Biomedical subjects

V Shusterman

Publications and source records attributed to V Shusterman.

9 recordsLinked to original sources

PubMed2001

Targeted replacement of KV1.5 in the mouse leads to loss of the 4-aminopyridine-sensitive component of I(K,slow) and resistance to drug-induced qt prolongation.

The K(+) channel mKv1.5 is thought to encode a 4-aminopyridine (4-AP)-sensitive component of the current I(K,slow) in the mouse heart. We used gene targeting to replace mKv1.5 with the 4-AP-insensitive channel rKv1.1 (SWAP mice) and directly test the role of Kv1.5 in the mouse ventricle. Kv1.5 RNA and protein were undetectable, rKv1.1 was expressed, and Kv2.1 protein was upregulated in homozygous SWAP hearts. The density of the K(+) current I(K,slow) (depolarizations to +40 mV, pA/pF) was similar in left ventricular myocytes isolated from SWAP homozygotes (17+/-1, n=27) and littermate controls (16+/-2, n=19). The densities and properties of I(peak), I(to,f), I(to,s), and I(ss) were also unchanged. In homozygous SWAP myocytes, the 50-micromol/L 4-AP-sensitive component of IK,slowwas absent (n=6), the density of the 20-mmol/L tetraethylammonium-sensitive component of I(K,slow) was increased (9+/-1 versus 5+/-1, P<0.05), and no 100- to 200-nmol/L alpha-dendrotoxin-sensitive current was found (n=8). APD(90) in SWAP myocytes was similar to controls at baseline but did not prolong in response to 30 micromol/L 4-AP. Similarly, QTc (ms) was not prolonged in anesthetized SWAP mice (64+/-2, homozygotes, n=9; 62+/-2, controls, n=9), and injection with 4-AP prolonged QTc only in controls (63+/-1, homozygotes; 72+/-2, controls; P<0.05). SWAP mice had no increase in arrhythmias during ambulatory telemetry monitoring. Thus, Kv1.5 encodes the 4-AP-sensitive component of I(K,slow) in the mouse ventricle and confers sensitivity to 4-AP-induced prolongation of APD and QTC: Compensatory upregulation of Kv2.1 may explain the phenotypic differences between SWAP mice and the previously described transgenic mice expressing a truncated dominant-negative Kv1.1 construct.

4-Aminopyridine↗

PubMed2001

Multidimensional rhythm disturbances as a precursor of sustained ventricular tachyarrhythmias.

Cardiac cycle dynamics reflect underlying physiological changes that could predict imminent arrhythmias but are obscured by high complexity, nonstationarity, and large interindividual differences. To overcome these problems, we developed an adaptive technique, referred to as the modified Karhunen-Loeve transform (MKLT), that identifies an individual characteristic ("core") pattern of cardiac cycles and then tracks the changes in the pattern by projecting the signal onto characteristic eigenvectors. We hypothesized that disturbances in the core pattern, indicating progressive destabilization of cardiac rhythm, would predict the onset of spontaneous sustained ventricular tachyarrhythmias (VTAs) better than previously reported methods. We analyzed serial ambulatory ECGs recorded in 57 patients at the time of VTA and non-VTA 24-hour periods. The disturbances in the pattern were found in 82% of the recordings before the onset of impending VTA, and their dimensionality, defined as the number of unstable orthogonal projections, increased gradually several hours before the onset. MKLT provided greater sensitivity and specificity (70% and 93%) compared with the best traditional method (68% and 67%, respectively). We present a theoretical analysis of MKLT and describe the effects of ectopy and slow changes in cardiac cycles on the disturbances in the pattern. We conclude that MKLT provides greater predictive accuracy than previously reported methods. The improvement is due to the use of individual patterns as a reference for tracking the changes. Because this approach is independent of the group reference values or the underlying clinical context, it should have substantial potential for predicting other forms of arrhythmic events in other populations.

Algorithms↗

PubMed2000

Enhancing the precision of ECG baseline correction: selective filtering and removal of residual error.

Reemergence of the problem of baseline correction is related to recent advancements in the electrocardiographic (ECG) analysis of beat-to-beat repolarization changes which play an important role in risk assessment and the prediction of sudden cardiac death. These alterations often have an amplitude of a few microvolts and duration of several milliseconds and their detection requires special accuracy of baseline estimation. Using detailed analysis of various types of residual errors we designed a two-step procedure for selective filtering of ECG and removal of residual error with minimal distortion of cardiac complexes and tested this approach on 100 simulated and 210 real ECG signals. Application of this procedure provided a twofold reduction in the error of baseline estimation and T-wave amplitude measurements compared to high-pass filtering. Selective application of this approach to the segments with low baseline drift allowed analysis of low-amplitude, beat-to-beat changes in repolarization during more than 70% of the recording time.

