Silencing of caspase‐3 stabilizes electrical stimulation‐induced deformation in isolated septic cardiomyoctes

Abstract

We hypothesized that the transfection of adult rat ventricular myocytes (ARVM) with caspase-3 siRNA would restore sepsis-induced decrease in time of deformation (TDEF) following continuous electrical stimulation. Male Sprague-Dawley rats (350–400g) were randomized into sham, 1, 3 and 7 day sepsis groups. Sepsis and sham-sepsis was induced using 200 mg/kg cecal inoculum and 5% sterile dextrose water i.p., respectively. Isolated ARVMs were subjected to 5.0 Hz continuous stimulation and the mechanical properties and TDEF (cutoff time 300s) were recorded. A progressive decrease in TDEF from day 1 to 7 was observed in septic ARVMs. Striking morphological alterations (deformed edges) were observed in NE-treated septic ARVMs, along with a decrease in TDEF. Basal length of 7 days septic ARVM exhibited a significant decrease compared to sham, 1 day sepsis and 7 day sepsis groups. Caspase-3 siRNA transfected septic ARVMs exhibited a significant increase in TDEF. The data suggested that caspase-3 silencing stabilized septic ARVM following continuous electric stimulation. We concluded that caspase-3 plays a pivotal role in sepsis-induced ARVM contractility alterations.