Tissue gas tensions and tissue metabolites for detection of organ hypoperfusion and ischemia.

BACKGROUND: The aim of this study was to evaluate how tissue gas tensions and tissue metabolites measured in situ can detect hypoperfusion and differentiate between aerobic and anaerobic conditions during hemorrhagic shock. We hypothesized that tissue PCO(2) (PtCO(2)) would detect hypoperfusion also under aerobic conditions and detect anaerobic metabolism concomitantly with or earlier than other markers. METHODS: Prospective experimental animal study with eight anesthetized pigs subjected to a continuous blood loss ∼8% of total blood volume per hour until death. We measured cardiac index, organ blood flows, and tissue levels of PO(2), PCO(2), glucose, pyruvate, lactate, and glycerol in intestine, liver, kidney, and skeletal muscle. RESULTS: With reduction in blood flow to the organs under aerobic conditions, PtCO(2) increased ∼1-4 kPa from baseline. With the onset of tissue hypoxia there was a pronounced increase of PtCO(2), lactate, lactate-pyruvate (LP) ratio, and glycerol. Tissue pH and bicarbonate decreased significantly, indicating that metabolic acid was buffered by bicarbonate to generate CO(2). CONCLUSION: Moderate tissue hypoperfusion under aerobic conditions is associated with increased PtCO(2), in contrast to metabolic parameters of ischemia (lactate, LP ratio, and glycerol) which remain low. From the onset of ischemia there is a much more rapid and pronounced increase in PtCO(2), lactate, and LP ratio. PtCO(2) can be used as a marker of hypoperfusion under both aerobic and anaerobic conditions; it gives an earlier warning of hypoperfusion than metabolic markers and increases concomitantly with or earlier than other markers at the onset of tissue anaerobiosis.

Microdialysis for monitoring inflammation: efficient recovery of cytokines and anaphylotoxins provided optimal catheter pore size and fluid velocity conditions.

Microdialysis emerges as a useful tool to evaluate tissue inflammation in a number of clinical conditions, like sepsis and transplant rejection, but systematic methodological studies are missing. This study was undertaken to determine the recovery of relevant inflammatory mediators using the microdialysis system, comparing microdialysis membranes with two different molecular weight cut-offs at different flow rates. Twenty and 100 kDa pore sizes CMA microdialysis catheters were investigated using velocities of 0.3, 1.0 and 5.0 microl/min. Reference preparations for cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10; m.w. 17-28 kDa] and chemokines (IL-8, MCP-1, IP-10 and MIG; m.w. 7-11 kDa) were prepared from plasma after incubating human whole blood with lipopolysaccharide. Reference preparation for complement anaphylatoxins (C3a, C4a, C5a; m.w. 9-11 kDa) was prepared by incubating human plasma with heat-aggregated immunoglobulin G. The reference preparations were quantified for the respective inflammatory molecules and used as medium for the microdialysis procedure. Through the 20 kDa filter only the four chemokines passed, but with low recovery (3-7%) and limited to the 1.0 microl/min velocity. The recovery with the 100 kDa filter was as follows: IL-1beta = 75%, MCP-1 = 55%, MIG = 50%, IL-8 = 38%, C4a = 28%, IP-10 = 22%, C5a = 20%, C3a = 16%, IL-6 = 11, IL-10 = 8% and TNF-alpha = 4%. The highest recovery for all chemokines and anaphylatoxins were consistently at velocity 1.0 microl/min, whereas IL-1beta and IL-10 recovered most efficiently at 0.3 microl/min. Thus, microdialysis using catheters with a cut-off of 100 kDa is a reliable method to detect inflammation as judged by a defined panel of inflammatory markers. These findings may have important implications for future clinical studies.