Skip to main content
SpringerLink
Log in

Preconditioning in humans

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Brief ischemia to the myocardium initiates a cascade of biochemical events in cardiac myocytes that protects the heart muscle during subsequent ischemic insults. This phenomenon is called ischemic preconditioning. If an acute myocardial infarction is preceded by preinfarction angina, it results in smaller infarction size, fewer cardiac arrhythmias, and better-left ventricular function. During coronary intervention, brief balloon inflation protects the heart during subsequent inflations. Patients vary in the degree of preconditioning and those patients who have the ability to demonstrate a significant preconditioning effect will have lesser incidence of subsequent cardiac events. Preconditioning protects the myocardium during coronary artery bypass surgery, particularly in the off-pump procedure, yet the thoracic surgery community has not universally adopted this technique.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lange R, Ingwall JS, Hale SL, Alker KJ, Kloner RA (1984) Effects of recurrent ischemia on myocardial high energy phosphate content in canine hearts. Basic Res Cardiol 79:469–478

    Article  PubMed  CAS  Google Scholar 

  2. Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136

    PubMed  CAS  Google Scholar 

  3. Kloner RA, Shook T, Przyklenk K, Davis VG, Junio L, Matthews RV, Burstein S, Gibson M, Poole WK, Cannon CP et al (1995) Previous angina alters in-hospital outcome in TIMI 4. A clinical correlate to preconditioning? Circulation 91:37–45

    PubMed  CAS  Google Scholar 

  4. Kloner RA, Shook T, Antman EM, Cannon CP, Przyklenk K, Yoo K, McCabe CH, Braunwald E (1998) Prospective temporal analysis of the onset of preinfarction angina versus outcome: an ancillary study in TIMI-9B. Circulation 97:1042–1045

    PubMed  CAS  Google Scholar 

  5. Rezkalla SH, Kloner RA (2004) Ischemic preconditioning and preinfarction angina in the clinical arena. Nat Clin Pract Cardiovasc Med 1:96–102

    Article  PubMed  Google Scholar 

  6. Kushwaha SS, Ambrose JA (2000) Does ischemic preconditioning limit infarct size in non-Q-wave myocardial infarction? Coron Artery Dis 11:191–194

    Article  PubMed  CAS  Google Scholar 

  7. Zdrenghea D, Ilea M, Predescu D, Potang E (1998) Ischemic preconditioning during successive exercise testing. Rom J Intern Med 36:161–165

    PubMed  CAS  Google Scholar 

  8. Rinaldi CA, Linka AZ, Masani ND, Avery PG, Jones E, Saunders H, Hall RJ (1998) Randomized, double-blind crossover study to investigate the effects of amlodipine and isosorbide mononitrate on the time course and severity of exercise-induced myocardial stunning. Circulation 98:749–756

    PubMed  CAS  Google Scholar 

  9. Lambiase PD, Edwards RJ, Cusack MR, Bucknall CA, Redwood SR, Marber MS (2003) Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment. J Am Coll Cardiol 41:1174–1182

    Article  PubMed  Google Scholar 

  10. Tomai F, Perino M, Ghini AS, Crea F, Gaspardone A, Versaci F, Chiariello L, Gioffre PA (1999) Exercise-induced myocardial ischemia triggers the early phase of preconditioning but not the late phase. Am J Cardiol 83:586–588, A7–8

    Article  PubMed  CAS  Google Scholar 

  11. Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T, Hori M (1999) Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation. J Exp Med 189:1699–1706

    Article  PubMed  CAS  Google Scholar 

  12. Abete P, Ferrara N, Cacciatore F, Sagnelli E, Manzi M, Carnovale V, Calabrese C, de Santis D, Testa G, Longobardi G, Napoli C, Rengo F (2001) High level of physical activity preserves the cardioprotective effect of preinfarction angina in elderly patients. J Am Coll Cardiol 38:1357–1365

    Article  PubMed  CAS  Google Scholar 

  13. Heidland UE, Heintzen MP, Schwartzkopff B, Strauer BE (2000) Preconditioning during percutaneous transluminal coronary angioplasty by endogenous and exogenous adenosine. Am Heart J 140:813–820

    Article  PubMed  CAS  Google Scholar 

  14. Mentzer RM Jr, Rahko PS, Molina-Viamonte V, Canver CC, Chopra PS, Love RB, Cook TD, Hegge JO, Lasley RD (1997) Safety, tolerance, and efficacy of adenosine as an additive to blood cardioplegia in humans during coronary artery bypass surgery. Am J Cardiol 79:38–43

