Protein synthesis is increased in heart failure induced by low dose adriamycin in rabbits.
Congestive heart failure was induced in rabbits by a chronic treatment with a low dose of adriamycin (0.75 mg/kg intravenously 3 times per week for 11 weeks). Twenty-four to 48 h after the last injection, adriamycin-treated rabbits had a three-fold increase in plasma norepinephrine, a seven-fold increase in plasma epinephrine, a 19 +/- 8% increase in heart rate, and a 54 +/- 10% decrease in the total tension generated by their isolated papillary muscles, when compared with normal age-matched controls. This demonstrated the occurrence of the cardiomyopathy and heart failure. The effect of adriamycin on myocardial and diaphragmatic protein synthesis was examined in vivo after a 1-h infusion with [3H]leucine and in vitro after a 2-h incubation of right ventricular papillary muscle with [3H]leucine. The rate of in vivo [3H]leucine incorporation into total protein was increased in the heart of the adriamycin-treated rabbits. The increases were 60 +/- 16% in the left ventricle, 49 +/- 18% in the septum, 32 +/- 18% in the right ventricle, and 66 +/- 16% in the atria. A similar increase was observed when measuring the rate of [3H]leucine incorporation into myosin, a myofibrillar protein, and when the rate of [3H]leucine incorporation into total protein was measured in vitro in papillary muscle. In contrast, the rate of [3H]leucine incorporation into total protein of the diaphragm was not significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS)
Paradis
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Centre de recherche, Hôpital du Sacré-Coeur, Montréal, Québec, Canada.
Rouleau
J L
JL
Shenasa
H
H
Brakier-Gingras
L
L
D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007930:Leucine / Q000378:metabolism; D008297:Male; D009218:Myosins / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects; D014176:Protein Biosynthesis; D011817:Rabbits
D004317:Doxorubicin; D009218:Myosins; D007930:Leucine