RESUMEN

Myotonic dystrophy results from a trinucleotide repeat expansion between the myotonic dystrophy protein kinase gene (Dmpk), which encodes a serine-threonine protein kinase, and the Six5 gene, which encodes a homeodomain protein. The disease is characterized by late bursts of skeletal muscle Na channel openings, and this is recapitulated in Dmpk -/- and Dmpk +/- murine skeletal muscle. To test whether deficiency of the nearby Six5 gene also affected Na channel gating in murine skeletal muscle, we measured Na currents from cell-attached patches in Six5 +/- mice and age-matched wild-type and Dmpk +/- mice. Late bursts of Na channel activity were defined as an opening probability >10% measured from 10 to 110 ms after depolarization. There was no significant difference in the occurrence of late Na channel bursts in wild-type and Six5 +/- muscle, whereas in Dmpk +/- muscle there was greater than fivefold increase in late bursts (P < 0.001). Compared with wild-type mice, Na current amplitude was unchanged in Six5 +/- muscle, whereas in Dmpk +/- muscle it was 36% reduced (P < 0.05). Thus, since Six5 +/- mice do not exhibit the Na channel gating abnormality of Dmpk deficiency, we conclude that Six5 deficiency does not contribute to the Na channel gating abnormality seen in dystrophia myotonica patients.

Asunto(s)

Proteínas de Homeodominio/metabolismo , Potenciales de la Membrana/fisiología , Músculo Esquelético/fisiología , Canales de Sodio/fisiología , Animales , Genotipo , Heterocigoto , Proteínas de Homeodominio/genética , Ratones , Ratones Endogámicos , Ratones Noqueados , Músculo Esquelético/citología , Proteína Quinasa de Distrofia Miotónica , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Serina-Treonina Quinasas/genética , Factores de Tiempo

RESUMEN

OBJECTIVES: This study assessed the coexistence of intra-atrial re-entrant tachycardia (IART) and isthmus-dependent atrial flutter (IDAF) in patients presenting with supraventricular tachyarrhythmias after surgical correction of congenital heart disease (CHD). BACKGROUND: In patients with CHD, atrial tachyarrhythmias may result from IART or IDAF. The frequency with which IART and IDAF coexist is not well defined. METHODS: Both IDAF and IART were diagnosed in 16 consecutive patients using standard criteria and entrainment mapping. Seven patients had classic atrial flutter morphology on surface electrocardiogram (ECG), whereas nine had atypical morphology. RESULTS: A total of 24 circuits were identified. Three patients had IDAF only, five had IART only, seven had both, and one had a low right atrial wall tachycardia that could not be entrained. Twenty-two different reentry circuits were ablated. Successful ablation was accomplished in 13 of 14 (93%) IART and 9 of 10 (90%) IDAF circuits. There was one IART recurrence. The slow conduction zone involved the region of the right atriotomy scar in 12 of 14 (86%) IART circuits. No procedural complications and no further recurrences were seen after a mean follow-up of 24 months. CONCLUSIONS: Both IDAF and IART are the most common mechanisms of atrial re-entrant tachyarrhythmias in patients with surgically corrected CHD, and they frequently coexist. The surface ECG is a poor tool for identifying patients with coexistent arrhythmias. The majority of IART circuits involve the lateral right atrium and may be successfully ablated by creating a lesion extending to the inferior vena cava.

Asunto(s)

Aleteo Atrial/diagnóstico , Cardiopatías Congénitas/complicaciones , Taquicardia Supraventricular/diagnóstico , Adolescente , Adulto , Anciano , Aleteo Atrial/complicaciones , Aleteo Atrial/epidemiología , Ablación por Catéter , Niño , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Femenino , Fluoroscopía , Estudios de Seguimiento , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Recurrencia , Taquicardia Supraventricular/complicaciones , Taquicardia Supraventricular/epidemiología