    Article  PubMed  CAS  Google Scholar 

  15. Mentzer RM Jr, Birjiniuk V, Khuri S, Lowe JE, Rahko PS, Weisel RD, Wellons HA, Barker ML, Lasley RD (1999) Adenosine myocardial protection: preliminary results of a phase II clinical trial. Ann Surg 229:643–649

    Article  PubMed  Google Scholar 

  16. Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW; AMISTAD-II Investigators (2005) A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol 45:1775–1780

  17. Kloner RA, Forman MB, Gibbons RJ, Ross AM, Alexander RW, Stone GW (2006) Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial. Eur Heart J 27:2400–2405

    Article  PubMed  CAS  Google Scholar 

  18. Kloner RA, Rezkalla SH (2006) Preconditioning, postconditioning and their application to clinical cardiology. Cardiovasc Res 70:297–307

    Article  PubMed  CAS  Google Scholar 

  19. Matsuo H, Watanabe S, Segawa T, Yasuda S, Hirose T, Iwama M, Tanaka S, Yamaki T, Matsuno Y, Tomita M, Minatoguchi S, Fujiwara H (2003) Evidence of pharmacologic preconditioning during PTCA by intravenous pretreatment with ATP-sensitive K+ channel opener nicorandil. Eur Heart J 24:1296–1303

    Article  PubMed  CAS  Google Scholar 

  20. Minamino T, Jiyoong K, Asakura M, Shintani Y, Asanuma H, Kitakaze M; The J-WIND Investigators (2004) Rationale and design of a large-scale trial using nicorandil as an adjunct to percutaneous coronary intervention for ST-segment elevation acute myocardial infarction: Japan-Working groups of acute myocardial infarction for the reduction of Necrotic Damage by a K-ATP channel opener (J-WIND-KATP). Circ J 68:101–106

  21. Kitakaze M. (2006) Large-scale trial using atrial natriuretic peptide or nicorandil as an adjunct to percutaneous coronary intervention for ST-segment elevation acute myocardial infarction. Late breaking clinical trials II. Presented at the American Heart Association, Chicago, IL, November 2006

  22. Leesar MA, Stoddard MF, Dawn B, Jasti VG, Masden R, Bolli R (2001) Delayed preconditioning-mimetic action of nitroglycerin in patients undergoing coronary angioplasty. Circulation 103:2935–2941

    PubMed  CAS  Google Scholar 

  23. Abete P, Ferrara N, Cacciatore F, Madrid A, Bianco S, Calabrese C, Napoli C, Scognamiglio P, Bollella O, Cioppa A, Longobardi G, Rengo F (1997) Angina-induced protection against myocardial infarction in adult and elderly patients: a loss of preconditioning mechanism in the aging heart? J Am Coll Cardiol 30:947–954

    Article  PubMed  CAS  Google Scholar 

  24. Abete P, Ferrara N, Cacciatore F, Sagnelli E, Manzi M, Carnovale V, Calabrese C, de Santis D, Testa G, Longobardi G, Napoli C, Rengo F (2001) High level of physical activity preserves the cardioprotective effect of preinfarction angina in elderly patients. J Am Coll Cardiol 38:1357–1365

    Article  PubMed  CAS  Google Scholar 

  25. Ishihara M, Inoue I, Kawagoe T, Shimatani Y, Kurisu S, Nishioka K, Kouno Y, Umemura T, Nakamura S, Sato H (2001) Diabetes mellitus prevents ischemic preconditioning in patients with a first acute anterior wall myocardial infarction. J Am Coll Cardiol 38:1007–1011

    Article  PubMed  CAS  Google Scholar 

  26. Ishihara M, Inoue I, Kawagoe T, Shimatani Y, Kurisu S, Nishioka K, Umemura T, Nakamura S, Yoshida M (2003) Effect of acute hyperglycemia on the ischemic preconditioning effect of prodromal angina pectoris in patients with a first anterior wall acute myocardial infarction. Am J Cardiol 92:288–291

    Article  PubMed  Google Scholar 

  27. Cleveland JC Jr, Meldrum DR, Cain BS, Banerjee A, Harken AH (1997) Oral sulfonylurea hypoglycemic agents prevent ischemic preconditioning in human myocardium. Two paradoxes revisited. Circulation 96:29–32

    PubMed  CAS  Google Scholar 

  28. Engler RL, Yellon DM (1996) Sulfonylurea KATP blockade in type II diabetes and preconditioning in cardiovascular disease. Time for reconsideration. Circulation 94:2297–2301

