Impaired Function in Rats Following Delayed Reversal of Volume Overload Heart Failure is Rescued by Levosimendan

Objectives. This study investigated if delayed surgical intervention in rats with aortocaval fistula (ACF)-induced volume overload HF adversely impacts LV functional recovery and if pre or post-surgical treatment with levosimendan (Levo, myofilament Ca2+ sensitizer) alters LV recovery. Methods and Results. ACF or Sham surgery was performed in male Sprague-Dawley rats (200-240 g) 4 or 8 weeks prior to reversing (REV) the shunt in a subset of rats. REV during established HF at 8 wks resulted in impaired LV systolic (%FS, Ees, PRSW: 31.7%, 0.428 mmHg/µL, 57.4 mmHg, respectively; p<0.05 vs Sham) and diastolic function (tau, dP/dtmin; 12.2 msec, -6294 mmHg/sec, respectively; p<0.05 vs Sham), while REV during pre-HF at 4 wks resulted in delayed, but improved LV systolic (%FS, Ees, PRSW: 39.7%; 0.813 mmHg/µL; 87.4 mmHg, p<0.05 vs ACF) and diastolic function (tau, dP/dtmin; 10.8 msec; -7128 mmHg/sec, p<0.5). A subset of ACF rats reversed at 8 wks received Levo (1 mg/kg) for 4 wks prior to REV (Levo-P) or for 11 w...