Algorithms↗

PubMed2000

Dynamics of low-frequency R-R interval oscillations preceding spontaneous ventricular tachycardia.

BACKGROUND: Increased sympathetic activity is believed to be an important trigger of sustained ventricular tachyarrhythmias (VT) and is believed to be responsible for the increased heart rate that we and others have reported before the onset of spontaneous VT. However, in the patients reported herein, heart rate variability (HRV) indexes that reflect sympathetic activity unexpectedly declined, whereas heart rate increased. To explain this apparent paradoxic behavior, we tested the hypothesis that baseline levels of HRV determine its reaction to short-term autonomic perturbations before the onset of VT. METHODS AND RESULTS: Holter electrocardiograms from 47 patients (ejection fraction 36% +/- 15%) with recorded VT were analyzed. Frequency domain HRV indexes (low-frequency power [LFP] 0. 04 to 0.15 Hz, high-frequency power [HFP] 0.15 to 0.4 Hz, and total power [TP] 0.01 to 0.4 Hz) were studied in 5-minute intervals and over a period of 24 hours. Patients were divided into those with a decrease in LFP in the 2-hour period before VT (group A, n = 32) and those with an increase or no change (group B, n = 15). The data were logarithmically transformed. Heart rate increased 15 minutes before the onset of VT compared with the 24-hour mean in both groups (group A: 80.3 +/- 15.4 to 86.1 +/- 20.0 beats/min, P =.005; group B: 80.6 +/- 13.5 to 86.7 +/- 14.0 beats/min, P =.017). Group A had higher TP, LFP, and LFP/HFP 2 hours before VT, and these variables decreased 15 minutes before the onset of VT (TP from 7.31 +/- 1.28 to 6.88 +/- 1.35, LFP from 6.09 +/- 1.28 to 5.38 +/- 1.33, LFP/HFP from 1.33 +/- 0.89 to 0.96 +/- 0.80, P <.001 for all 3 variables). HFP also decreased 15 minutes before VT compared with 2 hours (from 4.78 +/- 1.05 to 4.49 +/- 1.24, P =.028). In group B, which had lower baseline TP, LFP, and LFP/HFP at 2 hours before VT, these variables increased 15 minutes before the event (TP from 6.41 +/- 1.41 to 6.86 +/- 1.42, P =.004; LFP from 4.59 +/- 1.51 to 4.95 +/- 0.62, P <.001; LFP/HFP from 0.22 +/- 1.22 to 0.52 +/- 1.38, P =.10), whereas HFP did not change significantly (4.40 +/- 0.94 and 4.53 +/- 1.01, P =. 50). CONCLUSIONS: An increase in heart rate and a drop in the low-frequency oscillations of R-R intervals before the onset of VT occurred in patients with higher baseline level of oscillatory activity. These changes suggest a dissociation between the average and rhythmic modulation of R-R intervals. A decline of the low-frequency oscillations in the setting of increasing heart rate could reflect an abnormal response to increased sympathetic activity in most of the patients from the studied group. The different behaviors of the HRV indexes before the onset of VT in the 2 groups suggest that change in the dynamics of R-R intervals, rather than the direction of change, facilitates arrhythmogenesis.

Aged↗

PubMed1999

Changes in autonomic activity and ventricular repolarization.

