Functional results in children with retinopathy of prematurity treated with intravitreal bevacizumab.

BACKGROUND/AIM: The aim of the study is to describe the efficacy and to determine the functional outcome in terms of visual acuity and refractive defect of a single dose of intravitreal bevacizumab in patients with high-risk ROP type 1. METHODS: In this retrospective clinical study patients diagnosed between December 2013 and January 2018 with high-risk pre-threshold ROP type 1 and treated with intravitreal bevacizumab were selected. All patients were treated following the established protocol at our centre. Those patients with less than three-year follow-up were excluded. Visual acuity and cycloplegic refraction in the last visit were registered. Treatment efficacy was defined as the absence of retreatment with intravitreal anti-VEGF or laser during follow-up. RESULTS: A total of 38 infants (76 eyes) were included in the analysis. Twenty infants (40 eyes) completed visual acuity testing. Mean age was 6 years (IQR: 4-9). Median visual acuity was 0.8 (IQR: 0.5-1). Thirty-four eyes (85%) had good visual acuity (greater than or equal to 0.5). Thirty-seven patients (74 eyes) had cycloplegic refraction measured. Median spherical equivalent at the last visit was +0.94 (IQR: -0.25; 1.88). Treatment success rate was 96.05%. CONCLUSION: Intravitreal bevacizumab treatment showed good functional outcome in patients with high-risk ROP type 1. In our study, good response to treatment was observed with a success rate over 95%.

Outcomes After Vascular Surgery Procedures in Patients with COVID-19 Infection: A National Multicenter Cohort Study (COVID-VAS).

OBJECTIVES: To analyze the outcome of vascular procedures performed in patients with COVID-19 infection during the 2020 pandemic. METHODS: This is a multicenter, prospective observational cohort study. We analyzed data from 75 patients with COVID-19 infection undergoing vascular surgery procedures in 17 hospitals across Spain and Andorra between March and May 2020. The primary end point was 30-day mortality. Clinical Trials registry number NCT04333693. RESULTS: The mean age was 70.9 (45-94) and 58 (77.0%) patients were male. Around 70.7% had postoperative complications, 36.0% of patients experienced respiratory failure, 22.7% acute renal failure, and 22.7% acute respiratory distress syndrome (ARDS). All-cause 30-days mortality rate was 37.3%. Multivariate analysis identified age >65 years (P = 0.009), American Society of Anesthesiologists (ASA) classification IV (P = 0.004), preoperative lymphocyte count <0.6 (×109/L) (P = 0.001) and lactate dehydrogenase (LDH) >500 (UI/L) (P = 0.004), need for invasive ventilation (P = 0.043), postoperative acute renal failure (P = 0.001), ARDS (P = 0.003) and major amputation (P = 0.009) as independent variables associated with mortality. Preoperative coma (P = 0.001), quick Sepsis Related Organ Failure Assessment (qSOFA) score ≥2 (P = 0.043), lymphocytes <0.6 (×109/L) (P = 0.019) leucocytes >11.5 (×109/L) (P = 0.007) and serum ferritin >1800 mg/dL (P = 0.004), bilateral lung infiltrates on thorax computed tomography (P = 0.025), and postoperative acute renal failure (P = 0.009) increased the risk of postoperative ARDS. qSOFA score ≥2 was the only risk factor associated with postoperative sepsis (P = 0.041). CONCLUSIONS: Patients with COVID-19 infection undergoing vascular surgery procedures showed poor 30-days survival. Age >65 years, preoperative lymphocytes <0.6 (x109/L) and LDH >500 (UI/L), and postoperative acute renal failure, ARDS and need for major amputation were identified as prognostic factors of 30-days mortality.

Factors associated with the orthopaedic surgeon's decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1905 patients.

OBJECTIVE: To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA). DESIGN: Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0-4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country. RESULTS: In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69-4.97] and 3.30 [2.17-5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32-2.06] and 1.38 [1.15-1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA. CONCLUSION: Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR.

