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Reduced cardiac output is associated with decreased mitochondrial efficiency in the non-ischemic ventricular wall of the acute myocardial-infarcted dog

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Cell Research 2006年第03期16卷 297-305页

作者： Zakaria A Almsherqi Malgorzata B Slocinska Yuru Deng Department of Physiology,National University of Singapore,Block MD9,2 Medical Drive,Singapore 117597,Singapore Craig S McLachlan Peter Mossop Department of Medical Imaging,St Vincents Hospital,Melbourne,Fitzroy VIC 3065,Australia Francis E Sluse Rachel Navet Laboratory of Bioenergetics,Institute of Chemistry B6,University of Liége,Start Tilman,B-4000 Liége,Belgium Nikolai Kocherginsky Iouri Kostetski Biophysics Laboratory,Division of Bioengineering,National University of Singapore,Singapore 117576,Singapore Dong-Yun Shi Shan-Lin Liu Department of Biochemistry,Shanghai Medical College of Fudan University,Free Radical Regulation Research Center of Fudan University,Shanghai 200032,China DepartmentofPhysiology NationalUniversityofSingaporeBlockMD92MedicalDriveSingapore117597Singapore departmentofmedicallmaging StVincentsHospitalMelbourneFitzroyVIC3065Australia

Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction (MI).Understanding the mechanisms for acute pump failure is therefore *** aim of this study is to examine in anacute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated withpump *** MI was produced in dogs via ligation of left anterior descending (LAD) coronary artery,thatresulted in an infract size of about 30% of the left ventricular *** of hemodynamic status,mitochondrialfunction,free radical production and mitochondrial uncoupling protein 3 (UCP3) expression were determined over 24h *** measurements revealed a>50% reduction in cardiac output at 24 h post infarction when com-pared to *** samples were obtained from the posterior non-ischemic wall during acute ***/Oratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to theADP/O ratios within the same samples with and without palmitic acid (PA).GTP inhibition of (PA)-stimulated state 4respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarctionrespectively when compared to sham and pre-infarction *** would suggest that the mitochondria are uncoupledand this is supported by an associated increase in UCP3 expression observed on western blots from these same *** samples from the coronary sinus measured by electron paramagnetic resonance (EPR) methods showedan increase in reactive oxygen species (ROS) over baseline at 6 h and 24 h *** conclusion,mitochondrialbio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic *** ap-pear to be energetically uncoupled and this is associated with declining pump *** radical production may beassociated with the induction of uncoupling prot

关键词： mitochondria uncoupling proteins bioenergetics infarction cardiogenic shock non-ischemic ventricle

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