Cambios morfológicos secundarios a material de sutura quirúrgica / Morphological changes due to surgical suture material

Los materiales de sutura pueden ocasionar alteraciones o artefactos que en ocasiones nos plantearán dudas de diagnóstico diferencial con procesos tumorales o de otra naturaleza. Durante la realización de una autopsia el patólogo puede hallar una masa localizada en un órgano, tejido o vaso, que le puede llevar a pensar en un proceso tumoral, y un estudio histopatológico sorprenderlo con el diagnostico de reacción tisular por material de sutura (AU)

Suture materials can cause changes or artefacts that can occasionally raise doubts in the differential diagnosis of tumour processes or of any other nature. During the performance of an autopsy, the forensic pathologist may find a mass in organs, tissues or vessels that may lead him to think about a tumoral process, and the histopathological diagnosis surprise him with tissue reaction caused by suture material (AU)

Mega apófisis transversa (Síndrome de Bertolotti) y defecto parcial de fusión posterior sacra como signos con valor identificativo en antropología forense / Anomalous enlargement of the transverse process (Bertolotti's Syndrome) and sacral fusion defect as identification signs in forensic anthropology

Cuando se localizan restos esqueletizados el médico forense debe determinar en primer lugar si éstos son o no humanos. En caso afirmativo, diagnosticar el sexo, ancestro geográfico, edad, altura y si existe alguna patología que permita la identificación. Presentamos un caso con interesantes variaciones óseas: mega apófisis transversa lumbar y un defecto parcial de fusión sacra (AU)

When skeletalized remains are discovered the forensic anthropologist needs to establish first if the bones are human. If so, the sex, race, age, stature, and any pathology must be established in order to make an identification of the remains, determine manner and cause of death. We are presenting a case with interesting bone variations: anomalous enlargement of the transverse process (Bertolotti's syndrome) and partial sacral fusion defect (AU)

Lesiones múltiples por tenedor de mesa en el contexto de un homicidio / Multiple injuries by a table fork in a homicide

Las lesiones por tenedor de mesa no son frecuentes en el contexto de un homicidio ya que no son potencialmente letales. Presentamos un caso de homicidio por múltiples lesiones de arma blanca en el que también se encontraron otraslesiones características de haber sido producidas por un tenedor de mesa (AU)

Injuries by a table fork are uncommon in a homicide due to they are not potentially fatal. In this paper, a murder caused by multiple stab wounds and injuries by kitchen fork is presented (AU)

Hemoperitoneo secundario a rotura de carcinoma hepatocelular: Hallazgos de autopsia / Hemoperitoenum due to hepatocellular carcinoma. Autopsy findings

El hemoperitoneo secundario a la rotura de un carcinoma hepatocelular (CH) es una complicación poco frecuente en nuestro medio, siendo más infrecuente su hallazgo como causa de muerte en individuos no diagnosticados de CH. Presentamos el caso de una mujer de 87 años con antecedentes patológicos de hepatitis C crónica e hipertensión arterial y sin constancia de traumatismo abdominal previo, que debutó con un cuadro inespecífico de malestar general, náuseas y vómitos de varias horas de evolución, motivo por el cual se le prescribió y administró domiciliariamente metoclopramida. Falleció a las pocas horas de la atención médica, motivo por el cual se practicó la autopsia judicial. Durante la misma se evidenció un hemoperitoneo de 3.000 cc secundario a una rotura intratumoral sobre un hígado cirrótico (AU)

Hemoperitoneum secondary to rupture of hepatocellular carcinoma (CH) is a rare complication in our environment. His find, still more, is uncommon cause of death in individuals not diagnosed of CH. We report the case of a woman of 87 years-old with clinical history of chronic hepatitis C, hypertension, and abdominal trauma without evidence of prior, which debuted with a nonspecific malaise, nausea and vomiting several hours of evolution, why was prescribed and administered metoclopramide home. She died a few hours after care, which is why judicial autopsy was performed. The autopsy was shown a 3000 cc hemoperitoneum secondary to rupture intratumoral in a cirrhotic liver (AU)

Antropología forense como técnica complementaria en patología forense: A propósito de un caso / Forensic anthropology as a complementary technique in forensic pathology. Case report

