Search PubMed⌕ Search

Biomedical subjects

A Garfinkel

Publications and source records attributed to A Garfinkel.

At least 55 records · Page 3Linked to original sources
PubMed1997

Importance of location and timing of electrical stimuli in terminating sustained functional reentry in isolated swine ventricular tissues: evidence in support of a small reentrant circuit.

BACKGROUND: In excitable chemical media, a spiral wave is formed by reentrant excitation around a core and normal propagation away from the core. Whether or not this applies to cardiac muscle is unknown. METHODS AND RESULTS: In six isolated swine ventricular slices, we induced sustained episodes of functional reentry with a stationary core. A train of stimuli applied away from the core (7- to 8-mm distance) and near the core (within 1.6 mm) terminated 5 of 24 and 14 of 17 episodes of reentry, respectively (P<.001). When the stimulus was applied away from the core, successful terminations occurred when the line connecting the stimulus and the core was along the myocardial fiber orientation and when the coupling interval was 54+/-11% of the reentrant cycle length. Stimulation near the core terminated reentry primarily by propagation of the stimulus-induced wave fronts that closed up the excitable gap. However, in two episodes, the application of a stimulus near the core changed the electrogram morphology in only four bipolar pairs. This was sufficient to cause abrupt termination of reentry. CONCLUSIONS: (1) A thin layer of activation near the core is responsible for the maintenance of functional reentry. (2) Access to the tissue near the core is essential for the termination of functional reentry by a point stimulus. (3) To terminate reentry with a stimulus away from the core, the stimulus must occur at certain critical coupling intervals, and the line connecting the stimulus and the core must be roughly parallel to the fiber orientation.

Animals↗
PubMed1997

Quasiperiodicity and chaos in cardiac fibrillation.

In cardiac fibrillation, disorganized waves of electrical activity meander through the heart, and coherent contractile function is lost. We studied fibrillation in three stationary forms: in human chronic atrial fibrillation, in a stabilized form of canine ventricular fibrillation, and in fibrillation-like activity in thin sheets of canine and human ventricular tissue in vitro. We also created a computer model of fibrillation. In all four studies, evidence indicated that fibrillation arose through a quasiperiodic stage of period and amplitude modulation, thus exemplifying the "quasiperiodic transition to chaos" first suggested by Ruelle and Takens. This suggests that fibrillation is a form of spatio-temporal chaos, a finding that implies new therapeutic approaches.

Action Potentials↗
PubMed1997

Spirals, chaos, and new mechanisms of wave propagation.

The chaos theory is based on the idea that phenomena that appear disordered and random may actually be produced by relatively simple deterministic mechanisms. The disordered (aperiodic) activation that characterizes a chaotic motion is reached through one of a few well-defined paths that are characteristic of nonlinear dynamical systems. Our group has been studying VF using computerized mapping techniques. We found that in electrically induced VF, reentrant wavefronts (spiral waves) are present both in the initial tachysystolic stage (resembling VT) and the later tremulous incoordination stage (true VF). The electrophysiological characteristics associated with the transition from VT to VF is compatible with the quasiperiodic route to chaos as described in the Ruelle-Takens theorem. We propose that specific restitution of action potential duration (APD) and conduction velocity properties can cause a spiral wave (the primary oscillator) to develop additional oscillatory modes that lead to spiral meander and breakup. When spiral waves begin to meander and are modulated by other oscillatory processes, the periodic activity is replaced by unstable quasiperiodic oscillation, which then undergoes transition to chaos, signaling the onset of VF. We conclude that VF is a form of deterministic chaos. The development of VF is compatible with quasiperiodic transition to chaos. These results indicate that both the prediction and the control of fibrillation are possible based on the chaos theory and with the advent of chaos control algorithms.

Animals↗
PubMed1997

Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular protein implicated in nucleotide excision DNA repair.

The human immunodeficiency virus type 1 (HIV-1) vpr gene is an evolutionarily conserved gene among the primate lentiviruses HIV-1, HIV-2, and simian immunodeficiency viruses. One of the unique functions attributed to the vpr gene product is the arrest of cells in the G2 phase of the cell cycle. Here we demonstrate that Vpr interacts physically with HHR23A, one member of an evolutionarily conserved gene family involved in nucleotide excision repair. Interaction of Vpr with HHR23A was initially identified through a yeast two-hybrid screen and was confirmed by the demonstration of direct binding between bacterially expressed recombinant and transiently expressed or chemically synthesized protein products. Visualization of HHR23A and Vpr by indirect immunofluorescence and confocal microscopy indicates that the two proteins colocalize at or about the nuclear membrane. We also map the Vpr-binding domain in HHR23A to a C-terminal 45-amino-acid region of the protein previously shown to have homology to members of the ubiquitination pathway. Overexpression of HHR23A and a truncated derivative which includes the Vpr-binding domain results in a partial alleviation of the G2 arrest induced by Vpr, suggesting that the interaction between Vpr and HHR23A is critical for cell cycle arrest induced by Vpr. These results provide further support for the hypothesis that Vpr interferes with the normal function of a protein or proteins involved in the DNA repair process and, thus, in the transmission of signals that allow cells to transit from the G2 to the M phase of the cell cycle.

