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C D Wagner

Publications and source records attributed to C D Wagner.

17 recordsLinked to original sources
PubMed1998

Chaos in the cardiovascular system: an update.

Rhythmic changes of blood pressure, heart rate, and other cardiovascular measures have drawn the attention of several investigators, since these oscillations can shed light onto the activity of the underlying control network. The overwhelming proportion of circulatory variations, however, are not linear, i.e., they do not consist of perfectly rhythmic components. Thus, these fluctuations are more adequately analysed by non-linear techniques, most of which are adopted from chaos theory. A spotlight issue of 'Cardiovascular Research' (Vol. 31, 1996), focused on chaos in the cardiovascular system. This current review outlines today's understanding of this field by presenting the major discoveries and developments which have taken place since then.

Blood Vessels↗
PubMed1998

Correlation integral of blood pressure as a marker for exercise intensities.

The purpose of this study was to test the hypothesis that the correlation integral technique detects altered regulation of cardiovascular function during graded treadmill exercise. Arterial blood pressure (BP) was measured via telemetry before and during graded treadmill exercise in Sprague-Dawley rats. During treadmill running at mild, moderate, and heavy exercise intensities, the slope of the correlation integrals (SCI) continuously increased from 5.45 +/- 0.17 to 7.12 +/- 0.18, 7.92 +/- 0.23, and 8.40 +/- 0.23, respectively. However, corresponding changes in pulse interval, blood pressure, and systolic blood pressure with increasing workload were not consistently observed. Low-frequency, midfrequency, and high-frequency powers of BP were not different between adjacent exercise grades; only the low-frequency component of pulse interval was different between resting state and mild exercise, and BP variance was significantly different between mild and moderate grades. Comparison of the SCI values with those obtained from surrogate data sets suggests that these differences originate mainly from nonlinear components in the cardiovascular control system. These findings support the hypothesis that SCI detects alterations in cardiovascular regulation associated with graded exercise. Furthermore, SCI may be superior to linear techniques in detecting altered regulation with changing exercise intensities.

Animals↗
PubMed1998

Blood pressure variability and urine flow in the conscious dog.

Pressure-dependent urine production is considered to be a major factor in long-term blood pressure control. The phenomenon has been well characterized for fixed levels of renal perfusion pressure (RPP), but the influence of physiological fluctuations in RPP and spontaneous variations in renal blood flow (RBF) on short-term urine flow (UV) remain unclear. To clarify this issue, we studied the interdependence of RPP, RBF, and UV in 13 conscious foxhounds during a single-step pressure reduction, under normal conditions, and with induced pressure changes. Reducing RPP in a single step to approximately 80 mmHg revealed short response times of RBF (0.4 +/- 0.1 s, n = 7) as well as of UV (8.1 +/- 0.8 s, n = 7). Under control conditions, UV was coupled with spontaneous variations of RBF (r = 0.94, P < 0.001), in contrast to RPP, which showed no significant correlation with UV (r = 0.09, P = NS). To discern the pressure and blood flow dependency of UV at a reduced RPP, we induced 0.9-mHz blood pressure oscillations (80 +/- 10 mmHg), which phase shifted RPP and RBF. Conversely, under these conditions, UV was dependent on RPP (r = 0.95, P < 0.001). These results suggest that spontaneous fluctuations in RBF around a normal baseline level lead to concomitant changes in urine production, in contrast to physiological short-term oscillations in RPP, which are not correlated to changes in UV. However, during induced oscillations of perfusion pressure, the blood flow dependence was no longer observed and UV was entirely pressure dependent.

Animals↗
PubMed1998

Ratio encoding combinatorial libraries with stable isotopes and their utility in pharmaceutical research.

Combinatorial libraries are an important tool for lead discovery in the pharmaceutical industry. Advances in high throughput screening coupled with combinatorial chemistry can significantly reduce the time to find lead compounds. A major difficulty in developing large combinatorial libraries is the ability to identify active compounds. This paper describes a rapid and sensitive encoding/decoding methodology that utilizes stable isotopes and mass spectrometry. The ability of mass spectrometry to precisely determine the intensity of isotopic abundances provides a unique encoding strategy employing synthetically generated ratios of stable isotopes in a compound as the code. The application of ratio encoding is demonstrated using peptoid and imidazole chemistries. Supporting data demonstrate that the incorporation of one or more stable isotopes using unique-predetermined ratios can encode chemical libraries. In addition, the presence of a unique isotopic pattern in a ligand can facilitate the pharmacokinetic analysis. Isotope incorporation into a compound and subsequently into its metabolites reliably distinguishes products from other molecules in the mass spectrum. This is illustrated by metabolic analyses of peptoid and imidazole compounds.

