In spite of opposing changes in rates of
adenosine triphosphate turnover,
hypertrophy and
atrophy of the heart are accompanied by the same changes in gene expression, resembling a fetal genotype. Fetal hearts are characterized by increased
ischemia tolerance. We assessed respiratory capacity of mitochondrial subpopulations from unloaded and pressure-overloaded hearts before and after 15 minutes of normothermic
ischemia. Unloading was achieved by heterotopic rat
heart transplantation and overloading by aortic banding. Respiratory chain gene expression (
NADH dehydrogenase,
cytochrome c oxidase [COX]) were analyzed by
reverse transcriptase-polymerase chain reaction. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated by differential centrifugation.
Citrate synthase was used as mitochondrial marker
enzyme.
Adenosine diphosphate-stimulated oxygen consumption (state 3) was measured with a Clark-type
electrode. Unloading resulted in
atrophy, overloading in
hypertrophy. State 3 was reduced in atrophied hearts both in SSM and IFM (SSM: 204 +/- 79 vs 804 +/- 147 natoms
oxygen min(-1) mL(-1), P < .001; IFM: 468 +/- 158 vs 1141 +/- 296 natoms
oxygen min(-1) mL(-1), P < .05), but was unchanged in hypertrophied hearts.
NADH dehydrogenase and COX expression was also decreased with
atrophy and was unchanged with
hypertrophy.
Ischemia caused decreased recovery of
citrate synthase in isolates of SSM (P < .05) but not of IFM. State 3 in control hearts was reduced in IFM (-41%, P < .01) and SSM (-19%, not significant). This
ischemia-induced decrease was less pronounced in SSM (-2%) and IFM (-22%) of atrophied and IFM (-23%) of hypertrophied hearts. Subsarcolemmal mitochondria of hypertrophied hearts displayed the greatest
ischemia-induced decrease of state 3 (-32%, P < .05). In conclusion, (1) long-term changes in workload differentially affect maximal respiratory capacity and
ischemia tolerance of isolated mitochondria. The changes are not parallel to the changes in energy requirements. (2) Mitochondria of atrophied hearts appear to be more resistant against
ischemia than controls.