An increase in sympathetic activity, manifested by shortening of RR intervals (RRi) and changes in RRi variability, precedes and possibly triggers ventricular tachyarrhythmias (VTAs) by altering repolarization. We examined the effects of autonomic activity on the projection of repolarization as detected by body surface potential maps (BSPMs). We recorded 32 lead/192-point BSPMs during passive head-up tilt, tilt + infusion of isoproterenol, rapid atrial pacing, and atrial pacing + infusion of isoproterenol. Changes in QT; recovery time; activation-recovery interval (ARi); T-wave amplitude; and QT, QRST, and ST integrals and their dispersion were analyzed. Autonomic effects on sinus node were inferred from the Fourier transform-derived low and high frequency powers of RRi variability. Patients were divided into those with (SHD) and without structural heart disease (NSHD). Heart rate increased, whereas QT interval and ARi declined with tilt in both groups. RRi variability indices of sympathetic activity increased in NSHD but did not change in SHD. T-wave amplitudes declined in NSHD but did not change in SHD, suggesting altered responsiveness of ventricular repolarization to autonomic stimulation. Tilt and rapid atrial pacing during infusion of isoproterenol resulted in a paradoxical increase in T-wave amplitudes in some patients, similar to that observed before the onset of spontaneous arrhythmias. We conclude that altering autonomic activity by head-up tilt and/or infusion of sympathomimetic agents results in significant changes in the body surface projection of cardiac repolarization, which differ in patients with SHD from those without SHD. Similar paradoxical changes in the T-wave amplitude have been observed before the onset of spontaneous VTA, suggesting that abnormal response of repolarization to autonomic stimulation predisposes to arrhythmogenesis.

Adult↗

PubMed1999

Distinctive RR dynamics preceding two modes of onset of spontaneous sustained ventricular tachycardia. (ESVEM) Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring.

INTRODUCTION: We hypothesized that autonomic activity preceding spontaneous sustained monomorphic ventricular tachycardia (VTsm) as assessed by heart rate (HR) and RR interval variability (RRV) differs between type 1 VTsm which is initiated by morphologically distinct, early cycle, possibly triggering premature ventricular complexes (PVCs) and type 2 VTsm in which the initial complex has a QRS waveform identical to subsequent complexes. METHODS AND RESULTS: Baseline Holter tapes (1,646) from a clinical trial were scanned for VTsm. QRS complexes of VTsm were compared by two-lead cross-correlation to distinguish type 1 and type 2 VTsm. Frequency domain RRV index were estimated over 5 minutes, 15 minutes, and 24 hours. Type 1 and type 2 VTsm were present in 15 (group 1) and 33 (group 2) of 48 patients, respectively. HR did not change in group 1 (88.4+/-15.2 to 89.7+/-13.0 beats/min, P = 0.89), but increased before the onset of VTsm in group 2 (74.3+/-16.3 to 81.2+/-18.0 beats/min, P < 0.001). RRV index were severely depressed in both groups. No RRV index changed significantly before the onset of type 1 VTsm, whereas significant changes occurred before type 2 VTsm from 24-hour average to 30 minutes before VTsm in very low (very low-frequency power [VLFP]: 6.62+/-1.53 to 6.20+/-2.07 ln msec2, P = 0.036), low (low-frequency power [LFP]: 5.61+/-1.43 to 5.28+/-1.59 ln msec2, P = 0.004), normalized low (normalized low-frequency power [LFPn]: -0.48+/-0.58 to -0.55+/-0.64 normalized units [nu], P = 0.05) and the ratio of LFP to high-frequency power (HFP) (LFP/HFP: 4.20+/-3.47 to 3.45+/-2.53, P = 0.017). Declines in RRV index between 2 hours to the 30-minute period before VTsm occurred in group 2 but not group 1 in LFP (5.85 +/- 1.42 to 5.28 +/- 1.59 In msec, P = 0.043) and HFP (4.94 +/- 5.14 to 3.46 +/- 2.52 In msec2, P = 0.008), with a downward trend in LFP/HFP (4.94+/-5.14 to 3.45+/-2.53, P = 0.127) and LFPn (-0.38+/-0.36 to -0.55+/-0.64, P = 0.15), while HFPn tended to rise (-1.47+/-0.65 to -1.27+/-0.64, P = 0.15). CONCLUSIONS: HR and RRV did not change before type 1 VTsm, suggesting that short-term changes in autonomic activity were not essential to initiation of apparent PVC-triggered VTsm. In contrast, RR interval dynamics before type 2 VTsm suggested that short-term changes in neurohormonal activity contributed to arrhythmia initiation. Heterogeneities in arrhythmia onset may reflect distinct triggers and substrate properties that could provide a basis for effective therapeutic targets.

Autonomic Nervous System↗

PubMed1998

Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia. ESVEM Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring Trial.

