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Biomedical subjects

W Craelius

Publications and source records attributed to W Craelius.

36 records · Page 2Linked to original sources

Stretch activated ion channels in ventricular myocytes.

Patch-clamp recordings from ventricular myocytes of neonatal rats identified ionic channels that open in response to membrane stretch caused by negative pressures (1 to 6 cm Hg) in the electrode. The stretch response, consisting of markedly increased channel opening frequency, was maintained, with some variability, during long (greater than 40 seconds) stretch applications. The channels have a conductance averaging 120pS in isotonic KCl, have a mean reversal potential 31 mV depolarized from resting membrane potential, and do not require external Ca++ for activation. The channels appear to be relatively non-selective for cations. Since they are gated by physiological levels of tension, stretch-activated channels may represent a cellular control system wherein beat-to-beat tension and/or osmotic balance modulate a portion of membrane conductance.

Animals↗

QTU prolongation and polymorphic ventricular tachyarrhythmias due to bradycardia-dependent early afterdepolarizations. Afterdepolarizations and ventricular arrhythmias.

Polymorphic ventricular tachyarrhythmias occurred spontaneously during bradycardia in dogs given the inotropic polypeptide anthopleurin-A (AP-A). The arrhythmia was investigated in in vitro and in vivo experiments. In in vitro experiments, AP-A (50 micrograms/l) produced bradycardia-dependent prolongation of action potential duration that was more pronounced in Purkinje than in muscle fibers. Only Purkinje fibers developed early afterdepolarizations (EAD) and triggered activity. These effects could be abolished by rapid pacing, lidocaine (4 mg/l), or tetrodotoxin (1 mg/l). In vivo experiments were conducted in anesthetized healthy dogs with simultaneous recording of surface ECG, monophasic action potentials from the endocardial and epicardial surface of the left ventricle by contact electrode catheter technique, and transmembrane action potentials from the epicardial surface of the left ventricle with a floating microelectrode technique. AP-A in a dose comparable to that used in vitro (4 micrograms/kg, i.v. bolus) resulted in bradycardia-dependent marked prolongation of both monophasic and transmembrane action potentials. An EAD gradually appeared on both recordings but was more marked in endocardial monophasic action potentials. Eventually, a premature ventricular depolarization arose from or very close to the peak of the EAD. The prolongation of action potentials was associated with similar prolongation of the QTU interval in surface ECG, and in some experiments, the EAD corresponded to a distinct prominent U wave. A ventricular premature depolarization arose from the U or TU complex and initiated polymorphic ventricular tachyarrhythmias that terminated spontaneously or degenerated into ventricular fibrillation. These effects were reversed by rapid pacing or lidocaine (1 mg/kg). The present study provides evidence in support of the hypothesis that AP-A-induced ventricular tachyarrhythmias are due to bradycardia-dependent EAD and triggered activity.

Action Potentials↗

Signal processing options for detecting conduction abnormalities in ischemic ventricles.

Sources of error in averaging for late ventricular potentials include variations in the magnitude and timing of late potentials as well as variability in the temporal alignment of successive cardiac cycles during averaging. Since these errors can both attenuate high frequency signals and add artifactual components to the ECG, we developed methods to estimate and minimize them. Studies on patients indicated that small misalignments can obliterate high frequency components of the QRS, while broadening the low amplitude tail of the QRS, possibly leading to erroneous interpretations. The digital cross-correlation method of alignment was evaluated using simulated signals, and was shown to be relatively insensitive to gross variations in waveshape, and appeared to be less accurate than real-time pattern recognition schemes. A real-time alignment method based on a mathematical model was developed that could measure its accuracy, and was implemented in hardware. Our method improves alignment and average fidelity. Direct recordings from human and canine ventricles revealed that beat-to-beat variability in activation patterns of ischemic regions often followed a regular pattern such as 2:1 block. Spectral analysis of ECG recordings showed that a sub-harmonic, indicative of a 2:1 pattern, could be detected in the ECG during periods when ischemic regions of the ventricle were experiencing 2:1 block. These results suggest the possible utility of sub-harmonic analysis as a tool for detection of abnormal electrophysiological conduction.

Animals↗

Management of recurrent ventricular tachycardia: economic impact of therapeutic alternatives.

