Análisis de la regresión temporal en el ensanchamiento del intervalo QRS inducido por bupivacaína con la administración de Intralipid. Estudio en un modelo experimental porcino / Analysis of the temporal regression of the QRS widening induced by bupivacaine after Intralipid administration. Study in an experimental porcine model

Objetivo: La toxicidad cardiaca inducida por la bupivacaína (B) se relaciona con el bloqueo de los canales de sodio, que se traduce por un ensanchamiento del intervalo QRS. Estudios experimentales recientes, sugieren que el Intralipid (IL) es eficaz en revertir la toxicidad cardiaca de la B. Nuestro objetivo fue analizar la evolución temporal del ensanchamiento del QRS inducido por la B con la administración de IL. Material y método: Doce cerdos fueron anestesiados con tiopental sódico, 5 mg kg−1, y sevoflurano a concentración alveolar mínima de 2,6%. Tras la instrumentalización se administró un bolo de B de 4-6 mg kg−1 con el objetivo de inducir un aumento de 150% en la duración del QRS. El grupo IL recibió 1,5 mL kg−1 de IL seguido de 0,25 mL kg min−1; el grupo control (C) recibió salino. Se registraron los parámetros electrocardiográficos tras la infusión de B y a 1, 5,10 y 30 min de la administración de Intralipid/salino. Resultados: La administración de B (4,33°æ 0,81 mg/kg en el grupo IL y 4,66°æ 1,15 mg/kg en el grupo C) indujo cambios electrocardiográficos similares en ambos grupos; el porcentaje medio de incremento máximo en el QRS fue de 184°æ 62% en el grupo IL, y de 230°æ 56% en el grupo C. El IL revirtió el ensanchamiento del QRS inducido por la B, a los 10 min de su administración el intervalo QRS disminuyó 132°æ 56% vs. 15°æ 76%, en relación al máximo incremento inducido por la B, en el grupo IL y grupo C respectivamente. Conclusión: El IL revirtió eficazmente el ensanchamiento del intervalo QRS inducido por la B. El tiempo hasta la normalización de los parámetros electrocardiográficos puede prolongarse más de 10 min. Mientras persistan los fenómenos de toxicidad cardíaca, las medidas de resucitación y monitorización deben continuarse hasta que los parámetros de conducción cardíaca se hayan restaurado de forma adecuada (AU)

Objective: The principal mechanism of cardiac toxicity of bupivacaine relates to the blockade of myocardial sodium channels, which leads to an increase in the QRS duration. Recently, experimental studies suggest that lipid emulsion is effective in reversing bupivacaine cardiac toxicity. We aimed to evaluate the temporal evolution of the QRS widening induced by bupivacaine with the administration of Intralipid. Material and methods: Twelve pigs were anesthetized with intravenous sodium thiopental 5 mg kg−1 and sevoflurane 1 MAC (2.6%). Femoral artery and vein were canalized for invasive monitoring, analysis of blood gases and determination of bupivacaine levels. After instrumentation and monitoring, a bupivacaine bolus of 4-6 mg kg−1 was administered in order to induce a 150% increase in QRS duration (defined as the toxic point). The pigs were randomized into two groups of six individuals. Intralipid group (IL) received 1.5 mL kg−1of IL over one minute, followed by an infusion of 0.25 mL kg min−1. Control group (C) received the same volume of a saline solution. The electrocardiographic parameters were recorded, and blood samples were taken after bupivacaine and 1, 5, 10 and 30 minutes after Intralipid/saline administration. Results: Bupivacaine (4.33°æ 0.81 mg/kg in IL group and 4.66°æ 1.15 mg/kg in C group) induced similar electrocardiographic changes in both groups; mean maximal percent increase in QRS interval was 184°æ 62% in IL group, and 230°æ 56% in control group (NS). Lipid administration reversed the QRS widening previously impaired by bupivacaine. After ten minutes of the administration of IL, the mean QRS interval decreased to 132°æ 56% vs. 15°æ 76% relative to the maximum widening induced by bupivacaine, in IL and C group, respectively. Conclusion: Intralipid reversed the lengthening of QRS interval induced by the injection of bupivacaine. Time to normalization of electrocardiographic parameters can last more than 10 minutes. While the phenomena of cardiac toxicity persist, resuscitation measures and adequate monitoring should be continued until adequate heart conduction parameters are restored (AU)

A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents.

