Skip to main content
SpringerLink
Log in

Hypothermia during reperfusion does not reduce myocardial infarct size in pigs

  • ORIGINAL CONTRIBUTION
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

We previously described a method for regional myocardial cooling that reaches the target temperature within 4 min. The present study evaluated whether this method for regional myocardial cooling during reperfusion reduces myocardial infarct size (IS) in 75–kg pigs. Myocardial infarction was induced by inflation of an angioplasty balloon in the left anterior descendent artery for 45 min followed by 3 h reperfusion. First, 15 pigs were randomized to regional myocardial cooling during reperfusion (n = 8) or control (n = 7). As further control experiments, systemic hypothermia was induced prior to ischemia (n = 3) and during reperfusion (n = 3). IS and area at risk (AAR) were evaluated in vivo by single photon emission cardiac tomography (SPECT) and by standard histochemical staining.

Regional cooling during reperfusion did not reduce IS/AAR as assessed by histochemistry (cooling: 0.71 ± 0.8; control: 0.68 ± 0.10; p = ns) and SPECT (cooling: 0.90 ± 0.20; control: 0.88 ± 0.32; p = ns). Systemic hypothermia during ischemia reduced IS/AAR (histochemistry: 0.09 ± 0.11; SPECT: 0.25 ± 0.22; p < 0.001 and p = 0.01 vs control, respectively). Induction of systemic hypothermia during reperfusion had no significant effect on IS/AAR (histochemistry: 0.63 ± 0.07; SPECT: 0.74 ± 0.09; p = ns vs control for both comparisons).

In conclusion, hypothermia during ischemia is strongly myocardioprotective while hypothermia during reperfusion does not reduce myocardial infarct size in human–sized pigs.

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

Abbreviations

AAR:

Area At Risk

IS:

Infarct Size

RMC:

Regional Myocardial Cooling

SH:

Systemic Hypothermia

SPECT:

Single Photon Emission Cardiac Tomography

AMI:

Acute Myocardial Infarction

References

  1. Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, Abildgaard U, Pedersen F, Madsen JK, Grande P, Villadsen AB, Krusell LR, Haghfelt T, Lomholt P, Husted SE, Vigholt E, Kjaergard HK, Mortensen LS (2003) A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med 349:733–742

    Article  PubMed  Google Scholar 

  2. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K (2002) Treatment of comatose survivors of out–of–hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563

    Article  PubMed  Google Scholar 

  3. Dae MW, Gao DW, Stillson C, Chair K (2002) Effect of mild endovascular cooling on myocardial temperature, infarct size, and cardiac output in human–sized pigs. Am J Physiol Heart Circ Physiol 282:H1584–H1591

    PubMed  CAS  Google Scholar 

  4. Dixon SR, Whitbourn RJ, Dae MW, Grube E, Sherman W, Schaer GL, Jenkins S, Baim DS, Gibbons RJ, Kuntz RE, Popma JJ, Nguyen TT, O’Neill WW (2002) Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction. J Am Coll Cardiol 40:1928–1934

    Article  PubMed  Google Scholar 

  5. Duncker DJ, Klassen CL, Ishibashi Y, Herrlinger SH, Pavek TJ, Bache RJ (1996) Effect of temperature on myocardial infarction in swine. Am J Physiol 270:H1189–H1199

    PubMed  CAS  Google Scholar 

  6. Faxon DP, Gibbons RJ, Chronos NA, Gurbel PA, Sheehan F (2002) The effect of blockade of the CD11/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: the results of the HALT–MI study. J Am Coll Cardiol 40:1199–1204

    PubMed  CAS  Google Scholar 

  7. Felberg RA, Krieger DW, Chuang R, Persse DE, Burgin WS, Hickenbottom SL, Morgenstern LB, Rosales O, Grotta JC (2001) Hypothermia after cardiac arrest: feasibility and safety of an external cooling protocol. Circulation 104:1799–180

