The ECG in cardiovascular-relevant animal models of electrophysiology.

The most frequently used animal species in experimental cardiac electrophysiology are mice, rabbits, and dogs. Murine and human electrocardiograms (ECGs) show salient differences, including the occurrence of a pronounced J-wave and a less distinctive T-wave in the murine ECG. Mouse models can resemble human cardiac arrhythmias, although mice differ from human in cardiac electrophysiology. Thus, arrhythmia mechanisms in mice may differ from those in humans and should be transferred to the human situation with caution. Further relevant cardiovascular animal models are rabbits, dogs, and minipigs, as they show similarities of cardiac ion channel distribution with the human heart and are suitable to study ventricular repolarization or pro- and antiarrhythmic drug effects. ECG recordings in large animals like goats and horses are feasible. Both goats and horses are a suitable animal model to study atrial fibrillation (AF) mechanisms. Horses frequently show spontaneous AF due to their high vagal tone and large atria. The zebrafish has become an important animal model. Models in "exotic" animals such as kangaroos may be suitable for particular studies.

Changes of the corrected QT interval in healthy boys and girls over day and night.

AIMS: The study was designed to detect changes in corrected QT intervals over day and night in both sexes in healthy children. METHODS AND RESULTS: The corrected QT interval was calculated from 24 h ECGs obtained from 282 healthy children aged 6 months to 18 years. The QTc interval as measured by the 24 h recording differs to the standard ECG measurement which is in average of 40-50 ms shorter. The QTc interval changes little over a 24 h period and is remarkably constant despite significant heart rate changes in healthy children. CONCLUSION: The routine ECG-even if the calculated values differ markedly from those obtained over 24 h-seems to be a good screening method for the measurement of corrected QT intervals, because the corrected QT interval is kept constant over the whole day in healthy children.

Cardiomyopathy in congenital disorders of glycosylation.

Congenital disorders of glycosylation are a group of inherited metabolic multisystem disorders characterized by defects in the glycosylation of proteins and lipids. In most cases, neuromuscular disease is present. The purpose of this study was to characterize the cardiological aspects in this disorder. From the literature, we identified six children with congenital disorders of glycosylation associated with cardiac disease. We then screened for cardiovascular manifestations 20 patients diagnosed with congenital disorders of glycosylation at our own institution. Of the 6 patients identified in the literature, 4 had hypertrophic cardiomyopathy, while in the other 2 the cardiac diagnosis was unclear. The mean age at cardiac diagnosis was 5 months, with a range from 34 weeks to 24 months. Of the patients, five had died at a mean age of 3.5 months, with a range from 1.5 to 6 months, with one documented cardiac death. Three of our 20 patients (15%) had coexistent cardiomyopathy, and in three additional patients presenting with cardiomyopathy we made the diagnosis of a congenital disorder of glycosylation. In our cohort, dilated cardiomyopathy was found in two-thirds of the patients, with hypertrophic cardiomyopathy in the other third. The mean age at cardiac diagnosis was 19 months, with a range from 0.5 to 84 months. Of these patients, two died in infancy at a mean age of 4 months, specifically at 1.5 and 7 months, due to cardiac disease, with one dying suddenly. The remaining four patients are alive with minor to severe cardiac dysfunction. We conclude that congenital disorders of glycosylation have to be considered in the differential diagnosis of children presenting with cardiomyopathy, and that all patients with congenital disorders of glycosylation should be screened for an associated cardiomyopathy. Cardiac involvement contributes significantly to morbidity and mortality, and probably to sudden cardiac death in this disorder.

Severe transient myocardial ischaemia caused by hypertrophic cardiomyopathy in a patient with congenital disorder of glycosylation type Ia.

UNLABELLED: Severely affected children with congenital disorder of glycosylation type Ia (CDG-Ia; MIM 212065) may develop hypertrophic cardiomyopathy. In this report we describe the near-death of a 10-month-old girl with CDG-Ia due to acute left-ventricular outlet obstruction caused by hypertrophic cardiomyopathy and acute dehydration. The girl had multi-organ failure and signs of severe myocardial damage mimicking myocardial infarction. CONCLUSION: hypertrophic cardiomyopathy contributes to the high mortality of young children with congenital disorder of glycosylation type Ia. Even if cardiomyopathy in this disease is non-obstructive, acute fluid-loss might cause left ventricular outflow tract obstruction and life-threatening myocardial ischaemia. Patients with congenital disorder of glycosylation type Ia are at risk for cardiac complications and should be monitored regularly by echocardiography.

Impaired parasympathetic heart rate control in mice with a reduction of functional G protein betagamma-subunits.

Acetylcholine released on parasympathetic stimulation slows heart rate through activation of muscarinic receptors on the sinus nodal cells and subsequent opening of the atrial muscarinic potassium channel (K(ACh)). K(ACh) is directly activated by G protein betagamma-subunits. To elucidate the physiological role of Gbetagamma for the regulation of heart rate and electrophysiological function in vivo, we created transgenic mice with a reduced amount of membrane-bound Gbeta protein by overexpressing nonprenylated Ggamma(2)-subunits in their hearts using the alpha-myosin heavy chain promoter. At baseline and after muscarinic stimulation with carbachol, heart rate and heart rate variability were determined with electrocardiogram telemetry in conscious mice and in vivo intracardiac electrophysiological studies in anesthetized mice. Reduction of the amount of functional Gbetagamma protein by >50% caused a pronounced blunting of the carbachol-induced bradycardia as well as the increases in time- and frequency-domain indexes of heart rate variability and baroreflex sensitivity that were observed in wild types. In addition, sinus node recovery time and inducibility of atrial arrhythmias were reduced in transgenic mice. Our data demonstrate in vivo that Gbetagamma plays a crucial role for parasympathetic heart rate control, sinus node automaticity, and atrial arrhythmia vulnerability.