Abstract
When coronary perfusion is interrupted, the diastolic force generated by the myocardium first falls but eventually increases. The delayed rise in force, ischemic contracture, has been attributed either to ATP depletion or to elevation of the intracellular free calcium concentration ([Ca2+](i)). To distinguish between these possibilities, we measured [Ca2+](i) and ATP concentration ([ATP]) in ferret hearts using nuclear magnetic resonance (NMR) spectroscopy. Mean time-averaged [Ca2+](i) and [ATP] equaled 0.25 μM and 2.7 μmol/g wet wt, respectively, under control perfusion conditions. [Ca2+](i) increased and [ATP] fell during total global ischemia. Although [Ca2+](i) exceeded the usual systolic levels of 1.7 μM within 20-25 min of ischemia and reached a steady level between 2 and 3 μM by 30-35 min, force only began to rise after 40 min. In contrast, the time required for [ATP] to fall to <10% of control levels coincided closely with the onset of contracture. Ischemia in the presence of iodoacetate, an inhibitor of glycolysis, led to a precipitous fall in [ATP] and a concomitant rise in force, both of which preceded any elevation of [Ca2+](i). Thus changes in [Ca2+](i) are neither sufficient nor necessary for the initiation of ischemic contracture. We conclude that ATP depletion is primary and that the rise in resting force reflects the formation of rigor cross bridges.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 258 |
| Issue number | 1 27-1 |
| State | Published - 1990 |
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Keywords
- Calcium metabolism
- Glycolysis
- Iodoacetate
- Nuclear magnetic resonance spectroscopy
ASJC Scopus subject areas
- Physiology
Cite this
Mechanism of ischemic contracture in ferret hearts : Relative roles of [Ca2+](i) elevation and ATP depletion. / Koretsune, Y.; Marban, E.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 258, No. 1 27-1, 1990.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mechanism of ischemic contracture in ferret hearts
T2 - Relative roles of [Ca2+](i) elevation and ATP depletion
AU - Koretsune, Y.
AU - Marban, E.
PY - 1990
Y1 - 1990
N2 - When coronary perfusion is interrupted, the diastolic force generated by the myocardium first falls but eventually increases. The delayed rise in force, ischemic contracture, has been attributed either to ATP depletion or to elevation of the intracellular free calcium concentration ([Ca2+](i)). To distinguish between these possibilities, we measured [Ca2+](i) and ATP concentration ([ATP]) in ferret hearts using nuclear magnetic resonance (NMR) spectroscopy. Mean time-averaged [Ca2+](i) and [ATP] equaled 0.25 μM and 2.7 μmol/g wet wt, respectively, under control perfusion conditions. [Ca2+](i) increased and [ATP] fell during total global ischemia. Although [Ca2+](i) exceeded the usual systolic levels of 1.7 μM within 20-25 min of ischemia and reached a steady level between 2 and 3 μM by 30-35 min, force only began to rise after 40 min. In contrast, the time required for [ATP] to fall to <10% of control levels coincided closely with the onset of contracture. Ischemia in the presence of iodoacetate, an inhibitor of glycolysis, led to a precipitous fall in [ATP] and a concomitant rise in force, both of which preceded any elevation of [Ca2+](i). Thus changes in [Ca2+](i) are neither sufficient nor necessary for the initiation of ischemic contracture. We conclude that ATP depletion is primary and that the rise in resting force reflects the formation of rigor cross bridges.
AB - When coronary perfusion is interrupted, the diastolic force generated by the myocardium first falls but eventually increases. The delayed rise in force, ischemic contracture, has been attributed either to ATP depletion or to elevation of the intracellular free calcium concentration ([Ca2+](i)). To distinguish between these possibilities, we measured [Ca2+](i) and ATP concentration ([ATP]) in ferret hearts using nuclear magnetic resonance (NMR) spectroscopy. Mean time-averaged [Ca2+](i) and [ATP] equaled 0.25 μM and 2.7 μmol/g wet wt, respectively, under control perfusion conditions. [Ca2+](i) increased and [ATP] fell during total global ischemia. Although [Ca2+](i) exceeded the usual systolic levels of 1.7 μM within 20-25 min of ischemia and reached a steady level between 2 and 3 μM by 30-35 min, force only began to rise after 40 min. In contrast, the time required for [ATP] to fall to <10% of control levels coincided closely with the onset of contracture. Ischemia in the presence of iodoacetate, an inhibitor of glycolysis, led to a precipitous fall in [ATP] and a concomitant rise in force, both of which preceded any elevation of [Ca2+](i). Thus changes in [Ca2+](i) are neither sufficient nor necessary for the initiation of ischemic contracture. We conclude that ATP depletion is primary and that the rise in resting force reflects the formation of rigor cross bridges.
KW - Calcium metabolism
KW - Glycolysis
KW - Iodoacetate
KW - Nuclear magnetic resonance spectroscopy
UR - http://www.scopus.com/inward/record.url?scp=0025141834&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025141834&partnerID=8YFLogxK
M3 - Article
C2 - 2301617
AN - SCOPUS:0025141834
VL - 258
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 1 27-1
ER -