Development Of Therapeutic Strategies For Takotsubo Syndrome: Insights From A Rat Model

Introduction: Takotsubo syndrome (TS) results from an aberrant response to stimulation of myocardial NOS-coupled β2-adrenoceptors, occurring most commonly in the ageing female heart. TS is also associated with myocardial inflammation, with biochemical and immunohistochemical evidence of nitrosative stress and resultant activation of the energy-depleting enzyme poly(ADP-ribose) polymerase (PARP-1). Clinically, the main problems associated with TS are (i) impaired LV systolic function, which resolves slowly and (ii) risk of arrhythmic death, particularly in the early course of TS. Hypothesis: In the current study, we sought to compare the effects on mortality and short term LV systolic dysfunction of two interventions affecting the signal transduction pathway initiated by aberrant β2-adrenoceptor stimulation. Nω-Nitro-L-arginine methyl ester hydrochloride (LNAME) inhibits β2-adrenoceptor-coupled NOS stimulation, while 3-aminobenzamide (3AB) limits activation of PARP-1 secondary to nitrosative stress. Method...