Surgical Transplant Procedures

Surgical manipulation during organ harvest, that is, touching, retracting and moving of the organ, induces marked deterioration of the microcirculation, resulting in tissue hypoxia, parenchymal cell death, and, finally, a decrease of transplant survival [5]. The manipulation-induced microcirculatory derangements seem to involve Kupffer cell activation and oxygen free radical release, because inactivation or deletion of Kupffer cells can significantly reduce microcirculatory disturbances and parenchy-mal tissue hypoxia, thereby improving recipient survival. In experimental liver transplantation, it has been further demonstrated that the innervation of the organ also contributes to the manipulation-induced deterioration of the microcirculation, and that denervation before organ harvesting prevents circulatory deterioration and primary nonfunc-tion of the transplant.

The manifestation of post-transplant microcirculatory dysfunction depends additionally on the surgical procedure applied, in particular in liver transplants. Although it was found that the portal vein clamping time does not strongly determine the quality of graft microcirculation after transplantation, deterioration of hepatic arterial or portal venous inflow during reperfusion is well known to dramatically alter the function of the transplanted organ. A morphometric analysis in experimental rat liver transplantation revealed that liver samples from rats that underwent hepatic artery reconstruction had preserved lobular architecture and estimated bile duct and connective tissue volumes, whereas liver samples from rats that did not undergo hepatic artery reconstruction showed bile duct proliferation and an increase in connective tissue volume associated with a decrease in hepatocyte volume. In vivo experiments have further confirmed the importance of the hepatic dual blood supply, inasmuch as reconstruction of the hepatic artery with restitution of hepatic arterial blood flow has been shown to significantly reduce reperfusion-associated microcirculatory perfusion failure compared to liver grafts in which solely the portal vein was anastomosed. In addition, the simultaneous onset of hepatic arterial and portal venous blood flow after the transplantation procedure compared to the "classical" delayed onset of hepatic arterial reperfusion is considered effective in reducing microvascular perfusion failure, leukocyte adhesion, and Kupffer cell activation, which finally results in an improved primary graft function. These results have been confirmed in that in nonarterialized liver transplants a persistence of impaired hepatic microcirculation could be detected, which is associated with hepatocellular and endothelial cell swelling as well as bile duct injury. Apart from this, the prevention of intestinal congestion by insertion of a porto-jugular shunt during the surgical transplantation procedure also significantly reduces post-transplant reperfusion injury, including sinusoidal perfusion failure and microvascular leukocyte accumulation and adhesion.

In clinical practice, the preservation solution is flushed out by a rinse solution just prior to reperfusion of the transplant. Thus, the compounds of the preservation solution are removed before they can act during early reperfusion. Therefore, a rinse solution was designed to counteract early manifestation of reperfusion injury. This solution, named Carolina rinse, is composed of a variety of components potentially capable of counteracting post-transplant organ injury, including nicardipine, hydroxyethyl starch, fructose, glucose, and insulin, as well as adenosine and the three antioxidants desferrioxamine, glutathione, and allopurinol [6]. The first in vivo studies clearly indicated that this solution is a superior alternative to Ringer's solution to protect liver grafts from reperfusion injury. Further studies then could demonstrate that Carolina rinse prevents cold ischemia-reperfusion-induced endothelial cell killing and detachment, and improves the quality of early microvascu-lar reperfusion. The effectiveness of the rinse solution may additionally be increased by prewarming the solution before infusion into the donor organ. As demonstrated in rat liver and intestine, prewarming of either Carolina rinse or Ringer's lactate indeed reduces post-transplant no-reflow, ameliorates microvascular leukocyte adhesion, improves lymphatic capillary perfusion, and prevents graft failure.

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