RESUMEN

Phospholemman (PLM) is a small transmembrane cardiac protein that is the major sarcolemmal substrate for phosphorylation in response to adrenergic stimulation. PLM likely plays a role in muscle contractility and cell volume regulation through its function as a channel or a channel regulator. We are the first to describe the structure of the PLM gene and to demonstrate PLM cDNA splice variants. We cloned the murine PLM cDNA and used it as a probe to isolate the gene from a 129/SvJ genomic library. The gene contains seven introns and eight exons. The coding sequence is interrupted by five introns; the 5' untranslated region by two. Using rapid amplification of 5' cDNA ends we identified transcription start sites and four splice variants of the 5' untranslated domain. There was no TATA box or CAAT box in the putative promoter regions. The gene has several stretches of dinucleotide repeats. The 3' untranslated domains of mouse PLM cDNA clones show sequence differences not accounted for by alternative splicing. Mouse PLM shares 93, 83 and 80% amino acid identity with rat, dog, and human PLMs, respectively. Tissue expression of murine PLM parallels that in other species, being highest in heart, skeletal muscle, and liver.

Asunto(s)

Genes/genética , Proteínas de la Membrana/genética , Fosfoproteínas/genética , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Clonación Molecular , Cricetinae , ADN/química , ADN/genética , ADN/aislamiento & purificación , ADN Complementario/química , ADN Complementario/genética , Perros , Embrión de Mamíferos/metabolismo , Exones , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Intrones , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Microsomas/metabolismo , Datos de Secuencia Molecular , Miocardio/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Conejos , Ratas , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Distribución Tisular

RESUMEN

Na channels inactivate quickly after opening, and the very highly positively charged cytoplasmic linking region between homologous domains III and IV of the channel molecule acts as the inactivation gate. To test the hypothesis that the charged residues in the domain III to domain IV linker have a role in channel function, we measured currents through wild-type and two mutant skeletal muscle Na channels expressed in Xenopus oocytes, each lacking two or three charged residues in the inactivation gate. Microscopic current measures showed that removing charges hastened activation and inactivation. Macroscopic current measures showed that removing charges altered the voltage dependence of inactivation, suggesting less coupling of the inactivation and activation processes. Reduced intracellular ionic strength shifted the midpoint of equilibrium activation gating to a greater extent, and shifted the midpoint of equilibrium inactivation gating to a lesser extent in the mutant channels. The results allow the possibility that an electrostatic mechanism contributes to the role of charged residues in Na channel inactivation gating.

Asunto(s)

Citoplasma/química , Canales de Sodio/química , Animales , Activación del Canal Iónico , Cinética , Músculo Esquelético/metabolismo , Mutagénesis Sitio-Dirigida , Mutación , Oocitos/metabolismo , Concentración Osmolar , Técnicas de Placa-Clamp , Conformación Proteica , Ratas , Canales de Sodio/biosíntesis , Canales de Sodio/genética , Electricidad Estática , Xenopus

Asunto(s)

Antiarrítmicos/administración & dosificación , Antiarrítmicos/farmacocinética , Fibrilación Atrial/tratamiento farmacológico , Fenetilaminas/administración & dosificación , Fenetilaminas/farmacocinética , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacocinética , Potenciales de Acción/efectos de los fármacos , Administración Oral , Animales , Antiarrítmicos/efectos adversos , Aleteo Atrial/tratamiento farmacológico , Ensayos Clínicos Controlados como Asunto , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electrocardiografía/efectos de los fármacos , Técnicas Electrofisiológicas Cardíacas , Humanos , Fenetilaminas/efectos adversos , Potasio/metabolismo , Bloqueadores de los Canales de Potasio , Canales de Potasio/metabolismo , Tiempo de Reacción/efectos de los fármacos , Sulfonamidas/efectos adversos , Resultado del Tratamiento , Fibrilación Ventricular/tratamiento farmacológico

RESUMEN

Myotonic dystrophy, a progressive autosomal dominant disorder, is associated with an expansion of a CTG repeat tract located in the 3'-untranslated region of a serine/threonine protein kinase, DMPK. DMPK modulates skeletal muscle Na channels in vitro, and thus we hypothesized that mice deficient in DMPK would have altered muscle Na channel gating. We measured macroscopic and single channel Na currents from cell-attached patches of skeletal myocytes from mice heterozygous (DMPK(+/-)) and homozygous (DMPK(-/-)) for DMPK loss. In DMPK(-/-) myocytes, Na current amplitude was reduced because of reduced channel number. Single channel recordings revealed Na channel reopenings, similar to the gating abnormality of human myotonic muscular dystrophy (DM), which resulted in a plateau of Na current. The gating abnormality deteriorated with increasing age. In DMPK(+/-) muscle there was reduced Na current amplitude and increased Na channel reopenings identical to those in DMPK(-/-) muscle. Thus, these mouse models of complete and partial DMPK deficiency reproduce the Na channel abnormality of the human disease, providing direct evidence that DMPK deficiency underlies the Na channel abnormality in DM.

