Low-Dose Landiolol Reduces Heart Rate and Cardiac Oxygen Consumption Without Compromising Initial Hemodynamic Resuscitation in a Canine Model of Endotoxin Shock

In septic shock, it is not known whether β-blocker can be used to reduce heart rate (HR) safely during the initial phase of hemodynamic resuscitation. The purpose of this study was to experimentally investigate the effects of low-dose landiolol, a β-blocker, on initial hemodynamic resuscitation in dogs with endotoxin shock. In 13 anesthetized dogs [n = 7 in control (CT) group, n = 6 in β-blockade (BB) group], after endotoxin shock was induced by intravenous infusion of lipopolysaccharide (4 mg kg), we started hemodynamic resuscitation to restore mean arterial pressure (AP) and cardiac output (CO) by infusing noradrenaline (NA) and Ringer acetate solution (RiA). During 4 h of hemodynamic resuscitation, dose of NA and RiA were automatically titrated with use of a computer-controlled drug infusion system that we developed previously. In BB group, landiolol was administered at a low-dose range (1-10 μg kg min) to lower HR to lower than 140 bpm. Hemodynamic resuscitation using the system restored AP to 70 mmHg and CO to greater than 90% of baseline level similarly in both groups. Throughout resuscitation, HR and indices of cardiac contractility were significantly lower in BB group than in CT group. However, there were no significant intergroup differences in the dose of NA and RiA. During First 2 h of resuscitation, cardiac oxygen consumption was significantly lower in BB group than in CT group. In conclusion, low-dose landiolol may reduce HR without compromising initial hemodynamic resuscitation in septic shock. To clearly establish this, large-size randomized study using animal models more relevant to septic shock is needed.