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

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). Our aim was to evaluate the course of unloading-induced cardiac atrophy in rats with failing hearts, and to examine if increased isovolumic loading obtained by intraventricular implantation of an especially designed spring expander would attenuate this process. Heterotopic abdominal heart transplantation (HTx) was used as a rat model of heart unloading. HF was induced by volume overload achieved by creation of the aorto-caval fistula (ACF). The degree of cardiac atrophy was assessed as the weight ratio of the heterotopically transplanted heart (HW) to the control heart. Isovolumic loading was increased by intraventricular implantation of a stainless steel three-branch spring expander. The course of cardiac atrophy was evaluated on days 7, 14, 21, and 28 after HTx Seven days unloading by HTx in failing hearts sufficed to substantially decrease the HW (-59 ± 3%), the decrease progressed when measured on days 14, 21, and 28 after HTx Implantation of the spring expander significantly reduced the decreases in whole HW at all the time points (-39 ± 3 compared with -59 ± 3, -52 ± 2 compared with -69 ± 3, -51 ± 2 compared with -71 ± 2, and -44 ± 2 compared with -71 ± 3%, respectively; P<0.05 in each case). We conclude that the enhanced isovolumic heart loading obtained by implantation of the spring expander attenuates the development of unloading-induced cardiac atrophy in the failing rat heart.

• Keywords
• Cardiac atrophy, heart failure, heterotopic heart transplantation, mechanical heart unloading, spring expander,
• MeSH
• Aorta surgery   MeSH
• Atrial Natriuretic Factor genetics   metabolism   MeSH
• Atrophy metabolism   physiopathology   prevention & control   surgery   MeSH
• Biomarkers metabolism   MeSH
• Equipment Design MeSH
• Implants, Experimental MeSH
• Gene Expression MeSH
• Fibroblast Growth Factor 2 genetics   metabolism   MeSH
• Transplantation, Heterotopic MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Fistula MeSH
• Rats, Inbred Lew MeSH
• Glucose Transporter Type 1 genetics   metabolism   MeSH
• Sarcoplasmic Reticulum Calcium-Transporting ATPases genetics   metabolism   MeSH
• Heart physiopathology   MeSH
• Heart Ventricles physiopathology   surgery   MeSH
• Heart Failure metabolism   physiopathology   surgery   therapy   MeSH
• Tissue Expansion Devices * MeSH
• Heart Transplantation * MeSH
• Vena Cava, Superior surgery   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Atp2a1 protein, rat MeSH Browser
• Atrial Natriuretic Factor MeSH
• Biomarkers MeSH
• Fibroblast Growth Factor 2 MeSH
• Glucose Transporter Type 1 MeSH
• Sarcoplasmic Reticulum Calcium-Transporting ATPases MeSH
• Slc2a1 protein, rat MeSH Browser