La antropología forense suele limitarse al estudio de esqueletos, restos óseos, cadáveres en mal estado o en descuartizados, pero puede ser extraordinariamente útil como técnica complementaria en las autopsias convencionales en las que existan lesiones óseas. Presentamos un caso de un adolescente que sufrió una única herida por arma blanca en tórax. La esqueletización permitió evidenciar más lesiones costales de las que eran visibles durante la autopsia (AU)

Forensic anthropology usually only studies skeletons, human remains, corpses in bad condition or dismemberments, but it can also be outstandingly useful as a complementary technique in ordinary autopsies with bone injuries. The case we are presenting is about a teenager who suffered an unique incision in his chest and in whose post skeletonization more rib injuries became evident (AU)

Muerte súbita en un varón con astrocitoma no diagnosticado / Sudden death in a male due to undiagnosed astrocytoma

El diagnóstico de tumoraciones cerebrales en los servicios de patología forense es muy poco frecuente y suelen llegar a ellos ya sea como consecuencia de muertes súbitas o en el contexto de denuncias por mala praxis médica. Dentro de la escasa frecuencia, la mayoría de ellos son únicamente hallazgos incidentales de autopsia, como en el caso de muchos meningiomas, pero en otros puede ser la causa de muerte. Presentamos el caso de un varón paquistaní de 40 años, con barrera idiomática, que consultó en un servicio de urgencias por un cuadro de cefalea, náuseas y vómitos y que falleció después del alta médica con el diagnóstico de cuadro respiratorio de vías altas. La autopsia y los estudios anatomopatológicos evidenciaron un astrocitoma grado II (AU)

Brain tumors are seldom studied in forensic pathology services and they are seen in circumstances such as sudden unexpected death or in malpractice complaints. In most cases they are incidental findings, like meningioma, and in few cases they are the cause of death. We present the case of a 40 years old male Pakistani with linguistic barrier suffering from headache and vomiting who was diagnosed as a flue and died suddenly. Forensic autopsy and histopathologic studies showed a grade II astrocytoma (AU)

Agenesia de vena cava inferior en un caso de autopsia forense / Absence of the inferior cava vein in a case of forensic autopsy

La agenesia de vena cava inferior es una entidad congénita poco frecuente que a menudo se asocia con otras severas anomalías congénitas o malposiciones viscerales. También ha sido descrita como un factor de riesgo de trombosis venosa en pacientes jóvenes. La mayoría de los casos publicados proceden de estudios radiológicos y muy raramente aparece como hallazgo necrópsico. Presentamos un caso de agenesia de vena cava inferior, sin otras anomalías asociadas, que apareció como hallazgo incidental en una autopsia forense (AU)

The absence of the inferior vena cava is a rare congenital anomaly, often associated with severe congenital deformities and visceral position abnormalities. It has been described also as a risk factor for deep vein thrombosis in young patients. We present a case of congenital absence of inferior vena cava appeared as an incidental finding in a forensic autopsy (AU)

Enzyme replacement therapy with agalsidase alfa in a cohort of Italian patients with Anderson-Fabry disease: testing the effects with the Mainz Severity Score Index.

Anderson-Fabry disease (AFD) is a rare X-linked disorder caused by lysosomal storage of several glycosphingolipids, affecting virtually all organs and systems. Enzyme replacement therapy (ERT) for AFD has been available since 2001. Due to the highly variable nature of clinical manifestations in patients with AFD, it is very difficult to assess disease progression and the effects of therapy. We used the Mainz Severity Score Index (MSSI) as a measure of disease severity to study the effects of ERT in a population of 30 patients treated with agalsidase alfa for a median of 2.9 years (range, 1.0-6.2 years). Our data show that the MSSI captures the correlation between disease severity and both gender and age (1 - males performing worse than females at baseline and 2 - severity of diseases progresses with age in both sex). Furthermore, after at least 1 year of ERT, total MSSI scores were significantly lower than those at baseline (p < 0.001), suggesting a marked clinical improvement under ERT. In conclusion, the MSSI is a sensitive and useful tool for monitoring disease progression and assessing the effects of ERT in a population of patients from different treatment centres.

Triglycerides impair postischemic recovery in isolated hearts: roles of endothelin-1 and trimetazidine.