Simultaneous bilateral percutaneous nephrolithotomy: Effectiveness and safety. / Nefrolitotomía percutánea bilateral simultánea: Eficacia y seguridad".

OBJECTIVES: To evaluate the effectiveness and safety of simultaneous bilateral percutaneous nephrolithotomy performed in patients affected with bilateral renal calculi. MATERIALS AND METHODS: This is a prospective study from September 2012 to November 2016. Patients diagnosed of bilateral kidney stones with abdominal CT scan were included. Surgical technique prone position, renal puncture guided by fluoroscopy and tract dilation up to 24Ch. We reviewed demographic and stone characteristics, stone free rate, clinical success, complications and follow-up. RESULTS: During the study period, 732 percutaneous nephrolithotomies were performed. Eighteen patients were included (36 renal units, 2.5%), 13 men and 5 women, with a median age of 58 years and an interquartile range (IQR) of 40-66. Median stone burden was 228mm2 (IQR 134-389); median operative time, 150minutes (IQR 97-180); and median hospital stay, 5 days (IQR 5-15). Stone free rate was 80%. Residual calculi were encountered in 8 renal units (22.2%) and required other complementary techniques for their complete tesolution 4 external shockwave lithotripsies, one open ureterolithotomy, 2 ureteroscopies and one second look. Major complications included 4 cases of severe hemorrhage managed with angiographic embolization. The median follow-up was 36 months (range 26-46). CONCLUSIONS: Simultaneous bilateral percutaneous nephrolithotomy is an effective and safe procedure in patients affected with bilateral renal calculi. It is a surgical challenge that should be performed in selected patients and in centers with experience.

Our experience in the management of prostate cancer in renal transplant recipients. / Nuestra experiencia en el manejo del cáncer de próstata en pacientes trasplantados renales.

INTRODUCTION AND OBJECTIVES: The management of Prostate cancer (PCa) in renal transplant recipients (RTR) is challenging and remain controversial. Currently there is no consensus about this condition. The aim of the study was to analyse our experience in the diagnosis and management of PCa in RTR. METHOD: Retrospective monocentric study of a prospective and consecutive database from 2003-2017. Inclusion of RTR diagnosed of PCa. Staging and treatment in agreement with the contemporary guidelines. The main outcome measures included clinical staging, type of treatment, oncological outcomes and follow-up. RESULTS: 1,330 renal transplants were performed (787 males), diagnosed of PCa in 33 RTR (4.2%), mean age 66years±6.3 (51-78). Median PSA was 8.8ng/ml and PSA ratio 0.19. Mean time between renal transplantation and PCa diagnosis 130months±90 (2-236). TREATMENTS: Radical prostatectomy (RP) (n=22; 66.7%), Radiation therapy (RT) with Androgen deprivation therapy (ADT) (n=7; 21.2%), Active surveillance (n=3; 9.1%), ADT (n=1; 3%). No graft loss neither impaired renal function due to PCa treatment was reported. After RP two patients (9.1%) presented biochemical recurrence treated with RT. Remission of the 100%. Mean follow-up was 61months±37 (6-132). CONCLUSIONS: PCa in renal transplant patients can be managed with the same therapeutic options as in the general population. Active surveillance should also be provided in RTR despite being under immunosuppressive therapy.

The Latin American experience of allografting patients with severe aplastic anaemia: real-world data on the impact of stem cell source and ATG administration in HLA-identical sibling transplants.

We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P=0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P=0.18), and for grades III-IV was 2.6% vs 11.6% (P=0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P=0.002) and extensive 5% vs 23.6% (P=0.01). OS was 74% vs 76% for BM vs PBSCs (P=0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P=0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P=0.005) respectively. In multivariate analysis, aGvHD II-IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1-5.6, P=0.02) and aGvHD III-IV (HR 8.3 CI 3.4-20.2, P<0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients.

Spanish consensus document for acceptance and rejection of kidneys from expanded criteria donors.

