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Biomedical subjects

E Chow

Publications and source records attributed to E Chow.

At least 91 records · Page 5Linked to original sources

Myogenic electrical control activity in longitudinal muscle of human and dog colon.

1. The myogenic electrical activities of longitudinal muscle cells of the dog and human colon were investigated using intracellular microelectrodes. 2. The resting membrane potentials of dog and human longitudinal muscle cells at the serosal side of the muscle layer were -49.4 +/- 0.9 and -44.8 +/- 1.3 mV respectively. 3. Spontaneous electrical activity consisted of electrical oscillations of 13.7 +/- 1.1 mV and 8.6 +/- 2.1 mV amplitude, and 19.8 +/- 1.0 cycles/min and 26.1 +/- 1.6 cycles/min frequency for dog and human cells respectively. 4. Spiking activity only occurred superimposed on the electrical oscillations; the mean rate of rise of spikes was approximately 150 mV/s in the dog and approximately 260 mV/s in human cells and that of the oscillations was approximately 18 mV/s in the dog and approximately 16 mV in human cells. 5. Spiking activity was abolished by calcium influx blockers and 0.01 mM-calcium Krebs solution. The amplitude of the electrical oscillations was reduced to 0.2-1.0 mV 30 min after calcium influx blockade or 30 min in 0.01 mM-calcium Krebs solution. 6. Because of the high frequency of the oscillation-spike complexes, there was summation of associated contractile events in such a way that contraction frequency corresponded to frequency of bursts of oscillations and not to the frequency of the individual oscillations. 7. The resting membrane potential of the longitudinal muscle cells at the myenteric plexus side of the layer was -44.9 +/- 1.0 mV, significantly lower than at the serosal side. 8. A gradient in membrane potential and slow-wave amplitude exists in circular muscle of dog colon, with the highest value at the mucosal side (-68.4 and 28.1 mV respectively) and the lowest at the myenteric side (-62.5 and 8.6 mV) of the muscle layer. 9. Differences between resting membrane potential and electrical activity of longitudinal and circular muscle cells of the dog colon measured at the myenteric side of both muscle layers suggests absence of electrotonic coupling between the two types of cells. 10. Similarity of resting membrane potentials of longitudinal and circular muscle of the human colon suggests possible electronic coupling. 11. Since the electrical oscillations in longitudinal muscle control occurrence of spiking activity and type of contraction, they may be called 'electrical control activity'.

Action Potentials↗

Generation of spiking activity in circular muscle cells of the canine colon.

Spontaneous and current-induced electrical activity was recorded intracellularly to resolve the controversy whether or not the circular muscle layer of the colon generates spiking activity. Particularly in the first hour after mounting the tissue in the organ bath, spikes were recorded at both the submucosal and the myenteric plexus side of the muscle layer. Spikes were seen as part of the slow wave upstroke in the submucosal surface cells, and spikes occurred both at the upstroke potential and superimposed on the plateau potential in myenteric plexus surface cells. Spikes increased the force of contraction. The study supports earlier claims using extracellular recording techniques that circular muscle cells generate spiking activity, particularly in the presence of depolarizing stimuli, and that spikes contribute to contractile activity.

Animals↗

Coordination of electrical activities in muscle layers of the pig colon.

Simultaneous recording of electrical activities from the circular and longitudinal muscle layers of the pig colon was performed in vitro to study possible coordination of activities. The electrical activity of both muscle layers consisted of electrical oscillations with superimposed spikes. The frequency range of the electrical oscillations in the circular muscle was 0.5-3.5 cycles per minute (cpm) and in the longitudinal muscle 24-42 cpm. Coordination of the activities of both muscle layers occurred consistently only after stretch or cholinergic stimulation. Then it occurred in a unique fashion. Each oscillation in the circular muscle layer occurred at the same time as the onset of a burst of oscillations in the longitudinal muscle. In addition, multiple simultaneous recordings of the electrical activities from each muscle layer were obtained showing that within the circular muscle layer electrical oscillations were phase locked in the circumferential direction and along the long axis of the colon. They appeared to propagate in either the oral or aboral direction. In tetrodotoxin (with stretch as stimulus) and also in presence of carbachol, bursts of oscillations in the longitudinal muscle layer were phase locked circumferentially (in the different taeniae) and longitudinally. This study shows that the muscle layers in the colon, which have different myogenic electrical activities, can obtain a high level of coordination.

