Kuznetsov 2004 Am J Physiol Heart Circ Physiol

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Kuznetsov AV, Schneeberger S, Seiler R, Brandacher G, Mark W, Steurer W, Saks V, Usson Y, Margreiter R, Gnaiger E (2004) Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion. Am J Physiol Heart Circ Physiol 286:H1633–41.

» PMID: 14693685 Open Access

Kuznetsov AV, Schneeberger S, Seiler R, Brandacher G, Mark W, Steurer W, Saks V, Usson Y, Margreiter R, Gnaiger E (2004) Am J Physiol Heart Circ Physiol

Abstract: Mitochondria play a critical role in myocardial cold ischemia-reperfusion (CIR) and induction of apoptosis. The nature and extent of mitochondrial defects and cytochrome c (Cyt c) release were determined by high-resolution respirometry in permeabilized myocardial fibers. CIR in a rat heart transplant model resulted in variable contractile performance, correlating with the decline of ADP-stimulated respiration. Respiration with succinate or N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (substrates for Complexes II and IV) was partially restored by added Cyt c, indicating Cyt c release. In contrast, NADH-linked respiration (glutamate&malate) was not stimulated by Cyt c, owing to a specific defect of Complex I. CIR but not cold ischemia alone resulted in the loss of NADH-linked respiratory capacity, uncoupling of oxidative phosphorylation and Cyt c release. Mitochondria depleted of Cyt c by controlled hypoosmotic shock provided a kinetic model of homogenous Cyt c depletion. Comparison to Cyt c control of respiration in CIR-injured myocardial fibers indicated heterogeneity of Cyt c release. The Complex I defect and uncoupling correlated with heterogeneous Cyt c release, the extent of which increased with loss of cardiac performance. These results demonstrate a complex pattern of multiple mitochondrial damage as determinants of CIR injury of the heart.

Keywords: Heart preservation, Complex I injury, Permeabilized myocardial fibers

O2k-Network Lab: AT Innsbruck Gnaiger E, EE Tallinn Saks VA, FR Grenoble Saks VA, AT Innsbruck Oroboros, EE Tallinn Kaambre T


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mt-Medicine 

Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Heart  Preparation: Intact organ, Permeabilized tissue, SMP, Enzyme  Enzyme: Marker enzyme  Regulation: Coupling efficiency;uncoupling, Cyt c, Flux control, Threshold;excess capacity  Coupling state: LEAK, OXPHOS  Pathway: N, S, CIV, ROX  HRR: Oxygraph-2k