Skip to main content

Reduced expression of PPAR-β/δ limits the potential beneficial effects of GW0742 during septic shock in atherosclerotic swine


The PPAR-β/δ agonist GW0742 was shown to attenuate cardiac dysfunction in murine septic shock [1] and renal ischemia/reperfusion injury in diabetic rats [2]. Since these data originate from unresuscitated models, we investigated the effects of GW0742 during long-term, resuscitated porcine septic shock. In order to assess the role of pre-existing cardiovascular morbidity we used animals with familial hypercholesteremia (11.1 (7.4; 12.3) vs. 1.4 (1.3; 1.5) mmol/l in a healthy strain; P < 0.001) and consecutive, diet-induced ubiquitous atherosclerosis resulting in coronary artery disease [3], reduced glomerular filtration rate (76 (60; 83) vs. 103 (79; 120) ml/minute in healthy swine; P = 0.004) and presence of chronic histological kidney injury.


Anesthetized and instrumented animals randomly received vehicle (n = 9) or GW0742 (n = 10; 0.03 mg/kg) at 6, 12, 18 hours after induction of fecal peritonitis [4]. Hydroxyethyl starch and noradrenaline were infused to maintain normotensive, hyperdynamic hemodynamics. Creatinine clearance was measured from 0 to 12 hours and from 12 to 24 hours of sepsis, respectively. Data are median (quartiles).


GW0742 did not affect the noradrenaline infusion rate required to achieve target hemodynamics (0.57 (0.30; 3.83) vs. 0.56 (0.41; 0.91) μg/kg/minute; P = 0.775) nor the fall in creatinine clearance (GW0742: from 129 (114; 140) to 78 (55; 95) ml/minute, P = 0.002; vehicle: from 130 (91; 142) to 41(31; 84) ml/minute, P = 0.004; P = 0.967 and P = 0.191 between groups). Immune histochemistry analysis of kidney biopsies in sham-operated swine showed markedly reduced tissue expression of the PPAR-β/δ receptor in atherosclerotic swine (281 (277; 404) vs. 57 (53; 77)×103 densitometric units in healthy swine; P = 0.008).


Even early post-treatment with the PPAR-β/δ agonist GW0742 did not beneficially influence acute kidney injury during long-term, resuscitated fecal peritonitis-induced septic shock in swine with pre-existing impairment of kidney function and histological damage. The lacking beneficial effect of GW0742 was most likely due to the reduced expression of the PPAR-β/δ receptor.


  1. Kapoor , et al.: Am J Respir Crit Care Med. 2010, 182: 1506-1515. 10.1164/rccm.201002-0240OC

    CAS  Article  PubMed  Google Scholar 

  2. Collino , et al.: Free Radic Biol Med. 2011, 50: 345-353. 10.1016/j.freeradbiomed.2010.10.710

    CAS  Article  PubMed  Google Scholar 

  3. Thim D: Med Bull. 2010, 57: B4161.

    Google Scholar 

  4. Simon F, et al.: Crit Care. 2009, 13: R113. 10.1186/cc7959

    PubMed Central  Article  PubMed  Google Scholar 

Download references


Supported by the Else-Kröner-Fresenius-Stiftung.

Author information

Authors and Affiliations


Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Bracht, H., Simon, F., Matallo, J. et al. Reduced expression of PPAR-β/δ limits the potential beneficial effects of GW0742 during septic shock in atherosclerotic swine. Crit Care 16, P18 (2012).

Download citation

  • Published:

  • DOI:


  • Septic Shock
  • Familial Hypercholesteremia
  • Hydroxyethyl Starch
  • GW0742
  • Fecal Peritonitis