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PubMed1989

Characteristics of Doppler blood-velocity waveforms in a cardiovascular in vitro model. I. The model and the influence of pulse rate.

In order to study the indices describing the flow-velocity curves a cardiovascular in vitro model has been constructed. The model consists of two parts: (i) A heart simulator producing controllable cardiac output, pulse rate and pressure variations, (ii) a circulatory system made of elastic butyl rubber tubes with adjustable peripheral resistance bed. The flow-velocity curves were obtained by a Doppler velocity meter as a function of the pulse rate (PR) when pressure, volumetric flow, and peripheral resistances were constant. The four evaluated indices, pulsatility index (PI), peak velocity (Vpeak), rising slope (RS) and A/B ratio (A/B i.e. maximum/minimum velocity ratio) all showed significant correlation with pulse rate. PI, A/B and Vpeak showed a marked increased at low pulse rate and the inverse relation between these indices and pulse rate were best described by power functions, whereas RS was found to be inversely proportional to pulse rate. The results are in good agreement with the few existing clinical observations, and we suggest that the relations described are taken into consideration in the clinical interpretation of blood velocity indices.

Blood Circulation↗
PubMed2004

Associations between walking time, quadriceps muscle strength and cardiovascular capacity in patients with rheumatoid arthritis and ankylosing spondylitis.

The aim of this study was to examine whether there are any associations between walking time, quadriceps muscle strength and cardiovascular capacity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Thirty-one patients with RA and 26 patients with AS belonging to Steinbrocker's functional class I-II were examined. Cardiovascular capacity was calculated from the expired air during a bicycle test and quadriceps muscle strength by the peak torque from an isokinetic dynamometer test. Walking time was the time it took to walk a distance of 160 m on a flat floor and to climb up and down a staircase. In patients with RA, flat floor walking and stair climbing times correlated inversely with quadriceps muscle strength and cardiovascular capacity. Similar results were seen in patients with AS, although the association between cardiovascular capacity and stair-climbing time was not statistically significant. Multiple regression analysis was performed for all patients with quadriceps muscle strength and cardiovascular capacity applied as independent variables in two separate models. Cardiovascular capacity explained 32% and quadriceps muscle strength 21% of the variance in flat floor walking time. Quadriceps muscle strength, together with diagnosis and age, explained 38% of the variance in stair-climbing time, and cardiovascular capacity together with age and pain explained 36% of the variance. In conclusion, in spite of cardiovascular capacity and quadriceps muscle strength being associated with walking times, the findings suggest that they play only a modest role in explaining rapid walking on flat floor and in stairs.

Activities of Daily Living↗
PubMed1997

Cardiovascular regulation: a modelling approach.

A detailed analysis of autonomic cardiovascular control (ACVC) may provide a key to a better understanding of the mechanisms underlying postflight orthostatic hypotension. The central substrate of human ACVC is not directly accessible to measurements and observation in space research. Modelling--supporting inference and physiological reasoning--is a valuable tool to disclose its involvement We are currently determining the suitability of artificial neural networks (ANN's) as a model of the central substrate of ACVC. Having conducted a number of experiments with simulated tilt test data to clarify the choice of input coding and of architectural biases in network training we will now report on the approximation of data obtained from human subjects during preparation of the German MIR'97 and D-2 missions.

Adaptation, Physiological↗
PubMed2005

Bubble splitting in bifurcating tubes: a model study of cardiovascular gas emboli transport.

