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Introduction: It is unclear whether kidney/pancreas (KP) transplantation will prevent the progression of peripheral arterial disease (PAD) in patients with insulin dependent diabetes (IDDM) and end‐stage renal disease. We sought to determine the pre‐ and posttransplant prevalence of symptomatic PAD and changes in carotid artery intima‐media thickness (IMT) in KP recipients. Methods: In this single center study, outcomes were compared between KP recipients with and without a history of PAD. A subset of recipients underwent pre‐ and posttransplant IMT measurements. Results: Among the study group (N = 107), 18 (17%) recipients admitted to a pretransplant history of symptomatic PAD, comprised 11 foot infections and 7 amputations (5 minor and 2 major). Baseline characteristics of age, gender, race, years of diabetes, dialysis history, smoking history, years of hypertension, and history of coronary artery disease (CAD) were equivalent between PAD and non‐PAD cohorts. At a median follow‐up of 60 months (IQR: 28, 110), 16 (15%) KP recipients had suffered a PAD event. In multivariate analysis, a pretransplant history of PAD (hazard ratio [HR] 9.66, p < 0.001) and CAD (HR 3.33, p = 0.04) were independent predictors of posttransplant PAD events. Among a subset of 20 recipients (3 with PAD), mean IMT measurements pretransplant and at a median of 24 (range 18–24) months posttransplant, showed no evidence of disease progression. Conclusion: Based on IMT measurements and clinical results, KP transplantation stabilized PAD in most patients, but did not alter outcomes of symptomatic PAD recipients. A pretransplant history of PAD and CAD was an independent predictor of posttransplant PAD events. [ABSTRACT FROM AUTHOR]

Background: Solid organ transplant (SOT) recipients are predicted to have worse COVID-19 outcomes due to their compromised immunity. However, this association remains uncertain because published studies have had small sample sizes and variability in chronic comorbidity adjustment. Methods: In this retrospective cohort study conducted at a multihospital health system, we compared COVID-19 outcomes and survival up to 60 days following hospital admission in SOT recipients taking baseline immunosuppressants versus hospitalized control patients. Results: The study included 4,562 patients who were hospitalized with COVID-19 (108 SOT recipients and 4,454 controls) from 03/2020 to 08/2020. Mortality at 60 days was higher for SOT recipients (17% SOT vs 10% control; unadjusted odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.04–2.91, P = 0.04). We then conducted a 1:5 propensity matched cohort analysis (100 SOT recipients; 500 controls) using age, sex, race, body mass index, hypertension, diabetes, chronic kidney disease, liver disease, admission month, and area deprivation index. Within 28 days of admission, SOT recipients had fewer hospital-free days (median; 17 SOT vs 21 control; OR = 0.64, 95%CI 0.46–0.90, P = 0.01) but had similar ICU-free days (OR = 1.20, 95%CI 0.72–2.00, P = 0.49) and ventilator-free days (OR = 0.91, 95%CI 0.53–1.57, P = 0.75). There was no statistically significant difference in 28-day mortality (9% SOT vs 12% control; OR = 0.76, 95%CI 0.36–1.57, P = 0.46) or 60-day mortality (16% SOT vs 14% control; OR = 1.15, 95%CI 0.64–2.08, P = 0.64). Conclusions: Hospitalized SOT recipients appear to need additional days of hospital care but can achieve short-term mortality outcomes from COVID-19 that are similar to non-SOT recipients in a propensity matched cohort study. [ABSTRACT FROM AUTHOR]

Response to two doses of a nucleoside‐modified messenger ribonucleic acid (mRNA) vaccine was evaluated in a large solid‐organ transplant program. mRNA COVID‐19 vaccine was administered to transplant candidates and recipients who met study inclusion criteria. Qualitative anti‐SARS‐CoV‐2 Spike Total Immunoglobulin (Ig) and IgG‐specific assays, and a semi‐quantitative test for anti‐SARS‐CoV‐2 Spike protein IgG were measured in 241 (17.2%) transplant candidates and 1163 (82.8%) transplant recipients; 55.2% of whom were non‐Hispanic White and 44.8% identified as another race. Transplant recipients were a median (IQR) of 3.2 (1.1, 6.8) years from transplantation. Response differed by transplant status: 96.0% versus 43.2% by the anti‐SARS‐CoV‐2 Total Ig (candidates vs. recipients, respectively), 93.5% versus 11.6% by the anti‐SARS‐CoV‐2 IgG assay, and 91.9% versus 30.1% by anti‐spike titers after two doses of vaccine. Multivariable analysis revealed candidates had higher likelihood of response versus recipients (odds ratio [OR], 14.6; 95 %CI 2.19, 98.11; P =.02). A slightly lower response was demonstrated in older patients (OR.96; 95 %CI.94,.99; P =.002), patients taking antimetabolites (OR,.21; 95% CI.08,.51; P =.001). Vaccination prior to transplantation should be encouraged. [ABSTRACT FROM AUTHOR]

