Pulsatile Behavior Research Articles

Preparation of Novel Cationic Copolymer Microspheres and Evaluation of Their Function by In Vitro and In Vivo tests as Ph-Sensitive Drug Carrier Systems

ABSTRACTNovel pH-sensitive copolymer microspheres containing methylacrylic acid and styrene cross-linking with divinylbenzene were synthesized by free radical polymerization. The microspheres that were formed were then characterized by Fourier-Transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), size analysis, and X-ray analysis. The copolymer microspheres showed pulsatile swelling behavior whenthe pH of the media changed. The pH-sensitive microspheres were loaded with diltiazem hydrochloride (DH). The release characteristics of the free drug and the drug-loaded microspheres were studied under both simulated gastric conditions and intestinal pH conditions. The in vivo evaluation of the pulsatile preparation was subsequently carried out using beagle dogs as experimental subjects. The results demonstrated that the drug release exhibited a pulsatile character both in vitro and in vivo.

Novel Dual-Stimuli-Responsive Polymers Derived from Ethylpyrrolidine

This paper describes the synthesis and characterization of the new stimuli-responsive polymer poly(N-ethylpyrrolidine methacrylate), PEPyM. The polymer exhibits a phase separation transition temperature in water at 15 °C, being also sensitive to pH changes. The phase transition temperature can be modulated up to 80 °C by copolymerizing EPyM with different amounts of N,N‘-dimethylacrylamide (DMA). EPyM was cross-linked with low amounts of bisacrylamide (B-Aam), and PEPyM gels were also sensitive to temperature and pH, showing a pulsatile behavior in response to both stimuli. The water sorption process (swelling kinetics) of the hydrogels at different temperature and pH was also studied in distilled water and in different buffer solutions.

Modified carrageenan. 4. Synthesis and swelling behavior of crosslinked κC‐g‐AMPS superabsorbent hydrogel with antisalt and pH‐responsiveness properties

AbstractTo synthesize a novel biopolymer‐based superabsorbent hydrogel, 2‐acrylamido‐2‐methylpropanesulfonic acid (AMPS) was grafted onto kappa‐carrageenan (κC) backbones. The graft copolymerization reaction was carried out in a homogeneous medium and in the presence of ammonium persulfate (APS) as an initiator, N,N,N′,N′‐tetramethyl ethylenediamine (TMEDA) as an accelerator, and N,N′‐methylene bisacrylamide (MBA) as a crosslinker. A proposed mechanism for κC‐g‐AMPS formation was suggested and the hydrogel structure was confirmed using FTIR spectroscopy. The affecting variables on swelling capacity, i.e., the initiator, the crosslinker, and the monomer concentration, as well as reaction temperature, were systematically optimized. The swelling measurements of the hydrogels were conducted in aqueous solutions of LiCl, NaCl, KCl, MgCl2, CaCl2, SrCl2, BaCl2, and AlCl3. Due to the high swelling capacity in salt solutions, the hydrogels may be referred to as antisalt superabsorbents. The swelling of superabsorbing hydrogels was measured in solutions with pH ranging 1 to 13. The κC‐g‐AMPS hydrogel exhibited a pH‐responsiveness character so that a swelling–deswelling pulsatile behavior was recorded at pH 2 and 8. The overall activation energy for the graft copolymerization reaction was found to be 14.6 kJ/mol. The swelling kinetics of the hydrogels was preliminarily investigated as well. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 255–263, 2005

Modified carrageenan. 2. Hydrolyzed crosslinked κ-carrageenan-g-PAAm as a novel smart superabsorbent hydrogel with low salt sensitivity

