Skip to main content
SpringerLink
Log in

Effects on infarct size of reperfusion and pretreatment with β-blockade and calcium antagonists

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

Summary

The “mass of tissue at risk” and the myocardial infarct developed was studied in dogs subjected to either 24-h occlusion of the left anterior descending coronary artery or 2-h occlusion followed by 22-h reperfusion. The “mass of tissue at risk” was defined under anaesthesia at the time of occlusion using the microsphere technique. Twenty-four hours later the hearts were removed, sliced transversely and stained with 2,3,5-triphenyltetrazolium chloride to define the infarcted tissue. All myocardial tissue was mapped and cut into small pieces for weighing and radioactive counting. Radioactivity was present in all tissue, including the infarct. In the centre of the the infarct, counts remained low and then increased very rapidly with distance just beyond the edge. Tissue at risk from infarction was taken as that with less than 15% of the peak left ventricular (non-ischaemic) counts.

A linear relationship was found between the mass of the left ventricular infarct and the left ventricular “mass of tissue at risk”. The effect of 22 hours reperfusion was examined by this method and expressed by a regression equation. There was a significant decrease in slope for the regression line of the reperfusion data, (p<0.05, analysis of covariance), indicating less infarcted tissue for each gram of underperfused tissue.

None of the drug pretreatments explored had any effect on infarct size in the 24-h occlusion model. With reperfusion, propranolol and flunarizine diminished infarct size compared with reperfusion only (p <0.05 for reduced slope, the new slope being not significantly different from zero). The effect of diltiazem was not so marked. Thus infarct size can be reduced with pretreatment, as long as the myocardium is reperfused.

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. Baker JE, Hearse DJ (1983) Slow channel blockers and the calcium paradox; comparative studies in the rat with seven drugs. J Mol Cell Cardiol 15:475–485

    PubMed  Google Scholar 

  2. Bishop SR (1984): How well can we measure coronary flow, risk zones and infarct sizc? In: Hearse DJ, Yellon DM (eds) Therapcutic Approaches to Myocardial Infarct Size Limitation. Raven Press, New York, p 146

    Google Scholar 

  3. Borgers M (1985) Morphological arrangement of tissue protection. In: Godfraind T et al. (eds) Calcium Entry Blockers and Tissue Protection. Raven Press, NY, pp. 173–181

    Google Scholar 

  4. van den Bos GC, Drake AJ, Noble MIM (1979) The effect of carbon dioxide upon myocardial performance, blood flow and oxygen consumption. J Physiol (Lond) 287:149–161

    Google Scholar 

  5. Braunwald E, Maroko PR (1974) The reduction in infarct size — an idea whose time (for testing) has come. Circulation 66:1146–1149

    Google Scholar 

  6. Buckberg GD, Luck JC, Payne DB, Hoffman JIE, Archie JP, Fixler DE (1971) Some sources of error in measuring regional blood flow with radioactive microspheres. J Appl Physiol 31:598–604

    PubMed  Google Scholar 

  7. Carmeleit E, Xhonneux R (1981) Influence of lidoflazine on cardiac transmembrane potentials and experimental arrhythmias. Naun-Schmiedebergs Archiv Pharmacol 268:210–223

    Google Scholar 

  8. Carmeleit E, Xhonneux R, Verdonk F (1974) Electrophysiological aspects of the action of lidoflazine on the heart. Arzneim Forsch 26:16–23

    Google Scholar 

  9. Capurro NC, Goldstein RE, Aarnodt R, Smith HJ, Epstein SE (1979) Loss of microspheres from ischemic canine cardiac tissue: An important technical limitation. Circ Res 44:223–227

    PubMed  Google Scholar 

  10. Cosigny PM, Verrier ED, Payne BD, Edelit G, Jester J, Baer RW, Vlahakes GJ, Hoffman JIE (1982) Acute and chronic microsphere loss from canine left ventricular myocardium. Am J Physiol 248:H568-H576