Background: Elderly transplant recipients experience lower rates of acute rejection with higher rates of infectious complications compared to their younger counterparts. While less intensive immunosuppression may be preferable, there are no recommendations for depleting versus non‐depleting induction strategies. We sought to compare infectious complications between anti‐thymocyte globulin (ATG) and basiliximab (IL2RA) induction in elderly kidney transplant recipients (KTRs). Methods: We reviewed 146 KTRs ≥65 years receiving ATG or IL2RA induction. Per institution protocol, ATG was administered to patients with the following characteristics, irrespective of age: African American (AA), PRA ≥20%, and/or re‐transplantation. Infectious complications (bacterial, viral, and invasive fungal) at 1 year were compared. Results: There were significantly more AA, deceased donors, and sensitized KTRs in the ATG group, reflecting criteria for induction agent. ATG KTRs experienced higher rates of overall infectious complications (77% vs 56%, P =.01), driven by increased bacterial (54% vs 39%, P =.08) and viral infections (51% vs 35%, P =.05). Urinary tract infections (UTIs) and CMV in particular occurred at high rates among ATG patients (46% and 32%, respectively). In multivariate analysis, the only independent risk factor associated with increased risk for infection was induction with ATG (adjusted HR 1.71 [95% CI 1.04‐2.83], P =.04). Overall rates of immunologic outcomes were low. Conclusion: Elderly KTRs receiving ATG are at an increased risk for infectious complications, largely attributed to high rates of UTIs and CMV. Additional strategies aimed at mitigating these complications in elderly patients requiring ATG may be beneficial. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to assess vitamin D status of US non-pregnant adults using a standardised assay across 15 mL/min/1.73 m2 increments of kidney function, report the use of dietary supplements containing vitamin D and assess relationships between vitamin D and markers of bone resorption. Design This study is a cross-sectional evaluation. Setting The study is from the US National Health and Nutrition Evaluation Survey in 2001-2012. Participants The participants were non-institutionalised, non-pregnant adults, age ≥20 years. Primary and secondary outcome measures The primary outcome measure was serum 25OHD evaluated using liquid chromatography-tandem mass spectroscopy traceable to international reference standards. Secondary outcome measures were use of dietary supplements containing vitamin D and the serum intact parathyroid hormone and bone-specific alkaline phosphatase in a subset of participants. Results The median 25OHD concentration in 27 543 US non-pregnant adults was 25.7 ng/mL (range, 2.2-150.0 ng/ mL). Vitamin D supplements were used by 38.0%; mean (SE)=757 (43) international units/day. The range of 25OHD concentration across groups, stratified by kidney function, was 23.0-28.1 ng/mL. The lowest concentration of 25OHD observed was in people with higher kidney function (23.0 ng/mL for estimated glomerular filtration rate >105 mL/min/1.73 m2). Only 24% of people not taking a dietary supplement had a 25OHD concentration >30 ng/mL. Serum intact parathyroid hormone inversely correlated with 25OHD within all kidney function groups. Bone-specific alkaline phosphatase was also negatively associated with 25OHD concentration. Conclusions These data indicate that 25OHD concentrations and supplement use may be suboptimal in a significant proportion of the population, across all kidney function levels. The response of bone resorption markers further suggests that 25OHD levels could be improved. Together, these data support a re-evaluation of the 25OHD concentration associated with health in adults. [ABSTRACT FROM AUTHOR]

Abstract: Background: Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. Methods: We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas‐kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. Results: Twenty‐three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31 ± 17 days post‐transplant and accounted for 34 admissions with an average length of stay of 5.1 ± 3.4 days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy‐proven rejection, graft loss, death, or documented infections compared to UF‐free patients during the first‐year post‐transplant. Conclusion: UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first‐year post‐transplant. [ABSTRACT FROM AUTHOR]