There is growing evidence that hypertriglyceridemia exacerbates ischemic injury. We tested the hypothesis that triglycerides impair myocardial recovery from low-flow ischemia in an ex vivo model and that such an effect is related to endothelin-1. Hyperglycemic (glucose concentration = 12 mmol/l) and hyperinsulinemic (insulin concentration = 1.2 micromol/l) isolated rat hearts were perfused with Krebs-Henseleit buffer (PO(2) = 670 mmHg, pH 7.4, 37 degrees C) added with increasing triglycerides (0, 1,000, 2,000, and 4,000 mg/dl, n = 6-9 rats/group). Hearts were exposed to 60 min of low-flow ischemia (10% of basal coronary flow), followed by 30 min of reperfusion. We found that increasing triglycerides impaired both the diastolic (P < 0.005) and systolic (P < 0.02) recovery. The release of endothelin-1 during reperfusion increased linearly with triglyceride concentration (P = 0.0009). Elevated triglycerides also increased the release of nitrite and nitrate (NO(x)), the end products of nitric oxide, up to 6 micromol/min. Trimetazidine (1 micromol) further increased NO(x) release, blunted endothelin-1 release, and protected myocardial function during recovery. We conclude that high triglyceride levels impair myocardial recovery after low-flow ischemia in association with endothelin-1 release. The endothelium-mediated effect of triglycerides on both contractile recovery and endothelin-1 release is prevented by 1 microM trimetazidine.

Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients.

UNLABELLED: The aim of this study was to evaluate whether long-term administration of arginine acting through a normalization of NO/cyclic-guanosine-3' 5'-cyclic monophosphate (cGMP) pathway was able to ameliorate peripheral and hepatic insulin sensitivity in 12 lean type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A double-blind study was performed for 3 months. In the first month, patients were treated with their usual diet. Then they were randomly allocated into to groups. In group 1, patients were treated with diet plus placebo (orally three times per day) for 2 months. In group 2 patients were treated for 1 month with diet plus placebo orally, three times per day) and then for 1 month with diet plus L-arginine (3 g three times per day). At the end of the first and the second month of therapy, patients underwent a euglycemic-hyperinsulinemic clamp combined with [6,6-2H2] glucose infusion. A total of 10 normal subjects underwent the same test as control subjects. RESULTS: In group 1, no changes in basal cGMP levels, systolic blood pressure, forearm blood flow, glucose disposal, and endogenous glucose production were observed throughout. In group 2, L-arginine normalized basal cGMP levels and significantly increased forearm blood flow by 36% and glucose disposal during the clamp by 34% whereas it decreased systolic blood pressure and endogenous glucose production by 14 and 29%, respectively. However, compared with normal subjects, L-arginine treatment was not able to completely overcome the defect in glucose disposal. CONCLUSIONS: L-Arginine treatment significantly improves but does not completely normalizc peripheral and hepatic insulin sensitivity in type 2 diabetic patients.

Plasma nitric oxide concentrations are elevated in insulin-resistant healthy subjects.

The goal of this study was to compare plasma nitric oxide (NO) concentrations in healthy subjects, defined as either insulin-resistant or insulin-sensitive on the basis of the plasma insulin response to a 75-g oral glucose challenge. For this purpose, 404 healthy subjects were divided into quartiles on the basis of the plasma insulin response to glucose, and 49 individuals were selected from the quartile with the lowest insulin response and 49 from the quartile with the highest insulin response. The two groups of 49 each were selected to be essentially identical in terms of age, gender distribution, body mass index (BMI), and waist to hip ratio (WHR). The quartile with the greatest insulin response also had a significantly higher plasma glucose response to oral glucose, faster heart rate, higher blood pressure, and the combination of higher triglyceride and lower high-density lipoprotein (HDL) cholesterol concentrations. In addition to the latter changes, previously shown to be associated with hyperinsulinemia, NO concentrations were also higher in the hyperinsulinemic group. It is speculated that this increase in the NO concentration in hyperinsulinemic and presumably insulin-resistant, subjects represents a compensatory effort to overcome the untoward effects of insulin resistance and/or hyperinsulinemia.

Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of patients with type 2 diabetes.

