in a primate model of ischaemia with reperfusion. Br J Pharmacol 1990;99:5-6.PubMed
4.
go back to reference Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: Effects of the late sodium current inhibitor ranolazine. Heart 2006;92:6-14.CrossRef Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: Effects of the late sodium current inhibitor ranolazine. Heart 2006;92:6-14.CrossRef
5.
go back to reference Chaitman BR, Pepine CJ, Parker JO, et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: A randomized controlled trial. JAMA 2004;291:309-16.PubMedCrossRef Chaitman BR, Pepine CJ, Parker JO, et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: A randomized controlled trial. JAMA 2004;291:309-16.PubMedCrossRef
6.
go back to reference Chaitman BR, Skettino SL, Parker JO, et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol 2004;43:1375-82.PubMedCrossRef Chaitman BR, Skettino SL, Parker JO, et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol 2004;43:1375-82.PubMedCrossRef
7.
go back to reference Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol 2006;41:1031-8.PubMedCrossRef Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol 2006;41:1031-8.PubMedCrossRef
8.
go back to reference Hale SL, Leeka JA, Kloner RA. Improved left ventricular function and reduced necrosis after myocardial ischemia/reperfusion in rabbits treated with ranolazine, an inhibitor of the late sodium channel. J Pharmacol Exp Ther 2006;318:418-23.PubMedCrossRef Hale SL, Leeka JA, Kloner RA. Improved left ventricular function and reduced necrosis after myocardial ischemia/reperfusion in rabbits treated with ranolazine, an inhibitor of the late sodium channel. J Pharmacol Exp Ther 2006;318:418-23.PubMedCrossRef
9.
go back to reference Hale SL, Shryock JC, Belardinelli L, Sweeney M, Kloner RA. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol 2008;44:954-67.PubMedCrossRef Hale SL, Shryock JC, Belardinelli L, Sweeney M, Kloner RA. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol 2008;44:954-67.PubMedCrossRef
10.
go back to reference Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: The Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol 2007;49:1027-34.PubMedCrossRef Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: The Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol 2007;49:1027-34.PubMedCrossRef
11.
go back to reference Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L. Antianginal efficacy of ranolazine when added to treatment with amlodipine: The ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol 2006;48:566-75.PubMedCrossRef Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L. Antianginal efficacy of ranolazine when added to treatment with amlodipine: The ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol 2006;48:566-75.PubMedCrossRef
12.
go back to reference Zacharowski K, Blackburn B, Thiemermann C. Ranolazine, a partial fatty acid oxidation inhibitor, reduces myocardial infarct size and cardiac troponin T release in the rat. Eur J Pharmacol 2001;418:105-10.PubMedCrossRef Zacharowski K, Blackburn B, Thiemermann C. Ranolazine, a partial fatty acid oxidation inhibitor, reduces myocardial infarct size and cardiac troponin T release in the rat. Eur J Pharmacol 2001;418:105-10.PubMedCrossRef
13.
go back to reference Venkataraman R, Belardinelli L, Blackburn B, Heo J, Iskandrian AE. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images. JACC Cardiovasc Imaging 2009;2:1301-9.PubMedCrossRef Venkataraman R, Belardinelli L, Blackburn B, Heo J, Iskandrian AE. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images. JACC Cardiovasc Imaging 2009;2:1301-9.PubMedCrossRef
14.
go back to reference Al Jaroudi W, Iskandrian AE. Regadenoson: A new myocardial stress agent. J Am Coll Cardiol 2009;54:1123-30.PubMedCrossRef Al Jaroudi W, Iskandrian AE. Regadenoson: A new myocardial stress agent. J Am Coll Cardiol 2009;54:1123-30.PubMedCrossRef
15.
go back to reference Iskandrian AE, Garcia EV. Nuclear cardiac imaging: principles and applications. 4th ed. Oxford: Oxford University Press; 2008. Iskandrian AE, Garcia EV. Nuclear cardiac imaging: principles and applications. 4th ed. Oxford: Oxford University Press; 2008.