    Google Scholar 

  11. DeBoer LWV, Strauss HW, Kloner RA, Rude RE, Davis RF, Moroko PR, Braunwald E (1980) Autoradiographic method for measuring the ischemic myocardium at risk; effects of verapamil on infarct size after experimental coronary artery occlusion. Proc Natl Acad Sci 77:6119–6123

    PubMed  Google Scholar 

  12. Domenech RJ, Hoffman JIE, Noble MIM, Saunders KB, Henson RJ, Subijanto S (1969) Total and regional coronary blood flow measured by radioactive microspheres in conscious and anaesthetized dogs. Circ Res 25:581–596

    PubMed  Google Scholar 

  13. Drake AJ, Stubbs J Noble MIM (1978) Dependence of myocardial blood flow and metabolism on cardiac innervation. Cardiovasc Res 12:69–80

    PubMed  Google Scholar 

  14. Drake AJ Herbaczynska-Cerdo K, Ceremuzinski L, Czarnecki W, Noble MIM (1982) Metabolic and haemodynamic responses to adrenaline in normal dogs. Basic Res Cardiol 77:188–196

    PubMed  Google Scholar 

  15. Drake-Holland AJ (1983) Biochemical features of myocardial ischaemia. In: Warquier A, Borgers M, Amery WK (eds) Protection of Tissues against Hypoxia. Elsevier, Amsterdam, pp 87–93

    Google Scholar 

  16. Drake-Holland AJ, Noble MIM (1983) Myocardial protection by calcium antagonist drugs. Europ Heart J 4:823–825

    Google Scholar 

  17. Einwachter HM, Kern R, Herb J (1979) Effect of lidoflazine on membrane currents and contraction in voltage-clamped frog atrial fibres. Europ J Pharmacol 55:225–232

    Google Scholar 

  18. Factor SM, Cho S, Kirk E (1982) Non-specificity of triphenyl tetrazolium chloride (TTC) for the gross diagnosis of acute myocardial infarction. Circulation 66:Suppl II, 84

    Google Scholar 

  19. Flameng W, Daenen W, Xhonncux R, van de Water A, Thone, F. Borgers M (1980) Lidoflazine protection against normothermic myocardial ischaemia in the dog. Royal Soc Med Int Congress & Symposium Series, no 29. Academic Press & Royal Soc Med, p. 89–94

  20. Gibbs CL, Papadoyannis DE, Drake AJ, Noble MIM (1980) Oxygen consumption of the nonworking and potassium chloride-arrested dog heart. Circ Res 47:408–417

    PubMed  Google Scholar 

  21. (1982) Ventricular arrhythmic-associated with lidoflazine-side effects observed in a randomised trial. Europ Heart J 4:889–893

  22. Hearse DJ, Yellon DM (1984) Therapeutic Approaches to Myocardial Infarct Size Limitation. Raven Press, NY

    Google Scholar 

  23. Henderson AH (1984) The Clinicians View. In: Hearse DJ, Yellon DM (eds) Therapeutic Approaches to Myocardial Infarct Size Limitation. Raven Press, New York, pp 1–5

    Google Scholar 

  24. Henry PD (1980) Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 47:1047–1058

    Google Scholar 

  25. Heyman MA, Payne DB, Hoffman JIE, Rudolph AM (1977) Blood flow measurements with radionuclide labelled particles. Proc Cardiovasc Disease 20:55–61

    Google Scholar 

  26. Judgutt BI, Hutchins GM, Bulkley BH, Pitt B, Becker LC (1979) Effect of indomethicin on collateral blood flow and infarct size in the conscious dog. Circulation 59:734–743

    PubMed  Google Scholar 

  27. Judgutt BI, Hutchins GM Bulkley BH, Becker LC (1979) The loss of radioactive microspheres from canine necrotic myocardium. Circ Res 45:746–756

