Skip to main content
Log in

Determinants of infarct size in non-human primates

  • Original Contributions
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

To achieve a better understanding of the major factors that determine infarct size in non-human primates, a mathematical model was constructed using stepwise regression analysis. The model was developed on the basis of infarct size measurements, including the anatomical area at risk, regional myocardial blood flow measurements and hemodynamic determinants obtained in 23 control baboons undergoing up to 2 h of coronary artery thrombosis followed by thrombolysis.

In this model, the size of the perfusion bed of the occluded coronary artery and the duration of coronary artery occlusion were found to be the only important predictors of infarct size (expressed as a percentage of left ventricular mass). R2 (square or the multiple correlation coefficient) was 70% in this model. Collateral blood flow and rate-pressure product were not identified as important predictors of infarct size.

In a second group of eight baboons, atenolol (0.1 mg·kg−1) was administered intravenously 15 min after the onset of coronary artery thrombosis. Predicted infarct size (based on the mathematical model obtained in the control group) was larger than the observed infarct size in seven out of eight cases. In four instances observed infarct size was smaller than the 95% lower limit of the predicted value.

It is concluded that the determinants of infarct size in non-human primates differ from those in canine models with respect to collateral flow and estimates of myocardial oxygen consumption (rate pressure product). The developed mathematical model of infarct size prediction allows the detection of cardioprotective drug effects with an acceptable efficacy.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Baroldi G (1966) Myocardial infarct and sudden coronary heart death in relation to coronary occlusion and collateral circulation. Am Heart J 71:826–836

    PubMed  Google Scholar 

  2. Bush LR, Romson JL, Ash JL, Lucchesi BR (1982) Effects of diltiazem on extent of ultimate myocardial injury resulting from temporary coronary artery occlusion in dogs. J Cardiovasc Pharmacol 4:285–291

    PubMed  Google Scholar 

  3. Buss Dd, Hyde DM, Stefey EP (1983) Coronary collateral development in the rhesus monkey (Macaca mulatta). Basic Res Cardiol 78:510–517

    PubMed  Google Scholar 

  4. Cohen MV (1986) Coronary collaterals. Clinical and Experimental Observations. Futura Publishing Co, Mount Kisko, New York

    Google Scholar 

  5. Crozatier B, Rocs J Jr, Franklin D, Bloor C (1978) Myocardial infarction in the baboon: Regional function and the collateral circulation. Am J Physiol 235:H413–H421

    PubMed  Google Scholar 

  6. Draper MR, Smith H (1981) Applied Regression Analysis, 2nd Edition. John Wiley & Sons, New York

    Google Scholar 

  7. Flameng W, Van de Werf F, Vanhaecke J, Verstraete M, Collen D (1985) Coronary thrombolysis and infarct size reduction after intravenous infusion of recombinant tissue-type plasminogen activator in nonhuman primates. J Clin Invest 75:84–90

    PubMed  Google Scholar 

  8. Flameng W, Vanhaecke J, Vandeplassche G (1986) Studies on experimental myocardial infarction: dogs or baboons? Cardiovasc Res 20:241–247

    PubMed  Google Scholar 

  9. Fox K, Welman E, Selwyn A (1980) Myocardial infarction in the dog: effects of intravenous propranolol. Am J Cardiol 45:769–774

    PubMed  Google Scholar 

  10. Fulton WFM (1978) Intercoronary anastomoses studied by postmortem sterioarteriography: Relationship to coronary occlusion and myocardial damage. In: Kaltenbach M, Lichtlen P, Balcon R, Bussmann WD (eds) Coronary Heart Disease: 3rd International Symposium Frankfurt. Georg Thieme, Stuttgart, pp 2–11

    Google Scholar 

  11. Genth K, Hofmann M, Schaper W (1983) The effect of beta-adrenergic blockade on infarct size following experimental coronary occlusion. Basic Res Cardiol 76:144–141

    Google Scholar 

  12. Hammerman H, Kloner RA, Briggs LL, Braunwald E (1984) Enhancement of salvage of reperfused myocardium by early beta-adrenergic blockade blockade (timolol). J Am Cell Cardiol 3:1438–1443

    Google Scholar 

  13. ISIS-I (First International Study of Infarct Survival) Collaborative Group 1986. Randomized trial of intravenous atenolol among 16027 cases of suspected acute myocardial infarction. ISIS-I Lancet 2:57

    Google Scholar 

  14. Kato T (1976) A comparative study of the coronary arterial structure in the left ventricular free wall in infarcted and non-infarcted human hearts. Jpn Circ J 40:989–1003

    PubMed  Google Scholar 

  15. Kloner RA, Fishbein MC, Braunwald E, Maroko PR (1978) Effect of propranolol on the mitochondrial morphology during acute myocardial ischemia. Am J Cardiol 41:880–886