The clinical and economic results of antiarrhythmic therapy selected on the basis of electrophysiologic (EP) studies in patients with recurrent ventricular tachycardia (VT) were examined and compared with previously administered empiric therapy. Twenty-nine patients with recurrent VT and organic heart disease, aged 39 to 78 years (mean 59 +/- 11) were evaluated. All patients had empiric therapy before EP studies and EP-based therapy after EP evaluation. Hospital records were analyzed from arrhythmia diagnosis 1 to 39 months (mean 7.5 +/- 10.4) before EP evaluation until completion of follow-up 1 to 20 months (mean 13.3 +/- 7.4) after EP studies. Clinical efficacy was assessed by comparing actual arrhythmic deaths or recurrences during EP-based therapy with predicted values on empiric therapy. Charges based on diagnosis-related groupings for empiric and EP-based therapy were compared. Charges for EP evaluation were included in the calculation for EP-based therapy. During empiric therapy, 1 to 7 unsuccessful drug trials (mean 3.7 +/- 1.6) were performed, with arrhythmia recurrences noted in all patients during a mean 7.5-month VT duration. Twenty-seven of 29 patients required 1 to 70 electrical terminations. There were 64 hospitalizations (mean 2.1 +/- 1.7) with a total length of hospital stay of 913 days (mean 31.0 +/- 19.9). EP evaluation required 90 EP procedures (mean 3.0 +/- 1.5) with a length of stay of 690 days (mean 23.8 +/- 12.0). During a follow-up period of 1 to 26.5 months (13.3 +/- 7.4) on EP-based therapy, 1 patient died suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Studies on left ventricular function during sustained ventricular tachycardia.

The acute effects of rapid ventricular pacing and sustained ventricular tachycardia on left ventricular function were examined in patients with recurrent sustained ventricular tachycardia. Programmed electrical stimulation and left ventricular hemodynamic measurements were performed in 20 patients (19 men and 1 woman), with an age range of 49 to 79 years (mean 63 +/- 9). Indexes of left ventricular function that were analyzed included left ventricular peak systolic pressure, end-diastolic pressure, first derivative of peak left ventricular pressure (dP/dt) and negative left ventricular dP/dt. Measurements were obtained during sinus rhythm, after paced premature ventricular depolarizations, during rapid ventricular pacing (cycle lengths 600 to 250 ms) and immediately after induction of sustained ventricular tachycardia. Mean left ventricular peak systolic blood pressure was 123 +/- 19 mm Hg during sinus rhythm, decreased to 77 +/- 23 mm Hg (p less than 0.05) at the induction of ventricular tachycardia and remained decreased during arrhythmia (p less than 0.01). Mean left ventricular end-diastolic pressure was 22 +/- 5 mm Hg during sinus rhythm, did not change after arrhythmia induction (22 +/- 9 mm Hg, p greater than 0.2) and remained unchanged during sustained ventricular tachycardia (p greater than 0.2). Mean peak left ventricular dP/dt was 1,400 +/- 620 mm Hg/s in sinus rhythm, decreased to 810 +/- 580 mm Hg/s (p less than 0.05) at ventricular tachycardia induction and remained decreased during sustained ventricular tachycardia (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Neurotrophic regulation of GABA receptors at a crayfish inhibitory synapse.

Experiments were done on the inhibitory synapse of crayfish tonic muscle receptor organs (MROs) to determine whether gamma-aminobutyric acid (GABA) receptors would be affected by denervation or axotomy. It was found that severing the dorsal nerve containing the MRO sensory and inhibitory neurons usually induced, in 30 days or less, a dramatic transformation in the responses of MROs to ionophoretically applied GABA. In contrast to normal MROs which show only inhibitory responses to GABA, transformed MROs were substantially depolarized and excited by GABA application to numerous points found on the axon, soma, dendrites. Interspersed among the points of excitation, normal inhibitory points could still be found on the transformed cells. The results suggested that chronic lesions can induced structural changes in GABA receptors, whereby the Cl- ionophore is replaced by a cationic channel. It was possible to compare the effects of postsynaptic axotomy alone with those of postsynaptic plus presynaptic axotomy by testing MROs from animals whose ventral nerve cord was sectioned. These experiments suggested that interruption of the presynaptic neuron is an important factor in the transformation. It was not determined whether complete degeneration of the inhibitory synapse is necessary for the transformation, but the rapidity of the effect, coupled with the probability of long-term survival of synaptic contacts, suggested that complete degeneration was not necessary. Similarities were found in the GABA responses of transformed MROs and those MROs which normally receive no innervation, which are located in the sixth abdominal segment. These results support the idea that trophic regulation from inhibitory neurons is a factor in stabilizing the association of the Cl- ionophore with GABA receptor.

Animals↗

Iron deposits surrounding multiple sclerosis plaques.