Amino Acid Sequence↗
PubMed1997

Endogenous nitric oxide buffers blood pressure variability between 0.2 and 0.6 Hz in the conscious rat.

Shear stress is a potent stimulus for the formation and release of nitric oxide (NO). It seems, therefore, possible that a short-term increase in arterial blood pressure (ABP), which leads to a concomitant rise in endothelial shear stress, enhances NO release. The latter elicits a relaxation of vascular smooth muscle cells that, in turn, counteracts the initial rise in blood pressure (BP). Thus this chain of events may constitute a negative feedback loop reducing BP variability (BPV). To test this hypothesis, BP-time series were determined via telemetry in freely moving conscious Sprague-Dawley rats. Because it was reported recently that NO effects on ABP are more pronounced in females, the experiments were performed on 2 groups consisting of 10 female and 11 male animals. This was done under control conditions and after fixing NO plasma levels via an intravenous bolus of 15 mg/kg body wt N(G)-nitro-L-arginine methyl ester together with a continuous infusion of nitroprusside (15 +/- 0.8 microg/min). This combined infusion maintained mean ABP and heart rate at physiological levels, thus avoiding as much as possible interferences with other reflexes, e.g., the baroreflex. To quantitate BPV, fast Fourier transforms of the BP-time series were determined. The absolute power in the frequency range below 1 Hz increased during fixed NO to approximately 350% vs. control animals (female control, 2.1 x 10(9) +/- 1.5 x 10(8) mmHg2 vs. fixed NO, 8.0 x 10(9) +/- 1.3 x 10(9) mmHg2, P < 0.005; male control, 3.4 x 10(9) +/- 4.6 x 10(8) mmHg2 vs. fixed NO, 8.3 x 10(9) +/- 2.0 x 10(9) mmHg2, P < 0.05). This was mainly caused by a substantial rise in the power ranging from 0.2 to 0.6 Hz, which increased roughly fourfold in both females and males. It is concluded that the NO system is a potent buffer of spontaneous BP oscillations in the freely moving rat. This system is most efficient in buffering frequencies within the range of 0.2-0.6 Hz and shows no gender-specific differences with respect to its BP buffering capacity.

Animals↗
PubMed1997

Very low frequency oscillations in arterial blood pressure after autonomic blockade in conscious dogs.

The aim of this study was to investigate spontaneous variability of arterial blood pressure in conscious foxhounds in the absence of direct sympathetic and parasympathetic influences. Autonomic blockade was achieved by administration of the ganglionic blocking agent hexamethonium (n = 7). In contrast to the control group (n = 7), marked oscillations with a cycle length of 100 s (0.01 Hz) were observed. The relationship of the power densities of the oscillation band (0.01 +/- 0.005 Hz) to the total power increased threefold (0.213 +/- 0.007 vs. 0.057 +/- 0.005; P < 0.01). The 0.01-Hz oscillations typically commenced after some delay. To test whether the absence of the mechanoreceptor afferents was responsible for these fluctuations, we investigated an additional group of foxhounds that were subjected to total baroreceptor and cardiopulmonary receptor denervation (n = 7). Neither in this protocol, nor in a group subjected to denervation and ganglionic blockade (n = 6), did we observe sustained oscillations in this frequency range. Since the oscillations were not seen after combined afferent (mechanoreceptor denervation) and efferent (ganglionic) blockade, central oscillators as a source of the oscillations can be ruled out. A simple model of a circulating pressoric factor may explain the fluctuations, provided that there is a time delay between the stimulus and the release or action of the factor. The findings suggest that a circulating factor accounts for the 0.01-Hz oscillations, which is dependent on intact pathways from the cardiac receptors or baroreceptors to the central nervous system. This hypothesis is put forward since cardiopulmonary and baroreceptor denervation blocked the oscillations seen after ganglionic blockade.

Animals↗
PubMed1996

Blood-pressure variability is buffered by nitric oxide.

