• Jeejabai Radhakrishnan, Sufen Wang, Iyad M Ayoub, Julieta D Kolarova, Rita F Levine, and Raúl J Gazmuri.
• Division of Critical Care Medicine, Department of Medicine, Rosalind Franklin University of Medicine and Science, and North Chicago Veterans Affairs Medical Center, North Chicago, Illinois, USA.
• Am. J. Physiol. Heart Circ. Physiol. 2007 Feb 1; 292 (2): H767-75.

AbstractCa(2+) overload and reactive oxygen species can injure mitochondria during ischemia and reperfusion. We hypothesized that mitochondrial injury occurs during cardiac resuscitation, causing release of cytochrome c to the cytosol and bloodstream while activating apoptotic pathways. Plasma cytochrome c was measured using reverse-phase HPLC and Western immunoblotting in rats subjected to 4 or 8 min of untreated ventricular fibrillation and 8 min of closed-chest resuscitation followed by 240 min of postresuscitation hemodynamic observation. A sham group served as control. Plasma cytochrome c rose progressively to levels 10-fold higher than in sham rats 240 min after resuscitation (P < 0.01), despite reversal of whole body ischemia (decreases in arterial lactate). Cytochrome c levels were inversely correlated with left ventricular stroke work (r = -0.40, P = 0.02). Western immunoblotting of left ventricular tissue demonstrated increased levels of 17-kDa cleaved caspase-3 fragments in the cytosol. Plasma cytochrome c was then serially measured in 12 resuscitated rats until the rat died or cytochrome c returned to baseline. In three survivors, cytochrome c rose slightly to

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