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.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 286 |
| Issue number | 5 55-5 |
| DOIs | |
| State | Published - May 2004 |
| Externally published | Yes |
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Keywords
- Complex I injury
- Heart preservation
- Permeabilized myocardial fibers
- Respiration
ASJC Scopus subject areas
- Physiology
Cite this
Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion. / Kuznetsov, Andrey V.; Schneeberger, Stefan; Seiler, Rüdiger; Brandacher, Gerald; Mark, Walter; Steurer, Wolfgang; Saks, Valdur; Usson, Yves; Margreiter, Raimund; Gnaiger, Erich.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 286, No. 5 55-5, 05.2004.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion
AU - Kuznetsov, Andrey V.
AU - Schneeberger, Stefan
AU - Seiler, Rüdiger
AU - Brandacher, Gerald
AU - Mark, Walter
AU - Steurer, Wolfgang
AU - Saks, Valdur
AU - Usson, Yves
AU - Margreiter, Raimund
AU - Gnaiger, Erich
PY - 2004/5
Y1 - 2004/5
N2 - 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.
AB - 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.
KW - Complex I injury
KW - Heart preservation
KW - Permeabilized myocardial fibers
KW - Respiration
UR - http://www.scopus.com/inward/record.url?scp=11144357871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=11144357871&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00701.2003
DO - 10.1152/ajpheart.00701.2003
M3 - Article
C2 - 14693685
AN - SCOPUS:11144357871
VL - 286
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 5 55-5
ER -