The transport of long gas bubbles, suspended in liquid, through symmetric bifurcations, is investigated experimentally and theoretically as a model of cardiovascular gas bubble transport in air embolism and gas embolotherapy. The relevant dimensionless parameters in the models match the corresponding values for arteries and arterioles. The effects of roll angle (the angle the plane of the bifurcation makes with the horizontal), capillary number (a dimensionless indicator of flow), and bubble volume (or length) on the splitting of bubbles as they pass through the bifurcation are examined. Splitting is observed to be more homogenous at higher capillary numbers and lower roll angles. It is shown that, at nonzero roll angles, there is a critical value of the capillary number below which the bubbles do not split and are transported entirely into the upper branch. The value of the critical capillary number increases with roll angle and parent tube diameter. A unique bubble motion is observed at the critical capillary number and for slightly slower flows: the bubble begins to split, the meniscus in the lower branch then moves backward, and finally the entire bubble enters the upper branch. These findings suggest that, in large vessels, emboli tend to be transported upward unless flow is unusually strong but that a more homogeneous distribution of emboli occurs in smaller vessels. This corresponds to previous observations that air emboli tend to lodge in the upper regions of the lungs and suggests that relatively uniform infarction of tumors by gas embolotherapy may be possible.

Animals↗
PubMed1981

Interactions among ventilation, the circulation, and the uptake and distribution of halothane--use of a hybrid computer multiple model: I. The basic model.

The authors describe an 18-compartment hybrid computer multiple model of the uptake and distribution of halothane. This model uses 88 equations and 124 parameter settings. Three submodels are incorporated into the basic model: 1) The mass transport of halothane is simulated on the digital portion of the hybrid computer. 2) A breath-by-breath pulmonary model with two compartments describes air pressure-flow relations in the airway system. 3) A beat-to-beat cardiovascular model with 15 compartments describes in detail blood pressure-flow relations. In addition, a baroreceptor-heart rate loop is included: an increase in arterial pressure causes a decrease in heart rate. The slope of the baroreceptor response is progressively decreased by halothane until at 2 per cent there is no response. The model of halothane uptake and distribution is separate from the blood and air pressure-flow models, but is, in effect, driven by them. Myocardial "contractility" (stroke volume) and certain regional vascular resistances can be affected by the concentration of halothane in one or any proportion of any combination of three compartments: arterial blood (arteriolar concentrations), cerebral gray matter, or myocardial. In turn, these factors significantly affect the uptake and distribution of halothane. The responses to three steady-state concentration, as well as to a step change in concentration from 0 to 2 per cent, were examined. Twenty-four outputs were recorded, including halothane concentrations in ten compartments; myocardial "contractility"; left and right ventricular and right atrial pressures; cardiac output; stroke volume, R-R interval; and blood flows in six regions. Two variables--alveolar concentration of halothane and arterial blood pressure--were recorded during a step change of 0 to 5 per cent. The model describes the appropriate steady-state and dynamic cardiovascular responses to halothane. It also demonstrates the complex interrelationships among caridac output, regional blood flow distribution, and the uptake and distribution of halothane. During step change in halothane concentration, most of the responses occur early, a phenomenon also seen in man and goats. Thus, the model is useful not only for representing organ and tissue halothane concentrations, but also for gaining new insights into cardiovascular alterations produced by rapidly changing concentrations of halothane and into the complex interactions between the circulation and the uptake and distribution of halothane.

Anesthesia, Inhalation↗
PubMed2000

General compartmental models of the cardiovascular system.

A systematic discussion on linear as well as non-linear compartmental models of the cardiovascular system and its various feedback mechanism is given. Most of the results are independent of explicit functional expressions. The topological structure of the model is essential for the response to a local change in peripheral resistance. Inclusion of Parallel paths versus serial paths gives qualitatively different response. Global asymptotic stability follows from the general theory.

Baroreflex↗
PubMed2005

A bond graph model of the cardiovascular system.

