Evaluation of the Atrial Evoked Response for Capture Detection with High-Polarization Leads

AutoCapture™ based on the evoked response can be confounded by electrode polarization. In this study, polarization was measured in human subjects who had chronic atrial leads. The aim of the study was to determine whether electrode polarization can be measured using a time integral atrial evoked-response integral (AERI) of the negative portion of the atrial paced ER evoked-response signal and to determine whether high-polarization atrial leads unsuitable for AutoCapture™ can be identified a priori. Atrial intracardiac-electrogram (IEGM) signals from 39 patients with implanted pacemakers were recorded and analyzed. The signals were recorded during conventional atrial-threshold searches. A total of 221 atrial-capture thresholds were recorded, ranging from 0.25 to 2.75 V with a mean of 0.79 V. Each evoked response was evaluated using the AERI in a 36 ms window following the 0.4 ms atrial stimulus. The polarization was estimated as a linear function of stimulus voltage using the evoked-response signal integral of captured beats identified on the IEGM. The 221 threshold-search datasets were obtained using leads with eight different electrode materials. Polarization could be measured using AERI as a function of stimulus voltage. Furthermore, this polarization measure can be used to identify high-polarization leads, which are ill suited for the atrial AutoCapture™ algorithm.     

肿瘤抗原MAGE-2 HLA-A2限制性新CTL表位的鉴定

目的：寻求新的HLA-A2限制性肿瘤抗原MAGE-2 CTL表位。方法：经超基序与量公基序相结合预测的肿瘤抗原MA-GE-2的4个表位作为研究对象，标准的^51Cr实验与肽结合实验相结合进行验证。结果：预测表位肽MAGE-2220-228，MAGE-2271-279经体外刺激PBMC后可有效的诱导CTL效应产生，当效/靶为100：1时溶破靶细胞效率分别为74.4％，68.2％。HLA-A2分子亲和力分析，荧光系数分别为0.61、0.24阳性肽荧光系数为0.79。结论：多肽MAGE-2 220-228可作为新的HLA-A2限制性CTL表位。     

Adjusting Heart Rate During Sleep Using Activity Variance

In order to mimic the natural decrease in heart rate that occurs during sleep, an algorithm was devised to decrease the base rate to a programmable sleep rate. The algorithm was developed using activity and sinus rate data obtained from 18 normal subjects ranging in age from 22–80 years. The data were recorded in the event record of a "taped-on" pacemaker. The surface ECG signal was used to inhibit a pacer programmed to VVI at 45 ppm. The ECG documented the sinus rate while the accelerometer-based activity signals were recorded in an event record. An algorithm was used to estimate the smoothed acceleration variance every 26 seconds. The activity variance was stored in a histogram. Results : The lower 7/24ths of the histogram entries were primarily attributable to sleep. If the activity variance was entered into the lower 7/24ths of the histogram and the accelerometer reading was below rate responsive threshold, the base rate was switched to sleep rate. Using least mean squares to estimate optimal slope, base rate, and sleep rate, the root mean square error between activity derived heart rate and sinus rate was 12 beats/min. Conclusion : This study supports using an estimate of activity variance to automatically decrease pacing rate below programmed base rate. This decrease may be actuated during an afternoon nap or nighttime sleep.     

ENZYME-CATALYZED FORMATION OF SEMISYNTHETIC STAPHYLOCOCCAL NUCLEASE USING A NEW SYNTHETIC FRAGMENT, [48-GLYCINE] SYNTHETIC-(6–49)

While trypsin can catalyze resynthesis of the peptide bond between fragments in the noncovalent complex of nuclease-T-(6–48) and nuclease-T-(49–149), this reaction leads to excision of Lys 49 and formation of inactive [des Lys 49]-nuclease-(6–149). To provide a method for making active covalent semisynthetic nuclease, we chemically synthesized the fragment of residues 6 to 49 in which lysine 48 was replaced by glycine. This peptide was made using the recently described solid phase support, 4-(oxymethyl)phenylacetamidomethyl-polystyrene. The resultant crude polypeptide exhibited 30–50% of native nuclease-T enzymatic activity when added to native nuclease-T-(50–149). When the noncovalent complex formed by native nuclease-T-(50–149) and a 10-fold molar excess of [Gly 48]synthetic-(6–49) was equilibrated with trypsin in 90% glycerol, an increase in enzymatic activity from 8 to 32% (versus nuclease) was observed. Simultaneously, approximately 20% conversion of nuclease-T-(50–149) to nuclease-molecular weight material was observed by gel electrophoretic analysis. These data indicate that a covalent semisynthetic species is formed with activity about equal to that of native nuclease. The results confirm the importance of loop integrity on catalytic site organization. The Gly 48-containing fragment system defined above can allow preparation of semisynthetic nuclease sequence analogs.     

