A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

[Cerebral ptosis. Analysis of six cases]. / Investigación clínica de la ptosis cerebral. Presentación de seis nuevos casos.

BACKGROUND: Cerebral ptosis is understood as the bilateral paralysis of eyelid elevation linked to a stroke or hemorrhage of the middle cerebral artery (MCA). It is a transient condition, independent of the evolution of the lesion. AIM: To analyze six patients with the condition. PATIENTS AND METHODS: Report of five women and one male aged 42 to 72 years. RESULTS: All suffered an infarction or hemorrhage in the territory of the middle cerebral artery of the non-dominant hemisphere and developed a bilateral palpebral ptosis. The recovery started after the fourth day. At the tenth day, eye opening was effortless and did not require frontal help, despite the persistence of hemiplegia. CONCLUSIONS: Cerebral ptosis is a mimetic dysfunction of a specific non-injured area of the cerebral cortex, originated from a nearby parenchymal damage such as the middle cerebral artery of the same hemisphere. Cerebral ptosis expresses the inhibition of the voluntary eyelid elevation center, of prefrontal location in the non-dominant hemisphere.

[Spinal subacute combined degeneration after intrathecal chemotherapy. Report of two cases]. / Síndrome de degeneración combinada de la médula espinal y radiculopatía en dos pacientes por quimioterapia intratecal con metrotrexato y citarabina. Casos clínicos.

Intrathecal chemotherapy may be complicated with the development of myelopathies or toxic radiculopathies. This myeloradicular involvement, of toxic character, is unpredictable, since these patients have repeatedly received Intrathecal chemotherapy with the same drugs without apparent injury. The toxic effect should be mainly attributed to Cytarabine and not to methotrexate, since the central nervous system lacks Cytidine deaminase, the enzyme that degrades Cytarabine. We report two patients, an 18-year-old woman and a 16 years old male, who received systemic and intrathecal chemotherapy (methotrexate, cytarabine) for the treatment of an acute lymphoblastic leukemia and developed, in relation to this procedure, a spinal subacute combined degeneration. They had a proprioceptive and motor alteration of the lower extremities and neuroimaging showed selective rear and side spinal cord hyper intensity produced by central axonopathy. Two weeks later the woman developed a quadriplegia and the young man a flaccid paraplegia due to added root involvement.

[Sustained upgaze in a patient who ingested high doses of bupropion. Report of one case]. / Supraversión de la mirada en intoxicación mortal por bupropión.

Upgaze or sustained elevation of the eyes, is an alteration of ocular motility initially described in hypoxic coma. We report a 65-year-old woman admitted with hypotension and alteration of sensorium due to the ingestion of 9.5 g of Bupropion. She presented two seizures of short duration, without epileptic activity on the EEG. She had a persistent asynchronous myoclonus in extremities, tachycardia and prolonged Q-t. She suffered a cardiac arrest caused by asystole, which recovered quickly in five minutes. At that moment, upgaze appeared, associated with a persistent ocular opening, which persisted for days, but finally disappeared, without remission of coma. A magnetic resonance imaging done at the eighth day, showed hyperintensity of the oval center and corpus callosum which disappeared in a new imaging study done 30 days later, where images of hypoxia in the basal nuclei and cortex appeared. The patient died forty seven days after admission. Up-gaze is an ominous oculomotor alteration linked to an important but incomplete damage in the cerebral cortex, a condition that perverts some sequences of the ocular opening, reversing the Bell phenomenon and producing eyelid retraction.

[Giant cell arteritis of the vertebrobasilar system, posterior ischemia and palsy of the third nerve. Report of one case]. / Arteritis de células gigantes en el sistema vertebrobasilar, isquemias cerebelo-occipitales y parálisis III par. Caso clínico.

Giant cell arteritis is the most common vasculitis in patients aged over 50 years. We report an 89-year-old woman with significant weight loss and persistent frontal-occipital headaches lasting two months. The neurological examination at admission identified a decrease in visual acuity of the left eye, paralysis of the third cranial nerve of the right eye and alterations of body motility without objective signs of damage of the motor or sensitive pathways. Magnetic resonance imaging showed changes of the temporal artery wall and in both vertebral arteries, as well as bilateral cerebellar and occipital ischemic lesions. The Doppler ultrasound of the temporal arteries was compatible with Giant cell arteritis. Treatment with steroids was started. While receiving oral prednisone, the patient suffered new infarcts of the posterior territory, documented with a CAT scan.

