Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 10, October, p. 1409–1418

doi: 10.17219/acem/104541

Publication type: original article

Language: English

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Effectiveness and safety of intracoronary papaverine, alprostadil, and high dosages of nicorandil and adenosine triphosphate for measurement of the index of coronary microcirculatory resistance in a pig model

Tianbing Duan1,2,A,B,C,D,E,F, Jinxia Zhang2,B, Dingcheng Xiang2,A,E, Rui Song2,C, Ranran Kong2,C, Dingli Xu1,A,F

1 Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China

2 Department of Cardiology, Guangzhou General Hospital of Guangzhou Military Command, China

Abstract

Background. Papaverine is used to induce maximal hyperemia for index of coronary microcirculatory resistance (IMR) measurement in animal experiments, although it can lead to polymorphic ventricular tachycardia and ventricular fibrillation.
Objectives. This study investigated the effect of an intracoronary (IC) bolus of high adenosine triphosphate (ATP) and nicorandil doses for IMR measurement and explored the possibility of inducing maximal hyperemia with an IC alprostadil bolus.
Material and Methods. Index of coronary microcirculatory resistance was measured in a hyperemic state induced by 7 experimental conditions in 21 pigs (IC bolus of papaverine (18 mg), ATP (40 μg, 80 μg, 160 μg, and 240 μg), and nicorandil (2 mg and 4 mg)). The 7 conditions were induced sequentially, and the average IMR was calculated. Because of the long-term hyperemic condition in the pilot experiments, the IMR was measured 1, 3, 5, 8, and 10 min after an IC bolus of alprostadil (10 μg) in another 7 pigs.
Results. The IMR induced by 240 μg of ATP or 4 mg of nicorandil was not significantly different from that induced by 18 mg of papaverine (both p > 0.05). A strong linear correlation was observed between IMRs with papaverine (18 mg) and nicorandil (4 mg) (R2 = 0.936, p < 0.001) and with papaverine (18 mg) and ATP (240 μg) (R2 = 0.838, p < 0.05). The IC bolus of nicorandil (4 mg) produced the smallest changes, whereas papaverine caused the most significant changes in mean blood pressure and heart rate (p < 0.05). Tachypnea and transient ST depression were more common with increasing ATP dosages (especially 240 μg). Alprostadil (5 min) yielded a significant hyperemic response but reduced baseline blood pressure by almost 40% for a long time.
Conclusion. Intracoronary bolus administration of 4 mg of nicorandil was better than 18 mg of papaverine or 240 μg of ATP for induction of maximal hyperemia and IMR measurement in a pig model, whereas alprostadil was not suitable for IMR measurement.

Key words

papaverine, alprostadil, adenosine triphosphate, index of microcirculatory resistance, nicorandil

References (40)

