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J Randall Moorman

Publications and source records attributed to J Randall Moorman.

27 records · Page 2Linked to original sources
PubMed2003

A novel method for measuring dynamic changes in cell volume.

Many cell types regulate their volume in response to extracellular tonicity changes through a complex series of adaptive mechanisms. Several methods that are presently used to measure cell volume changes include Coulter counters, fluorescent techniques, electronic impedance, and video microscopy. Although these methods are widely used and accepted, there are limitations associated with each technique. This paper describes a new method to measure changes in cell volume based on the principle that fluid flow within a rigid system is well determined. For this study, cos-7 cells were plated to line the inner lumen of a glass capillary and stimulated to swell or shrink by altering the osmolarity of the perfusing solution. The cell capillary was connected in series with a blank reference capillary, and differential pressure changes across each tube were monitored. The advantages of this method include 1) ability to continuously monitor changes in volume during rapid solution changes, 2) independence from cell morphology, 3) presence of physiological conditions with cell surface contacts and cell-cell interactions, 4) no phototoxic effects such as those associated with fluorescent methods, and 5) ability to report from large populations of cells. With this method, we could detect the previously demonstrated enhanced volume regulation of cells overexpressing the membrane phosphoprotein phospholemman, which has been implicated in osmolyte transport.

Animals↗
PubMed2003

Sample asymmetry analysis of heart rate characteristics with application to neonatal sepsis and systemic inflammatory response syndrome.

We introduce the sample asymmetry analysis (SAA) and illustrate its utility for assessment of heart rate characteristics occurring early in the course of neonatal sepsis and systemic inflammatory response syndrome (SIRS). Conceptually, SAA describes changes in the shape of the histogram of RR intervals that are caused by reduced accelerations and/or transient decelerations of heart rate. Unlike other measures of heart rate variability, SAA allows separate quantification of the contribution of accelerations and decelerations. The application of SAA is exemplified by a study comparing 50 infants, who experienced a total of 75 episodes of sepsis and SIRS, with 50 control infants. The two groups were matched by birth weight and gestational age. RR intervals were recorded for all infants throughout their course in the Neonatal Intensive Care Unit. The sample asymmetry of the RR intervals increased in the 3-4 d preceding sepsis and SIRS, with the steepest increase in the last 24 h, from a baseline value of 3.3 (SD = 1.6) to 4.2 (SD = 2.3), p = 0.02. After treatment and recovery, sample asymmetry returned to its baseline value of 3.3 (SD = 1.3). The difference between sample asymmetry in health and before sepsis and SIRS was mainly due to fewer accelerations than to decelerations. Compared with healthy infants, infants who experienced sepsis had similar sample asymmetry in health, and elevated values before sepsis and SIRS (p = 0.002). We conclude that SAA is a useful new mathematical technique for detecting the abnormal heart rate characteristics that precede neonatal sepsis and SIRS.

Birth Weight↗
PubMed2003

Abnormal heart rate characteristics preceding neonatal sepsis and sepsis-like illness.

Late-onset neonatal sepsis is a significant cause of morbidity and mortality, and early detection could prove beneficial. Previously, we found that abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations occurred early in the course of neonatal sepsis and sepsis-like illness in infants in a single neonatal intensive care unit (NICU). We hypothesized that this finding can be generalized to other NICUs. We prospectively collected clinical data and continuously measured RR intervals in all infants in two NICUs who stayed for >7 d. We defined episodes of sepsis and sepsis-like illness as acute clinical deteriorations that prompted physicians to obtain blood cultures and start antibiotics. A predictive statistical model yielding an HRC index was developed on a derivation cohort of 316 neonates in the University of Virginia NICU and then applied to the validation cohort of 317 neonates in the Wake Forest University NICU. In the derivation cohort, there were 155 episodes of sepsis and sepsis-like illness in 101 infants, and in the validation cohort, there were 118 episodes in 93 infants. In the validation cohort, the HRC index 1) showed highly significant association with impending sepsis and sepsis-like illness (receiver operator characteristic area 0.75, p < 0.001) and 2) added significantly to the demographic information of birth weight, gestational age, and days of postnatal age in predicting sepsis and sepsis-like illness (p < 0.001). Continuous HRC monitoring is a generally valid and potentially useful noninvasive tool in the early diagnosis of neonatal sepsis and sepsis-like illness.

Heart Rate↗
PubMed2003

Abnormal Na channel gating in murine cardiac myocytes deficient in myotonic dystrophy protein kinase.

DMPK is a serine/threonine kinase implicated in the human disease myotonic muscular dystrophy (DM). Skeletal muscle Na channels exhibit late reopenings in Dmpk-deficient mice and peak current density is reduced, implicating DMPK in regulation of membrane excitability. Since complete heart block and sudden cardiac death occur in the disease, we tested the hypothesis that cardiac Na channels also exhibit abnormal gating in Dmpk-deficient mice. We made whole cell and cell-attached patch clamp recordings of ventricular cardiomyocytes enzymatically isolated from wild-type, Dmpk+/-, and Dmpk-/- mice. Recordings from membrane patches containing one or a few Na channels revealed multiple Na channel reopenings occurring after the macroscopic Na current had subsided in both Dmpk+/- and Dmpk-/- muscle, but only rare reopenings in wild-type muscle (>3-fold difference, P < 0.05). This resulted in a plateau of non-inactivating Na current in Dmpk-deficient muscle. The magnitude of this plateau current was independent on the magnitude of the test potential from -40 to 0 mV and was also independent of gene dose. Macroscopic Na current density was similar in wild-type and Dmpk-deficient muscle, as was steady-state Na channel gating. Decay of macroscopic currents was slowed in Dmpk-/- muscle, but not in Dmpk+/- or wild-type muscle. Entry into, and recovery from, inactivation were similar at multiple test potentials in wild-type and Dmpk-deficient muscle. Resting membrane potential was depolarized, and action potential duration was significantly prolonged in Dmpk-deficient muscle. Thus in cardiac muscle, Dmpk deficiency results in multiple late reopenings of Na channels similar to those seen in Dmpk-deficient skeletal muscle. This is reflected in a plateau of non-inactivating macroscopic Na current and prolongation of cardiac action potentials.