[Eyelid retraction of neurologic origin: Report of three cases]. / Retracción palpebral de causa neurológica: Presentación de tres pacientes, interpretación patogénica.

Eyelid retraction, has received limited attention and it has passively been interpreted as the result of an overactive levator palpebrae superioris muscle secondary to midbrain injury. However, eyelid retractions can occur in other neurological diseases, not directly related with the midbrain. We report three patients who developed eyelid retraction. One patient had a bilateral eyelid retraction, related with Creutzfeldt-Jakob disease (CJD). Another patient had a unilateral right eyelid retraction associated with a thalamic-mesencephalic infarct. The third patient had a bilateral pontine infarction on magnetic resonance imaging. In the patient with CJD, eyelid retraction did not subside. Among patients with infarctions, the retraction persisted after focal symptoms had subsided, showing an evolution that was apparently independent of the basic process. The analysis of these patients allows us to conclude that the pathogenesis of eyelid retraction includes supranuclear mechanisms in both the development and maintenance of the phenomenon. Unilateral or bilateral eyelid retraction does not alter the normal function of eyelid, which ever had normal close eye blink. In these reported cases, a hyperactivity of levator palpebrae superioris muscle was clinically ruled out.

[Toxic encephalopathy caused by liquefied gas exposure: Report of one case]. / Encefalopatía tóxica por isopropanol: Sobre-exposición accidental a gas propano.

Liquefied hydrocarbon gas, such as propane is considered safe. However there are reports that voluntary exposure to liquefied gas at least could originate hallucinatory states. We report a 20 years old woman who was found in a coma with extensor muscle hypertonia, brisk tendon reflexes and extensor plantar (Babinski) responses after being exposed to propane gas. The brain magnetic resonance imaging (MRI) showed lesions in both hippocampi and white matter in the oval center. The patient had a normal oxygen saturation of 98%, a carboxyhemoglobin of 1.6% and a metabolic acidosis with a pH of 7.01 with an anion gap of 16 mEq/l. This pattern suggested that it was a consequence of the intermediary metabolism of isopropanol. The recovery of the patient was slow and four months later she still had lesions on MRI and limitations in her cognitive sphere, memory and executive functions. Thus, liquefied gas exposure can cause a toxic encephalopathy with a persistent damage of the central nervous system.

[Fatal toxic leukoencephalopathy associated with consumption of pasta base of cocaine: Report of three cases]. / Leucoencefalopatía tóxica fatal: tres casos asociados al consumo de pasta base de cocaína.

The prevalence of drug-associated toxic encephalopathy is unknown, but it is an uncommon condition. Toxic leukoencephalopathy was described associated with heroin consumption, it has been less commonly described with the use of cocaine and there are no reports of its association with consumption pasta base of cocaine (PBC). We report two females aged 31 years and a male aged 19 years, consumers of PBC who developed a fatal toxic leukoencephalopathy. They initiated their disease with severe and persistent headache, sequential focal neurologic deficits and a progressive impairment of consciousness that culminated with their death. Laboratory parameters such as blood count, cerebrospinal fluid analyses or infectious biological indices were normal. MRI showed multifocal lesions in brain white matter of both hemispheres confirming the leukoencephalopathy. There was no response to the use of methylprednisolone.

Are plasma proteins a valid alternative for assessing nephrotic syndrome in children from low-income countries?

BACKGROUND: A diagnosis of nephrotic syndrome (NS) in children with edema relies on urinary albumin excretion and usually plasma protein (Pprot) and albumin (Palb) concentrations. METHODS: In order to fit laboratory tests to optimal healthcare in low-resource countries, we established correlations between Pprot and Palb in children with NS (217 measurements in 60 patients) and in children with exudative enteropathy and chronic hepatopathy/liver insufficiency (186 measurements in 21 patients); all patients had repeated measurements at various stages of their disease. RESULTS: There was a good correlation between Pprot and Palb in children with idiopathic NS and genetic NS (ICC=0.8, p < 0.0001, 95% CI: 0.8-0.9 and ICC=0.8, p < 0.0001, 95% CI: 0.7-0.8, respectively), whereas the correlation was average (exudative enteropathy) or absent (chronic hepatopathy) in those without renal protein loss. CONCLUSION: Since Palb measurement is around two times more expensive than Pprot measurement, these results suggest giving priority to total Pprot measurement in the diagnosis and follow-up of children with the NS, mainly in low-resource countries.