    PubMed  CAS  Google Scholar 

  29. Meier JJ, Gallwitz B, Schmidt WE, Mugge A, Nauck MA (2004) Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important? Heart 90:9–12

    Article  PubMed  CAS  Google Scholar 

  30. Wu ZK, Iivainen T, Pehkonen E, Laurikka J, Tarkka MR (2002) Ischemic preconditioning suppresses ventricular tachyarrhythmias after myocardial revascularization. Circulation 106:3091–3096

    Article  PubMed  Google Scholar 

  31. Airaksinen KE, Huikuri HV (1997) Antiarrhythmic effect of repeated coronary occlusion during balloon angioplasty. J Am Coll Cardiol 29:1035–1038

    Article  PubMed  CAS  Google Scholar 

  32. Gheeraert PJ, Henriques JP, De Buyzere ML, De Pauw M, Taeymans Y, Zijlstra F (2001) Preinfarction angina protects against out-of-hospital ventricular fibrillation in patients with acute occlusion of the left coronary artery. J Am Coll Cardiol 38:1369–1374

    Article  PubMed  CAS  Google Scholar 

  33. Argaud L, Rioufol G, Lievre M, Bontemps L, Legalery P, Stumpf M, Finet G, Itti R, Andre-Fouet X, Ovize M (2004) Preconditioning during coronary angioplasty: no influence of collateral perfusion or the size of the area at risk. Eur Heart J 25:2019–2025

    Article  PubMed  Google Scholar 

  34. Laskey WK, Beach D (2003) Frequency and clinical significance of ischemic preconditioning during percutaneous coronary intervention. J Am Coll Cardiol 42:998–1003

    Article  PubMed  Google Scholar 

  35. Matsuo H, Watanabe S, Segawa T, Yasuda S, Hirose T, Iwama M, Tanaka S, Yamaki T, Matsuno Y, Tomita M, Minatoguchi S, Fujiwara H (2003) Evidence of pharmacologic preconditioning during PTCA by intravenous pretreatment with ATP-sensitive K+ channel opener nicorandil. Eur Heart J 24:1296–1303

    Article  PubMed  CAS  Google Scholar 

  36. Rezkalla SH, Kloner RA (2002) No-reflow phenomenon. Circulation 105:656–662

    Article  PubMed  Google Scholar 

  37. Belhomme D, Peynet J, Florens E, Tibourtine O, Kitakaze M, Menasche P (2000) Is adenosine preconditioning truly cardioprotective in coronary artery bypass surgery? Ann Thorac Surg 70:590–594

    Article  PubMed  CAS  Google Scholar 

  38. Kawamura T, Kadosaki M, Nara N, Wei J, Endo S, Inada K (2005) Nicorandil attenuates NF-kappaB activation, adhesion molecule expression, and cytokine production in patients with coronary artery bypass surgery. Shock 24:103–108

    Article  PubMed  CAS  Google Scholar 

  39. Blanc P, Aouifi A, Bouvier H, Joseph P, Chiari P, Ovize M, Girard C, Jegaden O, Khder Y, Lehot JJ (2001) Safety of oral nicorandil before coronary artery bypass graft surgery. Br J Anaesth 87:848–854

    Article  PubMed  CAS  Google Scholar 

  40. Wu ZK, Tarkka MR, Pehkonen E, Kaukinen L, Honkonen EL, Kaukinen S (2000) Ischaemic preconditioning has a beneficial effect on left ventricular haemodynamic function after a coronary artery biopass grafting operation. Scand Cardiovasc J 34:247–53

    Article  PubMed  CAS  Google Scholar 

  41. Karthik S, Grayson AD, Oo AY, Fabri BM (2004) A survey of current myocardial protection practices during coronary artery bypass grafting. Ann R Coll Surg Engl 86:413–415

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Marshfield Clinic Research Foundation for its support through the assistance of Ingrid Glurich, Ph.D., Linda Weis, and Alice Stargardt in the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Department of Cardiology, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI, 54449, USA

    Shereif H. Rezkalla & Robert A. Kloner

  2. The Heart Institute, Good Samaritan Hospital, Los Angeles, CA, USA

    Robert A. Kloner

  3. Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Robert A. Kloner

Authors
  1. Shereif H. Rezkalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert A. Kloner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shereif H. Rezkalla.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rezkalla, S.H., Kloner, R.A. Preconditioning in humans. Heart Fail Rev 12, 201–206 (2007). https://doi.org/10.1007/s10741-007-9037-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-007-9037-y

Keywords

Search

Navigation