Asunto(s)

Activación del Canal Iónico , Músculo Esquelético/metabolismo , Distrofia Miotónica/genética , Proteínas Serina-Treonina Quinasas/genética , Canales de Sodio , Envejecimiento , Animales , Potenciales de la Membrana , Ratones , Músculo Esquelético/fisiopatología , Proteína Quinasa de Distrofia Miotónica , Técnicas de Placa-Clamp , Proteínas Serina-Treonina Quinasas/metabolismo

RESUMEN

The modulatory effect of protein kinase C (PKC) on the response of Xenopus oocyte-expressed Na channel alpha-subunits to halothane (2-bromo-2-chloro-1,1,1-trifluroethane) was studied. Na currents through rat skeletal muscle, rat brain and human cardiac muscle Na channels were assessed using cell-attached patch clamp recordings. PKC activity was increased by co-expression of a constitutively active PKC alpha-isozyme. Decay of macroscopic Na currents could be separated into fast and slow exponential phases. PKC co-expression alone slowed Na current decay in neuronal channels, through enhancement of the amplitude of the slower phase of decay. Halothane (1.0 mM) was without effect on any of the three isoforms expressed alone but, after co-expression of PKC, there was enhancement of Na current decay with reduction in charge movement through skeletal muscle and neuronal channels. Cardiac channels were relatively insensitive to halothane. Enhanced Na current decay resulted from suppression of the slow phase, without effect on the faster phase or on either decay tau. Suppression of Na current through skeletal muscle channels was concentration-dependent over the therapeutic range and was described by third order reaction kinetics, with an IC(50) of 0.55 mM. We conclude that the halothane suppresses skeletal muscle and brain Na channel activity in this preparation through a reduction in the slow mode of inactivation gating, but only after PKC co-expression. Cardiac Na channels were relatively insensitive to halothane. The mechanism is likely to involve phosphorylation of the channel inactivation gate, although phosphorylation of other sites in the channel may account for the isoform specific differences.

Asunto(s)

Halotano/farmacología , Canales de Sodio/efectos de los fármacos , Animales , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Activación del Canal Iónico/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Músculo Esquelético/metabolismo , Miocardio/metabolismo , Oocitos , Isoformas de Proteínas/efectos de los fármacos , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiología , Proteína Quinasa C/efectos de los fármacos , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , ARN Mensajero/administración & dosificación , ARN Mensajero/genética , Ratas , Canales de Sodio/genética , Canales de Sodio/fisiología , Xenopus laevis

RESUMEN

The genetic abnormality in myotonic muscular dystrophy, multiple CTG repeats lie upstream of a gene that encodes a novel protein kinase, myotonic dystrophy protein kinase (DMPK). Phospholemman (PLM), a major membrane substrate for phosphorylation by protein kinases A and C, induces Cl currents (I(Cl(PLM))) when expressed in Xenopus oocytes. To test the idea that PLM is a substrate for DMPK, we measured in vitro phosphorylation of purified PLM by DMPK. To assess the functional effects of PLM phosphorylation we compared I(Cl(PLM)) in Xenopus oocytes expressing PLM alone to currents in oocytes co-expressing DMPK, and examined the effect of DMPK on oocyte membrane PLM expression. We found that PLM is indeed a good substrate for DMPK in vitro. Co-expression of DMPK with PLM in oocytes resulted in a reduction in I(Cl(PLM)). This was most likely a specific effect of phosphorylation of PLM by DMPK, as the effect was not present in oocytes expressing a phos(-) PLM mutant in which all potential phosphorylation had been disabled by Ser --> Ala substitution. The biophysical characteristics of I(Cl(PLM)) were not changed by DMPK or by the phos(-) mutation. Co-expression of DMPK reduced the expression of PLM in oocyte membranes, suggesting a possible mechanism for the observed reduction in I(Cl(PLM)) amplitude. These data show that PLM is a substrate for phosphorylation by DMPK and provide functional evidence for modulation of PLM function by phosphorylation.

