ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Microelectrode technology is a promising tool for monitoring kidney ischemia and the changes induced by its therapeutic management. Ischemic preconditioning, that is, brief ischemic periods before sustained ischemia, has been shown to protect several organs, including the kidney, from ischemia-reperfusion injury. We tested whether the effect of preconditioning could be appraised by real-time measurement of parameters representative of tissue hypoxia.Methods.In a sample of pentobarbital-anesthetized and mechanically ventilated rats, we studied the effect of renal ischemic preconditioning (10-min ischemia and 10-min reflow interval) on subsequent ischemia-reperfusion (45 min and 60 min). Renal tissue electrical impedance, extracellular pH, and potassium concentration [K+] were measured continuously by implanted microelectrodes.Results.Ischemia induced an early, rapid rise in extracellular potassium and impedance module, followed by a phase of slower increase, whereas pH decreased rapidly, reaching a plateau. Preconditioning treatment did not cause significant changes in interstitial pH and [K+] but increased ischemic tissue impedance. During reperfusion, the three variables recovered progressively; however, after a decline, electrical impedance showed a clear postischemic increase. This rise was suppressed by preconditioning.Conclusions.Real-time measurement of any of the three parameters showed capability for early detection of ischemia. In contrast with findings in myocardial tissue, preconditioning in the kidney did not increase potassium cell loss during ischemia or improve ischemic acidosis or tissue impedance. Electrical impedance increased for a second time during reperfusion, indicating the presence of a postischemic cellular edema; concealing this episode was the most noticeable effect of the preconditioning treatment.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.The coronary oxygen persufflation (COP) technique has been previously shown to allow prolonged heart preservation of 14 hr with optimal recovery in a pig model of orthotopic transplantation. This technique may be applicable to hearts grafted from non–heart-beating donors (NHBD).Methods.Experiments were performed on pigs to test the effectiveness of oxygenated preservation, using COP for preservation of NHBD hearts. After 16 min of in situ normothermic ischemia, the hearts were flushed with histidine-tryptophan-ketoglutarate (HTK) solution or modified HTK solution (mBHTK) including 30 mmol/L 2,3-butanedione monoxime, 40 mg/L hyaluronidase,15 &mgr;mol/L adenosine, and 50 &mgr;mol/L calcium. Hearts were stored in the flush solutions for 3.3 hr or additionally persufflated with gaseous oxygen through the coronary arteries (COP) and transplanted orthotopically.Results.Simple storage in HTK did not allow recovery of these hearts, whereas mBHTK storage resulted in improved function with 1.1 L/min cardiac output. The cardiac output reached 2.8 L/min (68% of normal values) with a left ventricular developed pressure of 101 mm Hg only after mBHTK+COP. Then the hearts were able to guarantee the circulation of the recipient for the test period after weaning from the heart-lung machine.Conclusions.Even in an NHBD with more than 15 min of in situ ischemia, the use of COP in combination with mBHTK solution for 3.3-hr storage of the heart allows excellent recovery of transplanted hearts and normal weaning from the heart-lung machine. This indicates that COP combined with mBHTK may be an optimal preservation technique for use with NHBD hearts.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Analysis of hepatic microvascular perfusion in humans by direct imaging has been impossible so far. Orthogonal polarization spectral (OPS) imaging represents a new technology that combines simultaneous epi-illumination of the subject with linearly polarized light and noninvasive imaging of the microcirculation by reflectance spectrophotometry. The aim of this study was to evaluate the feasibility of studying the human hepatic microcirculation by OPS imaging in vivo and to define microcirculatory parameters for physiologic conditions.Methods.The hepatic microcirculation was analyzed in four different regions of both liver lobes in 11 healthy individuals undergoing partial liver resection for living-donor liver transplantation. The optical probe was gently positioned on the liver surface and sequences of at least 20 sec per measurement were recorded by a charge-coupled device camera on videotape. Microhemodynamic parameters were quantified off-line by single-frame and frame-to-frame analysis using