A New Automode Switch Algorithm for Supraventricular Tachycardias

Patients with complete heart block on a spontaneous, or iatrogenic basis who also have recurrent supraventricular tachycardias, particularly atrial fibrillation and flutter, are often difficult to manage. Various techniques include: independently programmable maximum tracking and maximum sensor rates, limiting the maximum atrial tracking rate to the sensor response of the pacemaker, or automatically switching from DDDR to VVIR based upon the sensed atrial rate. This article will describe a mode switch algorithm that allows for an independently programmable atrial tachycardia detection rate (ATDR). This allows mode switching to occur only in response to the patient's pathological tachyarrhythmia, and not during normal upper rate response. The ATDR is based upon a filtered atrial rate, which will prevent an isolated premature beat from initiating the algorithm. In addition, the unit can be programmed to switch to either DDI, DDIR, VVI, or VVIR. Extensive event counters in the pulse generator allows the system to record and store the number of algorithm activations, the average atrial rate which triggered each mode switch, and the duration of the mode switch. These reports are accessible at each follow-up visit.     

Effect of Pentaphasic Pulse Sequence as an Impedance Sensor on Standard Electrocardiographic Recordings

Two advances in cardiac pacing have resulted in an internal conflict in some pacemakers. One is the development of a standard lead physiological sensor and the other is protection from electromagnetic interference (EMI). One popular type of standard lead sensor uses sub-threshold pulses to measure intracardiac and intrathoracic impedance changes, i.e., minute ventilation. Recent clinical observations and extensive in vitro testing have verified that digital cellular phones can be troublesome. Large feedthrough capacitors (FCs), effective in blocking the EMI, will preclude sensing of the standard impedance-based signals. A variety of pulse configurations were studied that might be effective for a sensor-based impedance signal while allowing the pacemaker to continue to use large Fcs protecting them from environmental EMI. In comparison to both monophasic and biphasic pulse sequences, a pentaphasic pulse sequence was effective as an impedance sensor, still allows large FCs to function as an effective filter for environmental EMI, and would not produce artifacts on surface ECG.     

Activity-Controlled Circadian Base Rate

The current pacing rates are clustered around a fixed base rate since pacemaker patients are usually sedentary, resting, or sleeping most of the time. This fixed base rate is either too low for daytime hemodynamic support or too high for nighttime rest and recovery. Multiple Holter studies involving normal individuals have suggested that the resting base rate fluctuates during the course of the day. The circadian base rate (CBR) algorithm was designed to provide patients with a circadian change in paced resting rate and a normal rate distribution. The CBR algorithm, using a sophisticated accelerometer sensor, was developed and tested using the downloaded activity data from patients implanted with Trilogy DR+ pacemakers. Twenty-five patients (19 men, 6 women, age 72 ± 9 years) were studied. Trilogy DR+ is able to record the detailed sensor and system behavior data for a week. During outpatient visits, the pacemaker was interrogated and the data accumulated in the pacemaker memory were downloaded. The CBR algorithm was applied to the activity variance histogram to calculate the base rate and to construct its histogram. The base rates in the CBR histogram are generally below 100 ppm with a distribution that mimics the natural sinus rate distribution of normal subjects. The CBR algorithm provides the highest daytime rates for hemodynamic support and the lowest nighttime rates for cardiac recovery, with a smoothly changing base rate modeling the normal circadian variation in heart rate.     

Relationship Between Integrated Sucking Pressures and First Bottle-Feeding Scores in Premature Infants

Reasons for delays in initiating premature infant bottle-feeding and the complications associated with various methods of providing nutrition to premature infants are discussed. A quantitative, correlational study was undertaken to assess premature infants' readiness to bottle-feed. Thirty premature infants, weighing 1,230 to 2,020 g were studied to determine the relationship between integrated sucking pressures and bottle-feeding scores. Sucking pressures were measured with research nipples and an electronic suckometer. Feeding ability was measured using a complex research scale and a simpler clinical scale. Feeding scales correlated significantly (r = 0.79, p less than 0.001) while sucking pressures and feeding scores did not correlate significantly. Study limitations may have been responsible for the lack of a significant correlation between sucking pressures and feeding scores. Further research is needed to establish simple, quantitative safety parameters for beginning oral feedings for premature infants.