Asunto(s)

Proteínas de la Membrana/metabolismo , Distrofia Miotónica/enzimología , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Potenciales de la Membrana , Proteína Quinasa de Distrofia Miotónica , Oocitos/metabolismo , Oocitos/fisiología , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especificidad por Sustrato , Xenopus

RESUMEN

The significance of ST-segment elevation after resuscitation from arrhythmias not associated with ischemia was examined in a group of patients who received transthoracic shocks for hemodynamically unstable ventricular tachyarrhythmias during electrophysiologic studies. ST-segment elevation was seen in 15.4%, was transient, and was not associated with clinical evidence of myocardial infarction.

Asunto(s)

Cardioversión Eléctrica/métodos , Hemodinámica/fisiología , Taquicardia Ventricular/fisiopatología , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Taquicardia Ventricular/terapia , Tórax , Resultado del Tratamiento

RESUMEN

1. Voltage-gated Na channels, which are potential targets for general anaesthetics, are substrates for PKC, which phosphorylates a conserved site in the channel inactivation gate. We investigated the idea that PKC modulates the effect of volatile anaesthetics on Na channels via phosphorylation of this inactivation gate site. 2. Na currents through rat skeletal muscle Na channel alpha-subunits expressed in Xenopus oocytes were measured by two-microelectrode voltage clamp in the presence of the volatile anaesthetic agent halothane (2-bromo-2-chloro-1,1,1-trifluroethane). PKC activity was modulated by co-expression of a constitutively active PKC alpha-isozyme. 3. Halothane (0.4 mM) had no effect on Na currents. With co-expression of PKC, however, halothane dose-dependently enhanced the rate of Na current decay and caused a small, but statistically significant reduction in Na current amplitude. 4. The enhancement of Na current decay was absent in a Na channel mutant in which the inactivation gate phosphorylation site was disabled. Effects of halothane on amplitude were independent of this mutation. 5. Co-expression of a PKC alpha-isozyme permits an effect of halothane to hasten current decay and reduce current amplitude, at least in part through interaction with the inactivation gate phosphorylation site. We speculate that the interaction between halothane and Na channels is direct, and facilitated by PKC activity and by phosphorylation of a site in the channel inactivation gate.

Asunto(s)

Anestésicos por Inhalación/farmacología , Halotano/farmacología , Músculo Esquelético/metabolismo , Proteína Quinasa C/biosíntesis , Canales de Sodio/metabolismo , Animales , Isoenzimas/biosíntesis , Cinética , Microelectrodos , Músculo Esquelético/efectos de los fármacos , Oocitos/efectos de los fármacos , Oocitos/metabolismo , ARN Mensajero/biosíntesis , Ratas , Bloqueadores de los Canales de Sodio , Canales de Sodio/efectos de los fármacos , Xenopus laevis

RESUMEN

Phospholemman (PLM), the major sarcolemmal substrate for phosphorylation by cAMP-dependent kinase (PKA) protein kinase C (PKC) and NIMA kinase in muscle, induces hyperpolarization-activated anion currents in Xenopus oocytes, most probably by enhancing endogenous oocyte currents. PLM peptides from the cytoplasmic tail are phosphorylated by PKA at S68, by NIMA kinase at S63, and by PKC at both S63 and S68. We have confirmed the phosphorylation sites in the intact protein, and we have investigated the role of phosphorylation in the regulatory activity of PLM using oocyte expression experiments. We found: (1) the cytoplasmic domain is not essential for inducing currents in oocytes; (2) co-expression of PKA increased the amplitude of oocyte currents and the amount of PLM in the oocyte membrane largely, but not exclusively, through phosphorylation of S68; (3) co-expression of PKA had no effect on a PLM mutant in which all putative phosphorylation sites had been inactivated by serine to alanine mutation (SSST 62, 63, 68, 69 AAAA); (4) co-expression of PKC had no effect in this system; (5) co-expression of NIMA kinase increased current amplitude and membrane protein level, but did not require PLM phosphorylation. These findings point to a role for phosphorylation in the function of PLM.