Autopsy samples from cerebral areas of five brains from patients with multiple sclerosis (MS) and from six control brains were stained with Perls acid ferrocyanide to detect nonheme iron present as hemosiderin. Positive iron reactions were observed only in MS sections surrounding demyelinated plaques. Myelinated white matter near the lesion contained numerous iron-laden ovoid bodied and axons that stained positively for iron. Positive reactions were also found within blood vessels of gray matter near the lesion. A possible source of the iron was extravasated blood.

Adult↗

Release of 3H-gamma-aminobutyric acid (GABA) by inhibitory neurons of the crayfish.

Inhibitory neurons innervating the muscle receptor organ (MRO) of crayfish were used to study the uptake and release of tritiated GABA. MROs that have been directly exposed to 3H GABA for 60--75 min release radioactivity during low-frequency electrical stimulation. When ganglia containing the inhibitory cell bodies are exposed to 3H GABA, the isotope travels along a pathway unique to the inhibitory axon, at rates that range between 160 and 240 mm per day. Electrical stimulation of inhibitory axons whose cell bodies have been exposed to 3H GABA for 4--5 hr produces release of isotope from isolated MROs. Low calcium, high magnesium exposure prevents the stimulus-dependent release of radioactivity. Thin layer chromatographic analyses indicate that GABA comprises at least a major fraction of the radioactivity collected from stimulated preparations. A number of unidentified radioactive compounds are usually present with GABA, and it is suggested that most of these are catabolites of GABA.

Animals↗

Free fatty acid patterns in normal and multiple sclerosis white matter.

The relative compositions of free fatty acids (FFA) in white matter from six multiple sclerosis (MS) and seven control brains were determined by gas chromatography. The major components of all samples were oleic, stearic and palmitic acids, with lesser amounts of arachidonic acid, and a long chain fatty acid, identified as 24:4. MS samples had significantly less of the 24:4 fraction compared with controls, but no other differences were noted. The spectrum of FFA was similar in most respects to those reported for phosphatidylcholine and cholesterol esters. This supports current theories that a major pathway of lipid catabolism in the brain involves transfer of fatty acids from phosphatidylcholine to cholesterol.

Adult↗

Inhibition of mechanosensory interneurons in the crayfish. I. Presynaptic inhibition from giant fibers.

1. Sucrose-gap and intracellular recordings were used to study the primary afferent depolarization (PAD) produced in mechanosensory afferents by impulses in lateral and medial giant axons, which are the command cells for the tail flip escape response in the crayfish. 2. The lateral and medial giant axons produce PAD through a polysynaptic interneuronal pathway. The response has a relatively long intraganglionic latency (7--11 ms), and command-evoked PAD can be recorded in ganglia from which the giant axons have been experimentally disconnected. 3. The final neurons of the pathway that delivers inhibition are few in number and extensive in distribution; most appear to be common to lateral and medial giant pathways. 4. At least some of the inhibitory interneurons have axons in the interganglionic connectives and probably produce both presynaptic and postsynaptic inhibition. 5. Stimulation of the lateral, but not the medial, giant axons causes a small, short-latency deplorization that is stable at high repetition rates. This small potential can be accounted for by transmission across known electrical synapses between mechanosensory afferents and the lateral giants in each abdominal ganglion. 6. Repetitive stimulation of the lateral giant axons causes substantial augmentation of PAD, apparently through recruitment of additional interneurons. PAD evoked by a single medial giant (MG) stimulus is generally much larger than that elicited by a single lateral giant (LG) spike. However, MG-PAD summates little and so the maximum PAD deltaV reached during repetitive firing is equivalent for the two types of giant axons. 7. Iontophoresis of gamma-aminobutyric acid (GABA) into the ganglionic neuropil depolarizes the primary afferents and blocks activity in neurons that have axons in the interganglionic connective. 8. The extrapolated PAD reversal potential and pharmacological studies suggest that a GABA-mediated chloride conductance increase is involved in the production of PAD.

Animals↗

Comparative epidemiology of multiple sclerosis and dental caries.

The geographical distribution and other epidemiological characteristics of multiple sclerosis (MS) are compared with those of dental caries. The rates of death due to MS in Australian states are linearly related to the numbers of decayed, missing, and filled (DMF) teeth found in individuals from those states (r=0.97, P less than 0.002). In the United States of America, a strong positive correlation (r=0.55, P less than 0.001) also exists between MS death rates and dental caries indices. The prevalence of MS in 45 countries or areas correlates well with the frequencies of DMF teeth among children of school age in those locations (r=0.78, P less than 0.001). The prevalence of MS also correlates well with the percentage of edentulous individuals in certain countries (r=0.99, P less than 0.001). A review of the literature shows that the risk for dental caries is lower among the following groups: the lower socioeconomic classes in the United States of America; Chinese immigrants to England compared with natives; blacks compared with whites; and males compared with females. The dental caries risk is higher during pregnancy and lactation. All these trends have been described for MS as well. It is suggested that dental caries may be a more accurate epidemiological model for MS than poliomyelitis. It is also suggested that MS and dental caries may share certain aetiological factors, two of which may be dietary excess of certain fats, and vitamin D deficiency.