In this study, we have compared resistance to insulin-mediated glucose disposal and plasma concentrations of nitric oxide (NO) and cyclic-GMP in healthy volunteers with (n = 35) or without (n = 27) at least one sibling and one parent with type 2 diabetes. The 62 volunteers were further divided into groups of those with normal glucose tolerance or impaired glucose tolerance. Insulin-mediated glucose disposal was quantified by determining the insulin sensitivity index (ISI) in response to a low-dose, constant infusion of insulin (25 mU/kg x h) and glucose (4 mg/kg x min) for 150 min. The mean (+/-SEM) ISI [(mL kg(-1) min(-1)/pmol/L) x 10(3)] was significantly greater in those without a family history (30.3 +/- 2.3) as compared with nondiabetic volunteers with a family history of type 2 diabetes, whether they had normal glucose tolerance (17.0 +/- 7.2) or impaired glucose tolerance (9.5 +/- 1.4). In addition, basal NO levels, evaluated by the measurement of its stable end products [i.e. nitrite and nitrate levels (NO2-/ NO3-)], were significantly higher, and cyclic-GMP levels, its effector messenger, were significantly lower in those with a family history, irrespective of their degree of glucose tolerance, when compared with healthy volunteers without a family history of type 2 diabetes. Furthermore, when the 62 volunteers were analyzed as one group, there was a negative correlation between ISI and NO2-/NO3- levels (r = -0.35; P < 0.005) and a positive correlation between ISI and cyclic-GMP levels (r = 0.30; P < 0.02). These results have shown that alterations of the NO/cyclic-GMP pathway seem to be an early event in nondiabetic individuals with a family history of type 2 diabetes and these changes are correlated with the degree of insulin resistance.

Relationship between endothelin-1 concentration and metabolic alterations typical of the insulin resistance syndrome.

The purpose of the study was to examine the relationship between the endothelin-1 (ET-1) concentration and the metabolic variables characteristic of the insulin resistance syndrome ([IRS] hyperinsulinemia, insulin resistance, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, visceral obesity, and glycemic abnormalities). The measurement of circulating ET-1 is a well-recognized marker of endothelial atherosclerotic and cardiovascular disease. Two hundred subjects were divided into 3 groups. Group 1 included 50 subjects with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) with IRS. Group 2 included 50 subjects with IGT or NIDDM without IRS. Group 3 included 100 normal subjects as controls. ET-1 levels were higher in group 1 versus groups 2 and 3 in women (11.2 +/- 0.7 v 7.9 +/- 0.5 and 6.6 +/- 0.4 pg/mL, P < .01) and men (10.1 +/- 0.6 v 6.5 +/- 0.8 and 7.2 +/- 0.3 pg/mL, P < .01). No differences were found between groups 2 and 3. With simple regression analysis, ET-1 levels significantly correlated with insulin, glycosylated hemoglobin, body weight, waist to hip ratio, and triglyceride values. However, with multiple regression analysis, only triglycerides (P < .009) and glycosylated hemoglobin (P < .001) remained independently correlated with ET-1. In conclusion, this cross-sectional study indicates that glycosylated hemoglobin and triglycerides are independently correlated with ET-1 levels in patients with IRS.

Effects of endothelin-1 and nitric oxide on glucokinase activity in isolated rat hepatocytes.

To test the hypothesis that endothelin-1 (ET-1) and nitric oxide (NO) influence glucokinase (GK) activity in an opposite manner, we evaluated the effects of ET-1, L-NAME, an inhibitor of NO synthase, and L-arginine, a substrate for NO synthase, on GK activity and glycogen content in isolated rat hepatocytes. Moreover, to understand the receptor involved in the process, the effects of BQ 788, a specific antagonist of ETB receptor, and PD 142893, an antagonist of ETA-ETB receptors, were also evaluated. GK activity, cyclic guanosine monophosphate (cGMP), and glycogen intracellular content were measured on isolated hepatocytes, while glucose levels and NO as NO2-/NO3- were determined in the medium. High ET-1 levels induced a 20% decrease of NO2-/NO3- levels and cGMP intracellular content, followed by a 49% reduction of GK activity and a 15% decrease of glycogen. In parallel, a 10% increase of glucose in the medium was observed. In the presence of L-NAME, GK activity and glycogen levels showed analogous decrements as observed with ET-1. Also in this case, a significant decrease of the intracellular content of cGMP was observed. No synergistic effects of ET-1 and L-NAME were observed. L-Arginine was able to counteract the inhibitory effect of ET-1 on cGMP and GK activity. Glycogen content was slightly but not significantly reduced, and under those conditions, a significant decrease of glucose in the medium was observed. When hepatocytes were incubated with ET-1 plus BQ 788 or ET-1 plus PD 142893, GK activity was unchanged. Interestingly, no changes were observed in NO2-/NO3- levels and the intracellular content of cGMP was not modified when the antagonists of ET-1 receptors were added to the medium. In conclusion, the present study shows that the NO pathway seems to be an important regulator of GK activity and glycogen content through cGMP activity. In addition, ET-1 seems to be not active per se, but its activity seems mediated by a simultaneous decrease of NO levels.

Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries: comparison with subjects with insulin resistance syndrome and normal controls.

OBJECTIVES: This study was performed to characterize the endothelial and metabolic alterations of patients with angina and angiographically normal coronary arteries ("cardiac" syndrome X [CSX]) compared with subjects with insulin resistance syndrome ("metabolic" syndrome X [MSX]) and normal controls. BACKGROUND: Previous studies have found high endothelin-1 levels, impaired endothelium-dependent vasodilation and insulin resistance in patients with angina pectoris and angiographically normal coronary arteries. On the other hand, subjects with insulin resistance syndrome have shown high endothelin-1 levels. METHODS: Thirty-five subjects were studied: 13 patients with angina pectoris and angiographically normal coronary arteries (CSX group); 9 subjects with insulin resistance syndrome (MSX group) and 13 normal controls. All subjects received an acute intravenous bolus of insulin (0.1 U/kg) combined with a euglycemic clamp and forearm indirect calorimetry. Endothelin-1 levels, nitrite/nitrate (NOx) levels, end products of nitric oxide metabolism, glucose infusion rates (index of insulin sensitivity) and their incremental areas (deltaAUCs [area under curves]) were measured during this period. RESULTS: Basal endothelin-1 levels were higher in CSX and MSX groups than in normal controls (8.19 +/- 0.46 and 6.97 +/- 0.88 vs. 3.67 +/- 0.99 pg/ml; p < 0.01), while basal NOx levels were significantly higher in MSX group than in CSX and normal controls (36.5 +/- 4.0 vs. 24.2 +/- 3.3 and 26.8 +/- 3.2 mol/liter, p < 0.05). After insulin administration, the deltaAUCs of NOx (p < 0.05) were lower in CSX group than in MSX and normal controls, and the deltaAUCs of endothelin-1 were lower in group CSX than in normal controls. Glucose infusion rate was significantly lower in CSX and MSx groups than in normal controls (p < 0.01), suggesting that in both CSX and MSX groups insulin resistance is present. A positive correlation was found between the deltaAUCs of nitric oxide and the AUCs of glucose infusion rate. CONCLUSIONS: Blunted nitric oxide and endothelin responsiveness to intravenously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the microvascular dysfunction observed in these subjects.

Pelvic and paraortic lymph nodal status in advanced ovarian cancer and survival.

BACKGROUND: In order to analyze the prognostic role of node involvement in advanced ovarian cancer, we have analyzed data from a randomized clinical trial on advanced ovarian cancer. METHODS: Cases were 456 women who entered a randomized multicentric clinical trial comparing two cisplatin-based schemes of treatment after cytoreductive surgery for advanced stage III-IV ovarian cancer. They underwent selective pelvic and/or paraortic lymphadenectomy. RESULTS: A total of 161 (35.3%) cases had positive nodes. The frequency of positive nodes was statistically significantly higher in FIGO stage IV than in stage III. Also grade 3 tumors were more likely to have positive nodes than grade 1-2 tumors. No association was observed between nodal status and response to chemotherapy. The 3-year survival was 46.2 (standard error (SE) = 3.4 based on 147 deaths) and 44.6 (SE = 4.4, based on 84 deaths), respectively, in negative and positive node groups. The corresponding values, when the analysis was performed considering only subjects with residual tumor <1 cm or absent, after first-line cytoreductive surgery were 66.2 (SE = 5.7) and 62.4 (SE = 9.6). CONCLUSIONS: We did not find any association between nodal status and survival. Particularly, nodal status was not a prognostic factor for survival in the subgroup of women with residual tumor <1 cm or absent after cytoreductive surgery.

Mediation of the hepatic effects of growth hormone by its lipolytic activity.

