Recruitment of Ventricular Function with Adjunctive Nitrate Therapy after Late Reperfusion

  • Bodh I. Jugdutt
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 167)

Summary

Late reperfusion in acute myocardial infarction (MI) is associated with myocardial stunning and delayed functional recovery. Adjunctive nitrate therapy is of potential value in the short term, during late reperfusion, and throughout the healing process after MI for recruitment of left ventricular function and preservation of geometry.

Left ventricular function and geometry after acute myocardial infarction (MI) are major determinants of outcome [1,2]. Late coronary artery reperfusion in acute MI is associated with reperfusion injury, myocardial stunning, and delayed recovery of function [3]. Thus, reperfusion after 2hr of coronary occlusion in dogs results in partial recovery of function over 2–6 weeks [4–6]. However, late reperfusion can still preserve geometry and limit infarct expansion in dogs [7], even in the absence of myocardial salvage

Early recruitment of left ventricular function after late reperfusion in MI with adjunctive therapy might be possible and improve outcome. Experimental and clinical evidence suggest that nitrates might be candidates for such adjunctive therapy. Thus, short-term intravenous nitroglycerin infusion, begun up to 14hr after acute MI in patients, has been shown to produce prompt and persistent improvement in function [10–12] and attenuation of left ventricular remodeling [11,12]. Furthermore, prolonged nitrate therapy after anterior infarction preserves function and limits remodeling in dogs [13,14] and patients [15,16]. In several large trials, about 50% of patients with MI received nitrates during reperfusion therapy with thrombolytic agents [17–21]. However, there has been no systematic evaluation of adjunc-tive nitrate therapy after late reperfusion in animals or humans to date.