In the recent years, more than 60% of available deceased donors are either older than 50 yr or have significant vascular comorbidities. This makes the acceptance and rejection criteria of renal allografts very rigorous, especially in cases of younger recipients, and at the same time encourages live donations. In our country, there is a lack of homogeneity in the percentages of use of expanded criteria donor (ECD) allografts between the different autonomous communities. Furthermore, the criteria vary greatly, and in some cases, great importance is given to the biopsy while in others very little. In this study, we present a unified and homogenous criteria agreed upon by consensus of a 10-member Panel representing major scientific societies related to renal transplantation in Spain. The criteria are to be used in accepting and/or rejecting kidneys from the so-called ECDs. The goal was to standardize the use of these organs, to optimize the results, and most importantly to provide for the maximum well being of our patients. Finally, we believe that after taking into account the Panel's thorough review of specific scientific literature, this document will be adaptable to other national renal transplant programmes.

Long-term results of biopsy-guided selection and allocation of kidneys from older donors in older recipients.

In our old-for-old program, we discard or allocate older extended criteria donor kidneys to single (SKT) or dual kidney transplantation (DKT) depending on histological Remuzzi's score in recipients older than 60 years. Here, we analyze the long-term results of this program and try to identify independent predictors of patient and graft survival. Between December 1996 and January 2008, we performed 115 SKT and 88 DKT. Discard rate was 15%. Acute rejection incidence was higher in SKT than in DKT (22.6% vs. 11.4%, p = 0.04). Renal function was better in DKT than in SKT up to 5 years after transplantation. Surgical complications were frequent in DKT. Ten-year cumulative graft survival was significantly lower in the SKT group (31% vs. 53%, p = 0.03). In SKT, histological score 4 provided similar graft survival than 3 or less, whereas in DKT score 4, 5 or 6 displayed similar outcome. Finally, independent predictors of graft survival were history of major adverse cardiac event and 1-year serum creatinine, rather than SKT or DKT. In conclusion, this biopsy-guided old-for-old strategy resulted in acceptable long-term graft survival. Our results suggest that DKT should be considered for scores of 5 or 6 only.

JAK2V617F activating mutation is associated with the myeloproliferative type of chronic myelomonocytic leukaemia.

BACKGROUND: Chronic myelomonocytic leukaemia (CMML) is a haematopoietic malignancy with heterogeneous clinical and morphological features. It is classified in the World Health Organization myeloproliferative-myelodysplastic overlap category. JAK2(V617F) mutation can be found in a large percentage of patients with myeloproliferative neoplasms. AIMS: To investigate the association between JAK2(V617F) mutation and clinical, haematological and bone marrow histological features in CMML and to verify whether the mutation is associated with the myeloproliferative type of the disease. METHODS: 78 consecutive patients with newly diagnosed CMML from 2004 to 2008 were included in the study. JAK2(V617F) mutation was assessed using direct sequencing of exon 14 or by allele-specific PCR from total peripheral blood or bone marrow samples. RESULTS: JAK2(V617F) mutation was identified in eight cases (10.2%). All patients with the mutation presented with splenomegaly and had a significantly higher haemoglobin level and neutrophil count than patients without the mutation. All bone marrow biopsies of JAK2(V617F)-mutated CMML showed increased erythropoiesis, a marked myeloid and megakaryocytic hyperplasia with occasionally clustered megakaryocytes, and a mild or moderate (grade 1 or 2) fibrosis; six cases showed an increased number of dilated sinusoids and reactive lymphoid nodules. CONCLUSIONS: The results indicate that JAK2(V617F) mutation is associated with clinical and morphological features of the myeloproliferative type of CMML. Therefore, JAK2 mutation analysis together with bone marrow morphology could help in a more appropriate classification of the disease.

