Cardiac atrophy is the most common complication of prolonged application of the left ventricle (LV) assist device (LVAD) in patients with advanced heart failure (HF), obviously, it is a consequence of LVAD-induced mechanical unloading. Previous studies employing heterotopic heart transplantation (HTx) as a model of heart unloading after LVAD implantation discovered sex-linked differences in the course of unloading-induced in the healthy hearts. It remains to be clarified if sex-related differences are present in the failing hearts after heterotopic HTx. Therefore, we first compared the course of unloading-induced cardiac atrophy in the failing hearts in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to explore the influence of sex hormones on this process. Second, we examined if the animal's sex modifies the effects of increased isovolumic loading of the LV on the course of unloading-induced cardiac atrophy. Heterotopic abdominal heart transplantation (HTx) was used as a rat model of heart unloading. HF was induced by volume overload achieved by creation of aorto-caval fistula. Increased isovolumic loading was obtained by implantation of specially designed three-branch spring expander into the LV. The degree of cardiac atrophy was assessed as the whole heart weight (HW) ratio of the heterotopically transplanted to the native control heart. We found that decreases in HW after HTx were similar in intact male and female rats, similarly in intact and gonadectomized animals. Implantation of the expander significantly and comparably reduced decreases in HW in male and in female rats. We conclude that there are no sex-linked differences in the development of unloading-induced cardiac atrophy in the failing hearts. Our results also show that enhanced isovolumic heart loading obtained using the spring expander attenuates the development of unloading-induced cardiac atrophy in the failing hearts; the degree of attenuation is similar in both sexes. Key words Heart failure " Cardiac atrophy " Sex differences " Heterotopic heart transplantation " Mechanical heart unloading.

• MeSH
• Atrophy MeSH
• Transplantation, Heterotopic * adverse effects   MeSH
• Rats MeSH
• Myocardium * pathology   MeSH
• Heart-Assist Devices * adverse effects   MeSH
• Sex Characteristics * MeSH
• Rats, Wistar MeSH
• Sex Factors MeSH
• Heart Failure * pathology   physiopathology   surgery   MeSH
• Heart Transplantation * adverse effects   methods   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

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.

• MeSH
• Atrophy * MeSH
• Estradiol blood   MeSH
• Transplantation, Heterotopic * MeSH
• Rats MeSH
• Sex Characteristics * MeSH
• Gonadal Steroid Hormones * blood   MeSH
• Rats, Wistar MeSH
• Heart MeSH
• Testosterone blood   MeSH
• Heart Transplantation * adverse effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Estradiol MeSH
• Gonadal Steroid Hormones * MeSH
• Testosterone MeSH

No information is available about sex-related differences in unloading-induced cardiac atrophy. We aimed to compare the course of unloading-induced cardiac atrophy in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to obtain insight into the influence of sex hormones on this process. Heterotopic heart transplantation (HT((x)) was used as a model for heart unloading. Cardiac atrophy was assessed as the weight ratio of heterotopically transplanted heart weight (HW) to the native HW on days 7 and 14 after HTx in intact male and female rats. In separate experimental groups, gonadectomy was performed in male and female recipient animals 28 days before HT(x) and the course of cardiac atrophy was again evaluated on days 7 and 14 after HT(x). In intact male rats, HT(x) resulted in significantly greater decreases in whole HW when compared to intact female rats. The dynamics of the left ventricle (LV) and right ventricle (RV) atrophy after HT(x) was quite similar to that of whole hearts. Gonadectomy did not have any significant effect on the decreases in whole HW, LV, and RV weights, with similar results in male and female rats. Our results show that the development of unloading-induced cardiac atrophy is substantially reduced in female rats when compared to male rats. Since gonadectomy did not alter the course of cardiac atrophy after HTx, similarly in both male and female rats, we conclude that sex-linked differences in the development of unloading-induced cardiac atrophy are not caused by the activity of sex hormones.

• MeSH
• Atrophy pathology   MeSH
• Rats MeSH
• Myocardium pathology   MeSH
• Gonadal Steroid Hormones MeSH
• Heart * MeSH
• Heart Ventricles pathology   MeSH
• Heart Transplantation * adverse effects   methods   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Gonadal Steroid Hormones MeSH

Doxorubicin's (DOX) cardiotoxicity contributes to the development of chemotherapy-induced heart failure (HF) and new treatment strategies are in high demand. The aim of the present study was to characterize a DOX-induced model of HF in Ren-2 transgenic rats (TGR), those characterized by hypertension and hyperactivity of the renin-angiotensin-aldosterone system, and to compare the results with normotensive transgene-negative, Hannover Sprague-Dawley (HanSD) rats. DOX was administered for two weeks in a cumulative dose of 15 mg/kg. In HanSD rats DOX administration resulted in the development of an early phase of HF with the dominant symptom of bilateral cardiac atrophy demonstrable two weeks after the last DOX injection. In TGR, DOX caused substantial impairment of systolic function already at the end of the treatment, with further progression observed throughout the experiment. Additionally, two weeks after the termination of DOX treatment, TGR exhibited signs of HF characteristic for the transition stage between the compensated and decompensated phases of HF. In conclusion, we suggest that DOX-induced HF in TGR is a suitable model to study the pathophysiological aspects of chemotherapy-induced HF and to evaluate novel therapeutic strategies to combat this form of HF, which are urgently needed.

• Keywords
• chemotherapy-induced heart failure, doxorubicin, hypertension, renin-angiotensin-aldosterone system,
• MeSH
• Doxorubicin toxicity   MeSH
• Cardiotoxicity MeSH
• Blood Pressure * MeSH
• Rats MeSH
• Rats, Sprague-Dawley MeSH
• Antineoplastic Agents toxicity   MeSH
• Renin-Angiotensin System * MeSH
• Renin genetics   MeSH
• Heart Failure etiology   metabolism   physiopathology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Doxorubicin MeSH
• Antineoplastic Agents MeSH
• Renin MeSH