    PubMed  CAS  Google Scholar 

  8. Gunn AJ, Gunn TR (1998) The 'pharmacology' of neuronal rescue with cerebral hypothermia. Early Hum Dev 53:19–35

    Article  PubMed  CAS  Google Scholar 

  9. Hale SL, Dae MW, Kloner RA (2003) Hypothermia during reperfusion limits "no–reflow" injury in a rabbit model of acute myocardial infarction. Cardiovasc Res 59:715–722

    Article  PubMed  CAS  Google Scholar 

  10. Hale SL, Dave RH, Kloner RA (1997) Regional hypothermia reduces myocardial necrosis even when instituted after the onset of ischemia. Basic Res Cardiol 92:351–357

    PubMed  CAS  Google Scholar 

  11. Hale SL, Kloner RA (1997) Myocardial temperature in acute myocardial infarction: protection with mild regional hypothermia. Am J Physiol 273:H220–H227

    PubMed  CAS  Google Scholar 

  12. Hale SL, Kloner RA (1998) Myocardial temperature reduction attenuates necrosis after prolonged ischemia in rabbits. Cardiovasc Res 40:502–507

    Article  PubMed  CAS  Google Scholar 

  13. Hale SL, Kloner RA (1999) Ischemic preconditioning and myocardial hypothermia in rabbits with prolonged coronary artery occlusion. Am J Physiol 276:H2029–H2034

    PubMed  CAS  Google Scholar 

  14. Kastrati A, Mehilli J, Dirschinger J, Schricke U, Neverve J, Pache J, Martinoff S, Neumann FJ, Nekolla S, Blasini R, Seyfarth M, Schwaiger M, Schomig A (2002) Myocardial salvage after coronary stenting plus abciximab versus fibrinolysis plus abciximab in patients with acute myocardial infarction: a randomised trial. Lancet 359:920–925

    Article  PubMed  CAS  Google Scholar 

  15. Keeley EC, Boura JA, Grines CL (2003) Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 361:13–20

    PubMed  Google Scholar 

  16. Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, Vogel M, Sorensen K, Redington AN, MacAllister R (2002) Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 106:2881–2883

    Article  PubMed  CAS  Google Scholar 

  17. Kristensen J, Mortensen UM, Nielsen SS, Maeng M, Kaltoft A, Nielsen TT, Rehling M (2004) Myocardial perfusion imaging with 99mTc sestamibi early after reperfusion reliably reflects infarct size reduction by ischaemic preconditioning in an experimental porcine model. Nucl Med Commun 25:495–500

    PubMed  Google Scholar 

  18. Lindal S, Gunnes S, Ytrehus K, Straume BK, Jorgensen L, Sorlie D (1990) Amelioration of reperfusion injury following hypothermic, ischemic cardioplegia in isolated, infarcted rat hearts. Eur J Cardiothorac Surg 4:33–39

    Article  PubMed  CAS  Google Scholar 

  19. Maeng M, Kristiansen SB, Mortensen UM, Andersen HR (2003) Myocardial cooling for reperfusion injury protection achieved by organ specific hypothermic autologous perfusion. Scand Cardiovasc J 37:1–7

    Google Scholar 

  20. Mahaffey KW, Puma JA, Barbagelata NA, DiCarli MF, Leesar MA, Browne KF, Eisenberg PR, Bolli R, Casas AC, Molina– Viamonte V, Orlandi C, Blevins R, Gibbons RJ, Califf RM, Granger CB (1999) Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo–controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial. J Am Coll Cardiol 34:1711–1720

    Article  PubMed  CAS  Google Scholar 

  21. Matsumura K, Jeremy RW, Schaper J, Becker LC (1998) Progression of myocardial necrosis during reperfusion of ischemic myocardium. Circulation 97:795–804

    PubMed  CAS  Google Scholar 

  22. Mattu A, Brady WJ, Perron AD (2002) Electrocardiographic manifestations of hypothermia. Am J Emerg Med 20:314–326

    Article  PubMed  Google Scholar 

  23. Metha S, Yusuf S, Diaz R, Zhu J, Pais P, Xavier D, Paolasso E, Ahmed R, Xie C, Kazmi K, Tai J, Orlandini A, Pogue J, Liu L, and CREATE–ECLA Trial Group Investigators (2005) Effects of glucose–insulinpotassium infusion on mortality in patients with acute ST–segment myocardial infarction: the CREATE–ECLA randomized controlled trial. JAMA 293:437–446

