Attenuation of postischemic reperfusion injury is related to prevention of [Ca2+]m overload in rat hearts
Miyamae, M.; Camacho, S.A.; Weiner, M.W.; Figueredo, V.M.
American Journal of Physiology 271(5 Pt 2): H2145-H2153
1996
ISSN/ISBN: 0002-9513 PMID: 8945935 Document Number: 467995
Intracellular calcium overload has been implicated in postischemic reperfusion injury. In myocytes, mitochondrial free calcium concentration ((Ca-2+)-m), not cytosolic free calcium concentration ((Ca-2-)-c), overload is related to reoxygenation injury. We tested the hypothesis that (Ca-2+)-m, not (Ca-2+)-c, overload is an important mediator of reperfusion injury in whole hearts. (Ca-2+)-m and (Ca-2+)-c were assessed using indo 1 fluorescence in isolated rat hearts subjected to 45 min of ischemia and 20 min of reperfusion. Ruthenium red (RR), a selective inhibitor of mitochondrial calcium uptake at 0.025 mu-M, attenuated the increase of (Ca-2+)-m (4% RR vs. 57% control) over preischemic levels (230 +- 10 nM) but did not affect the increase of systolic (Ca-2+)-c (990 +- 100 nM RR vs. 1,010 +- 130 nM control). This was associated with improved recovery of left ventricular developed pressure (6 1% RR vs. 37% control) and attenuation of the increase of diastolic pressure (34 mmHg RR vs. 47 mmHg control). Contractile recovery was related to the degree of (Ca-2+)-m overload in both control and RR hearts (r-2 = 0.47, P = 0.001). This study is the first to demonstrate that (Ca-2+)-m, and not (Ca-2+)-c, overload is related to reperfusion injury in intact beating hearts.