The GRM7 gene, early response to risperidone, and schizophrenia: a genome-wide association study and a confirmatory pharmacogenetic analysis.

The search for biomarkers of response to antipsychotic medications is hindered by difficulties inherent in the topic or related to persistent methodological difficulties, such as high rates of anticipated discontinuation and consequent distortions in the imputation of missing data. Because early response to antipsychotics represents a sufficiently reliable index of the subsequent treatment response in patients with schizophrenia, we undertook a real-world, genome-wide association study (GWAS) with the aim of identifying genetic predictors of response to risperidone after 2 weeks in 86 patients with schizophrenia. Limited to the associations reaching significance in the GWAS, confirmatory analysis relative to risperidone response over 9 months was also designed involving 97 patients (European only) enroled in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) genetic substudy. The GWAS revealed a significant association (false discovery rate 0.02) of the single-nucleotide polymorphism rs2133450 inside the GRM7 gene with Emsley's positive domain derived from the positive and negative syndrome scale (PANSS). Patients with the rs2133450 CC genotype presented poorer improvement in the positive domain over 2 weeks, with odds ratios of 12.68 (95% CI, 3.51-45.76) and 6.95 (95% confidence interval (CI), 2.37-20.37) compared with patients with the AA and AC genotypes, respectively. Compared with A homozygotes, rs2133450 C homozygotes enroled in the CATIE-derived confirmatory analysis showed less improvement in Emsley's positive, excited and depression domains, positive and general PANSS subtypes, and total PANSS after 9 months of treatment with risperidone. The original GWAS and the CATIE-derived confirmatory analysis support the proposal that the rs2133450 may have translational relevance as a predictor of response to risperidone.

First-trimester euploid miscarriages analysed by array-CGH.

It is estimated that 10-15 % of all clinically recognised pregnancies results in a miscarriage, most of which occur during the first trimester. Large-scale chromosomal abnormalities have been found in up to 50 % of first-trimester spontaneous abortions and, for several decades, standard cytogenetic analysis has been used for their identification. Recent studies have proven that array comparative genomic hybridisation (array-CGH) is a useful tool for the detection of genome imbalances in miscarriages, showing a higher resolution, a significantly higher detection rate and overcoming problems of culture failures, maternal contamination and poor chromosome morphology. In this study, we investigated the possibility that submicroscopic chromosomal changes, not detectable by conventional cytogenetic analysis, exist in euploid miscarriages and could be causative for the spontaneous abortion. We analysed with array-CGH technology 40 foetal tissue samples derived by first-trimester miscarriages with a normal karyotype. A whole-genome microarray with a 100-Kb resolution was used for the analysis. Forty-five copy number variants (CNVs), ranging in size between 120 Kb and 4.3 Mb, were identified in 31 samples (24 gains and 21 losses). Ten samples (10/31, 32 %) have more than one CNV. Thirty-one CNVs (68 %) were defined as common CNVs and 14 were classified as unique. Six genes and five microRNAs contained within these CNVs will be discussed. This study shows that array-CGH is useful for detecting submicroscopic CNVs and identifying candidate genes which could account for euploid miscarriages.

A molecular strategy for routine preimplantation genetic diagnosis in both reciprocal and Robertsonian translocation carriers.

Preimplantation genetic diagnosis (PGD) for structural chromosome abnormalities traditionally uses fluorescence in situ hybridization (FISH) techniques. Although relatively straight forward, FISH is technically demanding with several process problems which include cell loss, cell overlap, variable cell fixation and hybridization as well as sample mosaicism. Increasingly, alternative techniques for chromosome analysis in embryos are being investigated in an attempt to improve on current test outcomes. Here, we report on the first routine application of a polymerase chain reaction (PCR)-based protocol for translocation analysis utilizing multiplexed short tandem repeat (STR) markers located on both segments of the translocated chromosomes. Resulting STR profiles permit the analysis of qualitative dosage of each chromosomal segment to identify translocation malsegregants from the balanced/normal chromosome complements. A total of 29 patients have undergone clinical PGD testing of 78 embryos using this method. The proportion of alternate segregations (i.e. balanced carrier and non-carriers) detected for reciprocal and Robertsonian translocation carriers was 33% and 77%, respectively. Fetal heart pregnancy rates per embryo transferred was 46% for reciprocal carriers and 40% for Robertsonian carriers (mean number of embryos transferred was 1.0). This novel approach can be applied easily within any existing PGD PCR laboratory and allows for a significant improvement in the identification of segregation types when compared with the standard FISH protocol using combinations of distal and proximal probes. This approach increases test robustness and reliability with improved interpretation of segregation outcomes, decreased analysis time and also enables the straight forward combining of structural chromosome analysis with monogenic testing.

