Ongoing research projects

Protein needs and feeding is a hot topic in the ICU. Many think that the critcally ill patients need more protein and also there is lots of believe that energy and protein should not be coupled anymore. Howver proof for these believs are scarse nad many studies we perform at the moment are related to this issue. Firrst of all are we studying the effect of feeding on whole protein turnover. In these measurements using stable isotope labeled amino acid we mainly focus on the protein balance and protein oxidation. The idea is that if we give more protein to the critically ill patinets that this improves the protein balance and that not all the extra amino acids are oxidised. In these studies we investigate the effects of differenet feeding regimens on whole body protein metabolism. Exemples are; 50 versus 100% of total nutritional needs; extra parenteral amino acids; parenteral versus enteral extra protein. However, the issue of protein feeding or feeding in general is not that easy in the critically ill. Although it feel snatural to feed also these patients at least their basic needs, recent studies show that early feeding can also have a negative effect on outcome. This affect has been blamed on autophagy. It is well known that feeding inhibits autophagy. On the other hand does autophagy take care of damaged proteins. The hypothesis is that the continuous feeding early during critical illness inhibts the autophagy that is supposed to take care of the massive amount of damaged proteins that are present during critical illness. This inhibition in the autophagy leads to the buildoup of damaged proteins and consequently to organ failure. As said this is a working hypothesis with some proof in literature. We are now developing an in vitro model using primary human muscle cells and hepatocyts to study the molecular and nutritional mechanisms leading to a potential block in the autophagy. One of the main questions we address is whether serum from critically ill patinets actual affects autopaghy in this system and what in serum is doing this?

Although we have been measuring lots of metabolites in the past we have now started a project to get into the field of Metabolomics. In our case this basically means that we are expending the range of metabolites we can measure. In addition to our amino acid analyses performed on a HPLC with fluorescence detection, are we now in the process of developing quantitative fatty acid analyses on a GC-MS. The project was started by Garret. He has now finished his 3 months project and was able to quantify at least 7 fatty acids. This activity is expended byu recent sponsoring by the EU. The metabolomics is now part of a consortium hunting for predictors for non-responders to exercise training. Predictors will be based on genomic and the metabolomic analyses. More info on the EU project can be found on our website for META-PREDICT.

We recently (beginning of 2011) started a new project in collaboration with Claes-Roland Martling from our south Solna campus. In this project we will study the fate of citrate used as a anti-coagulant during continuous renal replacement theray (CRRT) in ICU patients. A recent study has shown that CRRT using citrate in comparison with heparin improves survival of ICU patients with renbal failure. Since citrate is a key player in cellular energy metabolism we will study whether the citrate from the CRRT will end up in the patients circulation and if it can be utilised for energy production.

One of our main project concerns glutamine. This non-essential amino acid is nowadays considered to be conditionally essential during critical illness. We perform studies to ellucidate the derangements in glutamine metabolism, the effects of extra glutamine on this and the effects of extra glutamine on outcome.

Critically ill patients loose skeletal muscle mass at a dramatic rate which is related to their outcome and recovery. Within this project we study the physiology as well as the genetics that can explain this loss. We now also study if similar mechanisms apply to muscle loss due to cancer.

Mitochondrial derangement have been suggested to cause multiple organ failure. We have shown dramatic derangements in mitochondria in skeletal muscle of ICU patients. Within this project we now evaluate mitochondrial function in other organs and the molecular mechanisms responsible for these derangments in skeletal muscle.

Immune function or dysfunction is discussed a lot in connection with the patients change to survive sepsis and critical illness. However no good methods to assess immune function in vivo in patients are available. We developed a technique in which we measure turnover of immune cells in vivo for this. Currently we are evaluating immune function during different stages in the critical illness and the effects of lipid feeding.

All these critical ill patients have low albumin levels. We have previously shown that this happnes despite a very high albumin synthesis rate. We are currently investigating the dissapearance of albumin from plasma in conjunction with the synthsis rates in critically ill patients.

Both overfeeding and underfeeding of patients treated in the ICU couses problems in their outcome and response to treatment. Within this project we are evaluating different machines to measure the patients energy needs in the ICU. We are also investigating how much protein in their feeding these patients are able to utilise for making usefull proteins. These latter studies we are performing in the general ICU but also in the neuro-ICU and the pediatric-ICU.

Glucose control in the ICU has been and still is a reason for heated debates. Studies have shown both beneficial and detremental effects on patients outcome. We think that part of these problems are due to glucose monitoring. We are currently testing a on-line devise to monitor circulating glucose levels in real time. In addition we are studying the effects of glucose control during major surgery.

Glutathione is one of the most important free radical scanvengers and closely related to glutamine metabolism. We have previously described glutathione status in adult ICU patients. Currently we are studying glutathione status in pediatric ICU patients.