AIMS: Short-QT syndrome (SQTS) is a recently recognized disorder associated with atrial fibrillation (AF) and sudden death due to ventricular arrhythmias. Mutations in several ion channel genes have been linked to SQTS; however, the mechanism remains unclear. This study describes a novel heterozygous gain-of-function mutation in the inward rectifier potassium channel gene, KCNJ2, identified in SQTS. METHODS AND RESULTS: We studied an 8-year-old girl with a markedly short-QT interval (QT = 172 ms, QTc = 194 ms) who suffered from paroxysmal AF. Mutational analysis identified a novel heterozygous KCNJ2 mutation, M301K. Functional assays displayed no Kir2.1 currents when M301K channels were expressed alone. However, co-expression of wild-type (WT) with M301K resulted in larger outward currents than the WT at more than -30 mV. These results suggest a gain-of-function type modulation due to decreased inward rectification. Furthermore, we analysed the functional significance of the amino acid charge at M301 (neutral) by changing the residue. As with M301K, in M301R (positive), the homozygous channels were non-functional, whereas the heterozygous channels demonstrated decreased inward rectification. Meanwhile, the currents recorded in M301A (neutral) showed normal inward rectification under both homo- and heterozygous conditions. Heterozygous overexpression of WT and M301K in neonatal rat ventricular myocytes exhibited markedly shorter action potential durations than the WT alone. CONCLUSION: In this study, we identified a novel KCNJ2 gain-of-function mutation, M301K, associated with SQTS. Functional assays revealed no functional currents in the homozygous channels, whereas impaired inward rectification demonstrated under the heterozygous condition resulted in larger outward currents, which is a novel mechanism predisposing SQTS.

The preexcitation syndrome: epidemiological and genetic study.

A sample of 4210 subjects of both sexes aged 35-54 years was examined, chosen at random from six regions of Croatia. An electrocardiogram at rest was performed in all subjects and changes analyzed by the Minnesota code. A short P-R interval together with a widening QRS complex and a delta wave was found in 0.05%, while 42 (1.0%) of the examinees had a short P-R interval, but only 0.21% were symptomatic. Three years after the first examination 0.06% of the subjects had preexcitation with a delta wave, and in one subject it appeared after three years. 0.35% of the subjects had a short P-R interval after three years but only 0.18% were symptomatic and in 22 (0.65%) it had disappeared in three years. After 13 years these subjects did not appear for an examination, and the short P-R interval did not appear in any of other subjects during this period. There were more short P-R intervals: 3.22% in females and 1.96% in males, but 0.33% only were symptomatic. Antigens of the human leukocyte group A (HLA) system were analyzed in 46 patients: the Wolff-Parkinson-White syndrome was found in 35, while 11 had the Lown-Ganong-Levine syndrome. Antigens of the HLA-A, HLA-B and HLA-DR locuses were determined by the microlymphocytotoxicity method. The results of the frequency of HLA system antigens were compared to the results of the control group of a Croatian population consisting of 175 people. There was an increased frequency of HLA-A9 and HLA-B5 (P = 0.026 and 0.0092) in the investigated population as a whole. The participation of HLA-A3 antigen was significantly less among patients (P = 0.03), while HLA-B14 antigen was not found in patients with preexcitation. Within 10 HLA-DR locuses, HLA-DR7 antigen was rather more frequently present, although this was not statistically significant (P = 0.173).

[The inheritance of the ventricular pre-excitation syndrome]. / Nasledovanie sindroma prezhdevremennogo vozbuzhdeniia zheludochkov.

Medico-genetic studies including preparation of the family pedigree, interviews, examinations, electro- and echocardiography were carried out in the families of 75 patients with pre-excitation syndrome (PES). Of these, 35 patients presented with Wolff-Parkinson-White (WPW) syndrome and 40 with Clerc-Lévy-Cristesco (CLC) syndrome. The studies made in possible to define the autosomal-dominant type of the syndrome or PES inheritance and to diagnose for the first time WPW syndrome in 3, PES in 1, CLC syndrome in 32 and CLC phenomenon in 89 persons out of 233 relatives of the first and second degree kinship.