Correlation Between Release of Cytokines From Liver Graft and Hemodynamic Instability

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Correlation Between Release of Cytokines From Liver Graft and Hemodynamic Stability During Liver Transplantation

Conditions
-----------------
Liver Transplantation

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All adult patients scheduled for liver transplantation will be offered the opportunity to participate in this research. Exclusion Criteria: Patients unable or unwilling to provide adequate informed consent will be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Cytokines released from the liver graft could be a cause for negative inotropy and systemic vasodilatation. | A period of 20 minutes, beginning at the start of reperfusion and continuing until 20 minutes after reperfusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between the level of cytokines and hemodynamic stability during reperfusion. | 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 | A period of 20 minutes, beginning at the start of reperfusion and continuing until 20 minutes after reperfusion. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
liver failure, cytokines, hemodynamic instability