Correlation Between Release of Cytokines From Liver Graft and Hemodynamic Instability
The primary goal of this project is to identify the source of cytokines that are released into circulation during graft reperfusion. Seventeen patients scheduled to have adult cadaveric liver transplantation at the Milton S. Hershey Medical Center were contacted as prospective participants. Blood samples were obtained from the radial artery, the portal vein, and from the graft irrigation. The level of pro-inflammatory cytokines was verified and compared with the amount of catecholamines used to maintain hemodynamic stability.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Correlation Between Release of Cytokines From Liver Graft and Hemodynamic Stability During Liver Transplantation|
- Measurement of cytokine levels (TNF-alpha, IL-1, Il-2, IL-6, IL-8) in the portal vein, radial artery and "flush" (from irrigation of the liver used to remove preservation solution from the liver graft) blood. [ Time Frame: A period of 20 minutes, beginning at the start of reperfusion and continuing until 20 minutes after reperfusion. ] [ Designated as safety issue: No ]Cytokines released from the liver graft could be a cause for negative inotropy and systemic vasodilatation.
- Correlation between the level of cytokines and hemodynamic stability during reperfusion. [ Time Frame: A period of 20 minutes, beginning at the start of reperfusion and continuing until 20 minutes after reperfusion. ] [ Designated as safety issue: No ]First 20 minutes after liver graft reperfusion is a time of maximal hemodynamic instability. A correlation between the level of cytokines and hemodynamic instability could be important for understanding of this condition
Biospecimen Retention: Samples Without DNA
Blood samples were obtained. All blood samples were placed on ice and processed with centrifugation. The plasma supernatant was frozen at -80º Celsius.
|Study Start Date:||August 2008|
|Study Completion Date:||April 2010|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Reperfusion of the graft is the most critical part of liver transplantation because of the difficulties in managing the resulting severe hemodynamic instability. The patients who are accepted to be listed for liver transplantation undergo evaluation of their cardiac function and are usually relatively stable with, at most, minimal cardiac problems (a requirement for inclusion in the liver transplantation program). Additionally, we observe completely unpredictable hemodynamic reactions during and after the graft reperfusion, requiring vastly different doses of catecholamine in order to maintain an acceptable level of perfusion pressure. The adverse cardiopulmonary effects are thought to be associated with the preexisting level of various proinflammatory factors, including cytokines (TNF-alpha, IL-6) and proinflammatory phospholipase A2 (sPLA2) produced in the graft as a reaction to the conservation solution and cold temperature (necessary to keep the organ capable for transplantation) and released into the bloodstream during reperfusion. The massive release of cytokines after unclamping of the graft may be responsible for negative inotropy and significant vasodilatation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01120743
|United States, Pennsylvania|
|Penn State Milton S. Hershey Medical Center, Penn State College of Medicine|
|Hershey, Pennsylvania, United States, 17033-0850|
|Principal Investigator:||Dmitri Bezinover, MD, PhD||Penn State Milton S. Hershey Medical Center, Penn State College of Medicine|