In situ mitochondrial function in volume overload- and pressure overload-induced cardiac hypertrophy in rats.

Objectives: Little comparative information is available on mitochondrial function changes during experimentally-induced hypertrophy. Respiratory control mechanisms are not exactly the same in situ and in isolated mitochondria. This study assessed in situ mitochondrial function in two myocardial hypertrophy models.

Methods: Cytochrome aa3 (Cytaa3) and myoglobin (Mb) absorption changes were monitored in isolated rat hearts using dual wavelength spectrophotometry (Cytaa3: 605-630 nm, Mb: 581-592 nm). Hypertrophy was induced by creation of an aortic stenosis or of an aorto-caval fistula. Optical monitoring was performed on diastole-arrested perfused hearts using the sequence O2 perfusion, N2 perfusion during 4 min, and reoxygenation. The plateaus of the Cytaa3 and Mb curves were used to quantify oxidation-reduction and oxygenation levels. Respiratory kinetics were characterized by the slopes of transition phase curves.

Results: Myoglobin oxygenation was comparable in the hypertrophied and control hearts. However, Cytaa3 oxidation-reduction levels in the hypertrophied hearts showed a shift towards greater reduction in comparison with the controls (controls: 0.580 +/- 0.008 DO605/DO630 nm, n = 34; fistula: 0.530 +/- 0.023, n = 23; stenosis: 0.522 +/- 0.016, n = 20, p < 0.001). The rate of Cytaa3 reduction and the rate of myoglobin deoxygenation were significantly accelerated (p < 0.005) in the volume overload group (0.507 +/- 0.043, n = 23), whereas the respiratory rate in the pressure overload group (0.389 +/- 0.034, n = 20) was comparable to that in the control hearts (0.358 +/- 0.026 delta DO 605 nm/DO630 nm.min-1, n = 34).

Conclusion: We found mitochondrial function alterations in both volume overload- and pressure overload-induced cardiac hypertrophy, despite adequate cytosol oxygenation. The patterns of these alterations differed: the redox state showed a shift of similar magnitude toward greater reduction in both models, but the respiratory rate was increased in the volume-overloaded hearts and unchanged in the pressure-overloaded hearts. The modification in the oxidation-reduction state suggested that overload hypertrophy may induce changes in the metabolism of the myocardium, which may, in turn, load to persistent modifications in mitochondrial function. The differences between the two models suggest that adaptation to hypertrophy-inducing events exists at the level of the mitochondrion.