The baroreflex constitutes the only hitherto known buffer of rapid blood pressure oscillations. In order to investigate the influence of nitric oxide (NO) and the sinoaortic and cardiopulmonary baroreflex pathways on the dynamic properties of blood pressure control, we determined the power spectra of 24-h blood pressure time series of conscious dogs. This was done in the intact state (n = 6), during blockade of NO synthesis via the false substrate NG-nitro-L-arginine ((L-NNA), 16.5 +/- 2 mg/kg body weight i.v., n = 5) and in animals devoid of baroreceptor reflexes (n = 5). After L-NNA, blood pressure (BP) increased by roughly 20 mmHg to 137 +/- 6 mmHg (P < 0.01), heart rate decreased from 97 +/- 6 to 68 +/- 3 beats/min (P < 0.01). The power of blood pressure variations within the frequency range 0.1-0.5 Hz was tripled by L-NNA (P < 0.05). By comparison total sinoaortic and cardiopulmonary denervation increased power of slower oscillations ( < 0.1 Hz) by a factor of 4.7 (P < 0.05). Thus, NO and the baroreceptor reflex both play an important role as physiological blood pressure buffers, NO for rapid (0.1-0.5 Hz) and the baroreflex for slower fluctuations ( < 0.1 Hz).

Animals↗
PubMed1996

Isotope or mass encoding of combinatorial libraries.

BACKGROUND: Combinatorial chemistry using solid-phase synthesis is a rapidly developing technology that can result in a significant reduction in the time required to find and optimize lead compounds. The application of this approach to traditional medicinal chemistry has led to the construction of libraries of small organic molecules on resin beads. A major difficulty in developing large combinatorial libraries is the lack of a facile encoding and decoding methodology to identify active compounds. RESULTS: Several encoding schemes are described which use the ability of mass spectrometry to ascertain isotopic distributions. Molecular tags are attached to resin beads in parallel or on the linker used for chemical library synthesis. The tags are encoded via a controlled ratio of a number of stable isotopes on the tagging molecules, and range from a single to a complex isotopic distribution. CONCLUSIONS: A novel coding scheme is described that is useful for the generation of large encoded combinatorial libraries. The code can be cleaved after assay and analyzed by mass spectrometry in an automated fashion. An important element of the combinatorial discovery process is the ability to extract the structure-activity relationship (SAR) information made available by library screening. The speed and sensitivity of the mass-encoding scheme has the potential to determine the full SAR for a given library.

Chemistry, Organic↗
PubMed1996

Chaos in blood pressure control.

A number of control mechanisms are comprised within blood pressure regulation, ranging from events on the cellular level up to circulating hormones. Despite their vast number, blood pressure fluctuations occur preferably within a certain range (under physiological conditions). A specific class of dynamic systems has been extensively studied over the past several years: nonlinear coupled systems, which often reveal a characteristic form of motion termed "chaos". The system is restricted to a certain range in phase space, but the motion is never periodic. The attractor the system moves on has a non-integer dimension. What all chaotic systems have in common is their sensitive dependence on initial conditions. The question arises as to whether blood pressure regulation can be explained by such models. Many efforts have been made to characterise heart rate variability and EEG dynamics by parameters of chaos theory (e.g., fractal dimensions and Lyapunov exponents). These method were successfully applied to dynamics observed in single organs, but very few studies have dealt with blood pressure dynamics. This mini-review first gives an overview on the history of blood pressure dynamics and the methods suitable to characterise the dynamics by means of tools derived from the field of nonlinear dynamics. Then applications to systemic blood pressure are discussed. After a short survey on heart rate variability, which is indirectly reflected in blood pressure variability, some dynamic aspects of resistance vessels are given. Intriguingly, systemic blood pressure reveals a change in fractal dimensions and Lyapunov exponents, when the major short-term control mechanism--the arterial baroreflex--is disrupted. Indeed it seems that cardiovascular time series can be described by tools from nonlinear dynamics [66]. These methods allow a novel description of some important aspects of biological systems. Both the linear and the nonlinear tools complement each other and can be useful in characterising the stability and complexity of blood pressure control.

Animals↗
PubMed1996

Family needs of chronic hemodialysis patients: a comparison of perceptions of nurses and families.