Keywords

Placebo Ischemia Attenuation Prostaglandin Cardiol 

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References

  1. 1.
    Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 81:1161–1172, 1990.PubMedCrossRefGoogle Scholar
  2. 2.
    Jugdutt BI. Prevention of ventricular remodeling post myocardial infarction: Timing and duration of therapy. Can J Cardiol 9:103–114, 1993.PubMedGoogle Scholar
  3. 3.
    Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival: Should the paradigm be expanded? Circulation 79: 441–442, 1989.PubMedCrossRefGoogle Scholar
  4. 4.
    Théroux P, Ross J Jr, Franklin D, Kemper WS, Sasayama S. Coronary arterial reperfusion: III. Early and late effects on regional myocardial function and dimensions in conscious dogs. Am J Cardiol 38:599–606, 1976.PubMedCrossRefGoogle Scholar
  5. 5.
    Lavallee M, Cox D, Patrick TA, Vatner SF. Salvage of myocardial function by coronary artery reperfusion 1, 2, and 3 hours after occlusion in conscious dogs. Circ Res 53:235–247, 1983.PubMedCrossRefGoogle Scholar
  6. 6.
    Bush LR, Buja LM, Samowitz W, Rude RE, Wathen M, Tilton GD, Willerson JT. Recovery of left ventricular segmental function after long-term reperfusion following temporary coronary occlusion in conscious dogs: Comparison of 2-and 4-hour occlusions. Circ Res 53:248–263, 1983.PubMedCrossRefGoogle Scholar
  7. 7.
    Hochman JS, Choo H. Limitation of myocardial expansion by reperfusion independent of myocardial salvage. Circulation 75:299–306, 1987.PubMedCrossRefGoogle Scholar
  8. 8.
    Hirayama A, Adachi T, Asada S, Mishima M, Nanto S, Kusuoka H, Yamamoto K, Matsumura Y, Hori M, Inoue M, Kodama K. Late reperfusion for acute myocardial infarction limits the dilatation of left ventricle without the reduction of infarct size. Circulation 88:2565–2574, 1993.PubMedCrossRefGoogle Scholar
  9. 9.
    Kambayashi M, Miura T, Oh B-H, Murata K, Rockman HA, Parra G, Ross J Jr. Myocardial cell hypertrophy after myocardial infarction with reperfusion in dogs. Circulation 86:1935–1944, 1992.PubMedCrossRefGoogle Scholar
  10. 10.
    Jugdutt BI, Sussex BA, Warnica JW, Rossall RE. Persistent reduction in left ventricular asynergy in patients with acute myocardial infarction by intravenous infusion of nitroglycerin. Circulation 68:1264–1273, 1983.PubMedCrossRefGoogle Scholar
  11. 11.
    Flaherty JT, Becker LC, Bulkley BH, Weiss JL, Gerstenblith G, Kallman CH, Silverman KJ, Wei JY, Pitt B, Weisfeldt ML. A randomized prospective trial of intravenous nitroglycerin in patients with acute myocardial infarction. Circulation 68:576–588, 1983.PubMedCrossRefGoogle Scholar
  12. 12.
    Jugdutt BI, Warnica JW. Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion and complications. Effect of timing, dosage and infarct location. Circulation 78:906–919, 1988.PubMedCrossRefGoogle Scholar
  13. 13.
    Jugdutt BI. Effect of nitroglycerin and ibuprofen on left ventricular topography and rupture threshold during healing after myocardial infarction in the dog. Can J Physiol Pharmacol 66:385–395, 1988.PubMedCrossRefGoogle Scholar
  14. 14.
    Jugdutt BI, Khan MI. Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction. Circulation 89:2297–2307, 1994.PubMedCrossRefGoogle Scholar
  15. 15.
    Michorowski BL, Tymchak WJ, Jugdutt BI. Improved left ventricular function and topography by prolonged nitroglycerin therapy after acute myocardial infarction (abstract). Circulation 76(Suppl IV):IV128, 1987.Google Scholar
  16. 16.
    Jugdutt BI, Tymchak WJ, Humen DP, Gulamhusein S, Tang SB. Effect of thrombolysis and prolonged captopril and nitroglycerin on infarct size and remodeling in transmural myocardial infarction (abstract). J Am Coll Cardiol 19:205A, 1992.CrossRefGoogle Scholar
  17. 17.
    Pfeffer MA, Braunwald E, Moyé LA, et al. on behalf of the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 327:669–677, 1992.PubMedCrossRefGoogle Scholar
  18. 18.