OBJECTIVES: We hypothesized that neurohormonal activity contributes to the initiation of sustained ventricular tachycardia (VT) as reflected in indices of heart rate variability (HRV). BACKGROUND: Autonomic nervous system activity participates in experimental arrhythmias but clinical studies have been inconsistent. METHODS: Holter electrocardiograms from 53 patients with VT were analyzed. Heart rate variability indices were determined over 5 and 15 min and 24 h and examined for changes before the onset of VT. Heart rate variability indices in the frequency domain included ultra low frequency power (FP) (ULFP): 0-0.0033 Hz; very low FP (VLFP): 0.0033-0.04 Hz; low FP (LFP): 0.04-0.15 Hz; high FP (HFP): 0.15-0.4 Hz; total power (TP); normalized LFP (LFPn); normalized HFP (HFPn), and the ratio: LFP/HFP. RESULTS: Heart rate variability indices were severely diminished: TP: 12,009+/-11,076 ms2; ULFP: 10,087+/-9,565 ms2; VLFP: 1,416+/-1,571 ms2; LFP: 544+/-620 ms2; HFP: 161+/-176 ms2, and LFP/HFP: 3.68+/-2.83. Heart rate increased before VT (80.4+/-17.3 to 85.3+/-17.4 bpm, p < 0.001). Several HRV variables declined 30 min before VT compared to 24-h values (VLFP: -5.89+/-17.81%, p = 0.031; LFP: -5.23+/-14.3%, p = 0.003; HFP: -4.35+/-13.7%, p = 0.04). LFPn and the LFP/HFP ratio decreased significantly before the onset of VT (-17.7+/-46.9%, p = 0.035 and -8.24+/-38.8%, p = 0.037, respectively), whereas HFPn increased slightly (4.29+/-29.9%, p = 0.097). CONCLUSIONS: Heart rate rose, whereas LFP, LFPn and LFP/HFP fell before the onset of VT. This pattern of changes could be explained by a rise in sympathetic activity and saturation of the HRV signal resulting in dissociation of the average and rhythmical effects of sympathetic activity. These findings suggest that alterations in autonomic activity contributed to arrhythmogenesis in this group of patients.

Aged↗

PubMed1997

Spontaneous skin temperature oscillations in normal human subjects.

A noninvasive method based on high-resolution measurements and bandpass filtering of spontaneous skin temperature oscillations (approximately 4.0 x 10(-2) degrees C) in the low-frequency range (0.01-0.04 Hz) was investigated in normal human subjects. We hypothesized that the oscillations (temperature variability) originate from vasomotor activity of small arteries and arterioles in subcutaneous tissues. To test this hypothesis, continuous blood pressure waveforms were obtained with the use of an external piezoelectric sensor. The peak-to-peak envelope of the pressure signal (pressure variability) was used as an indicator of vasomotor activity. The variabilities of temperature and pressure were compared using cross-spectral and coherence analysis. The correlation between the peak frequency of the signals was 0.92, and the coherence was greater than 0.9. The signals demonstrated similar changes in spectral energy and peak frequency in response to mental stress. Reproducibility of the temperature variability in individual subjects was verified by repeating measurements 1-12 wk later. The differences in peak frequency were small (0.0155 +/- 0.001 Hz), and in each subject the signals exhibited similar patterns in response to stress. Correlation between spectral characteristics of the signals suggests that temperature variability can be attributed to changes in blood flow resulting from oscillations in vasomotor smooth muscle tone.

Activity Cycles↗

PubMed1995

Spectral characteristics of skin temperature indicate peripheral stress-response.

High-resolution measurement of skin temperature in 11 normal subjects revealed low-amplitude temperature oscillations (40 x 10(-3) degrees C). The temperature signal measured on two hands during baseline, stress, and recovery periods, was filtered to separate the low-amplitude oscillations from the temperature signal. Spectral analysis of the filtered signal showed that most of the energy of the signal is in a range of 0.01 to 0.03 Hz. Frequency shifts and amplitude changes of the largest component were observed in response to mental stress. In subjects with high baseline values of either of these two variables, a decrease was observed in response to stress. An opposite response was observed in subjects with significantly lower baseline levels. Stress-related changes in peak frequency ranged from -25% to +18.2%; changes in peak amplitude ranged from -74.6% to +280%. Changes in the mean temperature were limited to 2.4%. Thus, the oscillatory component showed higher sensitivity to psychological stress than mean temperature. The spectrum of this component was compared to the spectrum of the blood pressure waves measured noninvasively. Both exhibited similar dynamics of energy, peak amplitude, and peak frequency in response to psychological stress. This similarity suggests that the oscillatory temperature component reflects stress-related changes of peripheral vasomotor activity.

Adult↗