MiP2005: Session 8

Mitochondrial Physiology Network 10.9: 98-99 (2005) - download pdf

 

Inhibition of electron transport during ischemia prevents mitochondrial ischemic damage and protects the heart.

Q Chen, Charles L Hoppel, EJ Lesnefsky

Case Western Reserve Univ. and Louis Stokes VA Medical Center, Cleveland, OH, USA. - clh5@cwru.edu

    Mitochondrial dysfunction contributes to myocardial injury during ischemia (ISC) and reperfusion (REP). ISC damages the electron transport chain leading to a decrease in the rate of oxidative phosphorylation (OXPHOS). Reversible blockade of electron transport with amytal immediately before ISC attenuates ischemic damage to OXPHOS. We proposed that protection of OXPHOS during ISC will preserve OXPHOS and decrease myocardial damage during REP.

    Langendorff perfused rat hearts were treated with amytal (2.5 mM bolus for 1 min immediately before ISC) or vehicle and underwent 25 min global ISC (37 C) and 30 min REP without additional treatment. Subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria were isolated at end of REP to measure OXPHOS with glutamate as substrate. Left ventricular developed pressure (LVDP), diastolic pressure (DP) and lactate dehydrogenase (LDH) release were measured. Amytal pretreatment protected OXPHOS in SSM and IFM following ISC-REP with preserved state 3 and the decreased state 4 rates leading to improved respiratory control ratio (RCR). Amytal also prevented ischemic contracture (DP-ISC) and improved functional recovery during REP with increased left ventricular developed pressure (LVDP-REP) and decreased diastolic pressure (DP-REP). Amytal attenuated LDH release during REP and myocardial infarct size, indicating decreased myocyte cell death. Thus, reversible blockade of electron transport during ISC preserves mitochondrial OXPHOS and mitigates myocardial damage during REP.

 

OXPHOS during REP [nAO∙min-1∙mg-1]<o:p></o:p>

SSM<o:p></o:p>

State 3<o:p></o:p>

SSM<o:p></o:p>

State 4<o:p></o:p>

SSM<o:p></o:p>

RCR<o:p></o:p>

IFM<o:p></o:p>

State 3<o:p></o:p>

IFM<o:p></o:p>

State 4<o:p></o:p>

IFM<o:p></o:p>

RCR<o:p></o:p>

ISC-Rep (n=12)<o:p></o:p>

122 6<o:p></o:p>

57 4<o:p></o:p>

2.3 0.2<o:p></o:p>

173 10<o:p></o:p>

74 5<o:p></o:p>

2.5 0.2<o:p></o:p>

Amytal+ISC-Rep (n=11)<o:p></o:p>

172 9*<o:p></o:p>

35 4*<o:p></o:p>

5.4 0.5*<o:p></o:p>

274 17*<o:p></o:p>

43 3*<o:p></o:p>

6.6 0.6*<o:p></o:p>

Cardiac function <o:p></o:p>

DP-ISC

[mmHg]<o:p></o:p>

LVDP-REP

[mmHg]<o:p></o:p>

DP-REP

[mmHg]<o:p></o:p>

LDH

[mU∙min-1∙g-1]<o:p></o:p>

ISC-REP (n=12)<o:p></o:p>

54 6<o:p></o:p>

57 4<o:p></o:p>

37 4<o:p></o:p>

427 60  (n=11)<o:p></o:p>

Amytal+ISC-REP (n=11)<o:p></o:p>

  5 1*<o:p></o:p>

79 5*<o:p></o:p>

  2 1*<o:p></o:p>

273 28* (n=9)<o:p></o:p>

Mean SEM.  * P<0.05 vs. ISC+REP


to topPrint page

 
 

Mitochondrial Physiology