Asystole during outbursts of laughing in a child with Angelman syndrome.

A girl with Angelman syndrome had recurrent episodes of ventricular asystole and syncope caused by severe vagal hypertonia during outbursts of laughing. After intravenous administration of atropine, laughing no longer induced asystole or syncope. The vast majority of patients with Angelman syndrome have seizures. Since hypoxia associated with asystole can provoke convulsions, we suggest electrocardiographic evaluation of Angelman patients with symptomatic bradycardia, loss of consciousness, or convulsions related to laughing.

Propionibacterium acnes endocarditis on an annuloplasty ring in an adolescent boy.

Propionibacterium acnes, a constituent of the human cutaneous flora, infected both the native mitral valve and a Carpentier mitral annuloplasty ring in an adolescent patient. In the case of culture negative endocarditis, the incubation period of blood cultures should be prolonged to identify this pathogen.

Optimization of ventricular function by improving the activation sequence during ventricular pacing.

Abnormal electrical activation occurring during ventricular pacing reduces left ventricular (LV) pump function. Two strategies were compared to optimize LV function using ventricular pacing, minimal asynchrony and optimal sequence of electrical activation. ECG and hemodynamics aortic flowprobe, thermodilution cardiac output, LV pressure and its maximal rates of rise (LVdP/dtpos) and fall (LVdP/dtneg) were measured in anesthetized open-chest dogs (n = 7) with healthy hearts. The QRS duration (a measure of asynchrony of activation) was 47 +/- 5 ms during sinus rhythm and increased to 110 +/- 12 ms during DDD pacing at the right ventricular (RV) apex with a short AV interval. During pacing at the LV apex and LV base, the QRS duration was 8% +/- 7% and 15% +/- 7% (P < 0.05) longer than during RV apex pacing, respectively. Stroke volumes, LVdP/dtpos and LVdP/dtneg, however, were higher during LV apex (15% +/- 16%, 10% +/- 12% [P < 0.05], and 15% +/- 10%, respectively) and LV base pacing (11% +/- 12% [P < 0.05], 3% +/- 12%, and 3% +/- 11%, respectively) than during RV apex pacing. Systolic LV pressure was not influenced significantly by the site of pacing. Biventricular pacing (RV apex together with one or two LV sites) decreased the QRS duration by approximately 20% as compared with RV apex pacing, however, it did not improve stroke volumes, LVdP/dtpos and LVdP/dtneg beyond those during pacing at the LV apex alone. In conclusion, the sequence of electrical activation is a stronger determinant of ventricular function than the synchrony of activation. For optimal LV function the selection of an optimal single pacing site, like the LV apex, is more important than pacing from multiple sites.

Asynchronous electrical activation induces asymmetrical hypertrophy of the left ventricular wall.

BACKGROUND: Asynchronous electrical activation, induced by ventricular pacing, causes regional differences in workload, which is lower in early- than in late-activated regions. Because the myocardium usually adapts its mass and structure to altered workload, we investigated whether ventricular pacing leads to inhomogeneous hypertrophy and whether such adaptation, if any, affects global left ventricular (LV) pump function. METHODS AND RESULTS: Eight dogs were paced at physiological heart rate for 6 months (AV sequential, AV interval 25 ms, ventricular electrode at the base of the LV free wall). Five dogs were sham operated and served as controls. Ventricular pacing increased QRS duration from 47.2+/-10.6 to 113+/-16.5 ms acutely and to 133.8+/-25.2 ms after 6 months. Two-dimensional echocardiographic measurements showed that LV cavity and wall volume increased significantly by 27+/-15% and 15+/-17%, respectively. The early-activated LV free wall became significantly (17+/-17%) thinner, whereas the late-activated septum thickened significantly (23+/-12%). Calculated sector volume did not change in the LV free wall but increased significantly in the septum by 39+/-13%. In paced animals, cardiomyocyte diameter was significantly (18+/-7%) larger in septum than in LV free wall, whereas myocardial collagen fraction was unchanged in both areas. LV pressure-volume analysis showed that ventricular pacing reduced LV function to a similar extent after 15 minutes and 6 months of pacing. CONCLUSIONS: Asynchronous activation induces asymmetrical hypertrophy and LV dilatation. Cardiac pump function is not affected by the adaptational processes. These data indicate that local cardiac load regulates local cardiac mass of both myocytes and collagen.

Effective treatment of experimental cytomegalovirus-induced encephalo-meningitis in immunocompromised rats with HPMPC.

Cytomegalovirus (CMV)-induced encephalomeningitis is a dramatic complication in patients with the acquired immunodeficiency syndrome (AIDS) and treatment of this infection remains a major clinical problem. In order to study the pathogenesis and treatment of CMV-induced encephalomeningitis, we experimentally induced intracranial rat CMV (RCMV) infection in rats that were immunosuppressed by total body X-irradiation. CMV infection was monitored by viral plaque assay for estimation of the viral load. CMV-induced pathology, the presence of CMV-infected cells, as well as the presence of T-lymphocytes and monocytes/macrophages were studied by histopathologic and immunohistochemical staining techniques. The meninges showed CMV infection in mononuclear infiltrative cells and in endothelium of small blood vessels 8 days after intracerebral inoculation. This was accompagnied by multiple haemorraghes and inflammatory cell infiltration. The infection and inflammatory response persisted for at least 21 days p.i. Animals were treated with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), hyperimmune serum (HIS) and both DHPG and HIS combined. Treatment with one dosage of HPMPC at 20 mg/kg effectively reduced virus titers. However, all other treatment modalities were not effective. In conclusion, the pathology of RCMV-induced encephalomeningitis in immunocompromised rats closely resembles that of AIDS patients. The infection is effectively treated by HPMPC.

Combinations of ganciclovir and antibody for experimental CMV infections.

The effect of combined treatment with ganciclovir and hyper immune serum (HIS) was evaluated in three animal models. It concerned a generalized CMV infection model, a meningo-encephalitis model and an interstitial lung disease (ILD) model in immunocompromised rats. In the generalized model, the ganciclovir and HIS had a moderate synergistic effect on survival and greatly decreased virus titers in internal organs. In contrast, in the meningoencephalitis model, combined treatment had no effect on the local virus titers and the histopathology. Combined treatment with ganciclovir and HIS, however, effectively abolished CMV-induced ILD.