[Acute encephalopathy associated with the use of intravenous immunoglobulin. Report of one case]. / Encefalopatía aguda en un paciente tratado con inmunoglobulina endovenosa por un síndrome de Guillain-Barré

Adverse reactions to intravenous immunoglobulin (ivIg) therapy, such as anaphylaxis, acute encephalopathy, aseptic meningitis, or thrombotic phenomena are uncommon. We report a 58-year-old man with hypertension presenting with muscle weakness which led to paraparesia and respiratory failure. With the diagnosis of Guillain-Barré syndrome (GBS), he was treated with ivIg. He developed an acute encephalopathy few hours after the administration of ivIg, with a decreased level of consciousness and agitation. A CT scan revealed moderate and diffuse brain edema. Encephalopathy resolved 96 hours after ivIg withdrawal and use of plasma exchange. A CT scan performed seven days after showed the resolution of brain edema.

Prognosis of perioperative myocardial infarction after off-pump coronary artery bypass surgery.

AIM: Perioperative myocardial infarction (PMI) is associated with long-term morbidity and mortality. CKMB cut-off level and importance of Q-wave MI have not been specifically studied after off-pump coronary artery bypass (OPCAB) surgery. The aim of this paper was to study the impact of PMI (CKMB >/= 20 times the upper normal limit [UNL] 100 mg/L) and CKMB rise (5-20 UNL) on survival and recurrent major adverse cardiac event (MACE) after OPCAB surgery. METHODS: One thousand consecutive prospectively followed OPCAB patients operated between September 1996 and March 2004 were analyzed. Follow-up was complete in 97% of the cohort. Average follow-up was 66 +/- 28 months. RESULTS: Overall and cardiac survival at 10 years was 70 +/- 2.6% and 88 + 2.3%, respectively. Evolving MI (EMI) occurred in 1.8%, postoperative non-Q MI (NQMI) in 1.3%, and Q-wave MI (QMI) in 2.0%. Operative mortality was higher in PMI patients (P < 0.001). After adjusting for risk factors, survivors of EMI (HR: 2.0) and QMI (HR: 2.3) but not NQMI had a lower life expectancy and a higher long-term cardiac mortality (EMI: HR: 3.5; QMI: HR: 4.3) compare to non-PMI patients. EMI and QMI were associated with a decrease MACE-free survival. CKMB 5-10 UNL did not affect overall and cardiac mortality. CKMB 10-20 UNL was associated to lower cardiac survival. CONCLUSIONS: PMI (CKMB > 20 UNL) was a strong predictor of operative mortality. QMI and EMI were predictors of long-term mortality and cardiac morbidity after OPCAB surgery. CKMB 10-20 UNL affected long-term cardiac survival but not overall survival.

Median sternotomy: comparative testing of braided superelastic and monofilament stainless steel sternal sutures.

A new device to reduce the risk of post-operative complications following median sternotomy is proposed, made of a superelastic shape memory alloy and called a braided tubular superelastic (BTS) suture. This study compares the viability of the BTS suture with that of the standard monofilament stainless steel (MSS) suture. A custom test bench was developed to perform comparative testing of the two sternal closure systems. Sternal models made of polyurethane were closed using common wiring configurations. Static and dynamic tensile separation forces, up to a maximum of 1200 N, were then applied to the closed sternums. The MSS and BTS sutures are compared in terms of the force required to open completely the sternum, the compression force at the sternum midline, and the permanent sternum opening. With a smaller sternum opening and a higher tensile separation force, the MSS suture showed greater rigidity than the BTS suture. The BTS suture, however, displayed a better capacity to reapply compression forces at the sternum midline following the repetitive application and release of tensile separation forces. These results confirm the potential of the BTS suture technology, but further studies using cadaveric sterna are needed to attest definitely to the benefits of using the BTS suture to improve bone healing.