The aim of the study was to investigate the acute effect of GH per se, independent from its lipolytic activity, on glucose and lipid oxidation and glucose turnover in seven healthy subjects. Five tests lasting 360 min were performed. Each test consisted of a 4-h equilibration period followed by a euglycemic hyperinsulinemic (25 mU/kg x h) clamp lasting 2 h. In test 1 (control experiment) saline was infused, leaving GH and FFA at basal levels. In tests 2, 3, and 4, GH was infused (80 ng/kg x min) to increase GH levels. Whereas in test 2 FFA levels were free to increase due to GH lipolytic activity, in test 3 FFA elevation was prevented by using an antilipolytic compound (Acipimox) that allowed evaluation of the effect of GH at low FFA levels. In test 4 (GH+Acipimox+heparin) GH infusion was associated with the administration of Acipimox and heparin to maintain FFA at the basal level to evaluate the effect of GH per se independent from GH lipolytic activity. In test 5 Acipimox and a variable heparin infusion were given to evaluate possible effects of Acipimox other than the inhibition of lipolysis. During the euglycemic hyperinsulinemic clamp in the presence of high GH and FFA levels (test 2), glucose oxidation was significantly lower and lipid oxidation was significantly higher than in tests 1, 3, 4, and 5. During the same period, hepatic glucose production was completely suppressed in the control study (test 1; 94%) and in test 5 (99.6%), whereas it was significantly less inhibited (65%, 74%, and 73%) when GH was administered in tests 2, 3, and 4. In conclusion, these results suggest that GH directly mediates the reduction of insulin's effect on the liver. In addition, the effect of GH on glucose and lipid oxidation is not direct, but is mediated by its lipolytic activity.

Gluconeogenesis in isolated rat hepatocytes evaluated by gas chromatography/mass spectrometry using deuterated water.

Tritiated water and radioactive tracers have been used to monitor glucose production by primary cultures of hepatocytes. More recently, 3H2O has been replaced for by 2H2O in 'in vivo' studies addressed at the evaluation of the relative contribution of gluconeogenesis to total glucose production. In this work, the possibility of using 2H2O to determine the ratio between the glucogenic flux and the overall flux through glucose 6-phosphate in isolated liver cells in vitro was evaluated. For this purpose, hepatocytes from either fasted or fed rats were incubated with a medium containing 6, 12 and 25% of 2H2O in the presence of either 2 or 20 mM pyruvate. Isotopomer analysis of six different mass clusters (m/z 328, 314, 242, 212, 187 and 145) was carried out by gas chromatography/mass spectrometry (GC/MS) of glucose aldonitrile pentaacetate. For each cluster, ions at m/z +1, +2, +3 and +4 were monitored. From the combination of different clusters the enrichment at C-6 and C-2 of glucose was computed and the C-6/C-2 ratio was considered to represent the contribution of gluconeogenesis to total glucose production, as suggested previously. Based on the results obtained, conditions selected to be optimum for the use of the method in studies on the modulation of gluconeogenesis were as follows: incubation of hepatocytes with 20 mM pyruvate in 12% 2H2O followed GC/electron ionization MS analysis of the clusters of ions at m/z 328, 314 and 187 of the glucose derivative to calculate enrichment at the C-2 and C-6 positions of glucose.

Effects of low-dose heparin infusion on arterial endothelin-1 release in humans.

BACKGROUND: The aim of this study was to evaluate the effect of low-dose heparin infusion on arterialized endothelin-1 (ET-1) release in the presence of fasting or high insulin levels in healthy humans. METHODS AND RESULTS: Eleven normal subjects underwent two tests in random order lasting 240 minutes. A primed (250 IU), continuous heparin (600 IU/h) infusion was performed in test 1; saline was infused in test 2 as control. At 120 minutes, a euglycemic hyperinsulinemic clamp (25 mU.kg-1.h-1) was started that lasted 2 hours in both tests. Two hours after heparin infusion (test 1), ET-1 levels decreased by 32% (3.52 +/- 0.60 to 3.02 +/- 0.73 pg/mL), while nitric oxide (NO) and forearm blood flow increased by 29% and 14%, respectively. During saline infusion, ET-1, nitric oxide, and forearm blood flow remained unchanged. There was a significant interaction between the effect of decreasing ET-1 levels and the heparin treatment (F, 4.06; df, 3.30; P < .01). The decrease in ET-1 levels was significantly correlated with the increase in forearm blood flow in test 1 (r = .74; P < .01) but not in test 2. During the heparin/insulin period, ET-1 increased by 25%, returning to fasting values; nitric oxide levels increased by 12%; and forearm blood flow remained unchanged. CONCLUSIONS: The present study showed that it is possible to decrease ET-1 levels by use of low-dose heparin infusion in humans. This effect seems mediated by a simultaneous increase in nitric oxide levels and is completely reversed by a mild increase in insulin concentrations.