Mucosal perfusion and reactivity of the rat small intestinal allograft.

During acute rejection (AR), the endothelial targeting seen in the mucosal vessels of the intestinal allograft (IA) could impair the blood supply and response to luminal stimuli. To study the effect of AR in the perfusion and reactivity of the IA mucosa, we measured the mucosal blood flow in the ileum (IL) of 2 groups of control rats (Lewis and ACI) and in the native and grafted IL of syngeneic (ACI to ACI) and allogeneic (donor ACI to recipient Lewis) rats. Using reflectance spectrophotometry and laser-Doppler flowmetry, parameters of mucosal oxygen saturation (ISO2), hemoglobin content (IHB), and blood flow (FLOW) were obtained at baseline and after saline and 50% dextrose (D50) stimulation. When compared to controls, the isograft IL had similar perfusion (ISO2, IHB, and FLOW). The allograft IL showed ischemia (similar ISO2, and lower ISO2 and FLOW). In the allografts, the ISO2 and FLOW were lower than in the isografts. In response to D50, the native IL of all groups showed an increased IHB and FLOW (hyperemia); the isografts showed an increase only in IHB (partial response); the allografts did not show any response at all. In summary, the mucosal perfusion in the rejecting allografts, but not in the isografts, showed ischemia. The response to D50 seen in the native ilea was only partial in the isografts and absent in the allografts. Because these changes occurred before the onset of mucosal ulcerations, we postulate that they could be used as early indicators of AR.

Insulin requirements after liver transplantation and FK-506 immunosuppression.

Hyperglycemia and new-onset diabetes mellitus is a well-recognized complication of solid organ transplantation. With the advent of FK-506 as a new immunosuppressive drug used in orthotopic liver transplantation (OLT), much attention has been paid to its diabetogenic effects. Currently, there are no data on the long term effects of FK-506 in glucose metabolism after OLT. In the present study, we determined the need for outpatient insulin in 52 American veterans who received 58 liver transplants using primary immunosuppression with FK-506 and PRED, with a mean follow-up of 467 days (range 17-952 days). We also analyzed their plasma glucose and FK-506 levels as well as the doses of PRED and FK-506 that they received at various intervals post-OLT. There were 7/52 (13.6%) patients who required insulin for the first time after OLT. Of these, the number of patients on insulin at 3, 6, and 12 months post-OLT was 5/47 (10.6%), 6/44 (13.6%), and 1/26 (3.8%), with none requiring insulin de novo at 18, 24, and 30 months post-OLT. Three patients required insulin temporarily but subsequently became normoglycemic without additional therapy. The need for insulin was not related to the dose of FK-506 administered nor the plasma level. Patients who required outpatient insulin were receiving higher doses of PRED than those not requiring insulin. The need for insulin did not affect the long-term graft or patient survival. In conclusion, the need for insulin with FK-506 compares favorably to that of previous immunosuppressive regimens, and FK-506 may have a reversible diabetogenic effect that is not dose dependent.

Gastrointestinal bleeding after liver transplantation.

To investigate the causes of gastrointestinal bleeding (GIB) and its impact on patient and graft survival after orthotopic liver transplantation (OLTx), the first 1000 consecutive OLTx using tacrolimus were studied. Our patient population consisted of 834 adults. The bleeding episodes of patients with GIB (n=74) were analyzed, and patients without GIB (n=760) were used as controls. The mean age, gender, and United Network for Organ Sharing status were similar in both groups. Endoscopy was done in 73 patients with GIB and yielded a diagnosis in 60 patients (82.2%): 39 with a single, and 21 with multiple GIB episodes. In the remaining 13 patients (17.8%), the bleeding source was not identified. Of 92 GIB episodes with endoscopic diagnoses, ulcers (n=25) were the most common cause of bleeding, followed by enteritis (n=24), portal hypertensive lesions (n=15), Roux-en-Y bleeds, and other miscellaneous events (n=28). The majority (73%) of the GIB episodes occurred during the first postoperative trimester. The patient and graft survival rates were statistically lower in the GIB group compared with the control group. The adjusted relative risk of mortality and graft failure was increased by bleeding. In summary, the cumulative incidence of GIB was 8.9%. Endoscopy identified the source of GIB in most cases. Ulcers were the most common cause of GIB after OLTx. The onset of GIB after OLTx was an indicator of decreased patient and graft survival.