Glucokinase gene mutation screening in Argentinean clinically characterized MODY patients.

INTRODUCTION: Mutations in the glucokinase gene (GCK) produce a subtype of Maturity onset diabetes in the young (MODY), named MODY 2. To date over than 190 different mutations have been identified, distributed over the coding regions and the exon-intron boundaries of the gene. The aim of this work was to study the nature and frequency of mutations in the GCK gene, in a MODY clinically characterized Argentinean population. MATERIAL AND METHODS: Seventy unrelated individuals were selected based on MODY clinical features. The study methodology consisted in PCR amplification of the coding regions of the GCK gene, SSCP electrophoresis analysis of the amplified fragments and direct sequencing of the fragments with abnormal electrophoresis pattern. RESULTS: We identified a total of six patients with mutations in the GCK gene. This included two novel mutations: g.1831C>A, g.3792T>A, one already reported by our group, g.168fsdelC (same mutation in two non-related patients) and two already reported: p.Gln138Pro and p.Gly261Glu. With that data, we could establish the prevalence of MODY 2 among the patients in study reaching to 8.6%. DISCUSSION: The main contribution of this study is to inform about two novel mutations not described to date and to make an approach to the establishment of the prevalence of MODY 2 in the population under study. These findings contribute to confirm the allelic heterogeneity of GCK gene mutations and may provide an insight into the structure-function relationship of the GCK.

Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study.

OBJECTIVE: The influence of postprandial blood glucose on diabetes complications is intensively debated. We aimed to evaluate the predictive role of both fasting and postprandial blood glucose on cardiovascular events in type 2 diabetes and the influence of gender. METHODS: In a population of 529 (284 men and 245 women) consecutive type 2 diabetic patients attending our diabetes clinic, we evaluated the relationships, corrected for cardiovascular risk factors and type of treatment, between cardiovascular events in a 5-yr follow-up and baseline values of hemoglobin A1c (HbA1c) and blood glucose measured: 1) after an overnight fast, 2) after breakfast, 3) after lunch, and 4) before dinner. Continuous variables were categorized into tertiles. RESULTS: We recorded cardiovascular events in 77 subjects: 54 of 284 men (19%) and 23 of 245 women (9.4%). Univariate analysis indicated that cardiovascular events were associated with increasing age, longer diabetes duration, and higher HbA1c and fibrinogen in men, and higher systolic blood pressure, albumin excretion rate, HbA1c, and all blood glucose values in women. Smoking was more frequent in subjects with events. When all blood glucose values and HbA1c were introduced simultaneously in the models, only blood glucose after lunch predicted cardiovascular events, with hazard ratio of the third tertile vs. the first and the second tertiles greater in women (5.54; confidence interval, 1.45-21.20) than in men (2.12; confidence interval, 1.04-4.32; P < 0.01). CONCLUSIONS: Postprandial, but not fasting, blood glucose is an independent risk factor for cardiovascular events in type 2 diabetes, with a stronger predictive power in women than in men, suggesting that more attention should be paid to postprandial hyperglycemia, particularly in women.

Stent-graft treatment of complete acute aortic transection complicated by intussusception and pseudo-coartaction.

