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The inflammatory state provokes sexual dimorphism in left ventricular and electrocardiographic effects of chronic cyclosporine in rats

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ABSTRACT

Although cardiotoxicity has been recognized as an adverse effect of cyclosporine A (CSA), no information exists regarding sex specificity of CSA cardiotoxicity. We tested the hypothesis that left ventricular (LV) and electrocardiographic (ECG) effects of CSA and related inflammatory/histopathological derangements are sex related. CSA reduced the LV slope of end-systolic pressure volume relationship and increased isovolumic relaxation constant. These effects were more pronounced in male compared to female rats, suggesting LV systolic and diastolic dysfunction. ECG recordings showed elevated ST segments and increased QTc and T peak trend intervals in CSA-treated male rats, markers of LV ischemia and arrhythmogenesis. In female rats, CSA delayed AV conduction, as reflected by prolonged PR interval. Other sex-related effects for CSA included (i) increased blood cholesterol, and reduced rates of rise and fall in LV pressure and nuclear factor kappa B and angiotensin receptors type 1 expressions in male rats, and (ii) increased LV adiponectin in females. Histopatholgically, CSA caused vascular congestion, blood extravasation, and pyknotic or even absent nuclei in both sexes. In conclusion, rats exhibit sex-independent susceptibility to negative LV and histopathological influences of CSA. These effects become more intensified in male rats, perhaps on account of aggravated ischemic and inflammatory milieus.

No MeSH data available.


Photomicrographs (1200×, H & E) of heart sections obtained from male (M) and female (F) rats treated chronically with cyclosporine A (CSA, 15 mg/kg/day for 3 weeks, s.c.) or its vehicle.Hollow arrows point to cardiac muscle shrinkage and pyknosis. Solid arrows point to congested vascular space while circles point to extravascular blood cells between cardiac muscle.
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f5: Photomicrographs (1200×, H & E) of heart sections obtained from male (M) and female (F) rats treated chronically with cyclosporine A (CSA, 15 mg/kg/day for 3 weeks, s.c.) or its vehicle.Hollow arrows point to cardiac muscle shrinkage and pyknosis. Solid arrows point to congested vascular space while circles point to extravascular blood cells between cardiac muscle.

Mentions: CSA administration was associated with vascular congestion, blood extravasation, and a marked degeneration of cardiac muscle as indicated by the shrinkage of cardiac muscles and absence or pyknosis of cardiac muscle nuclei. These effects of CSA were demonstrated in both male and female rats (Fig. 5).


The inflammatory state provokes sexual dimorphism in left ventricular and electrocardiographic effects of chronic cyclosporine in rats
Photomicrographs (1200×, H & E) of heart sections obtained from male (M) and female (F) rats treated chronically with cyclosporine A (CSA, 15 mg/kg/day for 3 weeks, s.c.) or its vehicle.Hollow arrows point to cardiac muscle shrinkage and pyknosis. Solid arrows point to congested vascular space while circles point to extravascular blood cells between cardiac muscle.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5304161&req=5

f5: Photomicrographs (1200×, H & E) of heart sections obtained from male (M) and female (F) rats treated chronically with cyclosporine A (CSA, 15 mg/kg/day for 3 weeks, s.c.) or its vehicle.Hollow arrows point to cardiac muscle shrinkage and pyknosis. Solid arrows point to congested vascular space while circles point to extravascular blood cells between cardiac muscle.
Mentions: CSA administration was associated with vascular congestion, blood extravasation, and a marked degeneration of cardiac muscle as indicated by the shrinkage of cardiac muscles and absence or pyknosis of cardiac muscle nuclei. These effects of CSA were demonstrated in both male and female rats (Fig. 5).

View Article: PubMed Central - PubMed

ABSTRACT

Although cardiotoxicity has been recognized as an adverse effect of cyclosporine A (CSA), no information exists regarding sex specificity of CSA cardiotoxicity. We tested the hypothesis that left ventricular (LV) and electrocardiographic (ECG) effects of CSA and related inflammatory/histopathological derangements are sex related. CSA reduced the LV slope of end-systolic pressure volume relationship and increased isovolumic relaxation constant. These effects were more pronounced in male compared to female rats, suggesting LV systolic and diastolic dysfunction. ECG recordings showed elevated ST segments and increased QTc and T peak trend intervals in CSA-treated male rats, markers of LV ischemia and arrhythmogenesis. In female rats, CSA delayed AV conduction, as reflected by prolonged PR interval. Other sex-related effects for CSA included (i) increased blood cholesterol, and reduced rates of rise and fall in LV pressure and nuclear factor kappa B and angiotensin receptors type 1 expressions in male rats, and (ii) increased LV adiponectin in females. Histopatholgically, CSA caused vascular congestion, blood extravasation, and pyknotic or even absent nuclei in both sexes. In conclusion, rats exhibit sex-independent susceptibility to negative LV and histopathological influences of CSA. These effects become more intensified in male rats, perhaps on account of aggravated ischemic and inflammatory milieus.

No MeSH data available.