Liver function tests in non-parenteral cocaine users.

To investigate the effect of cocaine on standard liver function tests (LFT), we studied 46 cocaine users with no history of parenteral drug use or homosexuality. LFT were similar in 21 users of cocaine only (Group A) and 25 users of cocaine and alcohol (Group B). Only three patients, two of whom were hepatitis B carriers, had an alanine aminotransferase level more than five units above normal limits. Group B patients were significantly more likely to complain of headaches, irritability, and loss of memory. We conclude that (1) non-parenteral cocaine use is rarely associated with significant LFT abnormalities and (2) alcohol may potentiate some adverse effects of cocaine.

Time-course changes in gastric mucosal blood perfusion following portal vein constriction in rats.

BACKGROUND/AIMS: Gastric mucosal blood flow is increased in all experimental models of chronic portal hypertension, when portosystemic shunting and the hyperdynamic circulation are fully developed. However, some controversy exists concerning the time course of this event. This study was undertaken to investigate the chronological changes in gastric mucosal blood perfusion during the first 7 days after partial portal vein constriction. METHODS: Portal hypertensive and sham operated animals were studied. Gastric mucosal blood flow was measured by hydrogen-gas clearance and gastric oxygen and hemoglobin content by reflectance spectrophotometry, prior to and immediately after partial portal vein constriction, and 1, 2, 7 and 15 days after induction of portal hypertension. RESULTS: Immediately after partial portal vein constriction, gastric mucosal blood flow and gastric oxygen were significantly decreased by 27% and 32% respectively, and gastric hemoglobin significantly increased by 19%. On day 1, gastric mucosal blood flow was increased in both portal hypertensive and sham operated rats. However, while this parameter returned to normal in sham operated rats, it remained high on days 2, 7 and 15 in portal hypertensive rats. In portal hypertensive rats, gastric oxygen values were not significantly different from those in sham operated animals, but hemoglobin tended to increase with development of portal hypertension, being significantly higher than in sham operated rats at days 2 and 7. Similar results were obtained when analyzing gastric mucosal blood perfusion 2 and 7 days after two-staged total portal vein constriction. CONCLUSIONS: Increased gastric mucosal blood perfusion is present in portal hypertensive rats from the first day after partial portal vein constriction. The lack of significant differences in all parameters on day 1 between portal hypertensive and sham operated rats is probably related to an increased mucosal blood perfusion related to surgery.

Pathology of human intestinal transplantation.

BACKGROUND & AIMS: Intestinal transplantation is a developing therapeutic option for patients with irreversible intestinal failure or short bowel syndrome. The aim of this study was to delineate the histopathology of human intestinal allografts and to define the features of intestinal rejection. METHODS: The histological features of 3015 endoscopic biopsy specimens and 23 allograft specimens from 62 intestinal recipients were analyzed retrospectively and correlated with clinical findings. RESULTS: Acute allograft rejection was characterized by a varying combination of crypt injury, mucosal infiltration primarily by mononuclear cells (including blastic lymphocytes), and increased crypt cell apoptosis (more than 2 per 10 crypts). It represented a patchy, often ileal-centered process that could progress to mucosal ulceration; later episodes (more than 100 days posttransplant) tended to show lesser cellular infiltration and greater apoptosis than earlier episodes. Correlation with clinical rejection was good (false-positive rate of 9%; false-negative rate of 26%). Two resected specimens showed obliterative arteriopathy indicative of chronic rejection. In other specimens, preservation injury, cytomegalovirus infection, post-transplant lymphoproliferative disorder, and nonspecific features of active or past mucosal injury could be recognized. CONCLUSIONS: Mucosal biopsy specimens are a useful means of monitoring intestinal allografts. Based on features validated by clinical correlation, acute rejection can be identified reliably and can be differentiated from the other pathological processes affecting the intestinal allograft.