The study of the autonomic nervous system (ANS) function has shown to provide useful indicators for risk stratification and early detection on a variety of cardiovascular pathologies. However, data gathered during different tests of the ANS are difficult to analyse, mainly due to the complex mechanisms involved in the autonomic regulation of the cardiovascular system (CVS). Although model-based analysis of ANS data has been already proposed as a way to cope with this complexity, only a few models coupling the main elements involved have been presented in the literature. In this paper, a new model of the CVS, representing the ventricles, the circulatory system and the regulation of the CVS activity by the ANS, is presented. The models of the vascular system and the ventricular activity have been developed using the Bond Graph formalism, as it proposes a unified representation for all energetic domains, facilitating the integration of mechanic and hydraulic phenomena. In order to take into account the electro-mechanical behaviour of both ventricles, an electrophysiologic model of the cardiac action potential, represented by a set of ordinary differential equations, has been integrated. The short-term ANS regulation of heart rate, cardiac contractility and peripheral vasoconstriction is represented by means of continuous transfer functions. These models, represented in different continuous formalisms, are coupled by using a multi-formalism simulation library. Results are presented for two different autonomic tests, namely the Tilt Test and the Valsalva Manoeuvre, by comparing real and simulated signals.

Cardiovascular System↗
PubMed2003

Exercise assessment of transgenic models of human cardiovascular disease.

Exercise provides one of the most severe, yet physiological, stresses to the intact cardiovascular system and is a major determinant of the utilization of metabolic substrates. The adaptations to exercise are the result of a coordinated response of multiple organ systems, including cardiovascular, pulmonary, endocrine-metabolic, immunologic, and skeletal muscle. With the proliferation of genetically altered murine models of cardiovascular disease, the importance of developing methods of accurate physiological phenotyping is critical. There are numerous examples of transgenic models in which the baseline cardiovascular phenotype is unchanged or minimally changed from the wild type, only to become manifest during the stress of exercise testing. In this review, we cover the basics of the murine cardiovascular response to exercise and the importance of attending to strain differences, compare different exercise methodologies (constant workload treadmill, incremental workload treadmill, swimming) and hemodynamic monitoring systems, and examine the murine response to exercise conditioning. Several examples where exercise studies have contributed to the elucidation of cardiovascular phenotypes are reviewed: the beta-adrenergic receptor knockouts, phospholamban knockout, dystrophin knockout (mdx), and the mutant alpha-myosin heavy chain (R403Q) transgenic.

Animals↗
PubMed2005

A structural constitutive model for collagenous cardiovascular tissues incorporating the angular fiber distribution.

Accurate constitutive models are required to gain further insight into the mechanical behavior of cardiovascular tissues. In this study, a structural constitutive framework for cardiovascular tissues is introduced that accounts for the angular distribution of collagen fibers. To demonstrate its capabilities, the model is applied to study the biaxial behavior of the arterial wall and the aortic valve. The pressure-radius relationships of the arterial wall accurately describe experimentally observed sigma-shaped curves. In addition, the nonlinear and anisotropic mechanical properties of the aortic valve can be analyzed with the proposed model. We expect that the current model offers strong possibilities to further investigate the complex mechanical behavior of cardiovascular tissues, including their response to mechanical stimuli.

Algorithms↗
PubMed1981

[Mathematical modeling of human cardiovascular reactions under postural test and physical loading conditions].

The paper presents a mathematical model of the human cardiovascular system consisting of 34 compartments that represent arterial and venous subsystems of the systemic and pulmonary circulation, arterio-venous capillaries, right and left ventricles and atria of the heart. The model describes pulsating blood flows, changes in the pressures and volumes during a cardiac cycle in each compartment. The model has been used to study cardiovascular reactions to exercises and to determine efficiency of different compensatory reactions to postural tests.

Blood Circulation↗
PubMed2005

Endothelial progenitor cell therapy for atherosclerosis: the philosopher's stone for an aging population?

Much of the increased risk for atherosclerosis progression with age may be a result of age-related declines in the capacity of precursor cells to repair damage in the arterial endothelium. To estimate the impact of progenitor cell therapy for atherosclerosis on cardiovascular disease (CVD) mortality, life expectancy, and survival, as compared with the lifetime control of conventional risk factors, we modeled the health effects of bone marrow-derived endothelial progenitor cell therapy using data from the 1950 to 1996 follow-up of the Framingham Heart Study. To model cardiovascular disease mortality, we assumed that progenitor cell therapy was applied at age 30, with the effect assumed to be a 10-year delay in atherosclerosis progression. Age projections were constructed analytically using the stochastic process model for risk factor dynamics and mortality and microsimulation techniques. We considered three types of interventions: (i) keeping risk factors within selected limits to model current clinical recommendations; (ii) an age shift of 10 years to model the effects of progenitor cell therapy; and (iii) elimination of a competing risk (such as cancer). Our study suggests that progenitor cell therapy might increase life expectancy in the population as much as the complete elimination of cancer (in females, an additional 3.67 versus 3.37 years; in males, an additional 5.94 versus 2.86 years, respectively).

