Microdialysis-evaluated myocardial cyclooxygenase-mediated inflammation and early circulatory depression in porcine endotoxemia

Crit Care Med. 2003 Jun;31(6):1780-5. doi: 10.1097/01.CCM.0000075740.61294.a6.

Abstract

Objective: To evaluate the early myocardial biochemical inflammatory response with the microdialysis technique during porcine endotoxemia and to simultaneously monitor systemic hemodynamics.

Design: Prospective, randomized, placebo-controlled trial with parallel groups.

Setting: Animal research laboratory at the University Hospital of Uppsala, Sweden.

Subjects: Thirteen piglets aged 12-14 wks receiving general anesthesia.

Interventions: After thoracotomy and the insertion of microdialysis probes in standardized locations in the left ventricle of the heart and in the quadriceps muscle, seven pigs received a continuous infusion of endotoxin, initiating a severe endotoxemic shock. Six pigs received saline instead of endotoxin.

Measurements and main results: Endotoxemia caused a rapid and pronounced elevation of a metabolite obtained from prostaglandin degradation, 15-keto-dihydro-PGF(2alpha), in myocardial microdialysate fluid being specific of cyclooxygenase (COX)-mediated inflammation (p <.001 vs. saline-infused controls). Simultaneously, we observed a decrease in left ventricular stroke work index in the endotoxemic pigs (p <.01 vs. saline-infused controls). Endotoxemia did not alter 15-keto-dihydro-PGF(2alpha) levels in quadriceps muscle. Endotoxemia caused increases in taurine, hypoxanthine, and magnesium in myocardial microdialysate (p <.05 vs. saline-infused controls), whereas the contents of pyruvate, lactate, inosine, adenosine, and calcium were not significantly changed.

Conclusion: Endotoxemia induced a myocardial COX-mediated inflammation without signs of ischemia. In parallel, a depletion of myocardial energy substrates and a deterioration in myocardial performance were seen.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Dinoprost / analogs & derivatives*
  • Dinoprost / metabolism
  • Endotoxemia / immunology
  • Female
  • Hemodynamics / immunology*
  • Inflammation / metabolism*
  • Inflammation / microbiology
  • Male
  • Microdialysis
  • Myocardium / immunology
  • Myocardium / metabolism*
  • Prostaglandin-Endoperoxide Synthases / immunology
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Random Allocation
  • Shock, Septic / immunology*
  • Swine

Substances

  • 15-ketoprostaglandin F2alpha
  • Dinoprost
  • Prostaglandin-Endoperoxide Synthases