Aim of the study was to validate the use of endoluminal stent-graft treatment as an alternative to conventional surgery in patients affected by blunt chest trauma and aortic disruption with multiple associated lesions. We report the case of a young female admitted with diagnosis of descending thoracic aortic transection and multiple traumas following a car accident. Spiral computed tomography revealed circular disruption of thoracic aorta immediately after isthmus region with intussusception of leaflets and pseudo-coartation. Doppler analysis showed a 70 mmHg transaortic gradient. The hemodynamic evaluation confirmed the existence of severe transaortic gradient. A Gore-TAG endoprosthesis (26 x 100 mm) was selected. Intraoper-ative transesophageal echocardiography assessment was performed to monitoring the entire procedure. The final arteriogram showed an optimal sealing at proximal and distal site without endoleak with complete readjustment of intimal leaflets to the aortic wall and disappearance of transaortic gradient related to the pseudo-coartation. No complication was observed in the early postoperative and patient was discharged one month later once complete rehabilitation of associated lesion was obtained. Computed tomography scan performed before discharge revealed persistency of patent lumen of aorta with fibrosis of readjusted circumferential intimal flap. In conclusion endovascular repair of complete aortic transection may result safe and effective particularly in patients with extensive associated injuries. Indeed the severity of coexisting non-aortic lesions could be adversely affected by conventional surgery in consideration of high surgical morbidity due to open thoracotomy. Stent-graft repair allows the patient to timely undergo medical or surgical management of associated lesions and a prompt rehabilitation with shorter hospital stay.

[A study of the epidemiological behaviour of bovine paratuberculosis using time series in Tandil in the province of Buenos Aires, Argentina]. / Estudio del comportamiento epidemiológico de la paratuberculosis bovina mediante series cronológicas en Tandil, provincia de Buenos Aires, Argentina.

The authors present the results of a study conducted using time series data from the 1993--2001 period in order to characterise the clinical behaviour of bovine paratuberculosis. The case data, confirmed by macroscopic examination, enzyme-linked immunosorbent assay (ELISA) and comparative tuberculin test, came from the herd health register, located in Tandil in the province of Buenos Aires, Argentina. The upper limit of customary variation was observed in April, with an incidence of 2.5%. In 1997, 1999, 2000 and 2001 the disease was epidemic and a peak of 5.6% occurred in March 1999. Over the long term a rise in the total annual incidence was observed, from 0.7% in 1993 to 10.2% in 2001. Knowledge about the epidemiology of paratuberculosis will help to control the disease and minimise its impact on the national economy, and will also provide new information for use in public health.

Blood glucose pre-prandial baseline decreases from morning to evening in type 2 diabetes: role of fasting blood glucose and influence on post-prandial excursions.

BACKGROUND: To know the relationships between pre- and postprandial blood glucose (BG), i.e. BG profile shape, is a requisite for an appropriate therapy for type 2 diabetic patients. In non diabetic subjects, pre-breakfast, pre-lunch and pre-dinner BG are similar, so that BG postprandial excursions are superimposed on a stable BG preprandial baseline. We aimed to clarify: (a) whether BG preprandial baseline is stable also in type 2 diabetes and (b) whether fasting BG (FBG) influences the slope of BG preprandial baseline and the relationships between pre- and postprandial BG. DESIGN: We evaluated self-measured BG profiles of 237 type 2 diabetic patients on diet alone (M/F, 152/85; age 58.6 +/- 0.7 years; years from diagnosis 4.8 +/- 0.6; BMI 28.0 +/- 0.3 kg m-2): 536 profiles containing preprandial BG (corresponding HbA1c 6.8 +/- 0.06%) and 208 profiles containing both pre- and postprandial BG (corresponding HbA1c 6.8 +/- 0.09%). The profiles, measured by nurses, of 866 type 2 diabetic patients on diet alone were also considered (corresponding HbA1c 6.7 +/- 0.04%). RESULTS: In self-measured profiles containing only preprandial BG: (i) FBG (6.77 +/- 0.07 mmol L(-1)) is higher than pre-lunch BG (6.09 +/- 0.07 mmol L(-1)), P = 0.0001) and pre-dinner BG (5.84 +/- 0.06 mmol L(-1)), P =0.0001); (ii) the delta value between FBG and pre-dinner BG is correlated with FBG (r = 0.57, P = 0.0001), the highest FBG, the steepest the fall of BG preprandial baseline throughout the day. This trend is confirmed in profiles measured by nurses. In profiles containing both pre- and postprandial BG: (i) there is a trend to preprandial BG fall (P = 0.0001) and to postprandial BG increase (P = 0.0001) from morning to evening; (ii) postprandial excursions are influenced and sometimes masked by the slope of BG preprandial baseline, thus, in profiles with FBG < or = 6.7 mmol L(-1), all postprandial values are higher than FBG (P = 0.0001), whereas in profiles with FBG > 7.8 mmol L(-1), postprandial values are not significantly higher than FBG. CONCLUSION: In type 2 diabetes, the shape of BG profiles changes in relation to FBG, because it deeply influences the slope of BG preprandial baseline on which postprandial excursions are superimposed. Thus, before planning treatment policies, not only the extent of fasting and postprandial hyperglycaemia, but also the shape of profiles should be considered, to safely correct hyperglycaemia without inducing hypoglycaemia.

