Formoterol in the treatment of experimental cancer cachexia: effects on heart function

Abstract

Background and aims: Formoterol is a highly potent β2-adrenoceptor-selective agonist, which is a muscle growth promoter in many animal species, resulting in skeletal muscle hypertrophy. Previous studies carried out in our laboratory have shown that formoterol treatment in tumour-bearing animals resulted in an amelioration of muscle loss through different mechanisms that include muscle apoptosis and proteolysis.

Methods: The study presented involved rats bearing the Yoshida AH-130 ascites tumour model-which induces a high degree of cachexia-treated with the beta-2 agonist formoterol (0.3 mg/kg BW).

Results: The administration of formoterol to cachectic tumour-bearing rats resulted in a significant reduction of muscle weight loss. The treatment also increased lean body mass and body water. The treatment, however, did not influence heart weight, which was much decreased as a result of tumour burden. Untreated tumour-bearing rats showed important changes in parameters related with heart function:, left ventricle (LV) ejection fraction, fractional shortening, LV diameter and volume (diastolic) and LV stroke volume, LV mass and posterior wall thickness (PWT) (both systolic and diastolic). The administration of formoterol affected LV diameter and volume, LV stroke volume and LV mass.

Conclusions: The results suggest that formoterol treatment, in addition to reducing muscle wasting, does not negatively alter heart function-in fact, some cardiac parameters are improved-in animals affected by cancer cachexia.

Fig. 1

Body composition in tumour-bearing rats. Results are expressed as the difference between day 0 (tumour inoculation) and day 8; mean ± SEM. C control rats, C + F control rats treated with formoterol, T tumour-bearing rats, T + F tumour-bearing rats treated with formoterol. Statistical significance of the results by two-way analysis of variance (ANOVA). Statistically significant differences by post hoc Duncan test. Different letters in superscript indicate significant differences between groups

Fig. 2

Skeletal muscles and heart weights in tumour-bearing rats. Results are mean ± SEM. Muscle weights are expressed as mg/100 g of initial body weight (IBW). C control rats, C + F control rats treated with formoterol, T tumour-bearing rats, T + F tumour-bearing rats treated with formoterol. Statistical significance of the results by two-way analysis of variance (ANOVA). Statistically significant differences by post hoc Duncan test. Different letters in superscript indicate significant differences between groups