Adult↗
PubMed2000

Heart rate and blood pressure variability in normal subjects compared with data from beat-to-beat models developed from de Boer's model of the cardiovascular system.

The objective of this study was to assess the ability of de Boer's model of the cardiovascular system to reproduce the heart rate and blood pressure variability observed in a range of normal subjects, and to make modifications to improve its performance. ECG, blood pressure and chest wall movement were recorded from 12 normal human subjects during controlled breathing. For each beat, systolic pressure, diastolic pressure, arterial time constant and RR interval were extracted. RR interval and systolic pressure spectral power in low and high frequency bands and the baroreflex sensitivity index, alpha, were then determined. For each subject, mean values were input to the model and the beat-to-beat output compared with the actual data for that subject. Finally, the effects of reducing the influence of baroreflex on peripheral vascular resistance and of providing separate sympathetic and vagal baroreflex sensitivities were assessed. Simulations resulted in data which were qualitatively similar to those of each subject's recording. With the modifications, the log ratio of simulated to real data improved from 7.2 to 1.5 (p = 0.003) for low frequency RR, from 0.27 to 0.55 (p = 0.011) for high frequency RR and from 8.5 to 0.9 (p = 0.003) for low frequency systolic pressure. We conclude that de Boer's model reproduces many of the characteristics of heart rate and blood pressure variability, and our modifications to baroreflex sensitivities and the feedback effect on peripheral resistance resulted in significant improvements.

Adult↗
PubMed1998

Evaluation of dual-tip micromanometers during 21-day implantation in goats.

Investigative research efforts using a cardiovascular model required the determination of central circulatory haemodynamic and arterial system parameters for the evaluation of cardiovascular performance. These calculations required continuous beat-to-beat measurement of pressure within the four chambers of the heart and great vessels. Sensitivity and offset drift, longevity, and sources of error for eight 3F dual-tipped micromanometers were determined during 21 days of implantation in goats. Subjects were instrumented with pairs of chronically implanted fluid-filled access catheters in the left and right ventricles, through which dual-tipped (test) micromanometers were chronically inserted and single-tip (standard) micromanometers were acutely inserted. Acutely inserted sensors were calibrated daily and measured pressures were compared in vivo to the chronically inserted sensors. Comparison of the pre- and post-gain calibration of the chronically inserted sensors showed a mean sensitivity drift of 1.0 +/- 0.4% (99% confidence, n = 9 sensors) and mean offset drift of 5.0 +/- 1.5 mmHg (99% confidence, n = 9 sensors). Potential sources of error for these drifts were identified, and included measurement system inaccuracies, temperature drift, hydrostatic column gradients, and dynamic pressure changes. Based upon these findings, we determined that these micromanometers may be chronically inserted in high-pressure chambers for up to 17 days with an acceptable error, but should be limited to acute (hours) insertions in low-pressure applications.

Animals↗
PubMed1987

Tissue perfusion during normovolemic hemodilution investigated by a hydraulic model of the cardiovascular system.