Australia↗

The distribution of GABA sensitivity on crayfish muscle receptor organs.

1. The effectiveness of inhibition of gamma-aminobutyric acid (GABA) at various points on crayfish abdominal muscle receptor organs (MROs) was investigated by iontophoretic methods that have a spatial resolution of 8 mum. 2. The MROs in the rostral abdominal segments, which receive inhibitory innervation, were always strongly inhibited by focal iontophoretic application of GABA; MROs in the 6th abdominal segment, which do not receive inhibitory innervation, were usually not strongly inhibited. 3. In the rostral MROs, the magnitude of GABA current necessary to abolish stretch induced impulses was least for dendritic points; it increased as a function of distance from the dendrites, over an area extending from the receptor muscle to a point on the axon 200 mum from the cell body. 4. Outward currrents from NaCl-filled micropipettes had no effect on impulse production when applied to the dendritic region of rostral MROs, but could produce transient inhibition of impulses when applied to the axon. 5. It is suggested that a high degree of GABA sensitivity is localized to the rostral MRO dendrites, where inhibitory synapses are most numerous.

Aminobutyrates↗

Rheological behavior of rat mesangial cells during swelling in vitro.

The response of cells to mechanical forces depends on the rheological properties of their membranes and cytoplasm. To characterize those properties, mechanical and electrical responses to swelling were measured in rat mesangial cells (MC) using electrophysiologic and video microscopic techniques. Ion transport rates during hyposmotic exposures were measured with whole-cell recording electrodes. Results showed that cell swelling varied nonlinearly with positive internal pressure, consistent with a viscoelastic cytoplasm. The extrapolated area expansivity modulus for small deformations was estimated to be 450 dyne/cm. Cell swelling, caused either by positive pipet pressure or hyposmotic exposure (40-60 mOsm Kg-1), rapidly induced an outwardly rectifying membrane conductance with an outward magnitude 4-5 times the baseline conductance of 0.9 +/- 0.5 nS (p < .01). Swelling-induced (SI) current was weakly selective for K+ over Na+, partially reversed upon return to isotonicity, and was antagonized by 0.5 mM GdCl3 (p < 0.02; n = 6). Isolated cells treated with GdCl3 rapidly lysed after hypotonic exposure, in contrast to untreated cells that exhibited regulatory volume decrease (RVD). Our results indicate that volume regulation by MC depends upon a large swelling-induced K+ efflux, and suggest that swelling in MC is a viscoelastic process, with a viscosity dependent on the degree of swelling.

Animals↗

Persistent sodium currents induced by anthopleurin-A and their relationship to early afterdepolarizations in ventricular myocytes.

Prolonged Na+ current inactivation was induced in neonatal rat ventricular myocytes by exposure to Anthopleurin-A (80-240 nM). In control whole-cell voltage clamp recordings, prolonged Na+ current inactivated mono-exponentially from peak with time constant, tau h, averaging 1.5 msec +/- 0.2 msec at -30 mV and peak current averaging 0.7 +/- 0.3 nA (n = 10). Steady state inactivation was complete at -50 mV and there was little or no overlap of prolonged Na+ current inactivation and activation processes. One to 3 minutes following exposure to Anthopleurin-A, the rate of inactivation slowed, with tau h increasing to 21 +/- 5 msec at -30 mV, and peak prolonged Na+ current increasing to 1.3 +/- 0.5 nA (n = 10). Steady state inactivation was shifted in a positive direction, and complete inactivation did not occur even at +10 mV. Persistent inward currents were thus induced by Anthopleurin-A. They were most prominent at depolarizations slightly above threshold for activation and were selectively blocked by lidocaine (60 microM). Action potentials were prolonged by Anthopleurin-A, especially at slow stimulation rates, and were accompanied by early afterdepolarizations. The correlation between persistent inward currents and early afterdepolarizations, in terms of voltage dependence, appearance and pharmacology, suggests a possible causal role for persistent Na+ currents in this model of early afterdepolarizations.

Action Potentials↗