A novel pH-responsive superabsorbing hydrogel based on κ-carrageenan (κC) was prepared through polyacrylamide crosslinking grafting followed by alkaline hydrolysis. The hydrogel structure was confirmed using FT-IR spectroscopy. The hydrolysis conditions were systematically optimized to obtain a hydrogel with maximum swelling capacity. Thus, the reaction variables, including the hydrolysis time and temperature, concentration of sodium hydroxide, amount of hydrogel hydrolyzed and post-neutralization pH, were optimized. The swelling measurements of the hydrogels were conducted in 0.15 M aqueous solutions of LiCl, NaCl, KCl, CaCl2 and AlCl3. As observed for the hydrolyzed hydrogel (H-carragPAM), it was found that a 'charge screening' action of small cations and carboxylate anions affected the swelling in univalent salt solutions. In the case of the non-hydrolyzed hydrogel (carragPAM), however, a converse trend was observed. As a result, carragPAM and H-carragPAM superabsorbent hydrogels showed a maximum swelling of 45 and 135 g/g in LiCl and KCl solutions, respectively. Due to the high swelling capacity in salt solutions, the hydrogels may be referred to as anti-salt superabsrbents. The swelling of superabsorbing hydrogels was examined in buffer solutions with pH values ranging between 1 and 13. The H-carragPAM hydrogel exhibited a pH-responsie character so that a swelling-deswelling pulsatile behavior was recorded at pH 4 and 9. The swelling kinetics of H-carragPAM were preliminary investigated.

Experimental flow studies in an elastic Y-model

To determine the causes and history of atherosclerosis it is necessary to understand the hemodynamic parameters of blood circulation. Hemodynamic parameters play an important role in the formation of atherosclerotic plaques, especially near bends and bifurcations where the flow separates from the wall. Here the flow is laminar and non-axial with eddies, secondary flow, flow separation and stagnation points. Stenoses are found predominantly in flow separation areas. Therefore, it is important to separately study the following flow parameters: steady and pulsatile flow, wall elasticity and non-Newtonian flow behavior of blood. A simplified silicon elastic y-model simulating the human carotid artery was used for the analysis of these parameters. This model can be used for numerical studies as well. Flow was visualized at steady flow using dyes and at pulsatile flow with a photoelastic apparatus and a birefringent solution. The local axial velocity at steady and pulsatile flow was determined with a one-component Laser-Doppler-Anemometer (LDA). Pulsatile flow was generated by a piston membrane pump. A glycerin-water solution was used to simulate the Newtonian flow behavior of blood. A DMSO-Separan water solution was used to simulate the non-Newtonian flow behavior. Pulsatile flow creates higher and lower shear rates so called oscillating shear rate compare to steady flow depending on the velocity amplitude. The non-Newtonian fluid showed a markedly different flow behavior than the Newtonian fluid especially in areas of flow separation. Shear gradients were calculated from these velocity measurements using a bicubic spline interpolation. Shear stresses were calculated from these velocity shear gradients and the viscosity of the non-Newtonian fluid at these shear gradients. At special areas, high shear stresses > 10 Pa were found. The elasticity of the model wall also influences the flow behavior. The measurements showed that the characteristics of pulsatile flow and the elasticity of the model wall should be observed concomitantly. This paper presents the steady and pulsatile flow with a Newtonian and non-Newtonian fluid in an elastic model.

Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in heart failure.

The purpose of this study was to clarify whether the secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are pulsatile in patients with chronic heart failure (CHF), and whether the rhythmic oscillations for ANP and BNP are abnormal in patients with CHF. Several reports have shown that ANP and especially BNP are valuable indicators of the prognosis in CHF. Previously, a pulsatile secretion has been described for ANP and BNP in healthy humans and for ANP in CHF patients. More information about the secretion pattern of BNP in heart failure is necessary to increase the clinical usefulness of BNP in patients with CHF. Patients with left ventricular systolic dysfunction and CHF ( n =12) and controls ( n =12) were investigated. Plasma ANP and BNP levels were determined every 2 min during a 2-h period by radioimmunoassay and analysed for pulsatile behaviour by Fourier transformation. All patients and controls had significant rhythmic oscillations in plasma ANP levels, and 11 patients with CHF and 10 controls had significant rhythmic oscillations in plasma BNP levels. The amplitude of the main frequency was considerably higher in patients with CHF than in controls (ANP: CHF, 4.76 pmol/l; controls, 0.75 pmol/l; P <0.01. BNP: CHF, 3.24 pmol/l; controls, 0.23 pmol/l; P <0.001; all values are medians), but the main frequency did not differ significantly between the group with CHF and the control group for either ANP or BNP. Patients with CHF demonstrate pulsatile secretion of ANP and BNP with a much higher absolute amplitude, but with the same main frequency as healthy subjects.

Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in heart failure

The purpose of this study was to clarify whether the secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are pulsatile in patients with chronic heart failure (CHF), and whether the rhythmic oscillations for ANP and BNP are abnormal in patients with CHF. Several reports have shown that ANP and especially BNP are valuable indicators of the prognosis in CHF. Previously, a pulsatile secretion has been described for ANP and BNP in healthy humans and for ANP in CHF patients. More information about the secretion pattern of BNP in heart failure is necessary to increase the clinical usefulness of BNP in patients with CHF. Patients with left ventricular systolic dysfunction and CHF (n = 12) and controls (n = 12) were investigated. Plasma ANP and BNP levels were determined every 2min during a 2-h period by radioimmunoassay and analysed for pulsatile behaviour by Fourier transformation. All patients and controls had significant rhythmic oscillations in plasma ANP levels, and 11 patients with CHF and 10 controls had significant rhythmic oscillations in plasma BNP levels. The amplitude of the main frequency was considerably higher in patients with CHF than in controls (ANP: CHF, 4.76pmol/l; controls, 0.75pmol/l; P&lt;0.01. BNP: CHF, 3.24pmol/l; controls, 0.23pmol/l; P&lt;0.001; all values are medians), but the main frequency did not differ significantly between the group with CHF and the control group for either ANP or BNP. Patients with CHF demonstrate pulsatile secretion of ANP and BNP with a much higher absolute amplitude, but with the same main frequency as healthy subjects.

Lagrangian simulation of the unsteady near field dynamics of planar buoyant plumes

The unsteady dynamics of planar plumes is investigated numerically with particular emphasis on the pulsating instability characterizing the source (nozzle) near field. This instability manifests itself as the periodic shedding of vortical structures from the nozzle. The Lagrangian Transport Element Method is used to provide high resolution two-dimensional simulations of the unaveraged variable density flow. Comparison with experimental results verifies that the simulations capture the plume instantaneous behavior and reproduce the pulsation frequency. The latter is controlled by a Strouhal–Richardson number correlation which implies that the instability is inviscid in nature with a frequency that is mainly dependent on the gravitational acceleration and the nozzle width, f∼g/w. The presence of a horizontal wall surrounding the nozzle exit does not affect these results. Numerical results indicate that transition from nonpulsatile to pulsatile behavior obeys a Reynolds–Richardson number correlation of the form Re∼Ri−0.627 implying a balance between buoyant and viscous forces. Arguments based on vorticity dynamics trace the origin of the instability to the mechanism of vorticity generation by buoyancy. In the nonpulsatile flow, the circulation generated by buoyancy increases monotonically with height at a rate that is approximately constant. This arrangement can be altered via perturbations that create local circulation maxima and can lead to vortex formation. Once a first vortex pair is created, a subsequent pair precipitates via a mechanism that yields circulation maxima near the nozzle exit through the interaction of the local vorticity generation by buoyancy with the strain field induced by the preceding vortex pair. This mechanism is complex enough to suggest that simple theoretical models that predict the pulsation frequency are unlikely. It does help explain, however, the relative simplicity of the functionality of the frequency and its lack of sensitivity on a variety of boundary conditions and external parameters.