[About the choice of acceptability limits in external quality assessment schemes]. / Réflexion sur le choix des limites acceptables dans les programmes d'évaluation externe de la qualité

Quality control schemes are a practical tool used in clinical laboratories and an essential element for any quality assurance process. In France, external quality assessment schemes (EQAS) can be mandatory (as national quality control organized by AFSSAPS) or voluntary as those suggested by French associations (ProBioQual, CTCB or Asqualab). These EQAS usually evaluate participants according to their performances: this ranking depends on acceptability limits which are here compared. Various examples based on ProBioQual's background illustrate difficulties to plan out analytical quality specifications. A comment is given about the best criteria (state of the art or biological variation mainly) to be considered to delimit analytic goals. This discussion includes approaches suggested by French committee on accreditation (Cofrac). All criteria could be criticized but it is important to compare oneself laboratory to peers and also to take account of biological variation.

Bolus endovascular PDGFR-beta antisense treatment suppressed intimal hyperplasia in a rat carotid injury model.

BACKGROUND: Intimal thickening in accelerated arteriopathies relies on the migration of medial vascular smooth muscle cells (VSMCs) and their proliferation within the neointima. Activation of platelet-derived growth factor receptor-beta (PDGFR-beta) expressed in injured VSMCs is responsible for the migration of medial VSMCs to the intima. In the present study, we wanted to assess whether a single local endovascular delivery of antisense PDGFR-beta in injured rat carotid arteries would be sufficient to prevent intimal hyperplasia and how it might contribute to the vascular healing process. METHODS AND RESULTS: A bolus of antisense PDGFR-beta delivered into injured rat carotid arteries reduced PDGFR-beta protein overexpression by >90% from day 3 to 28 after injury. At day 28 after injury, compared with injured untreated carotids, treatment with antisense PDGFR-beta reduced intimal hyperplasia by 58% and medial VSMC migration by 49% and improved vascular reendothelialization by 100% and vascular reactivity (EC(50)) to acetylcholine by 5-fold. CONCLUSIONS: A single-bolus luminal delivery of antisense PDGFR-beta to injured rat carotids reduced intimal hyperplasia, improved the reendothelialization process, and led to the recovery of endothelium-dependent regulation of vascular tone.

Long-term reproducibility and significance of provokable ventricular arrhythmias after myocardial infarction.

The long-term reproducibility and significance of inducible ventricular arrhythmias were assessed in 21 survivors of a myocardial infarction. Programmed ventricular stimulation performed a mean of 12 +/- 2 days (range 8 to 18) after infarction provoked ventricular fibrillation in 2 patients, sustained monomorphic ventricular tachycardia in 8 and nonsustained ventricular tachycardia in 11. Patients were restudied using the same protocol a mean of 8 +/- 2 months (range 4 to 11) after infarction. All patients underwent programmed ventricular stimulation studies in the absence of antiarrhythmic drug treatment. Ventricular tachyarrhythmias could be reinitiated in 16 patients (76%): ventricular fibrillation in 2, sustained ventricular tachycardia in 5 (monomorphic in 4) and nonsustained ventricular tachycardia in 9. A preponderance of inferior infarction was observed among patients with reinducible tachycardias (9 of 16 patients versus 0 of 5 with noninducible tachycardias) (p less than 0.05). No significant difference existed between patients with and without reinducible arrhythmias with respect to severity of coronary artery disease, degree of left ventricular dysfunction, occurrence of ventricular fibrillation in the acute phase of infarction and ventricular arrhythmias detected by 24 hour ambulatory electrocardiographic (Holter) monitoring. There was no significant difference between patients with and without a positive late study in stimulation thresholds, ventricular refractory periods, time interval between initial and repeat testing and use of beta-adrenergic blocking agents. During a mean follow-up period of 17 months (range 10 to 23) one patient with inducible sustained monomorphic ventricular tachycardia at both studies died suddenly. The remaining patients have survived follow-up without experiencing an arrhythmic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of diabetes and bilateral internal thoracic artery grafts on long-term outcome for multivessel coronary artery bypass grafting.