OBJECTIVE: The objectives of this study were to (a) determine the psychosocial needs of families of ESRD patients receiving hemodialysis as perceived by nurses and family members; and (b) compare the differences of perception of needs between these two groups. DESIGN: The Norris and Grove Questionnaire (1986) was modified for the hemodialysis population to a 33 statement inventory of psychosocial needs. SAMPLE/SETTING: The sample consisted of 10 family members and nine registered nurses. The setting was a Midwestern Veterans Administration Medical Center hemodialysis unit. METHODS: A telephone survey interview was used for 9 family members; one survey was returned by mail. The RNs returned completed questionnaires to the unit. RESULTS: The findings of this study revealed 6 need statements that were statistically significantly different (p < 0.05) between the two groups. All of these need statements were perceived to be more important by the family members than the nurses. CONCLUSIONS: In this study, family members and nurses differed in what they perceived as important family needs. Families identified at least two psychosocial needs--the need for information and the need for comfort as being very important.

Adult↗
PubMed1995

On the origin of low-frequency blood pressure variability in the conscious dog.

1. Baroreceptor denervation increases blood pressure variability below 0.1 Hz. This study was undertaken to determine to what extent these fluctuations originate from the central nervous system or from cardiovascular sources. 2. Blood pressure was recorded at a rate of 10 Hz for approximately 3.5 h in conscious, resting dogs. Power density spectra were calculated from all 2(17) points of each recording session and integrated between 0.0002 and 0.1 Hz. 3. Blockade of the afferent limb of the baroreceptor reflex by surgical denervation of sinoaortic and cardiopulmonary afferents (Den; n = 6) significantly increased integrated power more than sixfold compared with a control group (n = 11). 4. Impairment of the efferent limb in non-deafferented dogs by either alpha 1-adrenergic blockade with prazosin (Praz; n = 7) or ganglionic blockade with hexamethonium (Hex; n = 6) failed to raise variability. 5. Both prazosin (n = 6) and hexamethonium (n = 3) reduced the increased variability in denervated dogs. 6. In non-deafferented dogs receiving hexamethonium, elevation of mean blood pressure to the hypertensive level of the Den group, by a continuous infusion of noradrenaline (n = 4), did not change the variability. 7. It is concluded that in the absence of changes in posture, most of the increased blood pressure variability after baroreceptor denervation is derived from the central nervous system. 8. Direct comparison of power spectra of the Den (total variability) and Hex groups (variability derived from the cardiovascular system only) suggests that the central nervous system is also the prevalent source of low-frequency blood pressure variability in intact animals.

Animals↗
PubMed1995

Nonlinear chaotic dynamics of arterial blood pressure and renal blood flow.

To determine whether arterial pressure (AP) and renal blood flow (RBF) are nonlinear dynamic processes (chaotic), we measured resting AP and RBF over 4 h in six conscious dogs. A catheter was placed in the aorta, and transit-time flowmeters were positioned around the renal artery. The average AP was 102 +/- 3 mmHg, and the mean RBF was 318 +/- 42 ml/min. We applied four analytic procedures to test the nature of AP and RBF time series, i.e., to determine if these variables are controlled randomly, if they consist of periodic oscillations, or whether they are best characterized as nonlinear dynamic processes. To this end, a fast Fourier transform was performed to quantify the amount of distinct periodic oscillations and nonperiodic variability in the very low frequency domain (< 0.01 Hz). The power spectrum of AP and RBF revealed broad band noise with no distinct peaks, which is commonly referred to as "1/f noise." As a second procedure, time-delayed phase return maps were constructed, and as a third approach the correlation dimensions were estimated via the Grassberger-Procaccia algorithm. The correlation dimensions of RBF and AP were similar (RBF 3.3 +/- 0.37 vs. AP 3.6 +/- 0.23; P = 0.2). The fourth method determined sensitive dependence on initial conditions, a hallmark of nonlinear "chaotic" dynamics. We determined the maximal Lyapunov exponents and found them to be positive for AP (0.1 +/- 0.01) and for RBF (0.04 +/- 0.01) indicating that they both are nonlinear dynamic processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Complexity and "chaos" in blood pressure after baroreceptor denervation of conscious dogs.