Forcing pulsatile behaviour in semiconductor lasers by periodic control

Abstract In this paper, we apply optimal control theory for the operation of a standard edge-emitter semiconductor laser so as to produce good quality pulsing output signals. This is achieved by using a sinusoidal injection current whose characteristics (frequency and amplitude) are suitably tuned. The performances obtained from this optimal control strategy are compared with those achievable with a novel self-pulsing device recently designed.

Pulsatile secretion of atrial natriuretic peptide and brain natriuretic peptide in healthy humans

Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are involved in sodium and water homoeostasis in healthy humans. The plasma concentrations of the natriuretic peptides can be used to differentiate between dyspnoea of cardiac and pulmonary origin, and the degree of elevation of the peptide levels in the plasma in heart failure is a measure of the severity of the disease. However, the patterns of secretion of ANP and BNP are not clear either in healthy humans or in patients. The purpose of the present study was to test the hypotheses that both ANP and BNP are secreted in pulses in healthy humans, and that this phenomenon can be revealed by determination of ANP and BNP in peripheral venous blood samples. In 12 healthy subjects, blood samples were drawn every 2 min through an intravenously inserted plastic needle over a period of 2 h. Plasma concentrations of ANP and BNP were determined by RIAs, and the results were analysed for pulsatile behaviour by Fourier transformation. Pulsatile secretion of ANP was seen in 10 out of 12 subjects [nu=0.028 min(-1) (median; range 0.013-0.047 min(-1)), i.e. a pulse of ANP with an interval of 36 min (range 21-77 min)]. Pulsatile secretion of BNP was seen in nine out of 12 patients [nu=0. 021 min(-1) (range 0.013-0.042 min(-1)), i.e. a pulse of BNP with an interval of 48 min (range 24-77 min)]. The main conclusion is that the secretion patterns of both ANP and BNP are pulsatile in most healthy humans. Consequently, it is important to study whether pulsatile secretion also occurs in heart failure in order to obtain the most informative predictive values both in the differential diagnosis of dyspnoea and in the evaluation of the severity of the disease.

Markov switching time series models with application to a daily runoff series

We consider a class of Bayesian dynamic models that involve switching among various regimes. As an example we produce a model for a runoff time series exhibiting pulsatile behavior. This model is a mixture of three autoregressive models which accommodate “rising,” “falling,” and “normal” states in the runoff process. The mechanism for switching among regimes is given by a three‐state Markov chain whose transition probabilities are modeled on the basis both of past runoff values and of a time series of rainfall data. We adopt the Bayesian approach and use the Gibbs sampler in the numerical analyses. A study of a daily runoff series from Lake Taupo, New Zealand, is given.

Pulmonary artery hemodynamics in primary pulmonary hypertension

Objectives. The present investigation compared and contrasted steady and pulsatile pulmonary hemodynamics at rest and during exercise in patients with primary pulmonary hypertension and normal control subjects.Background. A complete description of the relation between pressure and flow in the pulmonary circulation includes both steady and pulsatile hemodynamic behavior. Patients with primary pulmonary hypertension provide a unique opportunity to study the effects of primary alterations in pulmonary vasculature on pulmonary artery vascular hydraulic load.Methods. Catheter tip pressure and velocity recordings from the main pulmonary artery in 8 patients with primary pulmonary hypertension and 10 control subjects were used to derive the pulmonary artery input impedance spectrum and the extent of pulse wave reflection at rest and during exercise.Results. As expected, in patients with primary pulmonary hypertension, mean pulmonary artery pressure (50 ± 10 mm Hg) and pulmonary vascular resistance (880 ± 446 dynes·s·cm−5) were markedly elevated at rest and remained so during exercise (mean pressure 71 ± 15 mm Hg, mean resistance 750 ± 530 dynes·s·cm−5). Pulmonary artery characteristic impedance was elevated at rest and did not change with exercise (rest 55 ± 25 dynes·s·cm−5; exercise 66 ± 33 dynes·s·cm−5). Measures of arterial wave reflection indicated that the extent of wave reflection in the pulmonary bed in those with primary pulmonary hypertension is large at rest (reflection coefficient 0.89 ± 0.09) and that the composite reflected wave arrived during the midportion of right ventricular ejection. Although the extent of wave reflection decreased with exercise (reflection coefficient 0.81 ± 0.10, p < 0.05), the magnitude and timing of these reflections remained adverse. Furthermore, in patients with primary pulmonary hypertension, the stroke volume response to exercise was strongly related to rest levels of pulmonary artery diastolic pressure, pulmonary vascular resistance and the reflection factor, whereas no such relation was found in the control subjects.Conclusions. In addition to the expected abnormalities in steady measures of pulmonary artery hemodynamics at rest in patients with primary pulmonary hypertension, rest and exercise measures of oscillatory behavior (characteristic impedance and pulse wave reflection) are perturbed. Measures of steady and pulsatile behavior, particularly wave reflection, appear to have an important role in the exercise response of these patients.

