8-10 Y 9-10 Antiarritmicos

+20mV

Na+ Na+ ATPasa

- 95mV

K+ K

+

+

+

+2

Na Na Ca

K

+

K

+

K+

Rosen MR (2002) Circulation 106: 2173-9

ALTERACIONES DEL AUTOMATISMO Causas: Inflamación Tóxicos Catecolaminas, etc

1. Focos ectópicos: precoces 2. Postdespolarizaciones

R

Q

S

T

T

tardias

Ackerman y Clapham (1997) N Engl J Med 336: 1575 Figure 5. The Long-QT Syndrome. A person with the long-QT syndrome may have unexplained syncope, seizures, or sudden death (Panel A). More likely, the person will be asymptomatic and identified by electrocardiographic screening during a routine evaluation or the screening of a primary relative who is symptomatic. The strict electrocardiographic definition of a prolonged QT interval varies according to age and sex, but generally a QT interval corrected for heart rate (QTc) greater than 460 msec1/2 is considered abnormal. According to Bazett's formula, the QTc is calculated by dividing the QT interval by the square root of the R - R interval. In patients with the long-QT syndrome, the T-wave morphology is often abnormal. This base-line rhythm can degenerate into a polymorphic ventricular tachycardia, classically a torsade de pointes, as shown here, after a stimulus that is not precisely understood but that often takes the form of adrenergic arousal. The prolonged QT interval as measured on the electrocardiogram results from an increased duration of the cardiac action potential (Panel B). The ventricular action potential is maintained at a resting membrane potential (approximately -85 mV) by inwardly rectifying potassium currents (IK1, phase 4). Once an excitatory stimulus depolarizes the cell beyond a threshold voltage (for example, -60 mV), sodium currents are activated that quickly depolarize the cell (INa, phase 0). These sodium channels are rapidly inactivated, allowing transient potassium currents to return the action potential to the plateau voltage (phase 1). The plateau lasts about 300 msec and provides time for the heart to contract. The plateau is maintained by the competition between outward-moving potassium currents and inward-moving calcium currents (phase 2). Progressive inactivation of calcium currents and increasing activation of potassium currents repolarize the cell to the resting membrane potential (phase 3). On a molecular basis, the autosomal dominant LQT1 and LQT2 are caused by defects in potassium-channel genes (KvLQT1 and HERG) involved in phase 3 repolarization (Panel C). LQT3 is caused by a defective sodium-channel gene, SCN5A. A common SCN5A mutation in families with LQT3 involves a deletion of three amino acids ( KPQ) in the III – IV cytoplasmic linker loop, which is known to regulate inactivation. The mutant sodium channel fails to become completely inactivated, resulting in sustained depolarization and prolonging the cardiac action potential. The linear topology of the proteins responsible for LQT1, LQT2, and LQT3 is shown, with the amino acids numbered beginning with the N-terminal — a total of 581, 1159, and 2016 amino acids, respectively. The chromosomal locations for these genes are shown in parentheses.

Figure 1. Electrocardiographic findings of the patient. A, ECG recording obtained from the proband during treatment with acebutolol and pirmenol before prescription of cisapride. Normal sinus rhythm (heart rate, 73 bpm) with complete right bundle-branch block was evident, and the QT interval was within normal limits (QTc, 435 ms). B, ECG telemetry on admission showed severe bradycardia after prescription of cisapride (junctional rhythm, heart rate 30 bpm) with QT prolongation (QTc, 480 ms) and repetitive TdP. C, Time course of QT interval. Emergency pacing was performed (pacing rate, 80 bpm) at the first day. Marked QT prolongation was observed (QTc, 731 ms). It was shortened the next day after withdrawal of drugs (QTc, 594 ms). QT interval was normalized at the sixth day (QTc, 417 ms). D, ECG recordings on V2 lead during treadmill exercise test before exercise and at the maximum exercise are shown. Heart rate was increased from 66 to 93 bpm, and the QTc was prolonged from 408 to 457 ms. Makita N. y cols. (2002) Circulation 106: 1269-74

Weirich y Anatoni (1998) Basic Res Cardiol 93 (Suppl.1), 125-32.

ARRITMIAS CARDIACAS CON BASE GENÉTICA Corriente

Síndrome

F. Desencadenantes

Tratamiento

LQT1

↑ A. Simpática Ejercicio

Bloqueantes β−A

IKr

LQT2

Estímulos auditivos

Bloqueantes β-A Suplementos K+

INa

LQT3

Reposo

Mexiletine Flecainida

IKS

INa

S. Brugada

Antiarritmicos IC

Quinidina Cilostazol. etc

Shimlizul W. (2005) Curr Pharm Des 11: 1561-72

REENTRADA DEL IMPULSO CARDIACO

FACTORES QUE FAVORECEN LA REENTRADA:

3. 4. 5. 6.

Diferencias en PR de zonas contiguas ↓ Velocidad conducción ↓ PR ↑ Longitud de la via

REENTRADA EN NODO A-V Auricula

Nodo A-V

α P.R.β>P.R.α

Ventriculo

β

ACCIONES PROARRITMICAS DE LAS CATECOLAMINAS

•

↑ Pendiente Fase 4 de P.A.: Taquicardia sinusal, ↑ Automatismo

•

↑ Entrada de Ca+2: Postdespolarizaciones

•

↓ Periodo Refractario: Reentrada del impulso

•

↓ Kext.: Hipopotasémia

•

Cardiotoxicidad Directa

•

↑ Conducción A-V: Taquicardias Ventriculares

Correlation between MEGX values and the overall histological score

Correlation between MEGX values and the overall histological score

Conti F. y cols. (2004) Clin Transplant 18: 235-41

CAST (1989) N Engl J Med 321: 406-412

Bluish-grey discoloration of the face after 1 year of treatment with amiodarone in a 54-year-old man with a history of ventricular tachycardia (left). Discoloration has almost completely disappeared 9 months after the drug was discontinued (right). The patient was given an implantable cardioverter-defibrillator for recurrent sustained ventricular tachycardia. Sra J. y Siobhan B. (1998) Circulation 97: 1105

ACCIONES PROARRITMICAS DE LAS CATECOLAMINAS

•

↑ Pendiente Fase 4 de P.A.: Taquicardia sinusal, ↑ Automatismo

•

↑ Entrada de Ca+2: Postdespolarizaciones

•

↓ Periodo Refractario: Reentrada del impulso

•

↓ Kext.: Hipopotasémia

•

Cardiotoxicidad Directa

•

↑ Conducción A-V: Taquicardias Ventriculares