The present study was performed to establish whether a quantitative relationship exists between the degree of impairment of mitochondrial function and the level of uptake of technetium-99m stannous pyrophosphate (99mTc-PP(i)), which is a marker of irreversible cellular injury. Such data would indicate whether the severity of mitochondrial dysfunction reflects the extent and severity of myocardial ischemic damage. Dogs were subjected to left anterior descending coronary artery occlusion for 15 min (n = 4), 1 h (n = 18), or 24 h (n = 6). 99mTc-PP(i) was injected intravenously at end occlusion, and reperfusion was then provided for 90 min. An additional group of dogs (n = 3) was subjected to 15 min of permanent coronary occlusion without reperfusion. Left ventricular subendocardial and subepicardial tissues from ischemic and non-ischemic areas were removed and mitochondria isolated by Polytron and Nagarse methods. After 15 min of permanent coronary occlusion, mitochondrial function in the ischemic region was mildly depressed. After 15 min of ischemia and reflow, mitochondrial function in the ischemic region did not differ from control values, and no significant uptake of 99mTc-PP(i) occurred. After 60 min of ischemia and reflow, marked mitochondrial dysfunction and significant 99mTc-PP(i) uptake occurred in the ischemic samples. Similar changes were present after 24 h of ischemia. Good correlations occurred between the degree of 99mTc-PP(i) uptake in tissue and in isolated mitochondria (r = 0.89) and between the degree of 99mTc-PP(i) uptake and mitochondrial dysfunction (r = 0.92), as evidenced by alterations in oxygen consumption and citrate synthase activity. While these data do not establish the primary lesion in ischemia, they provide support for the notion that membrane damage associated with 99mTc-PP(i) accumulation and severe mitochondrial dysfunction occur coincidently with the development of irreversible cellular damage and that the degree of mitochondrial dysfunction reflects the extent and severity of myocardial ischemic damage.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|State||Published - Jan 1 1982|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)