Asunto(s)

Proteínas de Ciclo Celular , Canales Iónicos/biosíntesis , Proteínas de la Membrana/metabolismo , Oocitos/metabolismo , Fosfoproteínas/metabolismo , Proteínas Quinasas/biosíntesis , Secuencia de Aminoácidos , Animales , Sitios de Unión , Membrana Celular/metabolismo , Canales de Cloruro/biosíntesis , Proteínas Quinasas Dependientes de AMP Cíclico/biosíntesis , Expresión Génica , Proteínas de la Membrana/química , Datos de Secuencia Molecular , Quinasa 1 Relacionada con NIMA , Quinasas Relacionadas con NIMA , Fosfoproteínas/química , Fosforilación , Proteína Quinasa C/biosíntesis , Proteínas Serina-Treonina Quinasas/biosíntesis , Regulación hacia Arriba , Xenopus

RESUMEN

Phospholemman (PLM) is a 72-amino-acid peptide with a single transmembrane domain, the expression of which induces chloride currents in Xenopus oocytes. It has remained unknown whether PLM is an ion channel or acts as a channel regulator. Here we show, by measuring unitary anion currents across planar phospholipid bilayers to which immunoaffinity-purified recombinant PLM was added, that it does indeed form ion channels. Excised patches of oocytes expressing PLM had similar currents. Of the ions tested, the sulphonic amino acid taurine was the most permeant, and expression of PLM increased fluxes of radiolabelled taurine in oocytes. Phospholemman is the smallest protein in cell membranes known to form an ion channel and the taurine selectivity suggests that it is involved in cell volume regulation.

Asunto(s)

Canales Iónicos/metabolismo , Proteínas de la Membrana/metabolismo , Fosfoproteínas/metabolismo , Animales , Aniones , Línea Celular , Permeabilidad de la Membrana Celular , Células Cultivadas , Perros , Conductividad Eléctrica , Membrana Dobles de Lípidos , Proteínas de la Membrana/inmunología , Oocitos , Fragmentos de Péptidos/inmunología , Fosfoproteínas/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , Taurina/metabolismo , Xenopus

RESUMEN

BACKGROUND: In acute myocardial infarction patients who do not reperfuse their infarct arteries shortly after thrombolytic treatment have a high morbidity and mortality. Management of this high risk group remains problematic, especially in centres without access to interventional cardiology. Additional thrombolytic treatment may result in reperfusion and improved left ventricular function. METHODS: Failure of reperfusion was assessed non-invasively as less than 25% reduction of ST elevation in the electrocardiographic lead with maximum ST shift on a pretreatment electrocardiogram. 37 patients with acute myocardial infarction who showed electrocardiographic evidence of failed reperfusion 30 minutes after 1.5 MU streptokinase over 60 minutes were randomly allocated to receive either alteplase (tissue type plasminogen activator (rt-PA) 100 mg over three hours) (19 patients) or placebo (18 patients). 43 patients with electrocardiographic evidence of reperfusion after streptokinase acted as controls. Outcome was assessed from the Selvester Q wave score of a predischarge electrocardiogram and a nuclear gated scan for left ventricular ejection fraction 4-6 weeks after discharge. RESULTS: Among patients in whom ST segment elevation was not reduced after streptokinase, alteplase treatment resulted in a significantly smaller electrocardiographic infarct size (14% (8%) v 20% (9%), P = 0.03) and improved left ventricular ejection fraction (44 (10%) v 34% (16%), P = 0.04) compared with placebo. This benefit was confined to patients who failed fibrinogenolysis after streptokinase (fibrinogen > 1 g/l). In patients in whom ST segment elevation was reduced after streptokinase, infarct size and left ventricular ejection fraction were not significantly different from those in patients treated with additional alteplase. CONCLUSION: Patients without electrocardiographic evidence of reperfusion after streptokinase may benefit from further thrombolysis with alteplase.

