Milrinone attenuates arteriolar vasoconstriction and capillary perfusion deficits on endotoxemic hamsters

PLoS One. 2015 Feb 3;10(2):e0117004. doi: 10.1371/journal.pone.0117004. eCollection 2015.

Abstract

Background and objective: Apart 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 methods: After 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.

Results: Milrinone (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.

Conclusion: Our 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / therapeutic use
  • Animals
  • Capillaries / drug effects
  • Endotoxemia / complications*
  • Endotoxemia / drug therapy*
  • Endotoxemia / microbiology
  • Endotoxemia / physiopathology
  • Hemodynamics / drug effects
  • Male
  • Mesocricetus
  • Microcirculation / drug effects*
  • Milrinone / therapeutic use*
  • Norepinephrine / therapeutic use
  • Vasoconstriction / drug effects*
  • Vasodilator Agents / therapeutic use*

Substances

  • Adrenergic alpha-Agonists
  • Vasodilator Agents
  • Milrinone
  • Norepinephrine

Grants and funding

This study was supported by grants from CNPq (National Council for Scientific and Technological Development, Brasilia, Brazil, http://www.cnpq.br/; grant number 303836/2010-5) and FAPERJ (State of Rio de Janeiro Agency for Research Support, Rio de Janeiro, Brazil, http://www.faperj.br/; grant number E26/110.754/2012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.