REGULATION OF MITOCHONDRIAL [NADH] BY CYTOSOLIC [CA2+] AND WORK IN TRABECULAE FROM HYPERTROPHIC AND NORMAL RAT HEARTS

Pressure overload hypertrophy has previously been shown to reduce cont ractility but paradoxically to increase O-2 consumption rates at a giv en force. Because Oz consumption rates are related to mitochondrial [N ADH] ([NADH](m)), we tested the hypothesis that with hypertrophy, cont rol of [NADH](m) may be altered. Left ventricular trabeculae were isol ated from banded and control rat hearts, and fluorescence spectroscopy was used to monitor [NADH](m) and cytosolic [Ca2+] ([Ca2+](c)). The h earts from banded rats developed hypertrophy (heart-to-body weight rat io increased from 4.1+/-0.1 to 4.9+/-0.1 mg/g) and hypertension (systo lic arterial pressure increased from 117+/-4 to 175+/-5 mm Hg). Muscle workload was increased by stepwise increases in pacing frequency (up to 2 Hz). After increased work, [NADH](m) fell and then slowly recover ed toward control levels, When work was decreased, [NADH](m) overshot control values and then slowly returned. The Ca2+-independent initial fall was larger for trabeculae from rats with hypertrophied hearts tha n from control rats (eg, 17+/-2% versus 11+/-1% when work was increase d by increasing the frequency from 0.25 to 1 Hz), At 1 Hz, average [Ca 2+](c) was approximate to 280 nmol/L, and the Ca2+-dependent [NADH](m) recovery was larger for trabeculae from rats with hypertrophied heart s (17+/-4% versus 10+/-2%) despite similar average [Ca2+](c). At stead y state after Ca2+-dependent recovery, there was no difference in [NAD H](m) (fall of 1+/-2% versus 1+/-1%). Furthermore, the Ca2+-dependent overshoot was larger for trabeculae from hypertrophied than from contr ol hearts (increase of 14+/-2% versus 9+/-2% when frequency was decrea sed from 1 to 0.25 Hz), We conclude that (1) there is initially a larg er imbalance in NADH production versus consumption rate in hypertrophy (because NADH fell more) and (2) the Ca2+-dependent recovery mechanis m is enhanced in hypertrophy (because NADH recovered and overshot more ), thus compensating for the larger imbalance.