    Google Scholar 

  24. Nishio S, Chen ZF, Yunoki M, Toyoda T, Anzivino M, Lee KS (1999) Hypothermiainduced ischemic tolerance. Ann NY Acad Sci 890:26–41

    PubMed  CAS  Google Scholar 

  25. O'Neill WW, Dixon SR (2004) The year in interventional cardiology. J Am Coll Cardiol 43:875–890

    PubMed  Google Scholar 

  26. Pache J, Kastrati A, Mehilli J, Bollwein H, Ndrepepa G, Schuhlen H, Martinoff S, Seyfarth M, Nekolla S, Dirschinger J, Schwaiger M, Schomig A (2004) A randomized evaluation of the effects of glucose– insulin–potassium infusion on myocardial salvage in patients with acute myocardial infarction treated with reperfusion therapy. Am Heart J 148:e3

    Article  PubMed  Google Scholar 

  27. Schulz R, Gres P, Konietzka I, Heusch G (2005) Regional differences of myocardial infarct development and ischemic preconditioning. Basic Res Cardiol 100:48–56

    Article  PubMed  Google Scholar 

  28. Schwartz LM, Verbinski SG, Vander Heide RS, Reimer KA (1997) Epicardial temperature is a major predictor of myocardial infarct size in dogs. J Mol Cell Cardiol 29:1577–1583

    Article  PubMed  CAS  Google Scholar 

  29. Terrovitis J, Charitos C, Dolou P, Papalois A, Eleftheriou A, Tsolakis E, Charitos E, Mponios M, Karanastasis G, Koudoumas D, Agapitos E, Nana JN (2004) No effect of stem cell mobilization with GM–CSF on infarct size and left ventricular function in experimental acute myocardial infarction. Basic Res Cardiol 99:241–246

    Article  PubMed  CAS  Google Scholar 

  30. The hypothermia after cardiac arrest study group (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556

    Google Scholar 

  31. The magnesium in coronaries (MAGIC) trial investigators (2002) Early administration of intravenous magnesium to high–risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial. Lancet 360:1189–1196

    Google Scholar 

  32. van den Doel MA, Gho BC, Duval SY, Schoemaker RG, Duncker DJ, Verdouw PD (1998). Hypothermia extends the cardioprotection by ischaemic preconditioning to coronary artery occlusions of longer duration. Cardiovasc Res 37:76–81

    Article  PubMed  CAS  Google Scholar 

  33. van der Horst IC, Zijlstra F, van’t Hof AW, Doggen CJ, de Boer MJ, Suryapranata H, Hoorntje JC, Dambrink JH, Gans RO, Bilo HJ (2003) Glucose–insulin–potassium infusion in patients treated with primary angioplasty for acute myocardial infarction: the glucose–insulin–potassium study: a randomized trial. J Am Coll Cardiol 42:784–791

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Skejby Hospital, Aarhus University Hospital, Brendstrupgaardsvej, 8200, Aarhus N, Denmark

    M. Maeng MD, PhD, U. M. Mortensen MD, PhD, S. B. Kristiansen MD & H. R. Andersen MD, DMSc

  2. Department of Nuclear Medicine, Skejby Hospital, Aarhus University Hospital, Brendstrupgaardsvej, 8200, Aarhus N, Denmark

    J. Kristensen MD

Authors
  1. M. Maeng MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U. M. Mortensen MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Kristensen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. B. Kristiansen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. R. Andersen MD, DMSc
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Maeng MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maeng, M., Mortensen, U.M., Kristensen, J. et al. Hypothermia during reperfusion does not reduce myocardial infarct size in pigs. Basic Res Cardiol 101, 61–68 (2006). https://doi.org/10.1007/s00395-005-0550-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00395-005-0550-7

Key words

Search

Navigation