Ensayo preclinico de la vacuna candid #1 producida en Argentina contra la fiebre hemorragica Argentina / Preclinical assay of candid #1 vaccine against argentine hemorrhagic fever made in Argentina

Se comparó en cobayos la seguridad, inmunogenicidad y eficácia protectora de um lote de vacuna Candid #1 (C#1) fabricada en Estados Unidos de América (EE.UU.) y distintos lotes de la misma vacuna fabricados en Argentina (Arg.). El lote TSI 5-1-92 (EE.UU) y los lotes Exp N3, 7A y 8A (Arg) fueron inoculados (0.5ml, IM) en cobayos de 250400g. Para cada ensayo diez animales recibieron solución fisiológica y sirvieron como control. Todos fueron desafiados con la cepa patógena P23790 de vírus Junin. Se registro: a) temperatura rectal, b) peso corporal , c) presencia de anticuerpos neutralizantes (AcNT) pré y post-vacunación, d) respuesta al desafio . Todos los animales vacunados desarrollaron AcNT anti vírus Junin (rango= 4081920 y sobrevivieron al desafio. En cada grupo control 810 animales murieron (dia 23.3+_ 5.4 post- desaportada y los diferentes lotes de C#1 producidos en Argentina.

Cyclic recovery of adenovirus in a stem cell transplant recipient: an inverse association with graft-versus-host disease.

Adenovirus (AdV) infections have been increasingly recognized as significant pathogens that may cause severe morbidity and mortality among stem cell transplant (SCT) recipients. AdV can cause localized infections such as hemorrhagic cystitis (HC), pneumonia, hepatitis and also disseminated disease that can lead to death. We report a case of severe hemorrhagic cystitis in a SCT recipient who died 83 days after transplant. In this patient, AdV recovery was not constantly detected. In fact, fluctuations of the AdV detection in leukocytes and urine were observed by culture and PCR. When analyzing this viral cyclic recovery with different signs or symptoms in the patient, we observed an inverse association with the presence of acute graft-versus-host disease (GVHD). Whether these fluctuations represent donor-derived reactivity, indirectly manifested by the presence of GVHD, requires further study. This is the first case describing a dynamic pattern of AdV replication in leukocytes and urine samples from a patient with severe HC and the temporal correlation with GVHD.

Percutaneous endoscopic gastrostomy in head and neck cancer patients.

OBJECTIVE: To present our experience with the indications and complications of percutaneous endoscopic gastrostomy (PEG) in head and neck cancer patients. MATERIALS AND METHODS: In a retrospective study of the patients treated, we reviewed the records of 43 patients diagnosed with head and neck cancer at the Otorhinolaryngology Department, in which a PEG was performed by the Unit of Digestive Endoscopy. RESULTS: All cases had squamous cell carcinoma. Larynx was the most frequent primary site, with 21 cases (49%), followed by hypopharynx, 12 patients (28%). Indications for PEG were: dysphagia (53.5%) and pharyngocutaneous fistula (43.5%). The most frequent complication was a local infection. CONCLUSION: PEG is a good choice for long-term enteral feeding in head and neck cancer patients due to its low complication rate and easy handling.

Control of murine cytomegalovirus replication in salivary glands during acute infection is independent of the Fas ligand/Fas system.

The course of mouse cytomegalovirus (MCMV) infection was compared between mutant C57BL/6 (B6) mice deficient in either perforin (perf-/-), or perforin, granzyme A and B (perfxgzmAxB-/-), and B6 gld mice lacking functionally active Fas ligand to elucidate the contribution of the two main cytolytic pathways in the early control of MCMV infection. At 15 and 30 days post infection (p.i.) virus titers were elevated in salivary glands of perf-/- and perfxgzmAxB-/-, but almost undetectable in those of mutant gld and C57BL/6 wild-type mice. No virus was detectable in lung and spleen tissues of the mutant or B6 mice at the time points tested. At 15 days p.i., scanty lymphocytic periductal infiltration was seen in salivary glands of perf-/- and perfxgzmAxB-/; these pathological alterations were minimal at 30 days p.i.. In contrast, no pathological alterations were seen in the respective organs of infected B6 and gld mice at the two time points p.i.. At 15 days p.i., reactive follicles were observed in the white pulp of spleen tissues from both mutant and B6 mice, but at 30 days p.i. only in those of mutant mice. No inflammatory responses were seen in the lung tissues of any of the four mouse strains tested. Together with previous observations (Riera et al.. 2000), the results demonstrate that both perforin and granzymes A/B, but not the FasL/Fas system are critical for viral elimination in salivary glands during the acute phase of infection. However, for the long-term control of MCMV infection, neither of the two cytolytic pathways seem to be necessary.

