Microdialysis-evaluated myocardial cyclooxygenase-mediated inflammation and early circulatory depression in porcine endotoxemia.
OBJECTIVE
To evaluate the early myocardial biochemical inflammatory response with the microdialysis technique during porcine endotoxemia and to simultaneously monitor systemic hemodynamics.


METHODS
Prospective, randomized, placebo-controlled trial with parallel groups.


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


METHODS
Thirteen piglets aged 12-14 wks receiving general anesthesia.


METHODS
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.


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.


CONCLUSIONS
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.
Mutschler
D K
DK
Department of Surgical Sciences, Institute of Anesthesiology and Critical Care, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
Eriksson
M B
MB
Wikström
B G
BG
Lind
L
L
Larsson
A
A
Bergren-Kiiski
R
R
Lagrange
A
A
Nordgren
A
A
Basu
S
S
D000704:Analysis of Variance; D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism; D019446:Endotoxemia / Q000276:immunology; D005260:Female; D006439:Hemodynamics / Q000276:immunology*; D007249:Inflammation / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D017551:Microdialysis; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000276:immunology / Q000378:metabolism*; D011897:Random Allocation; D012772:Shock, Septic / Q000276:immunology*; D013552:Swine
C026528:15-ketoprostaglandin F2alpha; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases