β-blocker Combined with Left Ventricular Assist Device Synergistically Reduces Myocardial Oxygen Consumption in Acute Myocardial Infarction

Background: Reducing myocardial oxygen consumption (MVO₂) in acute myocardial infarction (AMI) decreases infarct size. Although β-blocker reduces MVO₂ through its negative chronotropic/inotropic effects, the same mechanisms could destabilize hemodynamics. If we can prevent the hemodynamic destabilization, we can maximize the benefit of β-blocker to spare MVO₂. Left ventricular assist device (LVAD) is known to unload LV, reduce MVO₂ and stabilize hemodynamics. We hypothesized that the combination of LVAD and landiolol, a short acting intravenous β-blocker, synergistically reduces MVO₂ without hemodynamic destabilization in AMI. Methods: In 5 mongrel dogs, we occluded the left circumflex coronary artery for 1 hour, and measured MVO₂ (Fick's rule) and hemodynamics. We compared those parameters among 4 conditions; Control, LVAD (transvascular LVAD, Impella), landiolol with LVAD (5 and 40 µg/kg/min). Results: Landiolol (40 µg/kg/min) reduced heart rate (−22 ± 5%, P < .01), decreased mean arterial pressure (−27 ± 16 mmHg, P < .05) and increased LV end-diastolic pressure: (18.6 ± 5.0 vs. 14.3 ± 5.3 mmHg, P < .05). LVAD reduced MVO₂ by 26 ± 26% compared with Control. The combination of LVAD with 5 and 40 µg/kg/min of landiolol further reduced MVO₂ by 40 ± 20% and 50 ± 18%, respectively, without compromising hemodynamics. Conclusions: The combination of LVAD and landiolol synergistically reduced MVO₂ without worsening hemodynamics. This powerful oxygen sparing effect of combination treatment may well be translated into the reduction of infarct size. This strategy will provide a new therapeutic option in AMI.