A model for the control of testosterone secretion

We produce here a model to explain the control of testosterone secretion. In this model the hypothalamic secretion of the hormone LHRH (luteinizing hormone releasing hormone) is controlled by a combination of local testosterone concentration and of the local concentration of the pituitary hormone LH (luteinizing hormone). Since LHRH stimulates the release of LH, and LH in turn stimulates the release of testosterone, the three hormones constitute a three-component "feedback" network. We show how this model is able to account for the pulsatility of the release of these three hormones. Furthermore, the model is consistent with results obtained from a wide range of experimental manipulations of the system. For example, it accounts for the changes observed in hormone release patterns after castration. In particular, it follows that no "neural clock", or "neural pulse-generator", is required to force the system into pulsatile behaviour.

Isosorbide dinitrate and pulsatile arterial haemodynamic variables in hypertension.

The effect of a sustained-release oral isosorbide dinitrate (ISDN) preparation on cerebral and forearm circulation was determined in 16 patients with mild to moderate essential hypertension. Measurements were made by pulsed Doppler velocimetry in the common carotid and the brachial arteries. Pulse wave velocity of the forearm was simultaneously recorded by means of strain gauge arterial mechanography allowing non-invasive evaluation of compliance and characteristic impedance of the brachial artery. Four hours after ISDN ingestion, the patients exhibited a significant decrease in blood pressure without a change in heart rate. An increase in carotid and brachial artery diameter was shown whereas blood flow increased only in the forearm. Resistance decreased significantly in both carotid and brachial vascular beds but only in the brachial vascular bed was the baseline resistance directly correlated with the change in brachial bed resistance. Concerning pulsatile large artery parameters, pulse wave velocity and characteristic impedance diminished, and brachial artery compliance increased significantly. The tangential tension of carotid and brachial arteries did not change. An increase in plasma renin activity was observed and related to the vasodilating effect on small arteries of the brachial vascular bed. This study showed that the antihypertensive effects of ISDN were accompanied by a strong vasodilatory action on small and large arteries and by an improvement in the pulsatile behaviour of large arteries.

Estimation of time-varying systolic properties of left ventricular mechanics.

A simple model which represents a linear approximation of the pressurel volume/flow relationship extensively used for describing ventricular mechanics, especially in simulation studies, is developed. In this model, the left ventricle is represented by a pressure generator in series with viscous and elastic time-varying elements. Despite its simplicity, the model elucidates the intimate connections between some current approaches for characterising pulsatile ventricular behaviour. A conventional identification scheme was used to estimate viscous and elastic parameters from data measured in both isolated rabbit hearts and open-chest dogs. Their variations with preload and afterload are shown to reflect known local characteristics of the inherently nonlinear cardiac pump, which correspond also to relevant features at muscular level. These results, together with some recent experimental evidence, substantially support the finding that both viscosity and elastance vary with time in linear proportion to the isovolumic pressure.