Nejvíce citovaný článek - PubMed ID 24779607
Ventricular assist devices in heart failure: how to support the heart but prevent atrophy?
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
- atrofie * MeSH
- estradiol krev MeSH
- heterotopická transplantace * MeSH
- krysa rodu Rattus MeSH
- pohlavní dimorfismus * MeSH
- pohlavní steroidní hormony * krev MeSH
- potkani Wistar MeSH
- srdce MeSH
- testosteron krev MeSH
- transplantace srdce * škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- estradiol MeSH
- pohlavní steroidní hormony * MeSH
- testosteron 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
- atrofie patologie MeSH
- krysa rodu Rattus MeSH
- myokard patologie MeSH
- pohlavní steroidní hormony MeSH
- srdce * MeSH
- srdeční komory patologie MeSH
- transplantace srdce * škodlivé účinky metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- pohlavní steroidní hormony 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.
- Klíčová slova
- Cardiac atrophy, heart failure, heterotopic heart transplantation, mechanical heart unloading, spring expander,
- MeSH
- aorta chirurgie MeSH
- atriální natriuretický faktor genetika metabolismus MeSH
- atrofie metabolismus patofyziologie prevence a kontrola chirurgie MeSH
- biologické markery metabolismus MeSH
- design vybavení MeSH
- experimentální implantáty MeSH
- exprese genu MeSH
- fibroblastový růstový faktor 2 genetika metabolismus MeSH
- heterotopická transplantace MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- píštěle MeSH
- potkani inbrední LEW MeSH
- přenašeč glukosy typ 1 genetika metabolismus MeSH
- sarkoplazmatická Ca2+-ATPáza genetika metabolismus MeSH
- srdce patofyziologie MeSH
- srdeční komory patofyziologie chirurgie MeSH
- srdeční selhání metabolismus patofyziologie chirurgie terapie MeSH
- tkáňové expandéry * MeSH
- transplantace srdce * MeSH
- vena cava superior chirurgie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Atp2a1 protein, rat MeSH Prohlížeč
- atriální natriuretický faktor MeSH
- biologické markery MeSH
- fibroblastový růstový faktor 2 MeSH
- přenašeč glukosy typ 1 MeSH
- sarkoplazmatická Ca2+-ATPáza MeSH
- Slc2a1 protein, rat MeSH Prohlížeč