    PubMed  Google Scholar 

  28. Karlsberg RP, Henry PD, Ahmed SA, Sobel BE, Roberts R (1963) Lack of protection of ischaemic myocardium by verapamil in conscious dogs. Biometrics 19:429–440

    Google Scholar 

  29. Koyanagi S, Eastham CL, Harrison DG, Marcus ML (1982) Transmural variation in the relationship between infarct size and risk area. Am J Physiol 242:H867-H874

    PubMed  Google Scholar 

  30. Lavellee M, Cox D, Patrick TA, Vatner SF (1983) Salvage of myocardial function by coronary artery reperfusion 1, 2 and 3 hours after occlusion in conscious dogs. Circ Res 53:235–247

    PubMed  Google Scholar 

  31. Lowe JE, Reimer KA, Jennings RB, (1978) Experimental infarct size as a function of the amount of myocardium at risk. Am J Pathol 90:363–380

    PubMed  Google Scholar 

  32. Malsky PM, Vokonas PS, Paul SJ, Robbins SL, Hood WB (1977) Autoradiographic measurement of regional blood flow in normal and ischemic myocardium. Am J Physiol 232:H576-H583

    PubMed  Google Scholar 

  33. Maroko PR, Kjekus JK, Sobel BE, Watanabe T, Covell JW, Ross J Jr, Braunwald E (1971) Factors influencing infarct size following experimentally artery occlusions. Circulation 43:67–82

    PubMed  Google Scholar 

  34. Melin JA, Becker LC, Hutchins GM (1984) Protective effect of early and late treatment with nifedipine during myocardial infarction in the conscious dog. Circulation 69:131–141

    PubMed  Google Scholar 

  35. Murdock RH, Cobb FR (1980) Effects of infarcted myocardium on regional blood flow measurements to ischemic regions in canine hearts. Circ Res 52:451–459

    Google Scholar 

  36. Murdock RH, Harlan DM, Morris JJIII, Pryor WW, Cobb FR (1983) Transitional blood flow zones between ischemic and non-ischemic myocardium in the awake dog. [Analysis based on distribution of the intramural vasculature Circ Res 52:451–459

    PubMed  Google Scholar 

  37. Nakajima H, Hoshiyama M, Yamashita K, Kiyomoto A (1975) Effect of diltiazem on electrical and mechanical activity of isolated cardiac ventricular muscle of guinea pig. Japan J Pharmacol 25:383–392

    Google Scholar 

  38. Nose YT, Nakamura T, Nakamura M (1985) The microsphere method facilitates statistical assessment of regional blood flow. Basic Res Cardiol 80:417–429

    PubMed  Google Scholar 

  39. Reimer KA, Jennings RB (1979) The changing anatomic base of evolving myocardial infarction. Circulation 60:866–876

    PubMed  Google Scholar 

  40. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB (1970) The wafefront phenomenon of ischaemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation 56:786–794

    Google Scholar 

  41. Reimer KA, Jennings RB, Cobb FR, Murdock RH, Greenfield JC, Becker LC, Bulkley BH, Hutchins GM, Schwartz RP, Bailey KR, Passamini ER (1985) Animal models for protecting ischemic myocardium. Results of the NHLBI cooperative study. Comparison of unconscious and conscious dog models. Circ Res 56:651–665

    PubMed  Google Scholar 

  42. Reimer KA, Long JB, Murry CB, Jennings RB (1987) Three dimensional distribution of collateral blood flow within the anatomic risk area after circumflex coronary artery occlusion in dogs. Basic Res Cardiol 82:473–485

    PubMed  Google Scholar 

  43. Ribeiro LG, Cheung W, Maroko PR (1982) Influence of the extent of the zone at risk on the effectiveness of drugs in reducing infarct size. Circulation 66:181–186

    PubMed  Google Scholar 

  44. Saikawa T, Nagamato Y, Arita M (1973) Electrophysiological effects of diltiazem, a new slow channel inhibitor, on canine cardiac fibres. Japanese Heart J 18:235–245