Programa de investigación para detectar sensores epidemiológicos en áreas del sudeste bonaerense, Argentina

[Introducción] En América Latina se desarrollaron diversos cambios en salud animal en los últimos años. Por un lado se lograron avances en el control y erradicación de diversas enfermedades, estableciéndose áreas y países libres de algunas de ellas, mientras que por otra parte se sufrió la aparición de enfermedades nuevas y/o emergentes. Esto determinó que se le brinde especial importancia en los sistemas de salud animal a los programas relacionados a la vigilancia epidemiológica (VE).

Diagnosis of porcine trichinellosis: parasitological and immunoserological tests in pigs from endemic areas of Argentina.

In order to compare the reliability of serological and parasitological techniques for the diagnosis of porcine trichinellosis from endemic areas in Argentina, 116 pigs were studied: 61 animals from two separate outbreaks and 55 from a small abattoir. Direct diagnostic techniques included trichinoscopy and the artificial digestion method. Indirect diagnostic tests used in this study were the enzyme-linked immunosorbent assay (ELISA), employing the excretory-secretory products of muscle larvae (ML) as antigen, and the indirect immunofluorescence assay using as antigen ML in suspension (IIF-susp), cryostat sections of infected rat muscle or of free ML (IIF-slide). The percentage of parasitologically positive pigs was invariably lower than that of serologically positive animals (IIF-slide), even when digestion studies were carried out individually with a greater amount of muscle sample than required by current regulations. Close correlation was found between IIF using as antigen tissue sections and IIF using free ML sections, while IIF-susp proved unsuitable for diagnosis since this assay presented a high percentage of false negative results (20%). The IIF-slide technique proved positive in all parasitologically positive animals. ELISA rendered a lower percentage of positive reactions than IIF-slide, especially when worm burden was low. Since most parasitologically positive animals rendered at least two positive serological tests (two variations of IIF or IIF plus ELISA), those negative by digestion and positive by two serological methods were strongly suspected of having trichinellosis. Upon studying swine from a abattoir it was found that 9% of the pigs were positive when assayed by two serological techniques, but Trichinella spiralis infection could not be parasitologically confirmed. To sum up, serological methods may be used for screening all pigs and positive findings should be tested by the digestion method by analysing a greater quantity of pork than that required by current regulations, above all in areas with reported clinical trichinellosis in humans, to ensure that the pork is safe for human consumption.

Experiencia preliminar en un consultorio interdisciplinario de factores de riesgo aterogenico (FRA): Informe de los hallazgos relevantes en 756 pacientes asistidos a lo largo de un año / Preliminary experience in an interdisciplinary clinic about atherogenic risk factors (ARF): report of relevant findings in 756 patients treated along a year

Se presenta la primer experiencia recogida en el primer consultorio interdisciplinario para el estudio integral de los factores de riesgo aterogenico (FRA) en la Argentina. Se analizan los resultados preliminares de esta accion medica en la prevencion primaria y secundaria de la enfermedad aterosclerotica y se realizan recomendaciones basadas en los hallazgos relevantes del estudio

Transvenous defibrillator implantation in patients with persistent left superior vena cava and right superior vena cava atresia.

In this report a transvenous cardioverter defibrillator implantation is described in two patients with a persistent left-sided superior vena cava and right SVC atresia. In the first case, manoeuvring of the guide wire inserted through the left subclavian vein into the SVC proved impossible, revealing a left SVC originating from the left brachiocephalic vein with an acute corner. Changing the side of implantation and inserting a CPI Endotak catheter through the right subclavian vein, the lead was easily advanced through the left SVC into the coronary sinus and then into the right atrium with the tip abutting the lateral atrial wall. Subsequent manoeuvres allowed passage of the tip of the catheter into the right ventricular apex with the proximal defibrillation coil of the Endotak lead in the low left SVC, with its distal limit at the junction with the coronary sinus. A biphasic waveform single pathway RV - > left SVC successfully defibrillated with a stored energy of 5 J. In the second patient, implantation of a transvenous Medtronic system was possible from a left infraclavicular approach. A tripolar RV coil was inserted into the right ventricle via the persistent left SVC and contiguous coronary sinus. Because of the acute angle required to enter the RV in this second case, the RV lead was looped in the right atrium in order to enter the RV in a satisfactory, albeit atypical RV location. This patient was successfully defibrillated with a 5 J monophasic waveform delivered between the RV coil, a CS/left SVC coil, and a subcutaneous patch. In conclusion, both of these patients illustrate the ability to use transvenous ICDs successfully in patients with persistent left superior vena cava although the implantation technique deviates substantially from traditional methods.

