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Oulun yliopiston väitöskirjat

INSIGHTS INTO HEALING RESPONSE IN SEVERE SEPSIS FROM A CONNECTIVE TISSUE PERSPECTIVE, ACTA UNIVERSITATIS OULUENSIS D Medica 1063

ISBN-13:	978-951-42-6253-1
Kieli:	englanti
Kustantaja:	Oulun yliopisto
Oppiaine:	Lääketiede, farmasia
Painosvuosi:	2010
Sidosasu:	pehmeäkantinen
Sijainti:	Print Tietotalo
Sivumäärä:	158
Tekijät:	GÄDDNÄS FIIA

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Sepsis is a major challenge for healing responses maintaining homeostasis. Coagulation andinflammation are activated at the whole-body level, even in undamaged tissues. Despiteconstantly growing knowledge and advances in care, high mortality in severe sepsis remains. Itwas hypothesised that tissue regeneration processes may also be altered in severe sepsis. The study population consisted of 44 patients with severe sepsis and 15 healthy controls.Serum samples were obtained during ten days of severe sepsis and twice again, three months andsix months later. Experimental suction blisters were performed twice during severe sepsis and at3 and 6 months. Serum samples were obtained and suction blisters were induced once in controls.Biochemical analyses were performed to assess the level of procollagen I and III aminoterminalpropeptides (PINP, PIIINP), reflecting the synthesis of corresponding collagens; in serum andsuction blister fluid. In addition collagen I degradationproduct in serum was measured.Physiological measurements of transepidermal water loss and blood flow were done in order toevaluate the re-epithelisation rate and blood flow in an experimental wound. Levels of matrixmetalloproteinases (MMPs) 2, 8 and 9 were measured from serum and suction blister fluid. Decrease in water evaporation from an experimental blister wound was slower in sepsis thanin controls. On the fourth day the sepsis patients had higher blood flow in the blister wound thanthe controls (both in the healing wound and in the newly induced wound). The procollagen IIIaminoterminal propeptide (PIIINP) levels were increased in serum in severe sepsis, whereasprocollagen I aminoterminal propeptide (PINP) levels were not, making up a pronounced PIIINP/PINP ratio. PIIINP and PINP levels were associated with disease severity and outcome. Inaddition, collagen I degradation measured with ICTP assay was increased in severe sepsis andPINP/ICTP ratio was lower. Furthermore, the overall protein concentration and PINP and PIIINPlevels were low in suction blister fluid, which implies that the balance of the extracellular matrixconsistence is disturbed in uninjured skin in severe sepsis. Then again in survivors the levels ofPINP and PIIINP were up-regulated at three months but returned to normal by six months. MMP-9 levels in serum and skin blister fluid were lower in severe sepsis than in controls during the tendays studied. The MMP-2 levels were found to be increased both in serum and in skin blister fluidin severe sepsis in comparison to the controls and MMP-2 was associated with disease severityand outcome. MMP-8 was increased in serum and in skin blister fluid. In conclusion, the balance of collagen turnover is altered in severe sepsis in serum and skin andepidermal re-epithelisation is delayed. The levels of MMP-2 and MMP-8 are increased whereaslevels of MMP-9 are depressed.

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