Determinants of infarct size in non-human primates
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.
Key wordsinfarct size baboons mathematical model coronary collateral flow
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- 4.Cohen MV (1986) Coronary collaterals. Clinical and Experimental Observations. Futura Publishing Co, Mount Kisko, New YorkGoogle Scholar
- 6.Draper MR, Smith H (1981) Applied Regression Analysis, 2nd Edition. John Wiley & Sons, New YorkGoogle 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 2–11Google 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 76:144–141Google 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 3:1438–1443Google 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 2:57Google 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 478–487Google Scholar
- 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 59:1148–1157Google Scholar
- 26.SAS User's Guide (1985) Statistics, Version 5. SAS Institute Inc, North CarolinaGoogle Scholar
- 27.Schaper W (1971a) Pathophysiology of coronary circulation. Prog Cardiovasc Res 14:275–296Google Scholar
- 28.Schaper W (1971b) The collateral circulation of the heart. North-Holland Publishing Co, AmsterdamGoogle 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 267–276Google 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 557–566Google 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 304:801–807Google 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 75:830–836Google Scholar