Serial protocol biopsies to quantify the progression of chronic transplant nephropathy in stable renal allografts.

AIM: To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy. METHODS: A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique. RESULTS: Chronic Banff scores increased during follow-up, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r = 0.57, p < 0.001), histocompatibility (r = 0.38, p = 0.01) and serum cholesterol (r = 0.31, p = 0.047). Vvinterstitium/cortex at 4 months correlated with recipient body surface area (r = 0.44, p = 0.004) and delayed graft function (p = 0.016). Power calculations showed that Vvintima/artery and Vvinterstitium/cortex allow an important reduction in minimum sample size of a hypothetical trial aimed to prevent chronic allograft nephropathy. CONCLUSIONS: Intimal thickening and interstitial widening progresses rapidly during the first 4 months after transplantation and slowly thereafter. These parameters can be considered as a primary efficacy variable in trials aimed to prevent chronic allograft nephropathy.

Prueba de neutralización del virus de la coriomeningitis linfocítica para diferenciar infecciones con dos arenavirus en Argentina / [Neutralization test for lymphocytic choriomeningitis virus for distinguishing between two arenavirus infections in Argentina]

The active coexistence of two pathogenic arenaviruses, Junin (JUNV) and lymphocytic choriomeningitis (LCMV), in the same region of Argentina, has been known since the early 70’s, and records of clinical and subclinical human infections by one and/or the other agent have been continuously produced for the last 25 years. Anti-LCMV antibody is currently searched only by indirect immunofluorescence, a test that shows cross reactions among a number of arenaviruses yielding, in the cases of LCMV and JUNV consecutive infections, a concomitant seroconversion for both viruses, as an inconclusive diagnostic result. In contrast, neutralization (NT) tests reveal arenavirus antibodies directed to unique epitopes on these virus envelopes, thus allowing to disclose the sequence in the cases of consecutive infections. In this paper, the characteristics of neutralization (NT) test for LCMV in cell cultures are described, as well as its performance in the field diagnosis of LCMV human infections. The native LCMV strain Cba An 13065 was inoculated on L-929 cell (ATCC CCL 1), and procedures were followed to perform a constant virus-variable serum NT test. Final points of sera titrations were expressed as the maximal serum dilution that yielded 75

of pfu inhibition. This NT test was assayed on paired serum samples of 36 patients with confirmed Argentine hemorrhagic fever (AHF) (a disease caused by JUNV), who had had a known previous contact with LCMV through IFI. The use of this one test led to confusing diagnosis of the disease due to concomitant seroconversion for JUNV and LCMV. By using NT test, it was shown that: some of them were possibly not infected by LCMV, and that 30/36 cases (83.3

) had a pre-existing level of LCMV antibody, with titers in the range of 5 to 640, remaining unchanged 60 days after the clinical AHF. This shows that NT antibodies to LCMV are not influenced by the outcome of the immune response to JUNV, thus confirming the efficiency of NT test as identificator among arenaviruses. To assess the performance of this NT test in individuals having only IFI antibodies to LCMV, 126 serum samples obtained through serological surveillance in a rural area of Argentina, were used. It was found that NT had improved coincidence with IFI as IFI titers increased. Interpretations were based on the pan-arenavirus antibody response obtained by using IFI as the only test. Results presented herein prove that the described NT test is a valuable tool for the detection of LCMV infections, particularly when a previous infection with LCMV has to be demonstrated during the acute phase of Argentine hemorrhagic fever.

