K Tarumi

Anti-rat IL-8 (CINC) monoclonal antibody administration reduces ischemia-reperfusion injury in small intestine

ISCHEMIA-reperfusion injury in transplantation can cause primary nonfunction and is a matter similar in importance to rejection. Recent studies indicate that neutrophil infiltration plays an important role in ischemiareperfusion injury. We previously reported that there was a correlation between the degrees of mucosal damage and the peak level of IL-8 (CINC), known as a leukocyte chemoattractant, after the reperfusion, and that IL-8 (CINC) is a potential mediator of the ischemia-reperfusion injury in rat small intestine. Thus, we investigated whether anti-rat IL-8 (CINC) monoclonal antibody (mAb IL-8) administration reduces the ischemia-reperfusion injury.

Induction of heat shock protein-70 (hsp-70) by intraarterial administration of geranylgeranylacetone

IN TRANSPLANTATION, the principal problems are ischemia-reperfusion injury, preservation injury, rejection, infection, and graft-versus-host disease (GVHD), etc. Of these, ischemia-reperfusion/preservation injury is especially important, because it can cause primary nonfunction and its improvement is thereby crucial for the success of organ transplantation. Recently, there have been reports that showing that induction of heat shock protein (hsp) protects against ischemia-reperfusion injury and preservation injury. However, the mechanisms of this protective effect remain unknown and, as yet, a nontoxic clinical procedure for induction of hsp remains unavailable. In this study, we focused on geranylgeranylacetone (GGA), which is an antiulcer drug developed in Japan and used clinically for the treatment of gastric ulcer and gastritis. Its protective effects in other organs as well as the stomach have been reported; for instance, in one study, an improved histologic status in subjects with chronic hepatic injury was seen. It has been suggested that GGA may exert cytoprotective action through an increase of prostaglandin E2, 7 maintenance of cNOS activity, or induction of hsp. Therefore, in this study we investigate whether intraarterial administration of GGA to rats could induce expression of hsp-70 in various organs.

Early detection of graft function using hepatic venous oxygen saturation in pig liver transplantation

In this study, we measured hepatic venous oxygen saturation (Shvo2) in pig liver transplantations in order to evaluate its usefulness as a predictor of early postoperative graft function. Shov2 of the grafts with good function was over 60% after reperfusion, and the mean Shov2 at end of the operations was 69.8+/-6.9%. Shov2 of the grafts with poor function never increased over 60%, and for most of the operation until its end, Shov2 was under 50%. At the end of the operations, the mean Shov2 was 39.7+/-5.5%. Shov2 levels of the grafts with good function were significantly higher than those of the grafts with poor function (P=0.0016). Corresponding with these Shov2 data, glutamic-oxaloacetic transaminase and lactate dehydrogenase levels of grafts with poor function were significantly higher than those of the grafts with good function. Shov2 represents a summation of the hemoglobin oxygen saturation at the venous end of the sinusoids of the liver and indicates adequate hepatic blood flow if the hepatic oxygen is constant. A decrease of Shov2 in poor graft function might indicate a disturbance of microcirculation in the sinusoids. Through the use of Shov2, we are able to recognize conditions of microcirculatory disturbance more quickly than with any other system. In conclusion, Shov2 is a useful indicator for an early and reliable prediction of outcome in liver transplantation.

The Plasma FK506-Binding Protein 12 Level is Related to Acute Cellular Rejection in Small Bowel Transplantation

Since FK506 binding protein (FKBP12) inhibits dose-dependently the immunosuppressive activity of FK506 in vitro, plasma FKBP12 levels were measured after rat small bowel transplantation (SBTx). The mean plasma FKBP12 level in untreated recipients increased significantly at the onset of acute cellular rejection (ACR) compared to that in FK506-treated recipients without rejection at the same time after SBTx (P < 0.05). In both groups, however, the mean plasma FKBP12 level did not increase at 1 day after SBTx. These results suggest that plasma FKBP levels may be affected by ACR, but not by ischemia-reperfusion injury. Therefore, the plasma FKBP12 level should be considered as one of the parameters related to the immunosuppressive activity of FK506 in SBTx.

Monitoring perioperative hepatic venous oxygen saturation (ShvO2) in hepatectomy—Changes of ShvO2 in hemorrhagic shock

Hepatic venous oxygen saturation (ShvO2) is an indicator of the hepatic oxygen supply-to-demand ratio, which can be used to estimate adequate hepatic blood flow if hepatic oxygen is constant. We monitored ShvO2 intraoperatively and postoperatively in a patient who underwent right hepatic lobectomy. Decreases in ShvO2 were noted during surgical maneuvers which included manipulation of the hepatic hilum and mobilization of the liver. The ShvO2 recovered immediately after termination of these procedures. After the operation the patient developed hypovolemic shock due to postoperative bleeding; blood pressure dropped from 120 to 90 mmHg and the ShvO2 fell from 70% to 30%. Dopamine (5μg/kg per min) was administered to maintain the blood pressure. Temporary cessation of the dopamine infusion caused a decrease in ShvO2 (from 85% to 75%) without a major change in blood pressure. Dopamine increases hepatic blood flow, and accordingly, this decrease in ShvO2 must have been caused by cessation of the dopamine infusion. This finding suggests that ShvO2 can be used to determine optimal dopamine dosage for maintaining hepatic blood flow. From these observations, ShvO2 accurately reflects changes in hepatic blood flow and ShvO2 monitoring was helpful in avoiding hepatic ischemia during the periperative period in a patient undergoing a hepatectomy. Unexpected changes in hepatic blood flow can be immediately identified by monitoring ShvO2, enabling more rapid intervention.