Abstract 18606: Diastolic Dysfunction in the Ischemic Pig Heart is Partially Restored by Dobutamine-Ivabradine Combination, but Not by Omecamtiv Mecarbil, Due to Increasing Lusitropy and Filling Time
Introduction: Acute diastolic failure in post-ischemic cardiogenic shock is associated with a grave prognosis. We assessed the impact of two novel inotropic strategies on the diastolic properties in a clinically relevant swine model of post-ischemic acute heart failure.
Hypothesis: Dobutamine-ivabradine and omecamtiv mecarbil treatments exert different lusitropic effects on early diastole in acute heart failure.
Methods: Anesthetized pigs were subjected to left ventricular ischemia through the injection of polystyrene microspheres into the coronary main stem (n=12). The animals were then randomized to receive omecamtiv (OM) (bolus 0.75 mg/kg plus 0.5 mg/kg/h) (n=6) or a combination of dobutamine (5 μg/kg/min) and ivabradine (0.29 ±0.16 mg/kg) (D+I) (n=6).
Results: Ischemia reduces stroke volume, despite an increase in left atrial pressure. This decrease in stroke volume is associated with impaired early relaxation, systolic dilatation and an increase in late diastolic stiffness. Both treatments reversed systolic dilatation, but only D+I was able partially to restore the stroke volume from 26 ± 5 to 33 ± 5 mL. D+I enhanced early relaxation (Tau decreased from 45 ± 11 to 29 ± 4 ms) and prolonged the diastolic filling time (DFT, increased from 338 ± 60 to 352 ± 40 ms), whereas OM prolonged Tau (42 ± 5 to 62 ± 10 ms) and shortened the DFT (from 326 ± 68 to 248 ± 84 ms).
Conclusions: Our data suggest that the lusitropic effect of dobutamine-ivabradine treatment, an effect not observed with omecamtiv, is necessary for the restoration of post-ischemic early diastolic function and thus restoration of stroke volumes in severe acute heart failure.
Author Disclosures: L. Ronning: None. J.P. Bakkehaug: None. L. Rodland: None. A.B. Kildal: None. T. Myrmel: None. O.J. How: None.
- © 2016 by American Heart Association, Inc.