Sb. Leichtweis et al., ISCHEMIA-REPERFUSION INDUCED ALTERATIONS OF MITOCHONDRIAL-FUNCTION INHYPERTROPHIED RAT-HEART, Acta Physiologica Scandinavica, 156(1), 1996, pp. 51-60
The impact of in vivo ischaemia and ischaemia-reperfusion (I-R) on mit
ochondrial respiratory function was investigated in hypertrophied (HP)
hearts with aortic constriction compared with control hearts using an
open-chest rat surgical model. Moreover. mitochondrial susceptibility
to superoxide radicals (O-2-radical-anion) in vitro was examined in H
P and control hearts with or without I-R. With the site I substrates p
yruvate-malate. mitochondrial state 4 (basal) respiration and the resp
iratory control index (RCI) were not affected by either ischaemia alon
e or I-R in both HP and control hearts. State 3 (ADP-stimulated) respi
ration was increased with I-R in control hearts. but showed a reductio
n after I-R in the HP hearts. Exposure of mitochondria to O-2-radical-
anion (20 nM hypoxanthine in the presence of 0.13 unit mL(-1) xanthine
oxidase) significantly increased state 4 respiration. whereas state 3
respiration and RCI were decreased in all treatment groups. I-R heart
s in both HP and control showed greater increases in state 4 respirati
on with O-2-radical-anion than either sham or ischaemic hearts. HP hea
rts exhibited a significantly lesser extent of inhibition in state 3 r
espiration and RCI by O-2-radical-anion compared with control hearts.
These changes in mitochondrial respiratory properties were not observe
d with the site II substrate succinate. Myocardial reduced vs. oxidize
d glutathione ratio was significantly decreased after I-R in both cont
rol and HP hearts. Malondialdehyde content showed an increase with I-R
, but the increase was significant only in control hearts. These data
indicate that short-term in vivo I-R does not impair heart mitochondri
al respiratory function. but renders the organelles more vulnerable to
imposed oxidative stress. Mitochondria from the HP hearts are more re
sistant to free radical damage under normal and ischaemic conditions;
however. this advantage is severely compromised after reperfusion.