OBJECTIVE: Diabetes mellitus is a major independent risk factor for morbidity and mortality after coronary artery bypass grafting (CABG). The aim of this study was to assess the effect of bilateral (B) internal thoracic artery grafting (ITA) in diabetic patients with multivessel CABG. METHODS: Between 1985 and 1995, 4382 patients underwent primary isolated multivessel CABG with ITA grafting and concomitant saphenous vein grafting (SVG). Outcome of diabetic and nondiabetic patients undergoing single (S) ITA+SVG (n=419 and 2079) and BITA+SVG (n=214 and 1594) grafting was obtained at a mean follow-up of 11+/-3 years. RESULTS: Diabetic patients were older, included more women, and had more obesity, hypertension and peripheral vascular disease than nondiabetic patients. Deep sternal wound infection rate was 1.9% for diabetic patients vs 1.2% for nondiabetic patients (P=0.2) and 30-day mortality was 1.7 vs 1.8% (P=0.9). Cox regression analysis with interaction term and propensity scoring showed that BITA grafting decreased the risk of death (Hazard Ratio=0.72 [0.57-0.91, 95%CI]) and coronary reoperation (HR=0.38 [0.19-0.77]) in both diabetic and nondiabetic patients, with no significant interaction noted. BITA grafting decreased the risk of myocardial infarction at long-term follow-up in nondiabetic patients (HR=0.72 [0.60-0.86]) but not in diabetic patients. Ten-year freedom rate from myocardial infarction in diabetic patients was 80 and 76% for SITA and BITA grafting patients, respectively. However, survival following myocardial infarction was better for patients who underwent BITA grafting, in both diabetic and nondiabetic subgroups. CONCLUSIONS: BITA+SVG grafting in diabetic patients improves survival and decrease coronary reoperation compared with SITA+SVG at long-term follow-up. Survival following myocardial infarction is improved with BITA grafting.

Major cardiovascular risk factors in Lyon hypertensive rats. A correlation analysis in a segregating population.

OBJECTIVE: To investigate the association of blood pressure with the other major cardiovascular risk factors in a large population of back-cross to Lyon hypertensive (LH) rats. METHODS: Mean arterial pressure was recorded in male freely moving Lyon normotensive (LN), LH, F1 and backcross to LH rats aged 30 weeks. Plasma cholesterol, triglycerides, insulin, creatinine, urea, fibrinogen and haematocrit levels, and the insulin: glucose ratio were measured in 31-week-old rats and 24h albuminuria in 6-week-old rats. RESULTS: Adult LH rats exhibited a significant increase in plasma lipids, insulin, fibrinogen, creatinine, urea and haematocrit levels compared with LN rats. In young LH rats, at an age at which blood pressure is slightly increased, albuminuria was increased to a greater extent than expected from their blood pressure levels. In the adult back-cross to LH rats, only the plasma cholesterol level was associated with blood pressure. Moreover, the plasma cholesterol level was related to fibrinogen and haematocrit levels. Finally, in the same rats, albuminuria developed early in life was positively related to hypercholinesterolaemia measured later in life. CONCLUSION: Plasma cholesterol, fibrinogen, haematocrit levels and early albuminuria could act synergistically in the enhancement or the development, or both, of vascular and kidney damage in the LH rat. Most interestingly, the association between plasma cholesterol level and blood pressure indicates that, as in essential hypertension, hypercholesterolaemia is a major phenotype associated with hypertension in the LH rat.

High blood pressure and metabolic disorders are associated in the Lyon hypertensive rat.

