Relationship between regional myocardial blood flow and mitochondrial function
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The purpose of this study was to clarify the relationship between myocardial mitochondrial dysfunction and the degree plus duration of restricted coronary blood flow. 135 anesthetized and open-chest dogs were divided into 3 groups according to coronary occlusion time: 10, 20, and 60 min. Regional myocardial blood flow (MBF) was determined in both ischemic and nonischemic areas before and during coronary occlusion using the hydrogen gas clearance method. Myocardial mitochondria were prepared from each area in which MBF was determined after 10, 20, or 60 min of coronary ligation, and their respiratory control index (RCI), ADP/O, and rate of oxygen consumption in state III O2 (St. III O2) were measured. The MBF measured in 135 dogs before coronary ligation was 103±25 ml/min/100 g (mean±SD) for the area to be rendered ischemic and 101±24 ml/min/100 g for the control area. The MBF in the ischemic area did not cease completely following coronary ligation, and the distribution of MBF showed variations which seemed atributable to individual differences. In the 10-min group, no index of mitochondrial function of the ischemic area differed from that of the nonischemic area at any level of MBF. When MBF was less than 20 ml/min/100 g, RCI of mitochondria from the ischemic area was significantly lower than that from the nonischemic area, in the 20- and 60-min groups. When MBF was less than 20 ml/min/100 g, St. III O2 of mitochondria from the ischemic area significantly decreased compared with that from the nonischemic area, in the 20-min group. In the 60-min group, MBF less than 30 ml/min/100 g, St. III O2 of mitochondria from the ischemic area was likewise significantly decreased. Moreover, with MBF below 20 ml/min/100 g, both RCI and St. III O2 of mitochondria from the ischemic area were significantly lower in the 60-min group than in the 20-min group. These results indicate that ischemia-induced mitochondrial dysfunction depends on the degree of decrease in the blood flow of the area involved as well as on the duration of ischemia, and the blood flow that is critical for survival, based on mitochondrial function, is approximately 20 ml/min/100 g, i.e., a reduction to 20% of normal value.
Key wordsregional ischemia canine heart mitochondrial function regional myocardial blood flow hydrogen gas clearance method
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- 3.Becker, L., R. Ferreira, M. Thomas: Regional left ventricular blood flow in experimental canine coronary occlusion. Eur. J. Clin. Invest.2, 271 (1972).Google Scholar
- 6.Estabrook, R. W.: Mitochondrial respiratory control and the polarographic measurement of ADP:O ratios. In: Methods in Enzymology, Vol. 10, R. W. Estabrook, M. E. Pullman, ed., Academic Press, pp. 41–47 (New York 1967).Google Scholar
- 8.Jennings, R. B.: Relationship of acute ischemia to functional defects and irreversibility. Circulation53 (Suppl. I), I26—I29 (1976).Google Scholar
- 9.Jennings, R. B., C. E. Ganote: Mitochondrial structure and function in acute myocardial ischemic injury. Circulat. Res.38 (Suppl. I), I80—I89 (1976).Google Scholar
- 10.Jennings, R. B., C. E. Ganote, K. A. Reimer: Ischemic tissue injury. Amer. J. Pathol.81, 179–198 (1975).Google Scholar
- 12.Kety, S. S.: Theory of blood-tissue exchange and its application to measurement of blood flow. In: Methods in Medical Research, Vol. 8, H. D. Brunner, ed., Year Book Publishers, pp. 223–227 (Chicago 1960).Google Scholar
- 13.Kirk, E. S., R. B. Jennings: Pathophysiology of myocardial ischemia, In: The heart, 5th ed., J. W. Hurst, ed., McGraw-Hill Book Company, pp. 976–1008 (New York 1982).Google Scholar
- 14.Koyama, T.: Local myocardial blood flow measured by the use of a needle-type Pt−H2 electrode. In: Recent Advances in Studies on Cardiac Structure and Metabolism, Vol. 10, P.-E. Roy, G. Rona, ed., University Park Press, pp. 525–538 (Baltimore 1975).Google Scholar
- 15.LaMorgese, J., J. M. Fein, K. Shulman: Polarographic and microsphere analysis of ultraregional cerebral blood flow rates in the cat. In: Blood Flow and Metabolism in the Brain, A. M. Harper, B. Jennet, D. Miller, et al., ed., Churchill-Livingstone, pp. 7.3–7.8 (Edinburgh 1975).Google Scholar
- 19.Neely, W. A., M. D. Turner, J. D. Hardy, W. D. Godfrey: The use of the hydrogen electrode to measure tissue blood flow. J. Surg. Res.5, 363–369 (1965).Google Scholar
- 24.Wood, J. M., H. G. Hanley, M. L. Entman, C. J. Hartley, J. A. Swain, U. Busch, C.-H. Chang, R. M. Lewis, W. J. Morgan, A. Schwartz: Biochemical and morphological correlates of acute experimental myocardial ischemia in the dog. IV. Energy mechanisms during very early ischemia. Circulat. Res.44, 52–61 (1979).PubMedGoogle Scholar