Exogenous adrenomedullin reduces the arterial lactate concentration and mean pulmonary arterial pressure in ovine endotoxemia

Introduction

Sepsis-associated arterial hypotension may be complicated by inadequate systemic and regional oxygen delivery resulting in lactic acidosis and multiple organ failure. We hypothesized that exogenous administration of adrenomedullin (AM), a vasodilatory peptide hormone with anti-inflammatory properties, may improve the oxygen delivery–demand relationship, thereby limiting the increase in arterial lactate concentrations in ovine endotoxemia.

Methods

Fourteen adult ewes were instrumented for chronic hemodynamic monitoring. Following 16 hours of endotoxemia (Salmonella typhosa endotoxin, 10 ng/kg/min) the animals received either a continuous infusion of AM at incremental doses (10, 50, 100 ng/kg/min; each for 30 min) or the vehicle (normal saline; n= 7 each).

Results

Endotoxin infusion contributed to a hypotensive–hyperdynamic circulation characterized by decreases in mean arterial pressure (MAP) and systemic vascular resistance index as well as increases in heart rate (HR), cardiac index (CI) and arterial lactate concentrations. AM infusion at 100 ng/kg/min increased the CI (12.2 ± 0.8 vs 7.8 ± 0.5 l/min) and oxygen delivery index (1,734 ± 121 vs 1,075 ± 63 ml/min/m²), thereby decreasing the arterial lactate concentration (0.7 ± 0.2 vs 1.7 ± 0.3 mg/dl) and mean pulmonary arterial pressure (18 ± 1 vs 24 ± 1 mmHg; each P < 0.001 vs control) noticed in the control group. However, AM infusion at 100 ng/kg/min was linked to a decrease in MAP (64 ± 2 vs 80 ± 4 mmHg, P < 0.001 vs control).

Conclusion

Despite decreasing MAP, infusion of AM reversed pulmonary hypertension and improved the oxygen supply–demand relationship in a dose-dependent manner, as indicated by a reduced arterial lactate concentration. However, due to the vasodilatory properties of AM, it may be rationale to combine AM with a vasopressor agent.