Abstract

Background Alterations of microcirculation are associated with organ hypoperfusion and high mortality in septic shock. This study is aimed at investigating the effects of unfractionated heparin (UFH) on intestinal microcirculatory perfusion and systemic circulation in a septic shock model. Methods Twenty-four beagle dogs were randomly allocated into four groups: (a) sham group: healthy controls, (b) shock group: septic shock induced by Escherichia coli, (c) basic therapy group: septic shock animals treated with antibiotics and 10 ml/kg/h saline, and (d) heparin group: septic shock animals treated with basic therapy plus UFH. Hemodynamic variables were measured within 24 h after E. coli administration. The intestinal microcirculation was simultaneously investigated with a sidestream dark-field imaging technique. Additionally, the function of vital organs was evaluated at 12 h postadministration (T12). Results E. coli induced a progressive septic shock in which the mean arterial pressure (MAP) decreased and lactate levels sharply increased, accompanied by deteriorated microvessel perfusion. While basic therapy partially improved the microvascular flow index and the perfused microvessel density in the jejunal villi, UFH significantly restored major microcirculation variables at T12. Physiological variables, including MAP, urine output, and lactate levels, were improved by UFH, whereas some hemodynamic indices were not affected by UFH. With respect to organ function, UFH increased the platelet count and decreased the creatinine level. Conclusions UFH improves microcirculatory perfusion of the small intestine independently of the changes in systemic hemodynamic variables in a canine model of septic shock, thereby improving coagulation and renal function.

Highlights

  • Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is associated with high mortality [1]

  • When the mean arterial pressure (MAP) decreased to 80% of the baseline, the timepoint was designated as the establishment of the septic shock model [21]. (c) Basic therapy group: when the septic shock model was established, the animals were intravenously administered with 0.9% saline at 10 ml/kg/h for fluid resuscitation

  • When the MAP decreased to 80% of the baseline, this was defined as the establishment of the septic shock model

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Summary

Introduction

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is associated with high mortality [1]. Alterations of microcirculation are associated with organ hypoperfusion and high mortality in septic shock. This study is aimed at investigating the effects of unfractionated heparin (UFH) on intestinal microcirculatory perfusion and systemic circulation in a septic shock model. E. coli induced a progressive septic shock in which the mean arterial pressure (MAP) decreased and lactate levels sharply increased, accompanied by deteriorated microvessel perfusion. While basic therapy partially improved the microvascular flow index and the perfused microvessel density in the jejunal villi, UFH significantly restored major microcirculation variables at T12. UFH improves microcirculatory perfusion of the small intestine independently of the changes in systemic hemodynamic variables in a canine model of septic shock, thereby improving coagulation and renal function

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