Norepinephrine Induces Systolic Failure and Inhibits Antiapoptotic Genes in a Polymicrobial Septic Rat Model

AIMS: We examined the effect of norepinephrine (NE) infusion on left ventricular function and apoptotic genes during progression of polymicrobial sepsis.

METHODS: Male Sprague-Dawley rats (350-400 g) were made septic by intraperitoneal (i.p.) administration of 200mg/kg cecal inoculum. Sham animals received 5% dextrose water, i.p. Echocardiography was performed at baseline, 3 days and 7 days post-sepsis/sham. NE (0.6 μgkg(-1)h(-1)) was infused for 2h, before the end of day 3 of echocardiography. At the end of day 7, rats were euthanized and heart tissues harvested for isolation of total RNA. PCR was performed using RT(2) profiler™ PCR array PARN-012 (Rat apoptosis array; SuperArray, MD) using RT(2) Real-Time™ SYBR Green PCR master mix PA-012.

KEY FINDINGS: NE-infusion resulted in a significant decrease in the left ventricular ejection fraction (EF) (62.56±2.07 from the baseline 71.11±3.23, p

SIGNIFICANCE: The data suggest that upregulation of a series of pro-apoptotic molecules could be responsible for systolic and diastolic dysfunction during 3 and 7 days post sepsis.