To investigate how arterial baroreceptors affect the dynamic properties of short-term blood pressure control, we determined Lyapunov exponents and correlation dimensions of blood pressure. Two groups of conscious dogs were studied: a control group (n = 7) and a group subjected to total sinoaortic and cardiopulmonary baroreceptor denervation (n = 7). As a measure of variability, standard deviation was determined and power spectra were calculated. In the lower frequency range (f < 0.1 Hz) power density was inversely related to frequency in both groups, indicating "1/f noise." Estimating the correlation dimension via the Grassberger-Procaccia algorithm as a quantification of complexity revealed a decrease after baroreceptor denervation (1.74 +/- 0.2 vs. 3.05 +/- 0.23 control; P < 0.05). Determination of the largest Lyapunov exponents lambda 1, which indicates the sensitive dependence on initial conditions, a hallmark of chaos, also yielded a diminution after denervation (lambda 1 = 0.74 +/- 0.08 vs. 1.85 +/- 0.18, P < 0.01). The results were cross-checked with surrogate data statistics. The null hypothesis, that there is no nonlinear structure in arterial blood pressure time series, was rejected. This shows that after baroreceptor denervation, blood pressure control is less complex and less sensitive to initial conditions ("chaos"). In contrast, variability (standard deviation) is increased (22.2 +/- 3.1 denervation vs. 8.3 +/- 1.4 control; P < 0.05). It is concluded that under physiological conditions, arterial and cardiopulmonary baroreceptors reduce variability of blood pressure, however, at the cost of blood pressure being less predictable. Thus the regulation is more sensitive depending on initial conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1994

Two ranges in blood pressure power spectrum with different 1/f characteristics.

Most time series of biological systems contain a considerable amount of 1/f noise. This form of noise is characterized by fluctuations in which power steadily increases at lower frequencies. To determine the origin of 1/f noise, blood pressure (BP) was measured over 4 h in conscious foxhounds. The power spectrum of BP was obtained by fast Fourier analysis. After log-log transformation, the power spectrum (log power vs. log frequency) characteristically revealed a linear regression. Surprisingly, there were two 1/f ranges. The first 1/f region was located within a low-frequency range (< 10(-1.7) Hz; slope -0.9; r = -0.9). The second 1/f range was identified at 10(-1.4) to 10(-1) Hz (slope -1.2; r = -0.7). After baroreceptor denervation (n = 7), the steepness of both slopes increased significantly (P < 0.05 for lower 1/f range, P < 0.001 for higher 1/f range), and the difference in slopes was clearly greater (slope in lower range -1.2; r = 0.96 vs. -3.1, r = -0.92 in the higher range; P < 0.001). Neither alpha-receptor (n = 6) nor beta-receptor blockade (n = 4) considerably changed the slopes after denervation. However, autonomic blockade (n = 5) restored the slope in the low-frequency range (-0.9; r = -0.9). In conclusion, there are two independently modulated 1/f frequency ranges in BP time series. Baroreceptors especially attenuate 1/f noise in the higher frequency range.

Animals↗
PubMed1994

The blood pressure buffering capacity of nitric oxide by comparison to the baroreceptor reflex.

To compare the contribution of nitric oxide (NO) to the buffering of short-term and circadian fluctuations of arterial blood pressure with that of the baroreceptor reflex, conscious foxhounds were subjected to continuous 24-h blood pressure recordings. A pressure transducer was placed into the lumen of the abdominal aorta. Telemetry recordings were done under control conditions, following blockade of NO formation by intravenous bolus injection of NG-nitro-L-arginine (L-NNA; 16.5 +/- 2 mg/kg body wt) and after total sinoaortic and cardiopulmonary denervation in five dogs each. L-NNA produced a sustained elevation of mean arterial pressure (MAP; 137.2 +/- 6.4 mmHg vs. control, 112.9 +/- 3.7 mmHg). After denervation, no significant increase of MAP was found (113.5 +/- 4.1 mmHg), but the standard deviation of the MAP histogram was significantly greater (22.5 +/- 3.1 vs. 10.6 +/- 0.9 mmHg, P < 0.05). Sequential spectral analysis showed that total power between 0 and 0.5 Hz was elevated more than twofold after L-NNA (P < 0.05). This was due primarily to increased power in the range above 0.1 Hz. After denervation, total power increased about three-fold (P < 0.05), almost exclusively occurring below 0.04 Hz. Power in the range above 0.2 Hz was diminished, although not significantly. It is concluded that in the conscious dog, NO, as well as the baroreceptor reflex, is an effective blood pressure buffer. NO is most effective above 0.1 Hz, whereas the baroreceptors primarily buffer fluctuations slower than 0.04 Hz.

Animals↗