Attenuation of postischemic reperfusion injury is related to
prevention of mitochondrial ca2+ overload in rat hearts.
Miyamae, Masami, S. Albert Camacho, Michael W. Weiner, and Vincent M.
Figueredo.
Department of Medicine (Cardiology), San Francisco General Hospital
and Magnetic Resonance Unit, Department Veterans Affairs Medical
Center, University of California, San Francisco, California,
94110
APStracts 3:0236H, 1996.
Intracellular calcium overload has been implicated in postischemic
reperfusion injury. In myocytes, mitochondrial free calcium
([Ca2+]m), not cytosolic free calcium ([Ca2+]c), overload is related
to reoxygenation injury. We tested the hypothesis that [Ca2+]m, not
[Ca2+]c, overload is an important mediator of reperfusion injury in
whole hearts. [Ca2+]m and [Ca2+]c were assessed using indo-1
fluorescence in isolated rat hearts subjected to 45 minutes ischemia
and 20 minutes reperfusion. Ruthenium red (RR), a selective inhibitor
of mitochondrial Ca2+ uptake at 0.025 [mu]M, attenuated the increase
of [Ca2+]m (4% RR versus 57% Control) over pre-ischemic levels
(230+/-10 nM), but did not affect the increase of systolic [Ca2+]c
(990+/-100 nM RR versus 1010+/-130 nM Control). This was associated
with improved recovery of left ventricular developed pressure (61% RR
versus 37% Control) and attenuation of the increase of diastolic
pressure (34 mmHg RR versus 47 mmHg Control). Contractile recovery
was related to the degree of [Ca2+]m overload in both Control and RR
(r2=0.47, p=0.001). This study is the first to demonstrate that
[Ca2+]m, and not [Ca2+]c, overload is related to reperfusion injury
in intact beating hearts.
Received 1 February 1996; accepted in final form 16 May 1996.
APS Manuscript Number H94-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96