Asunto(s)

Fibrinolíticos/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Estreptoquinasa/uso terapéutico , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Quimioterapia Combinada , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Estudios Prospectivos , Cintigrafía , Volumen Sistólico , Resultado del Tratamiento

RESUMEN

A history of atrial fibrillation and right atrial size are both determinants of procedural and long-term outcome after RF catheter ablation of type 1 atrial flutter. The results of this study suggest that patients with no history of atrial fibrillation and a normal right atrial size have the best short- and long-term results from this procedure.

Asunto(s)

Aleteo Atrial/cirugía , Ablación por Catéter , Anciano , Anciano de 80 o más Años , Aleteo Atrial/clasificación , Estimulación Cardíaca Artificial , Ablación por Catéter/instrumentación , Ablación por Catéter/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

BACKGROUND: Accelerated junctional rhythms have been observed before the development of AV nodal block during radiofrequency (RF) catheter ablation of the AV junction. However, the time course and temperatures required to induce an accelerated junctional rhythm and AV nodal block during this procedure have not yet been characterized. METHODS AND RESULTS: Nineteen patients underwent RF ablation of the AV junction with a thermistor ablation catheter. RF energy was initially delivered at 10 W for 9 seconds and then increased by 5-W increments for 9 seconds at each power level up to a maximum power of 50 W. If a junctional rhythm was observed during the power titration, a 30- to 60-second RF application was then delivered at the same power level. The power was then further increased to a maximum of 50 W if AV nodal block was not observed after 20 seconds of RF delivery. The procedure was successful in all 19 patients. A median of one RF application (range, one to eight applications) was required to produce permanent AV nodal block. An accelerated junctional rhythm was observed during 89% of successful attempts versus 70% of unsuccessful deliveries (P = NS). The median time to onset of the junctional rhythm was significantly shorter during successful compared with unsuccessful applications (1.8 versus 7.7 seconds, respectively; P < .001). Similarly, the mean time to appearance of AV nodal block was significantly shorter during successful compared with unsuccessful attempts (19.6 +/- 9.4 versus 36.8 +/- 19.0 seconds, respectively; P < .01). The catheter tip temperatures associated with the development of an accelerated junctional rhythm were significantly lower than those associated with the appearance of AV nodal block (51 +/- 4 degrees C versus 58 +/- 6 degrees C, respectively; P < .001). Mean temperatures in the range of 60 +/- 7 degrees C were required to produce permanent AV nodal block. CONCLUSIONS: The development of an accelerated junctional rhythm within 5 seconds and the appearance of AV nodal block within 30 seconds of RF onset were both highly characteristic of successful target sites during RF ablation of the AV junction. The accelerated junctional rhythm and AV nodal block were both highly temperature dependent. The temperatures associated with the onset of AV nodal block were significantly higher than the temperatures resulting in an accelerated junctional rhythm.

Asunto(s)

Nodo Atrioventricular/fisiopatología , Nodo Atrioventricular/cirugía , Ablación por Catéter , Bloqueo Cardíaco/fisiopatología , Anciano , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Electrocardiografía , Femenino , Bloqueo Cardíaco/etiología , Humanos , Masculino , Monitoreo Intraoperatorio , Taquicardia Supraventricular/cirugía , Temperatura , Factores de Tiempo

Asunto(s)

Profilaxis Antibiótica , Marcapaso Artificial , Humanos , Infusiones Parenterales , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

In myotonic muscular dystrophy, abnormal muscle Na currents underlie myotonic discharges. Since the myotonic muscular dystrophy gene encodes a product, human myotonin protein kinase, with structural similarity to protein kinases, we tested the idea that human myotonin protein kinase modulates skeletal muscle Na channels. Coexpression of human myotonin protein kinase with rat skeletal muscle Na channels in Xenopus oocytes reduced the amplitude of Na currents and accelerated current decay. The effect required the presence of a potential phosphorylation site in the inactivation mechanism of the channel. The mutation responsible for human disease, trinucleotide repeats in the 3' untranslated region, did not prevent the effect. The consequence of an abnormal amount of the kinase would be altered muscle cell excitability, consistent with the clinical finding of myotonia in myotonic dystrophy.