OBJECTIVE: A large population of F2 rats, obtained from a cross between male Lyon hypertensive (LH) rats and female Lyon normotensive (LN) rats, was studied in order to assess the relationship between increased body weight, hyperlipidaemia and high blood pressure which characterize LH rats. METHODS: Mean arterial pressure (MAP) was recorded in male, conscious, freely moving LH, LN, F1 and F2 rats aged 30 weeks. Plasma total cholesterol, high-density lipoprotein-, low-density lipoprotein- and very low-density lipoprotein-cholesterol, phospholipids, triglycerides, insulin and glucose were measured. RESULTS: In the F2 cohort it was observed that high MAP was a recessive trait that depends on several genes and was unrelated to body weight. The left ventricular weight, corrected for tibia length, was correlated with MAP. Plasma total and high-density lipoprotein-cholesterol and phospholipids concentrations were lower in the F1 rats than in the LN rats, suggesting an overdominance of the LN alleles. In the F2 rats MAP was related to total, high-density lipoprotein- and low-density lipoprotein-cholesterol. Plasma triglycerides, insulin and the insulin:glucose ratio, which were higher in the LH rats than in the LN rats, were also correlated with MAP in the F2 cohort. Using stepwise multiple regression analysis, MAP remained correlated with plasma total cholesterol, insulin and the insulin:glucose ratio, but not with triglycerides. CONCLUSIONS: Hypertension in LH rats is a recessive trait that is independent of body weight. In addition, the cosegregation of blood pressure with plasma cholesterol and, to a lesser degree, with insulin levels, which was observed in the present study provides the first direct evidence that these phenotypes are associated and are not due simply to genetic drift in the Lyon model.

The role of preservation solutions in coronary endothelial damage during cold storage.

The effects of cold storage and type of preservation solution on coronary endothelial function are not well understood. Experiments were designed to evaluate coronary endothelial-dependent relaxation after a 4-hr cold (4 degrees C) storage in different preservation solutions. Isolated rat hearts were studied in the Langendorff apparatus for coronary endothelial function. After 30 min of stabilization, hearts were arrested with a 10-min perfusion of 4 degrees C crystalloid hyperkalemic cardioplegic solution (CHCS) containing 24 mmol/L of KCl and stored for 4 hr in the following preservation solutions: CHCS, Krebs-Ringer's solution (KR), 0.9% NaCl (NS), and University of Wisconsin solution (UW). A fifth group was perfused and stored in UW solution. Endothelial-dependent and independent coronary artery vasorelaxation were tested, respectively, by infusing 5-hydroxytryptamine (5-HT) (1 x 10(-6) mol/L) and sodium nitroprusside (SNP) (1 x 10(-5) mol/L) before and 30 min after the storage period. In hearts stored in CHCS and KR, the coronary artery flow increase to 5-HT and SNP infusion were not significantly affected. However, in hearts preserved with NS and UW solutions, 5-HT coronary response was significantly decreased, indicating endothelial dysfunction. In addition to these findings, coronary flow increase to SNP infusion was decreased in the group perfused and stored with UW, suggesting smooth muscle damage. These experiments suggest that 4-hr cold storage in NS or UW impairs endothelial-dependent coronary relaxation in the isolated rat heart model.

Coronary artery endothelial dysfunction after ischemia-reperfusion and acute untreated rejection in a canine heterotopic heart transplantation model.

BACKGROUND: Acute rejection is a common problem in heart transplantation and may contribute to the development of cardiac allograft vasculopathy. This study was designed to evaluate the mechanisms of coronary endothelial dysfunction associated with ischemia-reperfusion and acute untreated rejection. METHODS: Two groups of mongrel dogs (n=7 per group) underwent heterotopic cervical heart transplantation without immunosuppression. Allografts were harvested on posttransplant day 1 (group 1) and day 5 (group 2). A third group of unoperated dogs served as control (group 3). After harvesting, epicardial coronary arteries were studied in organ chamber for endothelium-dependent and independent reactivity. RESULTS: Group 1 displayed multifocal ischemic damage without any rejection while hearts from group 2 reached grade IV rejection. Immunohistochemical studies for von Willebrand factor showed expression on coronary endothelial cells in all animals with scattered areas of denudation in transplanted groups. Endothelium-dependent responses to acetylcholine, calcium ionophore A23147, and bradykinin were unaffected in groups 1 and 2. Endothelial relaxations to sodium fluoride (Gi-protein activator) was significantly reduced in group 1 and significantly increased in group 2 compared with control. Responses to serotonin and UK14304 (receptors linked to Gi-protein) were significantly increased in group 2. Responses to thrombin were decreased in both groups. Endothelium-independent responses were unaffected. CONCLUSIONS: In the canine model of heterotopic heart transplantation, the early (24 hr) endothelial dysfunction seen after transplantation is specific to the thrombin receptor and the Gi-protein signaling pathway. Acute untreated rejection did not modify the alteration in endothelial reactivity to thrombin but enhanced the sensibility of the Gi-protein signaling pathways.