Evaluation of Antiarrhythmic Drug Efficacy in Patients with an ICD:

There are a number of novel ways in which implantable cardioverter defibrillator (ICD) endpoints can be used in clinical trials to evaluate antiarrhythmic drugs. The advances in ICD technology (storage, retrieval, and accurate interpretation of ICD electrograms) expand the potential to include the use of an ICD endpoint as a clinical surrogate for sudden death. The ICD also provides the necessary safety net to test new drugs. The frequent need for antiarrhythmic drugs in patients already fitted with an ICD (e.g., for atrial fibrillation) necessitates knowledge of the drugs' effect on defibrillator threshold. There are interpretative problems and challenges associated with all types of ICD trials. A particular difficult issue is the degree to which the results of data on antiarrhythmic drug efficacy and safety acquired in the context of an ICD endpoint trial might be extrapolated to patient populations in which the device is not used. These and other challenging issues are discussed, with the goal of enhancing the design and interpretation of clinical trials featuring ICD endpoints.     

Responsiveness to rapid atrial pacing of the specialized atrioventricular conduction system in children

Summary Responsiveness to rapid atrial pacing of the specialized atrioventricular (A-V) conduction system was studied in 25 patients aged 2 months to 18 years. Atrial pacing via a catheter placed at the right atrial superior vena cava junction was initiated at rates slightly greater than the sinus rate and gradually increased to rates as high as 600 stimuli per minute. His bundle electrograms were obtained in most patients. When the atrial pacing rate (x-axis) was plotted against the corresponding ventricular rate (y-axis), the curve was M-shaped. The initial ascending limb occurred during 1:1 A-V conduction with rates as high as 270 stimuli per minute. The first descending limb resulted from Wenckebach type A-V block occurring at rates of 160 to 300 stimuli per minute. The second ascending limb corresponded to periods of 2:1 A-V block observed at rates of 200 to 536 stimuli per minute, and the final descending limb was related to higher degrees of block at both the pacing site and the A-V node. The second descending limb was seen with pacing rates of 296 to 600 stimuli per minute. The rates required to produce Wenckebach type A-V block in this group of children were higher than those reported in adults. One patient with spontaneous first-degree A-V block developed 2:1 A-V block at a pacing rate of only 150 stimuli per minute.This technique for studying the response to rapid atrial pacing of the specialized A-V conduction system characterises its functional capacity. The technique can be applied rapidly and safely in selected patients.     

Effects of pressure support during an acute reduction of synchronized intermittent mandatory ventilation in preterm infants.

BACKGROUND: During weaning of synchronized intermittent mandatory rate in preterm infants, the spontaneous breaths must overcome the resistance of the endotracheal tube and the disease-induced respiratory loads. Pressure Support (PS) can be used as an adjunct to synchronized intermittent mandatory ventilation (SIMV) to partially unload the spontaneous breaths. OBJECTIVE: To evaluate the effects of two levels of PS as an adjunct to SIMV on gas exchange and breathing effort during an acute reduction in SIMV rate in preterm infants. METHODS: In all, 15 infants (birth weight 793 +/- 217 g, gestational age 26.4 +/- 1.5 weeks, postnatal age 15 +/- 16 days). Ventilatory support consisted of SIMV with peak inspiratory pressure (PTP) 16.3 +/- 1.3 cmH(2)O, positive end-expiratory pressure (PEEP) 4.3 +/- 0.6 cmH(2)O, and fraction of inspired oxygen (FiO(2)) 0.26 +/- 0.06. Infants were studied during four 30-minute periods: Two baseline SIMV periods and two periods of SIMV plus PS, in random order. During SIMV + PS, SIMV rate was lowered by 10 breaths per minute (b/minute) and PS was set at 3 and 6 cmH(2)O (SIMV+PS3 and SIMV + PS6, respectively). RESULTS: SIMV rate was reduced during SIMV + PS from 21.4 +/- 6.6 to 11.4 +/- 6.6 b/minute. Arterial oxygen saturation, transcutaneous carbon dioxide tension and FiO(2) remained unchanged. Minute ventilation, total respiratory rate and mean airway pressure were higher during SIMV + PS. Per-breath inspiratory effort was lower during SIMV + PS and this was more striking during SIMV + PS6. Spontaneous inspiratory effort per minute increased during SIMV + PS3, but this increase was averted during SIMV + PS6. CONCLUSION: Assistance of the spontaneous breaths with pressure support maintained gas exchange. PS of 6 cm H(2)O prevented an increase in breathing effort during an acute 50% reduction in SIMV rate.     

Clinical evaluation in therapy of patients with atrial fibrillation or flutter

The weight of evidence clearly indicates that both atrial fibrillation and atrial flutter are due to a reentrant mechanism. Atrial fibrillation seems almost certainly due to multiple circulating reentrant wavelets of the leading circle type, whereas atrial flutter appears to be caused by single reentrant circuit located in the right atrium. The diagnosis of both atrial fibrillation and atrial flutter should always be possible using either old or new techniques. The interruption of atrial flutter should be possible using pacing or direct current cardioversion techniques, and the conversion of atrial fibrillation to sinus rhythm also is most often possible by direct current cardioversion or antiarrhythmic drug therapy. Long-term antiarrhythmic drug therapy to suppress recurrent atrial fibrillation and atrial flutter may be a problem, but availability of newer antiarrhythmic agents holds promise for finding an effective regimen. Catheter ablation techniques may be used to cause complete heart block in the treatment of either atrial fibrillation or atrial flutter when these rhythms cannot be satisfactorily suppressed and are associated with unacceptably rapid ventricular response rates. Finally, recent data suggest that atrial flutter may be successfully treated on a chronic basis with an antitachycardia pacing device, may be cured with catheter ablation techniques applied to a critical portion of the atrial flutter reentry circuit, and may be treated successfully with innovative surgical techniques. The latter is also true for atrial fibrillation.     

IgA synthesis by lymphocytes from patients with IgA nephropathy and their relatives

To investigate the hypothesis that a predisposition to IgA nephropathy (IgAN) is linked to the major histocompatibility complex (MHC) and associated with poorly regulated IgA synthesis, we performed HLA typing and lymphocyte cultures on patients with IgAN and their relatives. Nineteen of 22 patients had elevated culture supernatant IgA concentrations (620 vs. 154 ng/2 X 10(6) cells, P = 0.007). Supernatant IgG and IgM were normal. No HLA antigen occurred with increased frequency in patients. There was an increased incidence of homozygous null C4 alleles in patients (P less than 0.01). In families, six of 11 mothers, six of 12 fathers, and seven of 15 siblings had elevated supernatant IgA concentrations. There was no segregation of abnormal IgA production with any HLA antigen or parental haplotype. The data confirm elevated in vitro IgA production by lymphocytes from patients with IgAN, but do not support a linkage with the MHC. The increased incidence of homozygous null C4 alleles may result from functional differences in C4 A and B gene products. The familial clustering of elevated IgA production without an obvious inheritance pattern suggest that shared environmental factors may be important in the development of IgAN.