Asunto(s)

Músculo Esquelético/metabolismo , Distrofias Musculares/fisiopatología , Proteínas Quinasas/biosíntesis , Proteínas Serina-Treonina Quinasas , Secuencias Repetitivas de Ácidos Nucleicos , Canales de Sodio/biosíntesis , Animales , Encéfalo/metabolismo , Feto , Humanos , Potenciales de la Membrana/fisiología , Distrofias Musculares/genética , Mutación , Miocardio/metabolismo , Proteína Quinasa de Distrofia Miotónica , Oocitos/fisiología , Técnicas de Placa-Clamp , Fosforilación , Proteínas Quinasas/metabolismo , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Ratas , Mapeo Restrictivo , Canales de Sodio/fisiología , Xenopus

RESUMEN

BACKGROUND: Patients who have coronary artery surgery normally occupy intensive care beds for less than 24 hours. Longer stays may result in under use of cardiac surgical capacity. One approach to optimise surgical throughput is prospectively to identify fast track patients--that is, those who occupy an intensive care bed for less than 24 hours. A prospective audit of patients was performed to identify fast track patients by simple clinical criteria. Total length of hospital stay was also assessed in an attempt to predict which patients were likely to have a short postoperative stay, defined as < or = 7 days. METHODS: Baseline demographic details, cardiovascular risk factors, angiographic and operative details were recorded for 431 consecutive patients who underwent coronary surgery at a regional centre over a nine month period. Outcome measures were the duration of the stay in the intensive care unit in hours and total duration of the postoperative stay in hospital in days. In addition, two groups of patients who were thought to be fast track were identified prospectively. Fast track 1 patients were identified by criteria selected by cardiovascular physicians. These were age less than 60 years, stable angina, good left ventricular function (ejection fraction > 50%), good renal function (serum creatinine < 120 mumol/l), and no obesity, diabetes, or other serious disease. Fast track 2 patients were identified by criteria defined by cardiovascular surgeons. These were male sex, age less than 65 years, good left ventricular function and no peripheral vascular disease, diabetes, or other serious disease. The efficacy of both sets of criteria in predicting outcome was tested. RESULTS: 344 (79.8%) patients were fast track. Significant factors for the prediction of fast track patients by univariate analysis (with positive predictive accuracy and sensitivity) were left ventricular ejection fraction > 50% (83%, 80%), left ventricular end diastolic pressure < 13 mm Hg (90%, 59%), creatinine less than 120 mumol/l (83%, 87%), and one or two vessel coronary disease (89%, 34%). Of the patients categorised as fast track 1 89% proved to be fast track (sensitivity 24%), however, the fast track 2 characteristics were not significant. Age, sex, obesity, diabetes, hypertension, a history of obstructive pulmonary disease and unstable angina were not predictive of the duration of intensive care stay. Multivariate analysis indicated that only left ventricular end diastolic pressure and the number of diseased coronary arteries predicted fast track patients. These criteria separated patients into three groups. Those who were good risk had one or two vessel disease and left ventricular end diastolic pressure < 13 mm Hg. They comprised 19% of the total and 93% of them were fast track. Those who were intermediate risk had either three vessel disease or left ventricular end diastolic pressure > 13 mm Hg but not both. They comprised 49% of the total and 85% of them were fast track. Those who were poor risk had both three vessel disease and left ventricular end diastolic pressure > 13 mm Hg. They comprised 32% of the total and 62% of them were fast track. The 106 (24%) patients who spent < or = 7 days in hospital after surgery were significantly younger (mean (SD) 55(8) v 58(8) years; P < 0.001) with a lower incidence of previous myocardial infarction (positive predictive accuracy 30%, sensitivity 53%), were less likely to have a history of obstructive pulmonary disease (25%, 98%), and more likely to have one or two vessel coronary disease (33%, 41%). They were more likely to have an internal mammary artery as a bypass conduit (27%, 89%) and more likely to need fewer than three distal anastomoses of the vein graft (29%, 63%). By multivariate analysis only age was significantly predictive of hospital stay. Total hospital stay could not be satisfactorily modelled on the basis of the criteria tested here. Sex, obesity, diabetes, hypertension, unstable angina, renal function, and left ventricular function were not associated with hospital stay. CONCLUSIONS-Most patients who had coronary artery surgery spent less than or equal to 24 hours in intensive care, but most spent > 7 days in hospital. The chance of a patient spending less than or equal to 24 hours in intensive care could be predicted by the number of coronary arteries diseased and the left ventricular end diastolic pressure. Poor risks patients (32%) had only a 62% chance of an intensive care unit stay of less than or equal to 24 hours. A policy of scheduling no more than one such patient for surgery per day would be simple to institute and would maximise the use of surgical capacity.