Amino Acid Sequence↗
PubMed1996

Dynamics of muscle sympathetic nerve activity in advanced heart failure patients.

Muscle sympathetic nerve activity (MSNA) is increased in patients with heart failure compared with healthy subjects. We applied spectral and correlation techniques to determine if qualitative as well as quantitative differences in MSNA differentiate heart failure patients from healthy subjects. We recorded MSNA, heart rate, and respiration in 11 heart failure patients and 10 healthy humans. Our results are as follows. 1) Statistically significant low-frequency modulation of MSNA at 0.029 +/- 0.002 Hz (mean +/- SE; range 0.026-0.038 Hz) was found in 10 of 11 heart failure patients but in only 2 of 10 healthy controls (differences between groups, P < 0.01; chi 2 test). 2) Heart rate and respiration also demonstrated significant low-frequency modulation in a similar range. 3) Spectral and correlation techniques revealed that low-frequency modulation of MSNA was highly correlated with low-frequency modulation of respiration in heart failure patients, but not in healthy subjects. In contrast, low-frequency modulation of MSNA did not correlate well with low-frequency modulation of heart rate. In summary, low-frequency modulation of respiration is coupled to low-frequency modulation of MSNA in heart failure patients, but not in normal subjects. We speculate that this low-frequency modulation of respiration may represent subclinical Cheyne-Stokes breathing, which has marked qualitative effects on MSNA in patients with heart failure.

Adolescent↗
PubMed1995

Three-dimensional structure of cat tibialis anterior motor units.

The motor unit is the basic unit for force production in a muscle. However, the position and shape of the territory of a motor unit within the muscle have not been defined precisely. The territories of five motor units in the cat tibialis anterior muscle were reconstructed three-dimensionally (3-D) from tracings of the glycogen-depleted fibers belonging to each unit. The motor unit territories did not span the entire length of the muscle and their cross-sectional areas tapered along the proximodistal axis producing a conical shape. In addition, the position of the territory of each unit shifted in an anterior-posterior plane along the longitudinal axis of the muscle, presumably as a consequence of the pinnation of the fibers. The area of the motor unit territory at any given level along the proximodistal axis was highly correlated with the number of fibers within the territory at that level. Connective tissue boundaries (outlining fascicles) appeared to have a strong influence on the shape of the territory, territories showed abrupt changes at connective tissue boundaries as groups of motor unit fibers within a fascicle often terminated together while motor unit fibers in neighboring fascicles did not terminate. It is likely that the mechanical impact of the recruitment of a motor unit is affected by the location and shape of motor units within the same muscle area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Spatial patterns of fiber types in atrophied skeletal muscle.

This study examined the spatial distributions of different fiber types in the soleus muscle of control rats and in rats subjected to hindlimb unloading for 28 days. The frequencies with which muscle fibers of one type were adjacent to each other and to fibers of other types were tabulated and compared to expectations generated from Monte Carlo simulations. In the normal rat, there is a tendency for Type I fibers to avoid adjacency with each other, a tendency that persisted in the hindlimb-suspended group, despite the substantial shrinkage in size of Type I fibers. We conclude that this treatment, unlike neurogenic pathologies, does not cause any remodeling of the adjacency relations of fibers.

Animals↗
PubMed1995

Estimation of critical power with nonlinear and linear models.

Sixteen young, healthy males each performed five to seven randomly assigned, exhaustive exercise bouts on a cycle ergometer, with each bout on a separate day and at a different power, to compare estimates of critical power (PC) and anaerobic work capacity (W') among five different models: t = W'/(Pmax-PC) (two-parameter nonlinear); t = (W'/P-PC))-(W'/(Pmax-PC)) (three-parameter nonlinear); P.t = W' + (PC.t) (linear (P.t)); P = (W'/t) + PC (linear (P)); P = PC + (Pmax-PC)exp(-t/tau) (exponential). The data fit each of the models well (mean R2 = 0.96 through 1.00 for each model). However, significant differences among models were observed for both PC (mean +/- standard deviation (SD) for each model was 195 +/- 29 W through 242 +/- 21 W) and W' (18 +/- 5 kJ through 58 +/- 19 kJ). PC estimates among models were significantly correlated (r = 0.78 through 0.99). For W', between-model correlations ranged from 0.25 to 0.95. For a group of six subjects, the ventilatory threshold for long-term exercise (LTE Tvent; 189 +/- 34 W) was significantly lower than PC for all models except the three-parameter nonlinear (PC = 197 +/- 30 W); PC for each model was, however, positively correlated with LTE Tvent (r = 0.69 through 0.91).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

ATP depletion: a novel method to study junctional properties in epithelial tissues. I. Rearrangement of the actin cytoskeleton.

