Relationship between regional myocardial blood flow and mitochondrial function.

Abstract

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 attributable 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.