Abstract
Background and ObjectiveApart from its inotropic property, milrinone has vasodilator, anti-inflammatory and antithrombotic effects that could assist in the reversal of septic microcirculatory changes. This paper investigates the effects of milrinone on endotoxemia-related microcirculatory changes and compares them to those observed with the use of norepinephrine.Materials and MethodsAfter skinfold chamber implantation procedures and endotoxemia induction by intravenous Escherichia coli lipopolysaccharide administration (2 mg.kg-1), male golden Syrian hamsters were treated with two regimens of intravenous milrinone (0.25 or 0.5 μg.kg-1.min-1). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables. Macro-hemodynamic, biochemical, and hematological parameters and survival rate were also analyzed. Endotoxemic non-treated animals, endotoxemic animals treated with norepinephrine (0.2 μg.kg-1.min-1), and non-endotoxemic hamsters served as controls.ResultsMilrinone (0.5 μg.kg-1.min-1) was effective in reducing lipopolysaccharide-induced arteriolar vasoconstriction, capillary perfusion deficits, and inflammatory response, and in increasing survival. Norepinephrine treated animals showed the best mean arterial pressure levels but the worst functional capillary density values among all endotoxemic groups.ConclusionOur data suggests that milrinone yielded protective effects on endotoxemic animals’ microcirculation, showed anti-inflammatory properties, and improved survival. Norepinephrine did not recruit the microcirculation nor demonstrated anti-inflammatory effects.
Highlights
Sepsis is an infection-related systemic inflammatory syndrome with high incidence, morbidity, mortality, and cost to healthcare system [1, 2]
Short-acting vasodilators have been used to recruit the microcirculation in patients with septic shock, mainly pediatric ones who remain in a state of low cardiac output and high systemic vascular resistance despite adequate therapy with an inotropic agent [5,6,7]
In the present study, milrinone proved to be beneficial in a validated endotoxemia rodent model that allows direct in vivo assessment of microcirculatory hemodynamics and perfusion dysfunction
Summary
Sepsis is an infection-related systemic inflammatory syndrome with high incidence, morbidity, mortality, and cost to healthcare system [1, 2]. Short-acting vasodilators have been used to recruit the microcirculation in patients with septic shock, mainly pediatric ones who remain in a state of low cardiac output and high systemic vascular resistance despite adequate therapy with an inotropic agent [5,6,7]. An alternative approach to open the microcirculation is based on the use of type III phosphodiesterase (PDE-3) inhibitors, like the inodilator milrinone With this class of drugs it would be possible to achieve microvessel dilatation while maintaining satisfactory perfusion pressure by increased cardiac output. There is increasing evidence that milrinone is able to interfere with the inflammatory cascade and platelet aggregation [12,13,14] Together, these effects may contribute to restoration of microcirculatory function, improving tissue perfusion and reducing organ failure. This paper investigates the effects of milrinone on endotoxemia-related microcirculatory changes and compares them to those observed with the use of norepinephrine
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