Asunto(s)

Puente de Arteria Coronaria , Unidades de Cuidados Coronarios , Tiempo de Internación , Auditoría Médica , Enfermedad Coronaria/patología , Enfermedad Coronaria/fisiopatología , Vasos Coronarios/patología , Diástole , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Factores de Riesgo , Presión Ventricular

RESUMEN

BACKGROUND: Pacemaker pocket infection is a potentially serious problem after permanent pacemaker implantation. Antibiotic prophylaxis is commonly prescribed to reduce the incidence of this complication, but current trial evidence of its efficacy is conflicting. A large prospective randomised trial was therefore performed of antibiotic prophylaxis in permanent pacemaker implantation. The intention was firstly to determine whether antibiotic prophylaxis is efficacious in these patients and secondly to identify which patients are at the highest risk of infection. METHODS: A prospective randomised open trial of flucloxacillin (clindamycin if the patient was allergic to penicillin) v no antibiotic was performed in a cohort of patients undergoing first implantation of a permanent pacing system over a 17 month period. Intravenous antibiotics were started at the time of implantation and continued for 48 hours. The trial endpoint was a repeat operation for an infective complication. RESULTS: 473 patients were entered into a randomised trial. 224 received antibiotic prophylaxis and 249 received no antibiotics. A further 183 patients were not randomised but were treated according to the operator's preference (64 antibiotics, 119 no antibiotics); these patients are included only in the analysis of predictors of infection. Patients were followed up for a mean (SD) of 19(5) months. Among the patients in the randomised group there were nine infections requiring a repeat operation, all in the group not receiving antibiotic (P = 0.003). In the total patient cohort there were 13 infections, all but one in the non-antibiotic group (P = 0.006). Nine of the infections presented as erosion of the pulse generator or electrode, three as septicaemia secondary to Staphylococcus aureus, and one as a pocket abscess secondary to Staphylococcus epidermidis. Infections were significantly more common when the operator was inexperienced (< or = 100 previous patients), the operation was prolonged, or after a repeat operation for non-infective complications (principally lead displacement). Infection was not significantly more common in patients identified preoperatively as being at high risk (for example patients with diabetes mellitus, patients receiving long term steroid treatment), although there was a trend in this direction. CONCLUSIONS: Antibiotic prophylaxis significantly reduced the incidence of infective complications requiring a repeat operation after permanent pacemaker implantation. It is suggested that antibiotics should be used routinely.

Asunto(s)

Estimulación Cardíaca Artificial , Floxacilina/uso terapéutico , Premedicación , Infección de la Herida Quirúrgica/prevención & control , Anciano , Anciano de 80 o más Años , Clindamicina/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reoperación , Factores de Riesgo

RESUMEN

We report radiofrequency ablation of a Mahaim fiber in a patient with wide complex supraventricular tachycardia. Pathway potentials from the lateral aspect of the right AV groove were recorded, which were distinct from the His potential. During atrial pacing, decremental properties of the fiber were demonstrated, which resulted in prolongation of the interval between the atrial electrogram and the Mahaim pathway potential. The pathway potentials, preexcitation, and tachycardia disappeared after a single application of radiofrequency energy, after which the patient has remained free of palpitations. Mapping of a Mahaim fiber by identifying pathway potentials thus allowed accurate localization and successful ablation with minimal energy. We therefore suggest that, where possible, recording of such Mahaim potentials may be the optimal technique for Mahaim fiber localization.

Asunto(s)

Ablación por Catéter/métodos , Preexcitación Tipo Mahaim/cirugía , Taquicardia Supraventricular/cirugía , Adulto , Electrocardiografía , Femenino , Humanos , Preexcitación Tipo Mahaim/fisiopatología , Taquicardia Supraventricular/fisiopatología