    Gruppo Italiano per lo Studio della Sopravvivenza nell’ Infarcto Miocardico. GISSI-3: Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet 343:1115–1122, 1994.Google Scholar
  19. 19.
    ISIS-4 Collaborative Group. Fourth International Study of Infarct Survival: Protocol for a large simple study of the effects of oral mononitrate, of oral captopril, and of intravenous magnesium. Am J Cardiol 68:87D–100D, 1991.CrossRefGoogle Scholar
  20. 20.
    ISIS collaborative group. ISIS-4: Randomization of oral isosorbide mononitrate in over 50,000 patients with suspected acute myocardial infarction (abstract). Circulation 88:1394, 1993.Google Scholar
  21. 21.
    Yusuf S. The SOLVD investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327:685–691, 1992.CrossRefGoogle Scholar
  22. 22.
    Jugdutt BI. Intravenous nitroglycerin unloading in acute myocardial infarction. Am J Cardiol 68.52D–63D, 1991.PubMedCrossRefGoogle Scholar
  23. 23.
    Jugdutt BI. Nitroglycerin. In: Thrombolysis and Adjunctive Therapy for Acute Myocardial Infarction. Bates E (ed). New York: Marcel Dekker M, 1992, pp 119–144.Google Scholar
  24. 24.
    Jugdutt BI. Nitrates in unstable angina and acute myocardial infarction. In: Nitrate Therapy and Nitrate Tolerance: Current Concepts and Controversies. Alpert JA, Rezakovic D (eds). Basel: Karger, 1993, pp 111–167.Google Scholar
  25. 25.
    Jugdutt BI. Nitrates as anti-ischemic and cardioprotective agents. In: Cardiovascular Pharmacology and Therapeutics. Singh BN, Dzau VJ, Vanhoutte P, Woosley RL (eds). New York: Churchill Livingston, 1993, pp 449–465.Google Scholar
  26. 26.
    Jugdutt BI, Becker LC, Hutchins GM, Bulkley BH, Reid PR, Kallman CH. Effect of intravenous nitroglycerin on collateral blood flow and infarct size in the conscious dog. Circulation 63:17–28, 1981.PubMedCrossRefGoogle Scholar
  27. 27.
    Jugdutt BI. Myocardial salvage by intravenous nitroglycerin in conscious dogs: Loss of beneficial effect with marked nitroglycerin-induced hypotension. Circulation 68:673–684, 1983.PubMedCrossRefGoogle Scholar
  28. 28.
    Jugdutt BI. Delayed effects of early infarct-limiting therapies on healing after myocardial infarction. Circulation 72:907–914, 1985.PubMedCrossRefGoogle Scholar
  29. 29.
    Jugdutt BI, Warnica JW. Tolerance with low-dose intravenous nitroglycerin therapy in acute myocardial infarction. Am J Cardiol 64:581–587, 1989.PubMedCrossRefGoogle Scholar
  30. 30.
    Thadani U, Hamilton SF, Olson E, Anderson JL, Prasad R, Voyles W, Doyle R, Kirsten E, Teague SM. Duration of effects and tolerance of slow-release isosorbide-5-mononitrate for angina pectoris. Am J Cardiol 59:756–762, 1987.PubMedCrossRefGoogle Scholar
  31. 31.
    Chrysant SG, Glasser SP, Bittar N, Shahidi FE, Danisa K, Ibrahim R, Watts LE, Garutti RJ, Ferraresi R, Casareto R. Efficacy and safety of extended-release isosorbide mononitrate for stable effort angina pectoris. Am J Cardiol 72:1249–1256, 1993.PubMedCrossRefGoogle Scholar
  32. 32.
    Pipilis A, Flather M, Collins R, Coats A, Conway M, Appleby P, Sleight P. Hemodynamic effects of captopril and isosorbide mononitrate started early in acute myocardial infarction: A randomized placebo-controlled study. J Am Coll Cardiol 21:73–79, 1993.CrossRefGoogle Scholar
  33. 33.
    McDonald KM, Francis GS, Matthews J, Hunter D, Cohn JN. Long-term oral nitrate therapy prevents chronic ventricular remodeling in the dog. J Am Coll Cardiol 21:514–522, 1993.PubMedCrossRefGoogle Scholar
  34. 34.
    Rezakovic DE, Goldner V, Batinic Z, Weiss M, Stalec J, Pavicic L. Intravenous isosorbide-5-mononitrate in the treatment of acute myocardial infarction. Am J Cardiol 65:50J–56J, 1990.PubMedCrossRefGoogle Scholar
  35. 35.
    Nichols WW, Mehta JL, Donnelly WH, Lawson D, Thompson, ter Riet M. Reduction in coronary vasodilator reserve following coronary occlusion and reperfusion in anesthetized dog: Role of endothelium-derived relaxing factor, myocardial neutrophil infiltration and prostaglandins. J Mol Cell Cardiol 20:943–954, 1988.PubMedCrossRefGoogle Scholar