Abstract: Renal transplantation remains the definitive treatment for end‐stage renal disease (ESRD). The shorter renal vein in right donor nephrectomies is associated with higher incidence of technical failure. We present here our experience with autologous internal jugular vein (IJV) conduits to facilitate living‐donor transplants. Six patients underwent right, living‐donor kidney transplant with simultaneous IJV harvest over a 1‐year period. All had bilateral jugular duplex scans preoperatively and were placed on aspirin 81 mg postoperatively. Patient demographics, comorbidities, and laboratories were retrospectively queried. Postoperative follow‐up and examination were performed per institutional protocol. The mean age and BMI were 51 ± 4.6 years and 30 ± 1.4 kg/m2, respectively. An average 4.5 ± 0.5 cm of IJV was taken, and anastomosed exsitu, end to end to the renal vein. One patient developed a perinephric hematoma requiring reexploration and another expired during follow‐up from septic shock of unknown etiology; there were no harvest site complications or deep vein thrombosis. All had immediate and stable graft function at 3.8 ± 1.7 (range: 0.7‐11.3) months follow‐up. Mean serum creatinine and estimated glomerular filtration rate were 1.3 ± 0.1 mg/dL and 55 ± 2.4 mL/min/1.73 m2, respectively. Internal jugular vein extension of short right renal veins for kidney transplant is a viable technique for ESRD patients with promising results. [ABSTRACT FROM AUTHOR]

Abstract: Background: We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC‐MMF) into tacrolimus/mTOR inhibitor (TAC‐mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. Methods: In this single‐center review, the TAC‐mTOR cohort (n = 39) was converted at 1 month post‐transplant to an mTOR inhibitor and reduced‐dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC‐MMF. Results: At 3 years post‐transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF‐treated cohorts. (P = ns). BK viremia‐free survival was better for the mTOR vs MMF‐treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR‐treated recipients displayed better CMV infection‐free survival compared to the MMF‐treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post‐transplantation. Conclusion: Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function. [ABSTRACT FROM AUTHOR]

Herein, we describe a case of early belatacept conversion in a human immunodeficiency virus ( HIV)-positive kidney transplant recipient in an effort to improve suboptimal graft function and avoid drug interactions following anti-thymocyte globulin ( ATG) administration. We observed improvement in renal function without HIV disease progression or opportunistic infections. Donor-specific antibodies appeared shortly after conversion but cleared without intervention. This case highlights belatacept as a means to improve renal function and avoid significant drug interactions even following ATG induction. [ABSTRACT FROM AUTHOR]

Background De novo donor-specific antibodies (dn DSA) after renal transplant are associated with acute rejection ( AR) and graft loss, yet most recipients with dn DSA have stable function and no AR. We assessed whether the persistence of dn DSA increased the risk of a detrimental outcome. Methods A single-center review of renal transplant recipients monitored for dn DSA at multiple time points post-transplant. An Isolated dn DSA was defined as one positive dn DSA and no additional positive tests, whereas ≥2 positive dn DSA was defined as persistent dn DSA. Results Of 708 recipients, 22% developed dn DSA, of whom 64% had persistent dn DSA. At median follow-up of 35 (range 12-74) months, there were fewer episodes of AR in the isolated dn DSA vs the persistent dn DSA group (2% vs 22%; P<.001,) and fewer graft losses with isolated dn DSA vs persistent dn DSA (0% vs 10%; P=.03). Within the persistent dn DSA group, recipients with dn DSA ≥60% of time points, had more AR (32% vs 16%, P=.10) and more graft losses (21% vs 2%; P=.003) than those with dn DSA<60%. Conclusions Persistence of dn DSA resulted in more AR and graft failure than a single positive value. Recipients with longer duration of dn DSA persistence had an additional increased risk of AR and graft failure. [ABSTRACT FROM AUTHOR]

Background The natural history of de novo donor-specific antibodies ( dn DSA) after lung transplantation is not well-described. We sought to determine the incidence and risk factors associated with dn DSA and compare outcomes between recipients with transient (or isolated) vs persistent dn DSA after transplantation. Methods A single-center review of all lung transplants from 1/2009-7/2013. DSAs were tested eight times in the first year and every 4 months thereafter. Outcomes examined included acute rejection and graft failure. Results Median follow-up was 18 months (range: 1-61 months), and 24.6% of 333 first-time lung-only transplant recipients developed a dn DSA. Ethnicity, HLA- DQ mismatches, post-transplantation platelet transfusion and Lung Allocation Score >60 were associated with dn DSA ( P<.05). Overall graft survival was worse for dn DSA-positive vs negative recipients ( P=.025). Of 323 recipients with 1-year follow-up, 72 (22.2%) developed dn DSA, and in 25 (34.7%), the dn DSA was transient and cleared. Recipients with transient dn DSA were less likely to develop acute rejection than those with persistent dn DSA ( P=.007). Conclusions Early post-lung transplantation, dn DSA occurred in 1/4 of recipients, was associated with peri-transplant risk factors and resulted in decreased survival. Spontaneous clearance of dn DSA, seen in one-third of recipients, was associated with a lower risk of acute rejection. [ABSTRACT FROM AUTHOR]