    Google Scholar 

  45. Schaper W (1971) The collateral circulation of the heart. North Holland, Amsterdam.

    Google Scholar 

  46. Schaper W (1978) Experimental coronary artery occlusion III. The determinants of collateral blood flow in acute coronary artery occlusion. Basic Res Cardiol 73:584–594

    PubMed  Google Scholar 

  47. Schaper W (1984) Measurement of infarct size. In: Hearse DJ, Yellon DM (eds) Therapeutic Approaches to Myocardial Infarct Size Limitation. Raven Press, New York, pp 81–82

    Google Scholar 

  48. Selwyn AP, Welman E, Fox K, Korlock, P, Pratt T, Klein M (1979) The effects of nifedipine on acute experimental myocardial ischaemia in dogs. Circ Res 44:16–23

    PubMed  Google Scholar 

  49. Snedecor GW, Cochran WG (1973) Statistical Methods. Iowa Sate University Press

  50. Vanderplassche G, Wouters L, Hermans C, Xhonneux R, Borgers M, Flameng W (1986) An efficient method to evaluate protective drugs against regional ischemia of the heart. Drug Development Res 8:417–424

    Google Scholar 

  51. Vatner S, Baig H, Manders WT, Maroko PR (1977) Effects of coronary artery reperfusion on myocardial infarct size calculated from creatine kinase. J Clin Invest 56:1048–1056

    Google Scholar 

  52. Vatner SF, Patrick TA, Knight DR, Manders WT, Fallon JT (1988) Effects of calcium channel blocker on responses of blood flow, function, arrhythmias, and extent of infarction following reperfusion in conscious baboons. Circ Res 62:105–115

    PubMed  Google Scholar 

  53. Wood AJ, Isted K, Hynd J, Main MJ, Noble MIM, Parker, J, Drake-Holland AJ (1985) Mioflazine, a potentially protective drug against ischaemic damage. A study in dogs. Europ Heart J 6:695–701

    Google Scholar 

  54. Yellon DM, Hearse DJ, Crome R, Granell J, Wyse RKH (1981) Characterisation of the lateral interface between normal and ischemic tissue in the canine heart during experimental myocardial infarction. Am J Cardiol 471:1233–1239

    Google Scholar 

  55. Yellon DM, Hearse DJ, Maxwell MP, Chambers DE, Downey JM (1983) Sustained limitation of myocardial necrosis 24 hours after coronary artery occlusion: Verapamil infusion in dogs with small myocardial infarcts. Am J Cardiol 51:1409–1413

    Article  Google Scholar 

Download references

Author information

Author notes

  1. S. Torr

    Present address: Cardiovascular Division, Washington University School of Medicine, 660 South Euclid Ave, Box 80 86, 63110, St. Louis, Missouri, USA

Authors and Affiliations

  1. Department of Medicine 1, St. George's Hospital Medical School, London, England

    S. Torr, A. J. Drake-Holland, M. Main & J. Hynd

  2. Department of Cardiac Surgery, St. George's Hospital Medical School, London, England

    K. Isted

  3. Academic Unit of Cardiovascular Medicine, Charing Cross and Westminster Medical School, London, England

    M. I. M. Noble

Authors
  1. S. Torr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. J. Drake-Holland
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Main
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Hynd
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Isted
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. I. M. Noble
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

S. Torr and M. Main were supported by grants from the Science and Engineering Research Council, UK; A.J. Drake-Holland was supported by a fellowship from the Janssen Research Foundation.

M.I.M. Noble is supported by the Garfield Weston Trust as the Weston Professor of Cardiovascular Medicine.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Torr, S., Drake-Holland, A.J., Main, M. et al. Effects on infarct size of reperfusion and pretreatment with β-blockade and calcium antagonists. Basic Res Cardiol 84, 564–582 (1989). https://doi.org/10.1007/BF01906942

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01906942

Key words

Search

Navigation