Action Potentials↗
PubMed2002

Use of global atrial fibrillation organization to optimize the success of burst pace termination.

OBJECTIVES: The purpose of this study was to determine if burst atrial pacing would have an effect on terminating atrial fibrillation. BACKGROUND: We hypothesized that frequency domain analysis of a filtered wide bipolar atrial electrogram describes the global organization of atrial fibrillation (AF) and should vary over time. Timing burst pacing to periods of high organization of AF should promote regional atrial conduction block and terminate AF. METHODS: Nine dogs were conditioned with rapid atrial pacing for 48 h. Electrogram recordings were made from a wide right atrium (RA) to left atrium (LA) bipole and digitally filtered. A fast-Fourier transform was performed every 0.5 s on a sliding 2-s window, and the organization index (OI) was calculated as a ratio of the area of the first four harmonic peaks to the total power of the spectrum. Organization indexes >0.5 indicated more organized AF activity. Right atrium and LA burst pacing (burst) (cycle length 50 ms, 9.9 ms, 9.9 mA, 1 to 4 s) was performed through decapolar catheters. Burst was either random or synchronized to OI >0.5. RESULTS: Burst termination was attempted 1,814 times (889 OI sync, 925 random) and succeeded in seven of nine dogs. Burst had an overall success rate of 11.1% versus 6.3% for random (p < 0.0003). Biatrial pacing had the highest efficacy for terminating AF, with a success rate of 16.5% for OI sync versus 8.2% for random (p < 0.0001). CONCLUSIONS: Timing the delivery of the burst pace when the OI is >0.5 increases the efficacy of burst pace termination of AF. Biatrial pacing is more effective than either RA or LA pacing alone.

Animals↗
PubMed2002

Effects of age and gene dose on skeletal muscle sodium channel gating in mice deficient in myotonic dystrophy protein kinase.

Myotonic muscular dystrophy (DM) is characterized by abnormal skeletal muscle Na channel gating and reduced levels of myotonic dystrophy protein kinase (DMPK). Electrophysiological measurements show that mice deficient in Dmpk have reduced Na currents in muscle. We now find that the Na channel expression level is normal in mouse muscle partially or completely deficient in Dmpk. Reduced current amplitudes are not changed by age or gene dose, and the reduction is not due to changes in macroscopic or microscopic gating kinetics. The mechanism of abnormal membrane excitability in DM may in part be silencing of muscle Na channels due to Dmpk deficiency.

Aging↗
PubMed2002

Effect of electrical and structural remodeling on spatiotemporal organization in acute and persistent atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) may originate from discrete sites of periodic activity. We studied the effect of structural and electrical remodeling on spatiotemporal organization in acute and persistent AF. METHODS AND RESULTS: Atrial effective refractory periods (AERPs) were recorded from five different sites at baseline and after pacing in acute AF (n = 8 dogs) and persistent AF (n = 8). Four persistent AF dogs subsequently were cardioverted to sinus rhythm to allow AERP recovery. Periodicity was quantified by calculating power spectra on left atrial electrograms obtained from a 64-electrode basket catheter. Left atrial size was measured by intracardiac echocardiography and structural changes were assessed by electron microscopy. Mean AERPs decreased after pacing in acute (128 +/- 16 msec to 108 +/- 29 msec, P < 0.001) and persistent AF (135 +/- 16 msec to 104 +/- 24 msec, P < 0.0001). AERP recovery was established after 7 days of sinus rhythm. Structural changes were mild in acute AF, severe in persistent AF, and remained severe after AERP recovery. A single dominant frequency was identified in 94% of acute AF bipoles, 57% in persistent AF, and 76% after AERP recovery. Average correlation coefficient was 0.82 among acute AF bipoles, 0.63 in persistent AF, and 0.73 after AERP recovery. CONCLUSION: Transition from acute to persistent AF is associated with loss of spatiotemporal organization. A single dominant frequency recruits the majority of the left atrium in acute AF. Persistent AF, however, is associated with structural remodeling and dominant frequency dispersion. Recovery of refractoriness only partially restores spatiotemporal organization, indicating a major role for structural remodeling in the maintenance of persistent AF.

Acute Disease↗
PubMed2002

Sample entropy analysis of neonatal heart rate variability.

Abnormal heart rate characteristics of reduced variability and transient decelerations are present early in the course of neonatal sepsis. To investigate the dynamics, we calculated sample entropy, a similar but less biased measure than the popular approximate entropy. Both calculate the probability that epochs of window length m that are similar within a tolerance r remain similar at the next point. We studied 89 consecutive admissions to a tertiary care neonatal intensive care unit, among whom there were 21 episodes of sepsis, and we performed numerical simulations. We addressed the fundamental issues of optimal selection of m and r and the impact of missing data. The major findings are that entropy falls before clinical signs of neonatal sepsis and that missing points are well tolerated. The major mechanism, surprisingly, is unrelated to the regularity of the data: entropy estimates inevitably fall in any record with spikes. We propose more informed selection of parameters and reexamination of studies where approximate entropy was interpreted solely as a regularity measure.

Entropy↗