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Updated: May 6, 2026
Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique
Published on: October 12, 2014
Sex-Linked Differences in Cardiac Atrophy After Heterotopic Heart Transplantation: No Direct Relation to the Actions
D M Kolesár1, P Kujal, I Mrázová
1Dept Cardiovasc Surgery, Inst Clin Exp Med, Prague, Czech Republic. dushan.michael.kolesar@ikem.cz.
Insights
Cardiac atrophy, a complication of heart assist devices, shows significant sex differences. Female rats experience less atrophy than males, regardless of sex hormone levels, indicating complex underlying mechanisms.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Transplantation Science
Background:
- Mechanical unloading of the heart, often via assist devices, can cause cardiac atrophy.
- Sex-linked differences in atrophy development after heterotopic heart transplantation (HTX) have been suggested.
- The influence of sex hormones on unloading-induced cardiac atrophy remains unclear.
Purpose of the Study:
- To investigate sex-linked differences in unloading-induced cardiac atrophy.
- To determine the role of sex hormones in cardiac atrophy using gonadectomy and cross-sex hormonal substitution in rats.
- To compare cardiac atrophy in female hearts transplanted into males and vice versa.
Main Methods:
- Heterotopic heart transplantation (HTX) in male and female rats.
- Gonadectomy followed by cross-sex steroid hormone substitution.
- Assessment of cardiac atrophy by comparing transplanted heart weight to native heart weight (HW) 14 days post-HTX.
Main Results:
- Female rats exhibited significantly less cardiac atrophy (reduced HW) compared to male rats under identical experimental conditions (-9 to -11% vs. -42 to -44%).
- These sex differences persisted even after gonadectomy and hormonal manipulation.
- Similar patterns of atrophy were observed in both the whole heart and individual ventricles.
Conclusions:
- Unloading-induced cardiac atrophy demonstrates significant sex-linked differences.
- The protective effect observed in female rats is not solely attributable to estradiol or the absence of testosterone.
- Further research is needed to elucidate the complex mechanisms underlying sex differences in cardiac atrophy.
Abstract:
An important complication of prolonged support of the left ventricle with an assist device when implanted in patients with heart failure is unloading-induced cardiac atrophy. Our recent study suggested that sex-linked differences in the development of atrophy induced by heterotopic heart transplantation (HTX) do exist, however, the role of the environmental conditions dependent on plasma concentrations of sex hormones remains elusive. We aimed to compare the course of HTX-induced cardiac atrophy in male and female rats after gonadectomy with substitution of steroid hormones of the opposite sex. In a separate series of experiments, we evaluated the course of unloading-induced cardiac atrophy in the female heart transplanted into a male recipient and vice versa. Cardiac atrophy was assessed as the ratio of the transplanted heart weight to native heart weight (HW), which was determined 14 days after HTX. In female rats, studied in both experimental variants, HTx resulted in significantly smaller decreases in whole HW when compared to those observed in male rats exposed to the same experimental conditions (-9 ± 1 and - 11 + 1 vs. -44 ± 2 and -42 ± 2 %, p?0.05 in both cases). The dynamic of changes in left and right ventricle was similar as in the whole HW. Our results show that the process of unloading-induced cardiac atrophy exhibits important sex-linked differences and that attenuation of this process in female rats cannot be simply ascribed to the protective effects of estradiol or to the absence of deleterious actions of testosterone. Keywords: Cardiac atrophy, Sex differences, Gonadectomy, Hormonal substitution, Heterotopic heart transplantation, Mechanical heart unloading.