    PubMed  Google Scholar 

  16. Lange R, Nieminen MS, Kloner RA (1984) Failure of pindolol and metoprolol to reduce the size of non-reperfused infarcts in dogs using area at risk techniques. Cardiovasc Res 18:37–43

    PubMed  Google Scholar 

  17. La Vallee W, Vatner F (1984) Regional myocardial blood flow and necrosis in primates following coronary occlusion. Am J Physiol 246:H635–H639

    PubMed  Google Scholar 

  18. Lubbe WF, Peisach M, Pretorius R, Bruyneel K (1974) Distribution of myocardial blood flow before and after coronary artery ligation in the baboon. Relation to early ventricular fibrillation. Cardiovasc Res 478–487

  19. Miura M, Thomas R, Ganz W, Sokol T, Shell WE, Toshimitsu T, Kwan AC, Singh BN (1979) The effect of delay in propranolol administration on reduction of myocardial infarct size after experimental coronary artery occlusion in dogs. Circ 59:1148–1157

    Google Scholar 

  20. Rasmussen MM, Reimer KA, Kloner RA, Jennings RB (1977) Infarct size reduction by propranolol before and after coronary ligation dogs. Circ 56:794–798

    PubMed  Google Scholar 

  21. Reimer KA, Jennings RB (1979) The “Wavefront phenomenas” of myocardial ischemic cell death. II. Transmural progression of necrosis within the framework of ischemic bed size (myocardium at risk) and collateral flow. Lab Invest 40:633–644

    PubMed  Google Scholar 

  22. Reimer KA, Jennings RB, Lobb FR, Murdock RH, Greenfield JC Jr, Becker LC, Healy Bulkey B, Hutchins GM, Schwartz RP Jr, Barley KR, Passamani ER (1985) Animal models for protecting ischemic myocardium: results of the NHLBI cooperative study. Circ Res 56:651–665

    PubMed  Google Scholar 

  23. Reimer KA, Lowe J, Jennings RB (1977) Effects of the calcium antagonist verapamil on necrosis following temporary coronary artery occlusion in dogs. Circ 55:581

    PubMed  Google Scholar 

  24. Reimer KA, Rasmussen MM, Jennings RB (1973) Reduction by propranolol of myocardial necrosis following temporary coronary artery occlusion in dogs. Circ Res 33:353–363

    PubMed  Google Scholar 

  25. Reimer KA, Rasmussen MM, Jennings RB (1976) On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs. Am J Cardiol 37:520–527

    PubMed  Google Scholar 

  26. SAS User's Guide (1985) Statistics, Version 5. SAS Institute Inc, North Carolina

    Google Scholar 

  27. Schaper W (1971a) Pathophysiology of coronary circulation. Prog Cardiovasc Res 14:275–296

    Google Scholar 

  28. Schaper W (1971b) The collateral circulation of the heart. North-Holland Publishing Co, Amsterdam

    Google Scholar 

  29. Schaper W, Flameng W, De Brabander M (1972) Comparative aspects of coronary collateral circulation. In: Bloor CM (ed) Comparative Pathophysiology of Circulatory Disturbances: Advances in Experimental Medicine and Biology, Vol 22. Plenum Press, New York, pp 267–276

    Google Scholar 

  30. Selpeskog EL, Hitchcock CR, Groover ME (1972) Coronary artery studies in the dog and Kenya baboon utilizing surgically induced myocardial infarctions. In: Vogtberg (ed) The Babbon in Medical Research. Univ of Texas Press, Austin, pp 557–566

    Google Scholar 

  31. Shatney CH, MacCarter DJ, Lillekei RC (1976) Effects of allopurinol, propranolol and methylprednisolone on infarct size in experimental myocardial infarction. Am J Cardiol 37:572–580

    PubMed  Google Scholar 

  32. The Norwegian Multicenter Study Group (1981) Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 304:801–807

    Google Scholar 

  33. Van de Werf F, Vanhaccke J, Jang IK, Flameng W, Collen D, De Geest H (1987) Reduction in infarct size and enhanced recovery of systolic function after coronary thrombolysis with tissue-type plasminogen activator combined with beta-adrenergic blockade with metoprolol. Circ 75:830–836

    Google Scholar 

  34. Weisse AB, Kearny K, Narang RM, Regars J (1976) Comparison of the coronary collateral circulation in dogs and baboons after coronary occlusion. Am Heart J 92:193–200

    PubMed  Google Scholar 

  35. Wüsten B, Flameng W, Schaper W (1974) The distribution of myocardial flow. Part I: Effects of experimental coronary occlusion. Basic Res Cardiol 69:422–434

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by grants from the “Nationaal Fonds voor Wetenschappelijk Onderzoek” and “Onderzocksfonds K. U. Leuven”.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Flameng, W., Lesaffre, E. & Vanhaecke, J. Determinants of infarct size in non-human primates. Basic Res Cardiol 85, 392–403 (1990). https://doi.org/10.1007/BF01907131

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01907131

Key words

Navigation