Invasive non-native species are widespread in freshwaters but their capacity to establish in new lakes has seldom been assessed. In this fouryear study (2006–2009), we used Side-scan Sonar and underwater video to illustrate how a 200 ha urban, amenity lake at Cardiff Bay (Wales, UK) was invaded extensively by zebra mussels Dreissena polymorpha (Pallas) within 2–3 years of creation in 2001. Veliger surveys and artificial substrates were used to assess conditions affecting juvenile settlement. Within 5–8 years of lake formation, all hard substrates at 0.5–7 m held mussel densities of 250–6600 m-2 which, coupled with a crude estimate of habitat available, suggested a lake-wide population of at least 9–31 million adults. Veligers reached 8 (± 2 SE) to 14 (± 4) L-1 during May–September when water temperatures were >14 °C, but densities and juvenile settlement declined at high discharge when lake flushing rates increased: settled densities in a drier year (2007) exceeded those in a wet year (2008) by 120× implying more effective colonisation under low flows and longer residence times. These data illustrate how rapid invasion by non-native species should be appropriately factored into planning and risk assessments for new water bodies, and potential effects on amenity, ecosystem processes and ecosystem services considered. Our data suggest that drought and low flow under future climates could be a particular risk factor affecting Dreissena colonisation. [ABSTRACT FROM AUTHOR]

Lymphocyte-depleting induction lowers acute rejection ( AR) rates among high-immunologic risk ( HIR) renal transplant recipients, including African Americans ( AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dn DSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin ( ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dn DSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor ( LD) recipients to 30% in younger AA deceased donor ( DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non- AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dn DSA among all HIR recipients. Development of both AR and dn DSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups. [ABSTRACT FROM AUTHOR]

Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients. Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013. Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p<0.001). For DKT versus SKT, the rates of delayed graft function (10.3 versus 9.2%) and acute rejection (20.7 versus 22.4%) were equivalent (p = ns). A higher than expected urologic complication rate in the DKT cohort (14 versus 2%, p<0.01) was reduced through modification of the ureteral anastomosis. Graft survival was equivalent between DKT and SKT groups (p = ns) with actuarial 3-year DKT patient and graft survivals of 100% and 93%. At 3 years, the groups had similar renal function (p = ns). Conclusions. By utilizing extended criteria donor organs as DKT, the donor pool was enlarged while providing excellent patient and graft survival. The DKT urologic complication rate was reduced by modification of the ureteral anastomosis. [ABSTRACT FROM AUTHOR]

Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by "indirect" viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovirresistant CMV disease. All patients initially developed "breakthrough" viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV. [ABSTRACT FROM AUTHOR]

Thepharmacokinetics of tacrolimus are influenced by many factors, including genetic variability, acute infections, liver dysfunction, and interacting medications, which can result in elevated concentrations.The most appropriate management of acute tacrolimus toxicity has not been defined though case reports exist describing the therapeutic use of enzyme inducers to increase tacrolimus metabolism and decrease concentrations. We are reporting on the utilization of phenytoin to assist in decreasing tacrolimus concentrations in a case series of four solid organ transplant recipients with acute, symptomatic tacrolimus toxicity presenting with elevated serum creatinine, potassium, and tacrolimus trough concentrations greater than 30 ng/mL. All four patients had the potential causative agents stopped or temporarily held and were given 300 to 400mg/day of phenytoin for two to three days.Within three days of beginning phenytoin, all four patients had a decrease in tacrolimus concentration to less than 15 ng/mL, a return to or near baseline creatinine concentration, and lack of phenytoin-related side effects.Therefore, phenytoin appears to be a safe and potentially beneficial treatment option in patients with symptomatic tacrolimus toxicity. [ABSTRACT FROM AUTHOR]

