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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.
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.
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| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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Study will include adult patients with end-stage liver disease accepted for liver transplantation.
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| Name | Affiliation | Role |
|---|---|---|
| Dmitri Bezinover, MD, PhD | Penn State Milton S. Hershey Medical Center, Penn State College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Penn State Milton S. Hershey Medical Center, Penn State College of Medicine | Hershey | Pennsylvania | 17033-0850 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21384515 | Derived | Bezinover D, Kadry Z, McCullough P, McQuillan PM, Uemura T, Welker K, Mastro AM, Janicki PK. Release of cytokines and hemodynamic instability during the reperfusion of a liver graft. Liver Transpl. 2011 Mar;17(3):324-30. doi: 10.1002/lt.22227. |
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| ID | Term |
|---|---|
| D017093 | Liver Failure |
| ID | Term |
|---|---|
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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Blood samples were obtained. All blood samples were placed on ice and processed with centrifugation. The plasma supernatant was frozen at -80ยบ Celsius.