Estudio de prevalencia de microalbuminuria y macroproteinuria en diabéticos y su relación con otras complicaciones / A collaborative study on the prevalence of microalbuminuriaand macroproteinuria in diabetic patients and their relation to other complications

Se determinó la prevalencia de microalbuminuria(Mi) y macroproteinuria(Ma) y otras complicaciones en diabéticos en un estudio multicéntrico en la Argentina. Se entrevistaron 214 pacientes sin selección previa, se evaluó historia clínica, se dividió por tipo de diabetes. La Mi se realizó por radioinmunoanálisis o inmunoturbidimétrico la Ma por método sulfosalicílico. Se relacionaron con edad, antig³edad y prevalencia de hipertensión,dislipemia y retinopatía. Se aplicó para análisis el método estadístico DBase con programa EPI INFO 50. Se calcularon estadísticas descriptivas, se aplicó prueba de chi cuadrado con unnivel de significación p=0.05. La población insulinodependiente (DID)n73(34,1), la no insulinodependinte (DNID) n101(47,2), la insulinorrequiriente(DIR)n40(18,7), la edad promedio del DID 34,88+ 16,3; el DNID 64,27 + 9,83; DIR 61,85 + 9,37,lo que mostró una diferencia estadísticamente significativa para el DID con respecto al DNID y al DIR. La antig³edad de la diabetes no mostró diferencias significativas, lo mismo sucedió con la hemoglobina glicosilada para los diferentes grupos.La prevalencia de Mi fue 26,22,23.17,30 y la Ma fue 21,13, 10,9,26,66 respectivamente. El 19,20 careció de datos para la proteinuria. La prevalencia de hipertensión arterial fue para el DID 15.06,DNID 54,45,DIR 57.50, la dislipemia 13,69, 39,60,47,50 y retinopatía 35,10,24.757 y 57,50 respectivamente,la hipertensión y dislipemia mostraron diferencias estadísticamente significativas si se comparaba los DNID y DIR con respecto DID (AU)

Estudio de prevalencia de microalbuminuria y macroproteinuria en diabéticos y su relación con otras complicaciones / A collaborative study on the prevalence of microalbuminuriaand macroproteinuria in diabetic patients and their relation to other complications

Se determinó la prevalencia de microalbuminuria(Mi) y macroproteinuria(Ma) y otras complicaciones en diabéticos en un estudio multicéntrico en la Argentina. Se entrevistaron 214 pacientes sin selección previa, se evaluó historia clínica, se dividió por tipo de diabetes. La Mi se realizó por radioinmunoanálisis o inmunoturbidimétrico la Ma por método sulfosalicílico. Se relacionaron con edad, antigüedad y prevalencia de hipertensión,dislipemia y retinopatía. Se aplicó para análisis el método estadístico DBase con programa EPI INFO 50. Se calcularon estadísticas descriptivas, se aplicó prueba de chi cuadrado con unnivel de significación p=0.05. La población insulinodependiente (DID)n73(34,1), la no insulinodependinte (DNID) n101(47,2), la insulinorrequiriente(DIR)n40(18,7), la edad promedio del DID 34,88+ 16,3; el DNID 64,27 + 9,83; DIR 61,85 + 9,37,lo que mostró una diferencia estadísticamente significativa para el DID con respecto al DNID y al DIR. La antigüedad de la diabetes no mostró diferencias significativas, lo mismo sucedió con la hemoglobina glicosilada para los diferentes grupos.La prevalencia de Mi fue 26,22,23.17,30 y la Ma fue 21,13, 10,9,26,66 respectivamente. El 19,20 careció de datos para la proteinuria. La prevalencia de hipertensión arterial fue para el DID 15.06,DNID 54,45,DIR 57.50, la dislipemia 13,69, 39,60,47,50 y retinopatía 35,10,24.757 y 57,50 respectivamente,la hipertensión y dislipemia mostraron diferencias estadísticamente significativas si se comparaba los DNID y DIR con respecto DID

[Post-tetanic count after 50 and 100 Hz tetanic stimulation for monitoring deep neuromuscular blockade with vecuronium]. / Il conteggio post-tetanico dopo tetano a 50 e a 100 Hz nel monitoraggio del blocco neuromuscolare profondo da vecuronio.