16.
go back to reference Mahmarian JJ, Cerqueira MD, Iskandrian AE, et al. Regadenoson induces comparable left ventricular perfusion defects as adenosine: A quantitative analysis from the ADVANCE MPI 2 trial. JACC Cardiovasc Imaging 2009;2:959-68.PubMedCrossRef Mahmarian JJ, Cerqueira MD, Iskandrian AE, et al. Regadenoson induces comparable left ventricular perfusion defects as adenosine: A quantitative analysis from the ADVANCE MPI 2 trial. JACC Cardiovasc Imaging 2009;2:959-68.PubMedCrossRef
17.
go back to reference Berecki G, Zegers JG, Bhuiyan ZA, Verkerk AO, Wilders R, van Ginneken AC. Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique. J Physiol 2006;570:237-50.PubMed Berecki G, Zegers JG, Bhuiyan ZA, Verkerk AO, Wilders R, van Ginneken AC. Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique. J Physiol 2006;570:237-50.PubMed
18.
go back to reference Kunze DL, Lacerda AE, Wilson DL, Brown AM. Cardiac Na currents and the inactivating, reopening, and waiting properties of single cardiac Na channels. J Gen Physiol 1985;86:691-719.PubMedCrossRef Kunze DL, Lacerda AE, Wilson DL, Brown AM. Cardiac Na currents and the inactivating, reopening, and waiting properties of single cardiac Na channels. J Gen Physiol 1985;86:691-719.PubMedCrossRef
19.
go back to reference Zaza A, Belardinelli L, Shryock JC. Pathophysiology and pharmacology of the cardiac “late sodium current”. Pharmacol Ther 2008;119:326-39.PubMedCrossRef Zaza A, Belardinelli L, Shryock JC. Pathophysiology and pharmacology of the cardiac “late sodium current”. Pharmacol Ther 2008;119:326-39.PubMedCrossRef
20.
go back to reference Rousseau MF, Pouleur H, Cocco G, Wolff AA. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol 2005;95:311-6.PubMedCrossRef Rousseau MF, Pouleur H, Cocco G, Wolff AA. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol 2005;95:311-6.PubMedCrossRef
21.
go back to reference Stone PH, Chaitman BR, Stocke K, Sano J, DeVault A, Koch GG. The anti-ischemic mechanism of action of ranolazine in stable ischemic heart disease. J Am Coll Cardiol 2010;56:934-42.PubMedCrossRef Stone PH, Chaitman BR, Stocke K, Sano J, DeVault A, Koch GG. The anti-ischemic mechanism of action of ranolazine in stable ischemic heart disease. J Am Coll Cardiol 2010;56:934-42.PubMedCrossRef
22.
go back to reference Iskandrian AE, Heo J, Mehta D, et al. Gated SPECT perfusion imaging for the simultaneous assessment of myocardial perfusion and ventricular function in the BARI 2D trial: An initial report from the Nuclear Core Laboratory. J Nucl Cardiol 2006;13:83-90.PubMedCrossRef Iskandrian AE, Heo J, Mehta D, et al. Gated SPECT perfusion imaging for the simultaneous assessment of myocardial perfusion and ventricular function in the BARI 2D trial: An initial report from the Nuclear Core Laboratory. J Nucl Cardiol 2006;13:83-90.PubMedCrossRef
23.
go back to reference Mahmarian JJ, Dakik HA, Filipchuk NG, et al. An initial strategy of intensive medical therapy is comparable to that of coronary revascularization for suppression of scintigraphic ischemia in high-risk but stable survivors of acute myocardial infarction. J Am Coll Cardiol 2006;48:2458-67.PubMedCrossRef Mahmarian JJ, Dakik HA, Filipchuk NG, et al. An initial strategy of intensive medical therapy is comparable to that of coronary revascularization for suppression of scintigraphic ischemia in high-risk but stable survivors of acute myocardial infarction. J Am Coll Cardiol 2006;48:2458-67.PubMedCrossRef
24.
go back to reference Shaw LJ, Berman DS, Maron DJ, et al. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: Results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 2008;117:1283-91.PubMedCrossRef Shaw LJ, Berman DS, Maron DJ, et al. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: Results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 2008;117:1283-91.PubMedCrossRef
Metadata
Title
The effect of ranolazine on the vasodilator-induced myocardial perfusion abnormality
Authors
Rajesh Venkataraman, MD, MPH
Wael Aljaroudi, MD
Luiz Belardinelli, MD
Jaekyeong Heo, MD
Ami E. Iskandrian, MD, MACC
Publication date
01-05-2011
Publisher
Springer-Verlag
Published in
Journal of Nuclear Cardiology / Issue 3/2011
Print ISSN: 1071-3581
Electronic ISSN: 1532-6551
DOI
https://doi.org/10.1007/s12350-011-9364-1

Other articles of this Issue 3/2011

Journal of Nuclear Cardiology 3/2011 Go to the issue