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Norepinephrine decreases ejection fraction and downregulates sepsis‐induced elevated antiapoptotic genes in a hyperdynamic polymicrobial septic rat model
Author(s) -
Chopra Mani,
Das Padmalaya,
Golden Honey B.,
Dostal David E.,
Sharma Avadhesh C.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.961.14
Subject(s) - sepsis , ejection fraction , downregulation and upregulation , medicine , norepinephrine , apoptosis , endocrinology , anesthesia , biology , heart failure , gene , dopamine , biochemistry
The present study was conducted to elucidate the signaling cascade targets and echocardiographic alterations following NE‐infusion during sepsis. Male Sprague‐Dawley rats (350–00g) were made septic using 200mg/kg cecal inoculum, ip. Echoacardiography was performed at the baseline and 3 and 7 days post sepsis. NE was infusedfor 2 hr, before the end of 3 rd day of echocardiographic measurements. On the 7 th day, each rat was euthanized and heart tissues were harvested for isolation of RNA. The PCR reactions were performed using RT 2 profiler ™PCR array PARN‐012 on a ABI Fast 7900 using RT 2 Real‐Time™ SYBR Green PCR master mix PA‐012. Echocardiography demonstrated that ejection fraction (EF) and fractional shortening (FS) were significantly decreased as the sepsis progressed from day 1 to day 7. The NE‐infusion further deteriorated the EF in sepsis at day 7. NE failed to improve sepsis‐induced decreased FS at days 3 and 7. Super array data revealed that during sepsis TNF‐alpha and anti‐apoptotic genes (Prok2 and IL‐10) were upregulated at day 1, while Bid 3 was uppregulated at day 3 compared to the sham group. At 7 day post sepsis, CD40lg, Bid 3 and Birc1b were upregulated compared to the sham group. The echocardiography alterations demonstrated that NE exacerbates sepsis‐induced depressed EF, which was associated with the reversal sepsis‐induced elevated expression of antiapoptotic genes during hyperdynamic sepsis.