For monitoring of vecuronium profound neuromuscular blockade post-tetanic count (PTC) following tetanic stimulation at frequency of 50 and 100 Hz was employed in 25 ASA I-II patients submitted to elective surgery, to evaluate the differences between the two patterns of stimulation and the possible clinical utility of the latter pattern of stimulation. The drugs employed for anaesthesia were: diazepam 0.15 mg kg-1 in premedication, thiopental 4-5 mg kg-1 for induction, suxamethonium 1.5 mg kg-1 for tracheal intubation. Anaesthesia was maintained with N2 + O2 (2:1). Analgesia was obtained with fentanyl at usual doses, and muscular relaxation with vecuronium. The ulnar nerve was stimulated at the wrist with Digistim III Plus and the responses evaluated by tactile method. The pattern of stimulation used was a cyclic one, as described by Howardy Hansen et al. The first dose of vecuronium (0.06 mg kg-1) was administered at recovery from suxamethonium (clinically evaluated) and the other doses (0.06 mg kg-1) when the third response to a train of four appeared. The results show that the PTC following 100 Hz tetanus was greater than the PTC following 50 Hz tetanic stimulation (P < 0.01). The results also show that PTC following 100 Hz tetanus leads to underestimate neuromuscular blockade; yet maybe it has any clinical employment in selected surgical situations such as middle ear and eye surgery, microvascular surgery, neurosurgery.

[Resistance to non-depolarizing myorelaxants. Our experience with 3 clinical cases]. / Resistenza ai miorilassanti non depolarizzanti. Nostra esperienza in tre casi clinici.

The Authors report their own experience in three patients that showed reduced sensitivity to atracurium or vecuronium. Two patients were affected by neoplastic diseases and one by hand trauma. Doses of 0.5 mg/kg of atracurium and 0.08 mg/kg of vecuronium were unable to establish a complete neuromuscular blockade. The Authors review the main clinical situations in which resistance to non-depolarizing muscle relaxants is known: burns, hepatic diseases, chronic therapy with anticonvulsant drugs. Possibly, such events are due to fast elimination of the drug, or to an increased number of acetylcholine nicotinic receptors, or to an unknown acutely acting circulating factor, or to increased binding of the drug to plasma proteins. Up to date, no well-established explanation is available.

The effect of cardiac electric anisotropy on epicardial potential fields during ventricular repolarization.

We tried to establish whether some of the manifestations of electrical anisotropy previously observed on the canine ventricular epicardium during the spread of excitation were also present during repolarization, with the appropriate polarity. To this end we determined the potential distribution on the ventricular surface of exposed dog hearts during ventricular excitation and repolarization. The ventricles were paced by means of epicardial or intramural electrodes. During the early stages of ventricular excitation following epicardial pacing we observed typical, previously described potential patterns, with negative, elliptical equipotential lines surrounding the pacing site, and two maxima aligned along the direction of subepicardial fibers. Intramural pacing gave rise to similar patterns. The axis joining the maxima, however, was oriented along the direction of intramural fibers. The repolarization potential pattern relating to epicardial excitation exhibited some features similar to those observed during the spread of excitation, namely the presence of families of elliptical equipotential lines around the pacing site, with pairs of potential extrema along the major or minor axes of the ellipses or both. The location of the extrema and the distribution of the epicardial potential gradients during repolarization suggested the presence of anisotropic current generators mainly oriented along the direction of deep myocardial fibers, with some contribution from more superficial sources which were oriented along the direction of subepicardial fibers. Deep stimulation elicited more complicated epicardial patterns whose interpretation is still obscure. We conclude that the electrical anisotropy of the heart affects the distribution of repolarization potentials and probably the strength of electrical generators during ventricular repolarization.