Elsevier

Resuscitation

Volume 70, Issue 1, July 2006, Pages 124-132
Resuscitation

Experimental paper
Resuscitation of severe but brief haemorrhagic shock with PFC in rabbits restores skeletal muscle oxygen delivery and does not alter skeletal muscle metabolism

https://doi.org/10.1016/j.resuscitation.2005.11.014Get rights and content

Summary

Studies have demonstrated that perfluorocarbon (PFC) emulsions associated with hyperoxia improved whole body oxygen delivery during resuscitation of acute haemorrhagic shock (HS). Nevertheless the microcirculatory effects of PFC and the potential deleterious effects of hyperoxic reperfusion are still of concern. We investigated (i) the ability of a newly formulated, small sized and highly stable PFC emulsion to increase skeletal muscle oxygen delivery and (ii) the effect of hyperoxic reperfusion on skeletal muscle metabolism after a brief period of ischaemia using an original, microdialysis-based method that allowed simultaneous measurement tissue oxygen pressure (PtiO2) and interstitial lactate and pyruvate. These measurements were carried out in anaesthetised and ventilated (FiO2 = 1) rabbits subjected to acute HS (50% of blood volume withdrawal) and either resuscitated with a PFC emulsion diluted with a 5% albumin solution (16.2 g PFC per kg body weight) (n = 10) or with a modified fluid gelatin solution (Gelofusine®) (n = 10). We found no difference between the two groups for the haemodynamic and haematological variables (except for the venous oxygen partial pressure). However, a significant difference was observed in the slope of the regression linear relationship exhibited between the mean arterial pressure (MAP) and the PtiO2, PFC group showing a much steeper slope than Gelofusine® group. In addition, PtiO2 values increased linearly with decreasing haematocrit (Hct) values in PFC-resuscitated animals and decreased linearly with decreasing Hct values in Gelofusine®-resuscitated animals. There were no differences between the two groups concerning the blood and interstitial lactate/pyruvate ratios suggesting no deleterious effect of hyperoxic resuscitation in skeletal muscle. In conclusion these results suggest that resuscitation of severe, but brief, HS with PFC increased skeletal muscle oxygen delivery without measurable deleterious effects.

Introduction

Haemorrhagic shock (HS) is a life-threatening condition resulting from inadequate blood supply to various organs sufficient to cause tissue hypoxia and cellular and organ function alterations.1 The sequential goals of resuscitation in HS are (i) to restore the circulating volume (and consequently the cardiac output and the arterial pressure); (ii) to restore the microvascular perfusion and the oxygen supply to vital organs (which can be altered by a decrease of functional capillary density through decreasing perfusion pressure and/or blood viscosity2 and oxygen content); (iii) to prevent or correct end-organ damage due to cardiac output redistribution (in order to protect the heart and the brain at the expense of splanchnic organs such as the liver or the kidney as well as other tissues such as skeletal muscles or skin).3

Artificial oxygen carriers based on perfluorocarbon (PFC) emulsions have been developed because they can increase oxygen transport in the initial stages of resuscitation.4 PFCs are chemically and biologically inert synthetic compounds (perfluorinated hydrocarbon compounds). PFCs transport gases (oxygen and carbon dioxide) exclusively in the physically dissolved form,4, 5 and they are characterized by a linear relationship between oxygen partial pressure and oxygen content. Elevated arterial oxygen partial pressures are thus beneficial to maximize the oxygen transport capacity of PFCs.6, 7

Despite encouraging preclinical and clinical results with PFCs, and their ability to increase whole body oxygen transport,4, 8, 9, 10 there are still unanswered questions concerning the ability of PFCs to restore perfusion in the microcirculation and to prevent end-organ damage, largely due to the documented microcirculatory effects of hyperoxia11 and to the risk of hyperoxic reperfusion in previously ischaemic organs.11, 12

In order to answer these questions we designed a study to investigate the effects of a newly formulated PFC emulsion stabilised with a fluorocarbon/hydrocarbon diblock compound13 on (i) the ability of PFC to restore skeletal muscle oxygen delivery (a tissue that undergoes severe vasoconstriction during HS14) and (ii) to test the hypothesis that hyperoxic reperfusion after a short period of ischaemia during HS would not alter skeletal metabolism estimated by the ratio of interstitial lactate/pyruvate concentrations.

Section snippets

Materials and methods

The study design was approved by the Animal Protection Bureau of the French Ministry for Fishing, Agriculture and Food, and the experiments were conducted in accordance with the Guiding Principles for Research Involving Animals.

Macrohaemodynamic variables

As expected, HS induced a significant decrease (57% average) in MAP (time point 60 min) (Table 1). Volume expansion increased the MAP progressively, which was restored to base values at the end of reperfusion for both groups (time point 100 min). Subsequently, in both groups, the MAP values decreased progressively until the end of the study period. No significant treatment-related changes were noted.

Blood gas measurements, haematology values and blood viscosity

As expected, volume expansion resulted in a further significant decrease in Hct values compared to

Discussion

There are a number of clinical situations where administration of a PFC emulsion could help to increase the circulating volume and the oxygen transport temporarily. This is particularly true during the prehospital “golden hour” period, where blood is not always immediately available.4, 5 PFC emulsions could provide a way to stabilise the patients waiting for surgery and could be used in an emergency. However, there are still questions concerning the microvascular effects of PFC and their

Conflict of interest statement

None.

References (29)

  • D.L. Dyess et al.

    Redistribution of organ blood flow after haemorrhage and resuscitation in full-term piglets

    J Pediatr Surg

    (1994)
  • J.G. Riess

    Oxygen carriers (“Blood substitutes”)-Raison d’être, chemistry, and some physiology

    Chem Rev

    (2001)
  • J.G. Riess

    Overview of progress in the fluorocarbon approach to in vivo oxygen delivery

    Biomater Artif Cells Immobil Biotechnol

    (1992)
  • O.P. Habler et al.

    Haemodilution and intravenous perflubron emulsion as an alternative to blood transfusion: effects on tissue oxygenation during profound haemodilution in anesthetized dogs

    Transfusion

    (1998)
  • Cited by (0)

    A Spanish translated version of the summary of this article appears as Appendix in the online version at doi:10.1016/j.resuscitation.2005.11.014.

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