  1. Li J, Li X, Wang Q, et al. ST-segment elevation myocardial infarction in China from 2001 to 2011 (the China PEACE-Retrospective Acute Myocardial Infarction Study): A retrospective analysis of hospital data. Lancet. 2015;385(9966):441–451.
  2. Menees DS, Peterson ED, Wang Y, et al. Door-to-balloon time and mortality among patients undergoing primary PCI. N Eng J Med. 2013;369(10):901–909.
  3. Niccoli G, Scalone G, Lerman A, Crea F. Coronary microvascular obstruction in acute myocardial infarction. Eur Heart J. 2016;37(13):1024–1033.
  4. Fearon W, Balsam L, Farouque H, et al. Novel index for invasively assessing the coronary microcirculation. Circulation. 2003;107(25):3129–3132.
  5. McGeoch R, Watkins S, Berry C, et al. The index of microcirculatory resistance measured acutely predicts the extent and severity of myocardial infarction in patients with st-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2010;3(7):715–722.
  6. Cuculi F, De Maria G, Meier P, et al. Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2014;64(18):1894–1904.
  7. Vrolix M, Piessens J, De Geest H. Torsades de pointes after intracoronary papaverine. Eur Heart J. 1991;12(2):273–276.
  8. van der Voort PH, van Hagen E, Hendrix G, van Gelder B, Bech JW, Pijls NH. Comparison of intravenous adenosine to intracoronary papaverine for calculation of pressure-derived fractional flow reserve. Cathet Cardiovasc Diagn. 1996;39(2):120–125.
  9. Wilson RF, White CW. Serious ventricular dysrhythmias after intracoronary papaverine. Am J Cardiol. 1988;62(17):1301–1302.
  10. Kern MJ, Deligonul U, Serota H, Gudipati C, Buckingham T. Ventricular arrhythmia due to intracoronary papaverine: Analysis of QT intervals and coronary vasodilatory reserve. Cathet Cardiovasc Diagn. 1990;19(4):229–236.
  11. Christensen CW, Rosen LB, Gal RA, Haseeb M, Lassar TA, Port SC. ­Coronary vasodilator reserve. Comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism. Circulation. 1991;83(1):294–303.
  12. Takeuchi M, Nohtomi Y, Kuroiwa A. Intracoronary papaverine induced myocardial lactate production in patients with angiographically normal coronary arteries. Cathet Cardiovasc Diagn. 1996;39(2):126–130.
  13. Egashira K, Inou T, Hirooka Y, Yamada A, Urabe Y, Takeshita A. Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms. N Engl J Med. 1993;328(23):1659–1664.
  14. De Bruyne B, Pijls NH, Barbato E, et al. Intracoronary and intravenous adenosine 5’-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans. Circulation. 2003;107(14):1877–1883.
  15. Layland J, Carrick D, Lee M, Oldroyd K, Berry C. Adenosine: Physiology, pharmacology, and clinical applications. JACC Cardiovasc Interv. 2014;7(6):581–591.
  16. Jang H, Koo B, Lee H, et al. Safety and efficacy of a novel hyperaemic agent, intracoronary nicorandil, for invasive physiological assessments in the cardiac catheterization laboratory. Eur Heart J. 2013;34(27):2055–2062.
  17. Gupta V, Rawat A, Ahsan F. Feasibility study of aerosolized prostaglandin E1 microspheres as a noninvasive therapy for pulmonary arterial hy-pertension. J Pharm Sci. 2010;99(10):1774–1789.
  18. Hülsmann M, Stefenelli T, Berger R, et al. Response of right ventricular function to prostaglandin e1 infusion predicts outcome for severe chronic heart failure patients awaiting urgent transplantation. J Heart Lung Transplant. 2000;19(10):939–945.
  19. Kilkenny C, Browne W, Cuthill I, Emerson M, Altman D. Improving bioscience research reporting the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.
  20. Niccoli G, Burzotta F, Galiuto L, Crea F. Myocardial no-reflow in humans. J Am Coll Cardiol. 2009;54(4):281–292.
  21. Fearon W, Shah M, Ng M, et al. Predictive value of the index of microcirculatory resistance in patients with st-segment elevation myocardial infarction. J Am Coll Cardiol. 2008;51(5):560–565.
  22. Ndrepepa G, Tiroch K, Fusaro M, et al. 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol. 2010;55(21):2383–2389.
  23. Hamirani Y, Wong A, Kramer C, Salerno M. Effect of microvascular obstruction and intramyocardial hemorrhage by CMR on LV remodeling and outcomes after myocardial infarction: A systematic review and meta-analysis. JACC Cardiovasc Imaging. 2014;7(9):940–952.
  24. Ng M, Yeung A, Fearon W. Invasive assessment of the coronary microcirculation: superior reproducibility and less hemodynamic dependence of index of microcirculatory resistance compared with coronary flow reserve. Circulation. 2006;113(17):2054–2061.
  25. Kumar M, Kasala ER, Bodduluru LN, et al. Animal models of myocardial infarction: Mainstay in clinical translation. Regul Toxicol Pharmacol. 2016;76:221–230.
  26. Kern MJ, Lerman A, Bech JW, et al; American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology. Physiological assessment of coro­nary artery disease in the cardiac catheterization laboratory: A scien­tific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology. Circulation. 2006;114(12):1321–1341.
  27. Jeremias A, Filardo S, Whitbourn R, et al. Effects of intravenous and intracoronary adenosine 5’-triphosphate as compared with adenosine on coronary flow and pressure dynamics. Circulation. 2000;101(3):318–323.
  28. Casella G, Leibig M, Schiele TM, et al. Are high doses of intracoronary adenosine an alternative to standard Intravenous adenosine for the assessment of fractional flow reserve? Am Heart J. 2004;148(4):590–595.
  29. Leone AM, Porto I, De Caterina A, et al. Maximal hyperemia in the assessment of fractional flow reserve: intracoronary adenosine versus intra-coronary sodium nitroprusside versus intravenous adenosine: The NASCI (Nitroprussiato versus Adenosina nelle Stenosi Coronariche Intermedie) study. JACC Cardiovasc Interv. 2012;5(4):402–408.
  30. De Luca G, Venegoni L, Iorio S, Giuliani L, Marino P. Effects of increasing doses of intracoronary adenosine on the assessment of fractio­nal flow reserve. JACC Cardiovasc Interv. 2011;4(10):1079–1084.
  31. Pijls N, Sels J. Functional measurement of coronary stenosis. J Am Coll Cardiol. 2012;59(12):1045–1057.
  32. Drenjancevic I, Koller A, Selthofer-Relatic K, Grizelj I, Cavka A. Assessment of coronary hemodynamics and vascular function. Prog Cardiovasc Dis. 2015;57(5):423–430.
  33. Markham A, Plosker G, Goa KL. Nicorandil: An updated review of its use in ischemic heart disease with emphasis on its cardioprotective effects. Drugs. 2000;60(4):955–974.
  34. Miyazawa A, Ikari Y, Tanabe K, et al. Intracoronary nicorandil prior to reperfusion in acute myocardial infarction. EuroIntervention. 2006;2(2):211–217.
  35. Hirohata A, Yamamoto K, Hirose E, et al. Nicorandil prevents microvascular dysfunction resulting from PCI in patients with stable angina pectoris: A randomised study. EuroIntervention. 2014;9(9):1050–1056.
  36. Lee J, Kato D, Oi M, et al. Safety and efficacy of intracoronary nicorandil as hyperaemic agent for invasive physiological assessment: A patient-level pooled analysis. EuroIntervention. 2016;12(2):e208–215.
  37. Kobayashi Y, Okura H, Neishi Y, et al. Additive value of nicorandil on ATP for further inducing hyperemia in patients with an intermediate coronary artery stenosis. Coron Artery Dis. 2017;28(2):104–109.
  38. Tanaka N, Takahashi Y, Ishihara H, Kawakami T, Ono H. Usefulness and safety of intracoronary administration of nicorandil for evaluating fractional flow reserve in Japanese patients. Clin Cardiol. 2015;38(1):20–24.
  39. Pijls N, van Son J, Kirkeeide R, De Bruyne B, Gould K. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation. 1993;87(4):1354–1367.
  40. Miller SB. Prostaglandins in health and disease: An overview. Semin Arthritis Rheum. 2006;36(1):37–49.
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