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The study of fetal rat model of intra-amniotic isoproterenol injection induced heart dysfunction and phenotypic switch of contractile proteins.

Li Y, Fang J, Hua Y, Wang C, Mu D, Zhou K - Biomed Res Int (2014)

Bottom Line: Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults.Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate.ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, No. 20, 3rd Section, South Renmin Road, Chengdu, Sichuan 610041, China.

ABSTRACT
To establish a reliable isoproterenol induced heart dysfunction fetal rat model and understand the switches of contractile proteins, 45 pregnant rats were divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated twice, and control groups. And 18 adult rats were divided into isoproterenol-treated and control groups. H&E staining, Masson staining, and transmission electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults. Then echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks later, respectively. Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart dysfunction were opposite to adult procedure. The administration of intra-amniotic isoproterenol to fetal rats could induce heart dysfunction and the regulation of contractile proteins of fetuses was different from adult procedure.

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Hemodynamic measurements on experimental animals with ultrasound. The structure of cardiac chambers and aorta were shown in (a) and (b); representative M-mode echocardiographic image from fetal heart on E18.5 was shown in C-H along with M-mode echocardiographic image from adult heart 6 weeks after ISO injection. (c) For adult Iso, (d) for adult Con, (e) for Iso1, (f) for Iso2, (g) for Sham2, and (h) for Con. The image of Sham1 was not presented with limited space. LV, left ventricle; RV, right ventricle.
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fig1: Hemodynamic measurements on experimental animals with ultrasound. The structure of cardiac chambers and aorta were shown in (a) and (b); representative M-mode echocardiographic image from fetal heart on E18.5 was shown in C-H along with M-mode echocardiographic image from adult heart 6 weeks after ISO injection. (c) For adult Iso, (d) for adult Con, (e) for Iso1, (f) for Iso2, (g) for Sham2, and (h) for Con. The image of Sham1 was not presented with limited space. LV, left ventricle; RV, right ventricle.

Mentions: The structure of cardiac chambers and aorta are shown in Figures 1(a) and 1(b). Representative M-mode echocardiographic image from fetal animal on E18.5 after initiating ISO is shown in Figures 1(e)–1(h). Worsening of LVEFs was observed in Iso2 groups. These data were all collected under chloral hydrate anesthesia. In the subset of fetus that achieved target LVEF, there was significant exacerbation of all echocardiographic parameters of ISO injection (Table 1). Mild LV hypertrophy was observed along with a much more profound reduction in systolic and diastolic contraction and shortening fraction. Besides, worsening of LVEFs was observed in animals of adult Iso group (Figures 1(c) and 1(d) and Table 1). Moreover, the worsening LVFS, LVDD, and LVSD demonstrated that there were damages of diastolic function among ISO-treated fetal and adult rats (Table 1).


The study of fetal rat model of intra-amniotic isoproterenol injection induced heart dysfunction and phenotypic switch of contractile proteins.

Li Y, Fang J, Hua Y, Wang C, Mu D, Zhou K - Biomed Res Int (2014)

Hemodynamic measurements on experimental animals with ultrasound. The structure of cardiac chambers and aorta were shown in (a) and (b); representative M-mode echocardiographic image from fetal heart on E18.5 was shown in C-H along with M-mode echocardiographic image from adult heart 6 weeks after ISO injection. (c) For adult Iso, (d) for adult Con, (e) for Iso1, (f) for Iso2, (g) for Sham2, and (h) for Con. The image of Sham1 was not presented with limited space. LV, left ventricle; RV, right ventricle.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127273&req=5

fig1: Hemodynamic measurements on experimental animals with ultrasound. The structure of cardiac chambers and aorta were shown in (a) and (b); representative M-mode echocardiographic image from fetal heart on E18.5 was shown in C-H along with M-mode echocardiographic image from adult heart 6 weeks after ISO injection. (c) For adult Iso, (d) for adult Con, (e) for Iso1, (f) for Iso2, (g) for Sham2, and (h) for Con. The image of Sham1 was not presented with limited space. LV, left ventricle; RV, right ventricle.
Mentions: The structure of cardiac chambers and aorta are shown in Figures 1(a) and 1(b). Representative M-mode echocardiographic image from fetal animal on E18.5 after initiating ISO is shown in Figures 1(e)–1(h). Worsening of LVEFs was observed in Iso2 groups. These data were all collected under chloral hydrate anesthesia. In the subset of fetus that achieved target LVEF, there was significant exacerbation of all echocardiographic parameters of ISO injection (Table 1). Mild LV hypertrophy was observed along with a much more profound reduction in systolic and diastolic contraction and shortening fraction. Besides, worsening of LVEFs was observed in animals of adult Iso group (Figures 1(c) and 1(d) and Table 1). Moreover, the worsening LVFS, LVDD, and LVSD demonstrated that there were damages of diastolic function among ISO-treated fetal and adult rats (Table 1).

Bottom Line: Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults.Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate.ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, No. 20, 3rd Section, South Renmin Road, Chengdu, Sichuan 610041, China.

ABSTRACT
To establish a reliable isoproterenol induced heart dysfunction fetal rat model and understand the switches of contractile proteins, 45 pregnant rats were divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated twice, and control groups. And 18 adult rats were divided into isoproterenol-treated and control groups. H&E staining, Masson staining, and transmission electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults. Then echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks later, respectively. Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart dysfunction were opposite to adult procedure. The administration of intra-amniotic isoproterenol to fetal rats could induce heart dysfunction and the regulation of contractile proteins of fetuses was different from adult procedure.

Show MeSH
Related in: MedlinePlus