Animals↗

Isofenphos and an in vitro activation assay for delayed neuropathic potential.

Organophosphorus compounds (OPs) that cause organophosphorus ester-induced delayed neuropathy (OPIDN) generally inhibit neurotoxic esterase (NTE). However, the assay itself, when conducted in vitro, misses OPs that are activated into OPIDN-causing agents in the body. A preparation of liver mixed-function oxidases and brain NTE was used to rapidly detect activations of OPs. The compounds (0.1 mM or less) to be tested were incubated with microsomes isolated from livers of phenobarbital-treated chick embryos (P-450 content averaged 1.81 +/- 0.27 nmol/mg protein, means +/- SD, N = 5) and NTE (average of 13.8 nmol/min/mg protein) from untreated chick embryo brains. The NTE was separated by calcium precipitation and its activity assayed as usual. The low inhibitions of NTE of compounds that were not neurotoxic (parathion, Diazinon) did not increase in the presence of NADPH; inhibitions of NTE of compounds that required activation (leptophos, S,S,S-tri-n-butyl phosphorotrithioate, and tri-o-cresyl phosphate) greatly increased with NADPH. Both the recently identified neuropathic OP isofenphos (IFP) and its oxon required activation to inhibit NTE (inhibitions of 20 and 80%, respectively). Evidence is presented that the possible neuropathic metabolite is des-N-isopropyl IFP oxon.

Animals↗

Electrical basis of excitation and inhibition of human colonic smooth muscle.

Excitation and inhibition of electrical activities of the musculature of the human colon and the consequent changes in motor activities were studied in vitro. The mechanisms of excitation and inhibition were very different from those of the small intestine and colons from animal models. Carbachol increased spiking activity and the frequency of bursts of electrical oscillations in longitudinal muscle. Each longitudinal muscle contraction was related to a burst of electrical oscillations. Carbachol induced one of three patterns of activity in circular muscle: (a) continuous electrical oscillatory activity (14-24 cpm) with spikes, associated with tonic contraction; (b) bursts of such electrical activity, associated with broad phasic contractions; or (c) prolonged membrane potential depolarizations (frequency 1-3 cpm) with superimposed intense spiking activity, associated with phasic contractions. Isoproterenol inhibited all electrical and mechanical activities in both muscle layers. These results may provide a better understanding of (a) the origins of the variable patterns of electrical and motor activities and (b) the relationship between electrical and mechanical activities of the human colon musculature.

Action Potentials↗

Electrophysiologic control of motility in the human colon.

Characteristics of electrical activities, and the relationship between electrical and motor activities, were studied in circular and longitudinal (taenia) muscle of the human colon that was obtained from 21 individuals. Recordings were obtained with suction electrodes, the sucrose-gap method, and microelectrodes. The circular muscle electrical activity consisted of oscillatory activity of relatively low amplitude, with a frequency range from 4.5 to 60 cycle/min. Spiking activity was present on most oscillations. Contractile activity was associated with individual oscillations at frequencies below 12 cycle/min. Contractions related to periods of oscillations at frequencies above 12 cycle/min showed summation resulting in prolonged contractions. In these periods, oscillations were either of relatively high amplitude, or had superimposed spiking activity. Longitudinal muscle activity consisted of slow electrical oscillations at frequencies between 24 and 36 cycle/min with spiking activity superimposed on most oscillations. Contractions were related to bursts of such activity. These findings provide the electrophysiologic basis for short and prolonged phasic contractions and for sustained contractions of the human colon muscle layers. Activities in both muscle layers were myogenic in nature, were very sensitive to stretch, and could be initiated or modulated by nervous activity.