a computer-assisted image analysis system.Results.OPS images of the hepatic microcirculation showed an acceptable quality with good resolution. Quantitative analysis revealed a sinusoidal red blood cell velocity of 0.97±0.43 mm/sec, a sinusoidal diameter of 8.8±0.9 &mgr;m, a sinusoidal volumetric blood flow of 58.2±9.6 pL/sec, an intersinusoidal distance of 22.6±2.5 &mgr;m, and a mean functional sinusoidal density of 391±30 cm−1. Apart from the sinusoidal red blood cell velocity, all data of the parameters studied matched the pattern of normal distribution.Conclusions.OPS imaging enabled for the first time direct in vivo visualization and quantification of the human hepatic microcirculation, providing significant insight into microvascular physiology of the human liver, to the extent that these data can be considered to represent physiologic values for human hepatic microcirculation.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.The purpose of this study was to investigate the metabolic alterations in the recipient and microcirculatory changes to the graft in the first 3 months after orthotopic liver transplantation (OLT) of nonsteatotic liver grafts from lean rats into obese Zucker rats.Methods.Body weight and plasma lipids were measured for 3 months post-OLT. Graft perfusion (hepatic microcirculatory perfusion [HMP]) and vascular structure were measured in vivo at 3 months. Liver biopsy specimens were obtained throughout for morphologic analysis. Sham-operation obese and lean Zucker rats acted as controls.Results.Plasma cholesterol levels were elevated from 2 months after OLT, whereas plasma triglyceride levels were reduced (P<0.05). Plasma high-density lipoprotein cholesterol concentrations increased from the first month after OLT (P<0.05). HMP in OLT animals (137±3 perfusion units [PU]) (P<0.05) was intermediate between lean (221±11 PU) and obese controls (113±5 PU). Hepatic cord width in the OLT group was similar to that in lean controls. Mean liver-to-body weight ratios in OLT animals (4.12%±0.39%) were significantly higher than in lean controls (3.25%±0.1%). The number of viable hepatocytes per high-power field in the OLT animals was lower than in the lean animals but higher than in obese controls (P<0.05). The transplanted livers showed moderate to marked microvesicular fatty change (MIFC) and glycogen deposition at 3 months after OLT.Conclusions.Transplantation of a nonsteatotic liver into an obese Zucker rat initially has a positive effect on lipid metabolism. However, 3 months after OLT, the donor liver became steatotic with MIFC changes and reduced perfusion. The authors’ results emphasize the importance of the recipient’s metabolic status in the maintenance of liver graft function after OLT.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Incidental celiac artery stenosis has been cited as an exclusion criterion for adult donor right hepatectomy.Methods.We report our experience involving right donor hepatectomy performed in the presence of isolated high-grade (greater than 80%) celiac trunk stenosis in two young healthy and asymptomatic adult living liver donors.Results.The immediate postoperative course was complicated by a superficial wound infection in one patient and a transient median nerve palsy caused by intraoperative positioning, which spontaneously resolved, in the second patient. Both were discharged within 7 to 10 days postoperatively. They are doing well at 1 year follow-up without any complaints and have both returned to 100% full employment.Conclusions.Our results show that right donor hepatectomy can be safely performed in the presence of significant celiac artery stenosis. However, careful long-term follow-up will be required to monitor for any future progression of mesenteric vascular disease.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Overexposure to cyclosporine is a risk factor for chronic allograft nephropathy (CAN) and dose reduction has been advocated. The purpose of this study was to determine the impact of adding the non-nephrotoxic immunosuppressant, rapamycin, after cyclosporine dose reduction in renal-allograft recipients with CAN.Methods.Thirty-one patients with biopsy-confirmed CAN were prospectively randomized to receive a 40% cyclosporine dose reduction with (rapamycin, n=16) or without (control, n=15) the addition of rapamycin 2 mg/day. Renal function and side-effect parameters were assessed. Patients had renal allograft biopsies taken at recruitment and after 6 months. Glomeruli were isolated from these and underwent total mRNA extraction followed by RT-PCR-ELISA to assess transforming growth factor-&bgr;1, collagen