The thymidylate synthase inhibitor ZD1694 potently inhibits murine and human cytomegalovirus replication in quiescent fibroblasts.

Tomudex (ZD1694) is a quinazoline-based folate analog and a powerful inhibitor of cellular thymidylate synthase and is approved in Europe for use in oncology. Here the first evidence of its activity against murine and human cytomegalovirus (MCMV and HCMV) is reported. ZD1694 irreversibly inhibited the replication and DNA synthesis of both viruses in quiescent fibroblasts. The corresponding 50% effective concentrations were 0.006 and 0.002 microM respectively, whereas the 50% cytotoxic concentration was >10 microM for both murine and human quiescent fibroblasts. A similar antiviral effect was observed against two ganciclovir-resistant HCMV strains isolated from AIDS patients. Taken as a whole these results demonstrate that cellular thymidylate synthase plays an essential role in viral replication and that ZD1694 merits further investigation as anticytomegaloviral agent.

[Langerhans cell histiocytosis of the temporal bone]. / Histiocitosis de células de Langerhans de hueso temporal.

Eosinophilic granuloma (EG) is a localized, benign form of Langerhans' cell histiocytosis. It is the least severe of the histiocytosis syndromes and characterized by lytic lesions of one or more bones. Temporal bone lesions usually occur in association with multifocal disease, but isolated lesions may occur in either the mastoid bone alone or in the entire temporal bone affecting other sites in the body. Two cases of EG of the temporal bone are reported and the literature is reviewed.

[Donor lymphocyte infusions as adoptive immunotherapy in patients with relapsed hematologic neoplasms post-allogenic transplant of hematopoietic progenitor cells]. / Infusiones de linfocitos de dador como inmunoterapia adoptiva en pacientes con neoplasias hematológicas recaídos post trasplante alogénico de células progenitoras hematopoyéticas.

An increasing body of literature has documented the usefulness of donor lymphocyte infusions in inducing remissions in patients relapsing post allogeneic hematopoietic progenitor cell transplantation. Efficacy was shown to depend on the disease entity; the best results have been reported in chronic myeloid leukemia in chronic phase, where the remission rate varied between 60 and 80%. In acute myeloid leukemia and myelodysplastic syndromes the remission rate ranged between 20 and 40% and in multiple myeloma the response rate was approximately 40%. In contrast, results have been poor in acute lymphoid leukemia with only 10-20% and even lower reported responses. Considering the efficacy of donor lymphocyte infusions in inducing responses in several hematologic neoplasias post allogeneic transplantation, as will be described in detail in this review, it is justified to anticipate an increasing role for this modality of treatment in relapsed non transplanted patients and as maintenance of the responses achieved with chemotherapy at conventional or high doses.

Hepatic preconditioning preserves energy metabolism during sustained ischemia.

We evaluated the possibility that ischemic preconditioning could modify hepatic energy metabolism during ischemia. Accordingly, high-energy nucleotides and their degradation products, glycogen and glycolytic intermediates and regulatory metabolites, were compared between preconditioned and nonpreconditioned livers. Preconditioning preserved to a greater extent ATP, adenine nucleotide pool, and adenylate energy charge; the accumulation of adenine nucleosides and bases was much lower in preconditioned livers, thus reflecting slower adenine nucleotide degradation. These effects were associated with a decrease in glycogen depletion and reduced accumulation of hexose 6-phosphates and lactate. 6-Phosphofructo-2-kinase decreased in both groups, reducing the availability of fructose-2, 6-bisphosphate. Preconditioning sustained metabolite concentration at higher levels although this was not correlated with an increased glycolytic rate, suggesting that adenine nucleotides and cAMP may play the main role in the modulation of glycolytic pathway. Preconditioning attenuated the rise in cAMP and limited the accumulation of hexose 6-phosphates and lactate, probably by reducing glycogen depletion. Our results suggest the induction of metabolic arrest and/or associated metabolic downregulation as energetic cost-saving mechanisms that could be induced by preconditioning.