  36. 36.
    Lefer DJ, Nakanishi K, Johnston WE, Vinten-Johansen J. Antineutrophil and myocardial protecting actions of a novel nitric oxide donor after acute myocardial ischemia and reperfusion in dogs. Circulation 88:2337–2350, 1993.PubMedCrossRefGoogle Scholar
  37. 37.
    Force T, Kemper A, Leavitt M, Parisi AF. Acute reduction in functional infarct expansion with late coronary reperfusjon: Assessment with quantitative two-dimensional echo-cardiography. J Am Coll Cardiol 11:192–200, 1988.PubMedCrossRefGoogle Scholar
  38. 38.
    Fujiwara H, Ashraf M, Sato S, Millard R. Transmural cellular damage and blood flow distribution in early ischemia in pig heart. Circ Res 51:683–693, 1982.PubMedCrossRefGoogle Scholar
  39. 39.
    Zhao M, Zhang H, Robinson TF, Factor SM, Sonnenblick EH, Eng C. Profound structural alterations of the excellular collagen matrix in postischemic dysfunctional (“stunned”) but viable myocardium. J Am Coll Cardiol 10:1322–1334, 1987.PubMedCrossRefGoogle Scholar
  40. 40.
    Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromocyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83:1774–1777, 1989.PubMedCrossRefGoogle Scholar
  41. 41.
    Itoh H, Pratt RE, Dzau VJ. Atrial natriuretic polypeptide inhibits hypertrophy of vascular smooth muscle cells. J Clin Invest 86:1690–1697, 1990.PubMedCrossRefGoogle Scholar
  42. 42.
    Jugdutt BI, Khan MI. Impact of infarct transmurality on remodeling and function during healing after anterior myocardial infarction in the dog. Can J Physiol Pharmacol 70:949–958, 1992.PubMedCrossRefGoogle Scholar
  43. 43.
    Rentrop P, Blanke H, Karsch KR, Kaiser H, Kostering H, Leitz K. Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circulation 63:307–317, 1981.PubMedCrossRefGoogle Scholar
  44. 44.
    Rentrop KP, Blanke H, Karsch KR. Effects of nonsurgical coronary reperfusion on the left ventricle in human subjects compared with conventional treatment. Study of 18 patients with acute myocardial infarction treated with intracoronary infusion of streptokinase. Am J Cardiol 49:1–8, 1982.PubMedCrossRefGoogle Scholar
  45. 45.
    Raizner AE, Tortoledo FA, Verani MS, van Reet RE, Young JB, Rickman FD, Cashion RW, Samuels DA, Pratt GM, Attar M, Rubin HS, Lewis JM, Klein MS, Roberts R. Intracoronary thrombolytic therapy in acute myocardial infarction: A prospective, randomized, controlled trial. Am J Cardiol 55:301–308, 1985.PubMedCrossRefGoogle Scholar
  46. 46.
    Simoons ML, Serruys PW, Brand M v/d, Bar F, De Zwaan C, Res J, Verheugt FWA, Krauss XH, Remme WJ, Vermeer F, Lubsen J. Improved survival after early thrombolysis in acute myocardial infarction. Lancet 2:578–581, 1985.PubMedCrossRefGoogle Scholar
  47. 47.
    Serruys PW, Simoons ML, Suryapranata H, Vermeer F, Wijns W, van der Brand M, Bar F, Zwaan C, Kraus XH, Remme WJ, Res J, Verheugt FWA, van Domburg R, Lubsen J, Hugenholtz PG. Preservation of global and regional left ventricular function after early thrombolysis in acute myocardial infarction. J Am Coll Cardiol 7:729–742, 1986.PubMedCrossRefGoogle Scholar
  48. 48.
    Hugenholtz PG. Acute coronary artery obstruction in myocardial infarction: Overview of thrombolytic therapy. J Am Coll Cardiol 9:1375–1384, 1987.PubMedCrossRefGoogle Scholar
  49. 49.
    Jugdutt BI, Tymchak WJ, Burton JR. Preservation of left ventricular geometry and function after late reperfusion and intravenous nitroglycerin in acute transmural myocardial infarction (abstract). Circulation 84:II(-)683, 1991.Google Scholar
  50. 50.
    Khan MI, Jugdutt BI. Isosorbide-5-mononitrate therapy improves ventricular function after late reperfusion in canine myocardial infarction (abstract). Can J Cardiol 10(Suppl A): 82A, 1994.Google Scholar

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© Springer Science+Business Media New York 1995

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  • Bodh I. Jugdutt

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