To meet the widely varying speed and power requirements of multifunctional mobile devices, an appropriate combination of technology features, circuit-level low-power techniques, and system architecture is implemented in a GSM/Edge baseband processor with multimedia and mixed-signal extensions. Power reduction techniques and performance requirements are derived from an analysis of relevant use cases and applications. The 44 mm² baseband processor is fabricated in a 90-nm low-power CMOS technology with triple-well option and dual-gate oxide core devices. The ARM926 core achieves a maximum clock frequency of 380 MHz at 1.4-V supply due to the usage of thin oxide (1.6 nm) devices. Power dissipation can be adapted to the performance requirements by means of combined voltage and frequency scaling to reduce active power consumption in medium-performance mode by 68%. To reduce leakage currents during standby mode, large SRAM blocks, nFET sleep transistors, and circuit components with relaxed performance requirements are implemented using devices with 2.2-nm gate oxide thickness. [ABSTRACT FROM AUTHOR]

Objective: [2-18F] 2-fluorodeoxyglucose (FDG) is widely used to trace glucose metabolism for cardiac imaging with positron emission tomography. Because the transport and phosphorylation rates differ for glucose and FDG, a lumped constant (LC) is used to correct for these differences. The effects of ischemia and reperfusion on the LC in vivo are unknown. To determine the validity of FDG as a tracer of glucose metabolism in post-ischemic myocardium in vivo, the relationship between glucose uptake (GU) and FDG metabolic rate (FDG-MR) was assessed early post-reperfusion following a transient ischemic event. Methods: FDG metabolic rate, measured with FDG and PET, was compared to invasive measurements of substrate metabolism in reperfused and global myocardium of dogs subjected to 25 min ischemia and 2 h reperfusion. Results: The FDG metabolic rate was decreased 20±4% in reperfused relative to remote myocardium. Glucose oxidation and lactate uptake were also decreased in reperfused relative to global myocardium, by 26±6% and 60±8% respectively. Glucose uptake did not differ significantly between reperfused and global myocardium. A linear correlation between FDG metabolic rate and glucose uptake was found in both reperfused and remote myocardium. Estimates of the LC from the slopes of the regression lines were similar in reperfused and remote myocardium, 1.25 and 1.44 respectively, and did not differ significantly from the LC determined in control dogs, 1.1. Conclusions: We conclude that the FDG metabolic rate continues to correlate well with glucose metabolism in reperfused myocardium. While FDG metabolic rate was modestly decreased in the absence of a significant change in glucose uptake, large alterations in the LC are not found 2 h post-reperfusion in vivo. [ABSTRACT FROM PUBLISHER]

Objective: Myocardial reperfusion following brief periods of ischaemia is associated with prolonged, reversible periods of metabolic dysfunction. As the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is inhibited in vitro by reactive oxygen species, we hypothesized that production of reactive oxygen species during reperfusion would lead to inhibition of GAPDH in post-ischaemic myocardium. Methods: Anaesthetized closed-chest dogs were subjected to 20 min balloon occlusion of the left anterior descending coronary artery. Biopsy samples were taken after 3 and 24 h of reperfusion, to determine the activity of GAPDH and the concentrations of glycolytic intermediates in post-ischaemic and remote, non-ischaemic territories. Results: A significant reduction in GAPDH activity was observed in post-ischaemic relative to remote tissue after 3 h reperfusion (4.8 ± 0.5 vs. 2.9 ± 0.2 μmol/min/mg protein; P < 0.01). Western blotting revealed no reduction in the levels of GAPDH protein. Analysis of enzyme kinetics showed the loss of activity to be associated with decreased Vmax (5.9 ± 0.5 vs. 3.2 ± 0.2 μmol/min/mg protein; P < 0.01) with no significant change in the Km for glyceraldehyde-3-phosphate (GAP). Incubation of the inhibited enzyme under both mild and strong reducing conditions failed to reactivate the enzyme. The acute reduction in enzyme activity in post-ischaemic tissue was accompanied by regional differences in glycolytic intermediates, notably a twofold accumulation of GAP (P < 0.05), and a reduction in the glucose metabolic rate (GMR) determined by positron emission tomography and [18F]2-fluorodeoxyglucose. By 24 h reperfusion, no regional differences in GAPDH activity, reaction Vmax or Km, GAP concentrations or GMR were detectable. Conclusions: These results suggest that inhibition of GAPDH activity may represent an important point at which glycolysis is limited during reperfusion, and further, that the mechanisms of enzyme inhibition do not involve simple oxidation or S-thiolation of critical active site thiol groups. [ABSTRACT FROM PUBLISHER]