Colon↗

Ouabain receptor binding of hydroxyprogesterone derivatives.

1 A specific and sensitive radioreceptor assay ahs been devised which is based on high affinity, saturable binding of 9 nM [3H]-ouabain to the total particulate fraction isolated from dog heart. Ouabain and other cardiac glycosides, including the aglycones, were about equipotent in their ability to displace [3H]-ouabain from its receptor, the IC50s ranging from 10 to 30 nM. 2 The only other substances found to compete significantly in the assay were derivatives of hydroxyprogesterone having a 17 alpha-acetate substituent: chlormadinone acetate, megestrol acetate, cyproterone acetate and medroxyprogesterone acetate, with IC50s of 2, 7.4, 9 and 21 microM, respectively. Prednisolone-3,20-bisguanyl-hydrazone, reported to have inotropic activity, gave an IC50 of 6.4 microM. Cyproterone-17 alpha-OH was less active (IC50 90 microM) than cyproterone-17 alpha-acetate. 3 A large number of peptide and protein hormones, steroid hormones and their metabolites, amines, and drugs were inactive.

Animals↗

pH dependence of the cooperative interactions and conformation of tryptophan oxygenase.

Allosteric interactions in the cupro-heme enzyme tryptophan oxygenase (EC 1.13.11.11) of Pseudomonas acidovorans are shown to be pH-dependent. Increasing the assay pH from 6.0 to 8.0 progressively desensitizes the enzyme from both homotropic and heterotropic ligand interactions. This pH-dependent reversible transition has a pK of 6.2. Hill coefficients for the substrate L-tryptophan of 2.0 and 1.4 were measured at pH 6.0 and pH 7.0, respectively. In attempting to identify the enzymatic residue (or residues) responsible for these pH-dependent effects, the enzyme was observed to be irreversibly inactivated by photoinduced oxidation in the presence of the sensitizer, methylene blue. The photoinactivated enzyme showed a loss of one-half its Soret (405 nm) absorption which accompanied the loss of one-half its heme and histidine contents. This first order photoinduced inactivation was pH-dependent and corresponded to a requirement for a protonated species with a pK of 6.2. These results suggest that histidine residues may be involved in the catalytic function and in mediating cooperative interactions of tryptophan oxygenase. Absolute and difference sedimentation velocity analyses indicate that the molecule undergoes a conformational transition when the pH is decreased from pH 8.0 to pH 6.0. This conformational alteration, measured as a 3.9% increase in S20, w can be regarded as an equivalent decrease in the frictional coefficient. If, a more or less spherical shape to the molecule is assumed, then, the 3.9% decrease in the frictional coefficient between pH 8.0 and 6.0 corresponds to a 12% decrease in apparent hydrodynamic volume of the enzyme. Thus, protonation of an enzymatic moiety, possibly histidine, determines both the conformational and functional interactions between enzymatic sites.

Allosteric Regulation↗

Computer model of ventricular interaction during left ventricular circulatory support.

The authors used a computer model of the heart and circulation to test the hypothesis that anatomic ventricular interactions are responsible for the observed instances of right ventricular failure during use of a left ventricular assist device. The model predicts that left ventricular pressure-unloading with a LVAD, in the presence of isolated systolic interaction, results in impairment of RV function, whereas with isolated diastolic interaction, RV function is improved. Due to competition between these two interactions, there is a negligible overall effect of ventricular anatomic interactions in determining right ventricular function in the normal heart.

Computer Simulation↗

Effects of left ventricular pressure unloading during LVAD support on right ventricular contractility.

The effects of left ventricular pressure (LVP) unloading with a left ventricular assist device (LVAD) on right ventricular (RV) end-systolic pressure volume relationships were studied. A Thoratec (Berkeley, CA) LVAD was implanted in open chest anesthetized pigs via apical cannulation, and an electromagnetic flow probe and computer controlled pneumatic occluder were attached to the pulmonary artery. RV and left ventricular (LV) pressures were measured with Millar catheters, and changes in RV volume during ejection were determined by integrating the flow signal. As an index of contractility, RV maximal systolic elastance (Emax) was calculated as the slope of the end systolic, pressure volume relationship between an isovolumic beat and a series of transiently occluded beats at different times in the ejection phase. After an 83 +/- 15% decrease in LV pressure time integral during LVAD pumping, there were no significant changes in cardiac output, mean systemic arterial pressure, or in RV dP/dtmax. Most important, RV Emax during LVAD unloading (0.63 +/- 0.16 mmHg/ml) was unchanged from control (0.62 +/- 0.10 mmHg/ml). Therefore, in the normal intact porcine heart, the effective contractility of the right ventricle is not altered by significant LV pressure unloading produced with a LVAD.

Animals↗

Comparison of right ventricular and biventricular circulatory support in a porcine model of right heart failure.

The effects of right ventricular (RVAD) and biventricular assist devices (BVAD) in an acute porcine model of right heart ischemic failure produced by occluding the right coronary artery for 2 min (RCAO) were compared. Right and left ventricular pressures were measured with Millar transducers and respective septal-to-free wall dimensions (RVSFWD, LVSFWD) with ultrasonic crystals. RCAO alone resulted in significant right heart failure, marked by a 36 +/- 5% reduction in cardiac output (pulmonary artery flow) and a 54 +/- 16% reduction in RV stroke work. Isolated RVAD significantly improved the hemodynamic conditions by restoring pulmonary blood flow and left heart filling to control levels. RVAD also resulted in reduced RVSFWD to control levels and increased LVSFWD via a rightward septal shift due to right heart unloading. Biventricular support resulted in the same hemodynamic improvement, but estimated LV peak systolic wall stress was reduced by 65 +/- 15% compared with control, due to concomitant LV unloading and reductions in LVSFWD. Therefore, either right or biventricular devices are effective in treating RV failure. The advantage of biventricular support is that the left ventricle is also unloaded, thus allowing improved circulatory support with minimal LV wall stress.

Animals↗

Anatomic interaction between the right and left ventricles during univentricular and biventricular circulatory support.

Left heart unloading with a prosthetic ventricle has been shown to result in a leftward shift of the interventricular septum, changing the geometry and possibly the performance of the right heart. The effects of univentricular and biventricular support on septal shifting were compared. In 10 anesthetized pigs Thoratec left (LPV) and right prosthetic ventricles (RPV) were connected from the LV apex to the ascending aorta and the right atrium to the pulmonary artery, respectively. Each heart was instrumented with ultrasonic crystals for LV and RV free wall-to-septum dimensions, RV and LV pressures, and cardiac output (CO). LV and RV end-diastolic pressure and dimensions (EDD), and peak systolic pressures (PSP) and dimensions were analyzed on a computer under control conditions, and during EKG synchronized RPV, LPV, and biventricular (BPV) support. During LPV the septum shifted to the left, and during RPV it shifted to the right, with LVEDD and RVEDD changing in opposite directions under each condition. With BPV septal position changed in the same way as with LPV, although to a smaller degree. The amount of septal movement was linearly related to the change in transseptal gradient produced by the prosthetic ventricles. Each 10 mmHg decrease in left minus right transseptal pressure gradient resulted in a 22% reduction (r = 0.83) in LVEDD and a 27% increase (r = 0.87) in RVEDD at end-diastole, and a 2% reduction (r = 0.87) in LV dimensions and a 2% increase (r = 0.83) in RV dimensions at peak systole.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