The effect of cellular injury caused by depletion of intracellular ATP stores was studied in the Madin-Darby canine kidney (MDCK) and JTC cell lines. In prior studies, it was shown that ATP depletion uncouples the gate and fence functions of the tight junction. This paper extends these observations by studying the changes in the actin cytoskeleton and tight junction using electron microscopy and confocal fluorescence microscopy in combination with computer-aided three-dimensional reconstruction. Marked regional differences in the sensitivity to the effects of ATP depletion were observed in the actin cytoskeleton. Actin depolymerization appears to first affect the cortical actin network running along the apical basal axis of the cell. The next actin network that is disrupted is the stress fibers found at the basal surface of the cell. Finally, the actin ring at the level of the zonulae occludens and adherens is compromised. The breakup of the actin ring correlates with ultrastructural changes in tight junction strands and the loss of the tight junction's role as a molecular fence. During the process of actin network dissolution, polymerized actin aggregates form in the cytoplasm. The changes in the junctional complexes and the potential to reverse the ATP depletion suggest that this may be a useful method to study junctional complex formation and its relationship to the actin cytoskeletal network.

Actins↗
PubMed1993

The physiological cross-sectional area of motor units in the cat tibialis anterior.

The physiological cross-sectional area (CSA) of a motor unit (MU), taken as the sum of fiber areas measured on a single section through the approximate midlength of the MU, has been compared with the physiological CSA more strictly defined as the sum of the maximal areas to be found anywhere along the length of each of the MU fibers. The CSA at intervals along the fiber length was measured in fibers selected from four glycogen-depleted, isolated MUs in the cat tibialis anterior (TA), and profiles of the summed areas made. In one MU, measurements were also taken on all the MU's fibers at less frequent intervals. The profiles demonstrate that the summed CSA based on each fiber's maximum CSA may exceed that derived from observation on any single section by as much as 20%. As a consequence, values that have been reported for specific tension (force per unit area) of MUs in the TA and probably other muscles may have been overestimated, especially for those MUs of fast type. Estimates were also made of the share of the MU's total force transmitted directly to the tendons of origin and insertion via endings of the blunt musculotendinous type as distinct from tapering intrafascicular endings acting through in-series connective tissue and non-MU fibers. In two MUs of slow type in which most fibers ran from tendon to tendon, "partial tapering" extending over 1 cm of the fiber length accounted for a third of the total physiological CSA, and indicated yet another mode for relay of the MU's force to the tendon.

Animals↗
PubMed1992

Controlling cardiac chaos.

The extreme sensitivity to initial conditions that chaotic systems display makes them unstable and unpredictable. Yet that same sensitivity also makes them highly susceptible to control, provided that the developing chaos can be analyzed in real time and that analysis is then used to make small control interventions. This strategy has been used here to stabilize cardiac arrhythmias induced by the drug ouabain in rabbit ventricle. By administering electrical stimuli to the heart at irregular times determined by chaos theory, the arrhythmia was converted to periodic beating.

Action Potentials↗
PubMed1992

Heart rate dynamics after acute cocaine administration.

We examined heart rate (HR) patterns after a bolus intravenous (i.v.) administration of a high (10 mg/kg) dose of cocaine in unrestrained cats. Mean R-R intervals, SD, and other measures of variability were assessed in three periods: waking baseline, early postcocaine administration, and later recovery periods. Cocaine resulted in initial tachycardia and reduced HR variability. This reduction in variability was independent of changes in the average rate: during the recovery period, HR returned to baseline values, but the reduced variability persisted. Nonlinear methods of assessment yielded additional results: Cocaine introduces a high correlation between one beat and the next and a tendency for cardiac accelerations to be followed immediately by decelerations and vice versa. The overall effect of the drug is to restrict deviation from a fixed rate.

Animals↗
PubMed1992

Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome.

