Skeletal muscle abnormalities in rats with experimentally induced heart hypertrophy and failure.
BACKGROUND
In congestive heart failure (CHF), function and metabolism of skeletal muscles are abnormal.


OBJECTIVE
To evaluate whether the reduced oxidative capacity of skeletal muscles in CHF is due to impaired O(2) utilisation.


METHODS
CHF was induced in rats by injecting 50 mg/Kg monocrotaline. Several animals received the same dose of monocrotaline but only compensated right ventricular hypertrophy and no sign of congestion resulted. Two age- and diet-matched groups of control animals were also studied. In soleus and extensor digitorum longus (EDL) muscles, we studied skeletal muscle blood flow, oxidative capacity and respiratory function of skinned muscle fibres.


RESULTS
In CHF, we observed a decrease of muscle blood flow (statistically significant in the soleus, p < 0.05 vs. controls). In compensated rats, a similar trend in blood flow was observed. In both soleus and EDL, a significant reduction of high energy phosphate and a shift of the redox potential towards accumulation of reducing equivalents were observed. The reduction of energy charge was not correlated to the decrease of blood flow. In skinned myofibres, the ratio of O(2) utilised in the presence and in absence of ADP (an index of phoshorilating efficiency) was reduced from 8.9 +/- 1.9 to 2.7 +/- 0.2 (p < 0.001) and from 5.7 +/- 1.0 to 2.0 +/- 0.3 (p < 0.01) in soleus and EDL, respectively. Activity of the different complexes of respiratory chain was investigated by means of specific inhibitors, showing major abnormalities at the level of complex I. In fact, inhibition of VO(2) by rotenone was decreased from 83.5 +/- 3.2 to 36.4 +/- 9.6 % (p < 0.005) and from 81.8 +/- 6.1 to 38.2 +/- 7.4 % (p < 0.005) in soleus and EDL, respectively.


CONCLUSIONS
In rats with CHF, abnormalities of oxidative phosphorylation of muscles occur and complex I of the respiratory chain seem to be primarily affected. The metabolic alterations of skeletal muscles in CHF may be explained, at least in part, by an impaired O(2) utilisation.
Bernocchi
Palmira
P
Cardiovascular Research Centre, Fondazione S. Maugeri, IRCCS, 25064 Gussago (Brescia), Italy.
Cargnoni
Anna
A
Vescovo
Giorgio
G
Dalla Libera
Luciano
L
Parrinello
Giovanni
G
Boraso
Antonella
A
Ceconi
Claudio
C
Ferrari
Roberto
R
D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000139:chemically induced / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology; D016686:Monocrotaline / Q000633:toxicity; D018482:Muscle, Skeletal / Q000098:blood supply / Q000503:physiopathology*; D010085:Oxidative Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D016686:Monocrotaline