III, TIMP-1, TIMP-2, and matrix metalloproteinase-2 expression. Samples were also stained with Sirius red and the percentage interstitial volume fraction quantified by computerized histomorphometric analysis. Data are presented as mean (±SD).Results.Patient characteristics and cyclosporine trough levels after dose reduction (rapamycin 68 [±21] vs. control 56 [±19] ng/mL,P=NS) were similar in both groups. Rapamycin patients had a significant fall in Cr-51 radioisotope glomerular filtration rate (31.6 [±8.9] to 27.3 [±8.6] mL/min,P<0.01) that was not significant in controls (29.5 [±10.4] to 27.0 [±8.0] mL/min,P=NS). Transforming growth factor-&bgr;1 expression fell over time in control but remained constant in rapamycin patients. Conversely collagen III expression increased over the 6-month follow-up in rapamycin patients but not in controls. Both had comparable increases in TIMP-1 and matrix metalloproteinase-2 but only rapamycin patients developed a significant increase in TIMP-2. Sirius red-stained interstitial volume fraction fell over the study in controls (15.3–11.2%,P=0.06) but not in rapamycin patients (16.2–16.3%,P=NS).Conclusion.Rapamycin (2 mg/day) did not improve functional, molecular, or histological outcome in patients with CAN after cyclosporine dose reduction. Further studies involving larger numbers of patients are necessary to confirm these findings.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Because allograft rejection results from specific T-cell activation by donor human leukocyte antigens (HLA), new immunomodulatory therapies for organ-transplant recipients are used to selectively block T-cell activity without global immunosuppression. We investigated whether blockade of the high-affinity interleukin (IL)-2 receptor effectively prevented T-cell alloreactivity in cardiac transplantation.Methods and Results.A study of a humanized monoclonal antibody against the high-affinity IL-2 receptor (daclizumab) was performed in 70 adult, cardiac-transplant recipients. Patients were stratified based on the degree of donor-recipient HLA-DR matches. Primary and secondary endpoints were incidence and frequency of high-grade allograft rejections, IL-2-dependent, T-cell outgrowth from biopsy sites as measured by lymphocyte growth assay, and production of anti-HLA antibodies. Treatment with daclizumab significantly prevented development of high-grade acute rejection in recipients with at least one donor HLA-DR locus match during the first 3 months posttransplantation; in this group 0 of 13 (0%) treated with daclizumab experienced at least one high-grade rejection versus 3 of 13 (23%) controls (P=0.05). In addition, 1 of 12 (9%) daclizumab-treated patients experienced one or more episodes of IL-2-dependent, T-cell outgrowth versus 5 of 12 (42%) patients in the untreated group (P=0.05). In contrast, daclizumab used at the same dose and schedule was not as effective in fully HLA–DR-mismatched recipients. After cessation of daclizumab, allograft rejection increased to levels seen in controls.Conclusions.IL-2-receptor blockade is effective for preventing alloreactivity and high-grade rejection in cardiac transplantation; however, its efficacy seemed to be influenced by the degree of donor-recipient, HLA-DR locus mismatching.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.In an attempt to reduce calcineurin inhibitor toxicity, transplant patients treated with tacrolimus can be switched to maintenance treatment with sirolimus.Methods.In a prospective, randomized, multicenter trial, 33 kidney transplant recipients on steroid-free maintenance treatment with tacrolimus and mycophenolate mofetil continued tacrolimus and mycophenolate mofetil (control group, n=18) or were converted from tacrolimus to sirolimus (study group, n=15) at 1 year after transplantation.Results.The study was prematurely stopped as a result of a cluster of nine patients suffering from painful oral ulcerations in the study group. Oral ulcerations did not occur in the control group. The authors here report on the individual cases suffering from this side effect of the instituted immunosuppressive regimen.Conclusions.The authors review the literature with respect to the occurrence of oral ulcers associated with the use of sirolimus or mycophenolate mofetil and speculate on the causes of the high incidence of oral ulcers in their study group. Possible explanations are overimmunosuppression during the period of the conversion from tacrolimus to sirolimus without antiviral prophylaxis, the use of the oral emulsion instead of tablets, or the lack of corticosteroid co-administration.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID