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T M Griffith

Publications and source records attributed to T M Griffith.

At least 37 records · Page 2Linked to original sources
PubMed1999

Minimal model of arterial chaos generated by coupled intracellular and membrane Ca2+ oscillators.

We have developed a mathematical model of arterial vasomotion in which irregular rhythmic activity is generated by the nonlinear interaction of intracellular and membrane oscillators that depend on cyclic release of Ca2+ from internal stores and cyclic influx of extracellular Ca2+, respectively. Four key control variables were selected on the basis of the pharmacological characteristics of histamine-induced vasomotion in rabbit ear arteries: Ca2+ concentration in the cytosol, Ca2+ concentration in ryanodine-sensitive stores, cell membrane potential, and the open state probability of Ca2+-activated K+ channels. Although not represented by independent dynamic variables, the model also incorporates Na+/Ca2+ exchange, the Na+-K+-ATPase, Cl- fluxes, and Ca2+ efflux via the extrusion ATPase. Simulations reproduce a wide spectrum of experimental observations, including 1) the effects of interventions that modulate the functionality of Ca2+ stores and membrane ion channels, 2) paradoxes such as the apparently unpredictable dual action of Ca2+ antagonists and low extracellular Na+ concentration, which can abolish vasomotion or promote the appearance of large-amplitude oscillations, and 3) period-doubling, quasiperiodic, and intermittent routes to chaos. Nonlinearity is essential to explain these diverse patterns of experimental vascular response.

Animals↗
PubMed1999

Integration of non-linear cellular mechanisms regulating microvascular perfusion.

It is becoming increasingly evident that interactions between the different cell types present in the vessel wall and the physical forces that result from blood flow are highly complex. This short article will review evidence that irregular fluctuations in vascular resistance are generated by non-linearity in the control mechanisms intrinsic to the smooth muscle cell and can be classified as chaotic. Non-linear systems theory has provided insights into the mechanisms involved at the cellular level by allowing the identification of dominant control variables and the construction of one-dimensional iterative maps to model vascular dynamics. Experiments with novel peptide inhibitors of gap junctions have shown that the coordination of aggregate responses depends on direct intercellular communication. The sensitivity of chaotic trajectories to perturbation may nevertheless generate a high degree of variability in the response to pharmacological interventions and altered perfusion conditions.

Animals↗
PubMed1999

Reconstruction of blood flow patterns in human arteries.

Local haemodynamic factors in large arteries are associated with the pathophysiology of cardiovascular diseases such as atherosclerosis and strokes. In search of these factors and their correlation with atheroma formation, quantitative haemodynamic data in realistic arterial geometry become crucial. At present no in vivo non-invasive technique is available that can provide accurate measurement of three-dimensional blood velocities and shear stresses in curved and branching sites of vessels where atherosclerotic plaques are found frequently. This paper presents a computer modelling technique which combines state-of-the-art computational fluid dynamics (CFD) with new noninvasive magnetic resonance imaging techniques to provide the complete haemodynamic data in 'real' arterial geometries. Using magnetic resonance angiographic and velocity images acquired from the aortic bifurcation of a healthy human subject, CFD simulations have been carried out and the predicted flow patterns demonstrate the non-planar-type flow characteristics found in experimental studies.

Aorta, Abdominal↗
PubMed1998

Central role of heterocellular gap junctional communication in endothelium-dependent relaxations of rabbit arteries.

1. The contribution of gap junctions to endothelium-dependent relaxation was investigated in isolated rabbit conduit artery preparations pre-constricted by 10 microM phenylephrine (PhE). 2. Acetylcholine (ACh) relaxed the thoracic aorta by approximately 60 % and the superior mesenteric artery (SMA) by approximately 90 %. A peptide possessing sequence homology with extracellular loop 2 of connexin 43 (Gap 27, 300 microM) inhibited relaxation by approximately 40 % in both artery types. Gap 27 also attenuated the endothelium-dependent component of the relaxation induced by ATP in thoracic aorta but did not modify force development in response to PhE. 3. NG-nitro-L-arginine methyl ester (L-NAME, 300 microM), an inhibitor of NO synthase, attenuated ACh-induced relaxation by approximately 90 % in the aorta but only by approximately 40 % in SMA (P < 0.05). Residual L-NAME-insensitive relaxations were almost abolished by 300 microM Gap 27 in aorta and inhibited in a concentration-dependent fashion in SMA (approximately 50 % at 100 microM and approximately 80 % at 10 mM). Gap 27 similarly attenuated the endothelium-dependent component of L-NAME-insensitive relaxations to ATP in aorta. 4. Responses to cyclopiazonic acid, which stimulates endothelium-dependent relaxation through a receptor-independent mechanism, were also attenuated by Gap 27, whereas this peptide exerted no effect on the NO-mediated relaxation induced by sodium nitroprusside in preparations denuded of endothelium. 5. ACh-induced relaxation of 'sandwich' mounts of aorta or SMA were unaffected by Gap 27 but completely abolished by L-NAME. 6. We conclude that direct heterocellular communication between the endothelium and smooth muscle contributes to endothelium-dependent relaxations evoked by both receptor-dependent and -independent mechanisms. The inhibitory effects of Gap 27 peptide do not involve homocellular communication within the vessel wall or modulation of NO release or action.

Acetylcholine↗
PubMed1998

Magnetic resonance image processing and structured grid generation of a human abdominal bifurcation.

Magnetic resonance angiography (MRA) offers a non-invasive approach to the acquisition of anatomically accurate human arterial structure. Combining the latest computational fluid dynamics (CFD) techniques with clinical data from MRA, the detailed haemodynamics information in the human circulation system can be obtained. In this paper, a novel computer method is presented, which generates automatically a computational grid for a human abdominal bifurcation from a set of conventional MRA images. The method covers the complete sequence from MR image segmentation, 3-D model construction, grid generation, to grid quality evaluation. Results demonstrate that the computer program developed is capable of generating a good quality grid for human arterial bifurcations from MRA images with minimum user input. The resultant grid can be used directly for further computer simulation of the flow.

Abdomen↗
PubMed1998

Spatial heterogeneity in the mechanisms contributing to acetylcholine-induced dilatation in the rabbit isolated ear.

1. Using an X-ray microangiographic technique in rabbit isolated perfused ears preconstricted with 5-HT (300 nM) and histamine (300 nM), we investigated the combined actions of N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin on acetylcholine-induced depressor responses. 2. Under control conditions, acetylcholine (10 nM-30 microM) induced a concentration-dependent reversal of the pressor response, reaching a maximum of 66.0+/-13.6% (n = 6). In the presence of L-NAME (300 microM) and indomethacin (10 microM), this depressor action was reduced, reaching a maximum of 38.6+/-5.9% (n = 6). 3. The control response was associated with substantial vasodilatation in the central ear artery (G0), a smaller dilatory action on first generation branch arteries (G1) and no effect on second generation branch arteries (G2). In the presence of L-NAME and indomethacin, vasodilatation occurred in G2 with no effect in G0 or G1. 4. Two calcium-activated K+ channels blockers, charybdotoxin (ChTX; 10 nM) and penitrem A (100 nM), further inhibited, but did not abolish, the L-NAME- and indomethacin-resistant response to acetylcholine (10 nM-300 microM). Both agents abolished the vasodilatory action of acetylcholine in G2. 5. In conclusion, L-NAME and indomethacin induced a shift in acetylcholine-induced vasodilatation from G0 and G1 to G2. This is consistent with the suggestion that nitric oxide dominates in larger vessels whilst other mechanisms dominate in smaller vessels. The L-NAME- and indomethacin-resistant component was inhibited by ChTX and penitrem A, suggesting it is mediated, at least in part, by activation of K(Ca) channels and could therefore involve a hyperpolarising mediator such as endothelium-derived hyperpolarising factor.

Acetylcholine↗
PubMed1998

Inhibition of the gap junctional component of endothelium-dependent relaxations in rabbit iliac artery by 18-alpha glycyrrhetinic acid.

The gap junction inhibitor 18-alpha-glycyrrhetinic acid (alpha-GA, 100 microM) attenuated endothelium-dependent relaxations to acetylcholine and cyclopiazonic acid by approximately 20% in rings of pre-constricted rabbit iliac artery. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 300 microM) inhibited relaxations to both agents by approximately 65% and these were further attenuated by alpha-GA to < 10% of control. In endothelium-denuded preparations, relaxations to sodium nitroprusside were not affected by alpha-GA. Heterocellular gap junctional communication may therefore account for nitric oxide-independent relaxations evoked both by receptor-dependent and -independent mechanisms in rabbit iliac artery.

Acetylcholine↗
PubMed1998

Simplification of the quasiperiodic route to chaos in agonist-induced vasomotion by iterative circle maps.

We have shown that the patterns of vasomotion induced by histamine in isolated rabbit ear resistance arteries can be described in terms of iterative circle maps that model the dynamics of coupled nonlinear oscillators. Cyclopiazonic acid (CPA), an inhibitor of the sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase pump, consistently transformed chaotic behavior into characteristic periodic oscillations known as mixed-mode responses, which consist of mixtures of large- and small-amplitude excursions and represent frequency-locked states. Quasiperiodicity, which reflects the interaction of oscillators with incommensurate frequencies, was also observed, although in a smaller number of experiments. The patterns of mixed-mode complexes found at different CPA concentrations allowed the derivation of firing numbers, i.e., number of large oscillations/sum of number of small and large oscillations, and the sequences in which they emerged conformed to Farey arithmetic. Two-dimensional return maps derived by Poincaré section of phase space representations of the dynamics were used to compute the mean number of rotations per iteration on the circle, i.e., the winding number. Plots of winding number against firing number revealed a devil's staircase-type structure. Experiments with verapamil, a voltage-operated L-type Ca(2+)-channel antagonist, confirmed that influx of extracellular Ca2+ was essential to sustain chaos, quasiperiodicity, and mixed-mode responses. Nonlinear coupling between cytosolic and membrane events in rabbit ear arteries thus results in a self-organized dynamics that collapses to that predicted by the theory of simple circle maps.

Animals↗
PubMed1998

The combination of magnetic resonance angiography and computational fluid dynamics: a critical review.

Computational Fluid Dynamics (CFD) has proven to be a valuable technique in the study of blood flow in arteries because of its capability of obtaining quantitatively velocities and wall shear stress. However, the "bottleneck" problem limiting the application of CFD is the difficulty of constructing anatomically realistic arterial geometries. In this survey, an overview is presented of the progress over the last decade in the development of magnetic resonance angiography (MRA) techniques, medical image processing and CFD, as well as the combination of these techniques in hemodynamics research. It is demonstrated that with modern angiographic techniques such as MRA, noninvasive measurement of human angiograms becomes possible and practical. Together with digital medical image processing and analysis techniques, computational models can be constructed for the "real" human arteries without making any geometric assumptions. When allied with state-of-the-art CFD codes, velocity and wall shear stress distributions, as well as particle trajectories, can be determined in the arteries.

Animals↗
PubMed1997

Peptides homologous to extracellular loop motifs of connexin 43 reversibly abolish rhythmic contractile activity in rabbit arteries.

1. Phenylephrine (10 microM) evoked rises in tension in isolated rings of endothelium-denuded rabbit superior mesenteric artery. These increases consisted of a tonic component with superimposed rhythmic activity, the frequency of which generally remained constant over time but whose amplitude exhibited cycle-to-cycle variability. 2. The amplitude, but not the frequency, of the rhythmic activity was affected by a series of short peptides possessing sequence homology with extracellular loops 1 and 2 of connexin 43 (Cx43). Oscillatory behaviour was abolished at concentrations of 100-300 microM (IC50 of 20-30 microM), without change in average tone. No synergy was evident between peptides corresponding to the extracellular loops, and cytoplasmic loop peptides were biologically inactive. 3. The putative gap junction inhibitor heptanol mimicked the action of the extracellular loop peptides and abolished rhythmic activity at concentrations of 100-300 microM without effects on frequency. However, in marked contrast to the peptides, heptanol completely inhibited the contraction evoked by phenylephrine (IC50, 283 +/- 28 microM). 4. The presence of mRNA encoding Cx32, Cx40 and Cx43 was detected in the rabbit superior mesenteric artery by reverse transcriptase-polymerase chain reaction. Western blot analysis showed that Cx43 was the major connexin in the endothelium-denuded vessel wall. 5. We conclude that intercellular communication between vascular smooth muscle cells via gap junctions is essential for synchronized rhythmic activity in isolated arterial tissue, whereas tonic force development appears to be independent of cell-cell coupling. The molecular specificity of the peptide probes employed in the study suggests that the smooth muscle relaxant effects of heptanol may be non-specific and unrelated to inhibition of gap junctional communication.

Alcohols↗
PubMed1997

Differential actions of charybdotoxin on central and daughter branch arteries of the rabbit isolated ear.

1. By use of rabbit isolated perfused intact ears and isolated perfused segments of central and first generation daughter branch ear arteries, we investigated the actions of charybdotoxin (ChTX), a blocker of calcium-activated K+ channels (KCa channels), and N omega-nitro-L-arginine methyl ester (L-NAME) on pressure-flow and diameter-flow relationships. 2. ChTX (1 nM) induced an upwards shift in the pressure-flow curve in the rabbit intact isolated ear preconstricted with 5-hydroxytryptamine (5-HT; 100 nM) with subsequent administration of L-NAME (100 microM) inducing a further upwards shift. L-NAME itself induced an upwards shift in the pressure-flow curve, but subsequent administration of ChTX was without significant effect. 3. Microangiographic analysis revealed a tendency of ChTX (1 nM) to decrease vessel diameter in the central ear artery (G0) with little effect on the first two generations of daughter branch arteries (G1 and G2) in the intact ear. Subsequent addition of L-NAME (100 microM) did not significantly further decrease vessel diameter in G0, but did decrease vessel diameter in G1 and G2. L-NAME itself showed a tendency to decrease vessel diameter in G0, G1 and G2 vessels with subsequent addition of ChTX being without significant effect. 4. In an isolated G0 preparation which was preconstricted with 5-HT (100 nM), ChTX (1 nM) caused an upwards shift in the pressure-flow curve which was augmented by subsequent addition of L-NAME (100 microM). L-NAME (100 microM) itself caused an upwards shift in the pressure-flow curve but subsequent addition of ChTX (1 nM) had no significant effect. 5. In comparison, in an isolated G1 preparation which was preconstricted with 5-HT (100 nM), ChTX (1 nM) had no significant effect on the pressure-flow curve relative to control, but subsequent addition of L-NAME (100 microM) caused an upwards shift. L-NAME (100 microM) itself induced an upwards shift in the pressure-flow curve with subsequent addition of ChTX (1 nM) being without significant effect. 6. ChTX (10 pM-10 nM) caused a concentration-dependent increase in perfusion pressure in isolated G0 and G1 preparations at fixed flow rates of 2 ml min-1 and 0.5 ml min-1, respectively. These responses were enhanced in the presence of L-NAME (100 microM) in G1 but not G0 preparations. 7. We conclude that at 1 nM, ChTX exhibits differential actions on central and daughter branch arteries of the intact ear of the rabbit, which are also apparent in the corresponding arteries when studied in isolation. The action of 1 nM ChTX in G0 vessels may reflect inhibition of either the release or action of nitric oxide as it was blocked in the presence of L-NAME. At higher concentrations of ChTX, there would appear to be a direct constrictor effect on vascular smooth muscle which is apparent in both G0 and G1 vessels. This observed heterogeneity could reflect different distributions of KCa channels between central and daughter branch arteries at either the endothelial or smooth muscle levels, or both.

Animals↗
PubMed1997

Central role of intracellular calcium stores in acute flow- and agonist-evoked endothelial nitric oxide release.

1. We have used a cascade bioassay system and isolated arterial ring preparations to investigate the contribution of Ca2+ release from endothelial intracellular stores to nitric oxide (NO) production evoked by increases in shear stress and by acetylcholine in rabbit aorta. 2. Experiments were performed before and following incubation with either the endoplasmic reticulum Ca(2+)-ATPase inhibitors cyclopiazonic acid (CPA, 10 microM) and thapsigargin (TSG, 1 microM) or ryanodine (30, 100 microM) which binds to a specific endoplasmic reticulum Ca(2+)-release channel. 3. In cascade bioassay all three agents induced relaxations of the recipient ring (CPA, 24.4 +/- 3.8%; TSG, 51.5 +/- 10.6%; ryanodine, 17.4 +/- 1.6%) which were significantly attenuated by preincubation of the donor with 100 microM NG-nitro-L-arginine methyl ester (L-NAME). However, in isolated rings, only CPA and TSG induced L-NAME-sensitive relaxations (CPA 52.7 +/- 6.5%; TSG 61.3 +/- 7%). 4. Addition of superoxide dismutase (SOD) to the donor perfusate evoked relaxations of the recipient ring in cascade bioassay (13.3 +/- 1.4%, n = 22). Prior administration of SOD attenuated relaxations to TSG (23.2 +/- 3.8% n = 4) and ryanodine (1.7 +/- 0.8%, n = 4), and pre-incubation with TSG and ryanodine blunted SOD-induced responses (4 +/- 1.5%, n = 4 and 8.9 +/- 1.1%, n = 4, respectively). By contrast, no interaction was observed between the relaxations evoked by SOD and CPA. In isolated rings, SOD exerted no direct relaxant and did not modulate relaxations to CPA, TSG or ryanodine. 5. In cascade bioassay studies time-averaged shear stress was manipulated with dextran (1-4% w/v, 800000 MW) to increase perfusate viscosity. NO-dependent relaxation of the recipient ring induced by increased perfusate viscosity was significantly attenuated by CPA (P < 0.01; n = 6) and TSG (P < 0.05; n = 7), but not by ryanodine (n = 6). 6. Endothelium-dependent relaxations to acetylcholine (0.1-30 microM) in cascade bioassay and in isolated aortic ring preparations were markedly attenuated by pretreatment with CPA and TSG, but were unaffected by ryanodine. Ryanodine and CPA caused only a small attenuation of endothelium-independent relaxations to sodium nitroprusside (0.001-10 microM), whereas TSG had no effect. 7. We conclude that release of Ca2+ from CPA- and TSG-sensitive endothelial stores is necessary for NO release evoked by acute flow changes and agonists in rabbit abdominal aorta. Ca(2+)-induced Ca2+ release via the ryanodine-sensitive release channel plays no direct role in these responses. Free radical interactions may complicate the interpretation of findings in cascade bioassay compared with isolated ring preparations.

Acetylcholine↗
PubMed1997

Ca2+ sequestration as a determinant of chaos and mixed-mode dynamics in agonist-induced vasomotion.

We have investigated the contribution of smooth muscle Ca2+ stores to chaotic vasomotion in isolated rabbit ear resistance arteries. In preparations constricted by histamine, exposure to cyclopiazonic acid (CPA) and thapsigargin (TSG), which inhibit the Ca2+-adenosinetriphosphatase (ATPase) pump of the sarcoplasmic reticulum, first induced then abolished highly characteristic mixed-mode oscillatory behavior. The fractal dimension of the vasomotion, which reflects the minimum number of contributing dynamic variables, remained between 2 and 4 until the point at which oscillations disappeared completely. By contrast, ryanodine, which attenuates Ca2+-induced Ca2+ release, decreased the fractal dimension of the responses to <2 in a graded concentration-dependent fashion by selectively suppressing a slow subcomponent of the overall rhythmic activity. CPA-associated oscillations were insensitive to ryanodine but could be abolished by verapamil and modulated in an inhibitory or stimulatory fashion by charybdotoxin, which blocks Ca2+-activated K+ channels, and by ouabain, which blocks the Na+-K+-ATPase. We conclude that there is nonlinear cross talk between CPA/TSG-sensitive Ca2+ stores and a membrane oscillator that regulates Ca2+ influx and that the kinetics of Ca2+ uptake by the CPA/TSG-sensitive pool can be distinguished dynamically from the kinetics of Ca2+ release from its ryanodine-sensitive subcomponent.

Animals↗
PubMed1997

Entrained ion transport systems generate the membrane component of chaotic agonist-induced vasomotion.

We have analyzed the contribution of membrane ion transport systems to chaotic vasomotion induced by histamine in isolated rabbit ear resistance arteries. Dynamic complexity was monitored as a fractal correlation dimension that provides an estimate of the minimum number of control variables contributing to an irregular time series and generally took a value between 2 and 4. A distinct subcomponent of the overall oscillatory activity (frequency approximately 0.06 Hz) was selectively suppressed by blockade of Ca(2+)-activated K+ channels (KCa) with tetraethylammonium, Ca(2+)-activated Cl- channels with low extracellular Cl- concentration and niflumic acid, the Na(+)-K+ adenosine-triphosphatase (ATPase) with ouabain, and Na+/Ca2+ exchange with low-Na+ buffer. Each of these interventions caused a fall in average fractal dimension to a value < 2, whereas inhibition of voltage-dependent K+ channels with 4-aminopyridine or the Ca(2+)-ATPase extrusion pump with vanadate were without effect on the form and complexity of the vasomotion. There was no systematic correlation between the changes in fractal dimension induced by the various interventions and their effects on perfusion pressure. Our findings suggest that nonlinearity in the kinetics of multiple coupled ion transport systems leads to entrainment and the emergence of a composite membrane oscillator, thus accounting for the low fractal dimension of the vasomotion observed in these arteries.

Animals↗
PubMed1996

Mechanotransduction through the endothelial cytoskeleton: mediation of flow- but not agonist-induced EDRF release.

1. We have used a cascade bioassay system and isolated arterial ring preparations to investigate the contribution of the endothelial microfilament and microtubule cytoskeleton to EDRF release evoked by time-averaged shear stress and by acetylcholine in rabbit abdominal aorta. 2. Cytochalasin B (1 microM) and phalloidin (100 nM) were used to depolymerize and stabilize, respectively, F-actin microfilaments. Colchicine (500 nM) was used to inhibit tubulin dimerization and thus disrupt the microtubule network. Experiments were performed before or 1 h after administration of agents to the donor perfusate or organ bath. 3. In cascade bioassay studies, time-averaged shear stress was manipulated with dextran (1-4% w/v, 80,000 MW), to increase perfusate viscosity. EDRF release induced by increased perfusate viscosity was significantly (P < 0.01) attenuated by cytochalasin B, phalloidin and colchicine. 4. Endothelium-dependent relaxations to acetylcholine (0.01-30 microM) in cascade bioassay and in isolated aortic ring preparations were unaffected by pretreatment with any of these agents both in terms of their EC50 and maximal responses. Endothelium-independent relaxations to sodium nitroprusside (0.001-10 microM) were similarly unaffected. 5. We conclude that the endothelial F-actin microfilament and microtubule networks are involved in the mechanotransduction pathway for flow-evoked EDRF release in rabbit abdominal aorta. However, these cytoskeletal elements appear to play no role in acetylcholine-induced EDRF release in this tissue.

Acetylcholine↗
PubMed1996

Ionic mechanisms contributing to the vasorelaxant properties of iodinated contrast media: a comparison of iohexol and iodixanol in the rabbit isolated aorta.

1. We have used rings of rabbit thoracic aorta to investigate the vasorelaxant properties of two different classes of non-ionic iodinated radiographic contrast media (IRCM) and the mechanisms, underlying their mode of action. Iohexol (a triiodinated monomer) was compared with iodixanol (a hexaiodinated dimer). 2. Iohexol and iodixanol both relaxed phenylephrine (0.3 microM) constricted rabbit aorta in a concentration-dependent manner that did not depend on the presence of an intact endothelium. When expressed as a function of iodine concentration, iodixanol caused significantly less relaxation than iohexol. However, the extent of relaxation was similar for both IRCM when expressed on a molar basis. Furthermore, increasing the molarity of the buffer to comparable levels with mannitol evoked only a small (approximately 15%) relaxation of phenylephrine-induced tone. 3. Ouabain (10 microM) significantly inhibited both iohexol- and iodixanol-induced relaxations by approximately 30%. 5-(N-Ethyl-N-isopropyl)-amiloride (EIPA, 100 nM) significantly inhibited iohexol-induced relaxation to the same extent as ouabain, but did not alter the vasorelaxant effect of iodixanol. Co-incubation with ouabain and EIPA had an additive effect in the case of iohexol, increasing inhibition of relaxation to approximately 60%, whereas inhibition of iodixanol-induced relaxation by the combination of ouabain plus EIPA did not differ from that of ouabain alone. 4. Replacing NaCl with N-methyl-D-glucamine (NMDG) to lower extracellular [Na+] and thereby inhibit Na(+)-Ca2+ exchange, attenuated the relaxation evoked by iohexol or by iodixanol (by approximately 25%) in each case. 5. We conclude that iohexol- and iodixanol-induced vasorelaxation in rabbit aorta is mediated through a direct action on vascular smooth muscle that is not simply a consequence of altered osmolality. It involves modulation of the Na(+)-K+ ATPase and, in the case of iohexol, Na(+)-H+ exchange. Both agents also appear to modulate Na(+)-Ca2+ exchange, through direct and/or indirect mechanisms. This is the first study to show specific pharmacological differences between monomeric and dimeric contrast media in vascular smooth muscle.

Animals↗
PubMed1996

Prediction of arterial "burst" activity and transitions between chaotic attractors with a multilayer perceptron optimized by a new stopping criterion.

We have explored the potential of an artificial neural network to capture the dynamics of chaotic temporal fluctuations in arterial pressure and flow. Model generated signals that simulate this ubiquitous physiological phenomenon in both form and complexity were used to train a Multilayer Perceptron (MLP) after first locating the optimum time delay to unfold the attractor governing the dynamics. Prediction horizons were maximized with a new stopping criterion capable of continuously tracking the trajectories of the model system. Single-step predictions were consistently good throughout the study. Long-term predictions obtained by using the MLP as a signal generator were very successful when the number of hidden nodes was carefully chosen. Moreover, short- and long-term predictions could also be obtained even when the dynamics was nonstationary.

Algorithms↗