Infants who subsequently succumb to the sudden infant death syndrome (SIDS) have higher heart rates and reduced heart rate variation compared with other infants. We examined dynamic changes in cardiac interbeat intervals to explore these differences in cardiac control. Recordings of electrocardiographic activity and respiratory movement were acquired from 13 SIDS victims before their deaths. Moment-to-moment changes in R-R intervals during quiet sleep, rapid eye movement sleep, and waking were compared with values of 13 matched control infants. For each sleep-waking state, every R-R interval was plotted against the previous interval (Poincaré plots), and each change in interbeat interval was plotted against the previous change. Dispersion of interbeat intervals at different heart rates was reduced in SIDS victims, resulting in Poincaré plots markedly different from those of controls. The dispersion, sampled at the 10th and 90th percentiles of heart rates, was reduced across all sleep-waking states in SIDS victims. At high heart rates, the difference between groups disappeared after correcting for basal rate; however, the reduced range at low heart rates was independent of basal rate. SIDS victims also showed smaller beat-to-beat changes in heart rate and fewer sustained runs of consistent heart rate changes during waking relative to controls. The differences in cardiac rate dynamics suggest altered autonomic control in infants who succumb to SIDS. We speculate that the autonomic disturbance may lead to cardiac instability or may indicate CNS alterations with the potential to affect other vital functions.

Autonomic Nervous System↗
PubMed1991

Physiological and developmental implications of motor unit anatomy.

There is increasing evidence that the architectural design and arrangement of the fibers within a motor unit have important physiological and developmental ramifications. Limited data, however, are available to directly address this issue. In the present study the physiological properties of one motor unit in each of seven cat tibialis anterior (TA) muscles were determined. Each of these units then was repetitively stimulated to deplete the glycogen in all muscle fibers within the unit. Subsequently, the length, type of ending, and spatial distribution of fibers sampled from these physiologically and histochemically typed motor units were determined. Four fast fatigable (FF), one fast, fatigue resistant (FR), and two slow (S) motor units (MU) were studied. The samples consisted of all those glycogen-depleted fibers (9-27) contained within a single fascicle or a circumscribed area of each of the motor unit territories. The mean fiber lengths for the two slow motor units were 35.9 and 45.5 mm. The mean fiber lengths for the fast motor unit samples ranged from 8.8 to 48.5 mm. Some fibers of both the fast and slow units reached lengths of 58 mm. Most of the fibers in the slow units extended the entire distance between the proximal and distal musculotendinous planes, had relatively constant cross-sectional areas, and terminated at the tendon as blunt endings. In contrast, the majority of the fibers in the fast units terminated intrafascicularly at one end, and the cross-sectional area decreased progressively along their lengths, that is, showed a tapering pattern for a significant proportion of their lengths. Therefore, the force generated by units that end midfascicularly would appear to be transmitted to connective tissue elements and/or adjacent fibers. All fibers of a fast unit within a fascicle were located at approximately the same proximo-distal location. Thus, developmentally the selection of muscle fibers by a motoneuron would seem to be influenced by their spatial distribution. The architectural complexities of motor units also have clear implications for the mechanical interactions of active and inactive motor units. For example, the tension capabilities of a motor unit may be influenced not only by the spatial arrangement of its own fibers, but also by the level of activation of neighboring motor units.

Animals↗
PubMed1991

Dynamic characteristics of cardiac R-R intervals during sleep and waking states.

Traditional assessment of cardiac R-R intervals during sleep-wake states uses summary statistics such as mean and interquartile range. Such summary statistics are less able to provide information about instantaneous or dynamic aspects of beat-to-beat control. We examined state-dependent beat-to-beat patterning by plotting each cardiac R-R interval against the previous interval (Poincaré plots). This procedure provides an indication of the probability of occurrence of one interval from its predecessor and allows assessment of dynamic properties of R-R interval variation. Cardiac R-R intervals were determined over 5-12-minute periods of wakefulness (AW), quiet sleep (QS) and rapid eye movement sleep (REM) from six cats; each interval was plotted on the y-axis against the previous value on the x-axis resulting in an RRn + 1 vs. RRn plot. These plots provided evidence that the correlation between an interval and its successor was greater in REM than in QS, even though the overall range was greater in REM. The results suggest that short-term cardiac control during REM may be influenced by more closely regulated mechanisms than suggested by classic concepts.

Animals↗
PubMed1991

Nonlinear analysis of EEG sleep states.

Recent advances in the field of nonlinear dynamics have provided new conceptual models as well as novel analytical techniques applicable to neuropsychopharmacologic studies. One measurement technique that has been recently developed in an attempt to characterize nonlinear systems in physics and biology is the estimation of dimension. Dimension may be seen as a measure of the information required to describe the current behavior of a system. We have applied these techniques to the analysis of the sleep EEG, and have found that the dimension of rapid eye movement (REM) sleep is significantly higher than non-rapid-eye-movement (NREM) sleep. These data support a preliminary hypothesis that EEG dimension may represent the number of nonlinear modes activated in the brain. Thus, sleep states of low arousal or low input would be envisioned as having low dimension (e.g., slow-wave sleep) whereas increased arousal (REM) would activate more nonlinear modes. Although more investigations will be needed to explore this hypothesis, these studies suggest that further development of nonlinear approaches to the analysis of brain systems are likely to generate new clinical measures as well as new ways of viewing brain electrical function.

Adult↗