Normovolemic hemodilution on a whole body basis is studied by means of a steady flow, hydraulic analogue simulation of the cardiovascular system, based on the Casson's model and current hemodynamic and rheological data. The vasculature is divided into serially connected compartments whose hydraulic resistance is characterized by the average diameter, length, number of vessels, and the corresponding rheological properties of blood formulated by Dintenfass (1971) and Lipowsky et al. (1980). This model computes the pressure distributions in all compartments, where the calculated venous pressure modulates the cardiac function according to the Starling mechanism for cardiac performance. The alterations of flow induced by the action of the heart are added to the effects due to changes in peripheral vascular resistance as a result of hematocrit variation. This model shows that when the response of heart to the changes of venous pressure is impaired, the maximum oxygen carrying capacity occurs at 40% hematocrit (H) where it is 1% higher than normal hematocrit (H = 44%). The normal cardiac response to the changes of venous pressure, causes the maximum oxygen carrying capacity to occur at 32% H where it is 12% greater than that at normal hematocrit. Mean arteriolar pressure and capillary pressure increase while venular pressure is slightly reduced during normovolemic hemodilution.

Blood Pressure↗
PubMed2005

Do angiotensin II receptor blockers increase the risk of myocardial infarction?

AIMS: The uncertainty surrounding safety of angiotensin receptor blockers (ARBs) increased after publication of experimental and clinical studies which suggested an excess risk of myocardial infarction (MI) in people treated with ARBs. METHODS AND RESULTS: We performed a meta-analysis of randomised clinical trials, which compared ARBs with either a placebo or active drugs different from ARBs. Overall, ARBs were not associated with an excess risk of MI [odds ratio (OR): 1.03 in a random-effect model and 1.02 in a fixed-effect model]. In pre-specified subgroup analyses, incidence of MI did not differ between ARBs and either placebo (OR: 0.96; 95% CI: 0.84-1.10) or angiotensin-converting enzyme (ACE)-Inhibitors (OR: 0.99; 95% CI: 0.91-1.07). Incidence of MI was slightly higher with ARBs than with drug classes different from ACE-Inhibitors (OR: 1.16; P=0.06 in a random-effect model and 0.017 in a fixed-effect model). Cardiovascular mortality did not differ between ARBs and drugs different from ARBs (OR: 1.00 in a random-effect model and 0.99 in a fixed-effect model) and it was slightly lesser with ARBs than with placebo (OR: 0.91; 95% CI: 0.83-0.99; P=0.042) in a pre-specified subgroup analysis. CONCLUSION: Our findings do not support the hypothesis that ARBs increase the risk of MI.

Angiotensin II Type 1 Receptor Blockers↗
PubMed1993

Gadolinium-ethoxybenzyl-DTPA, a new liver-directed magnetic resonance contrast agent. Absence of acute hepatotoxic, cardiovascular, or immunogenic effects.

RATIONALE AND OBJECTIVES: Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a recently introduced experimental magnetic resonance (MR) contrast agent for hepatic imaging. Although liver enhancement has been investigated in a number of animal models, tolerance evaluations of Gd-EOB-DTPA injection have been limited. METHODS: The authors investigated acute hepatotoxicity in an isolated perfused rat liver model, cardiovascular effects in the anesthetized rat, and potential immunogenicity of Gd-EOB-DTPA using detection of specific antibodies. RESULTS: Using perfused rat liver model, no significant deviation could be observed for functional parameters, liver enzymes, or potassium release, comparing Gd-EOB-DTPA to a control, but there was a significant choleresis (+250% bile flow). Hemodynamic effects of Gd-EOB-DTPA were observed after femoral bolus injection, but only with relatively high dosages (0.3-0.5 mmol/kg, 10-fold the likely clinical dose in humans). Experimental conditions, idealized for antibody induction, failed to cause an IgG immune response to Gd-EOB-DTPA in the intact rat. CONCLUSIONS: The results further support preliminary conclusions that Gd-EOB-DTPA is a well-tolerated MR contrast agent.

Animals↗
PubMed2004

Barosensitive neurons in the rat tractus solitarius and paratrigeminal nucleus: a new model for medullary, cardiovascular reflex regulation.

The nucleus of the solitary tract (NTS), a termination site for primary afferent fibers from baroreceptors and other peripheral cardiovascular receptors, contains blood pressure-sensitive neurons, some of which have rhythmic activity locked to the cardiac cycle, making them key components of the central pathway for cardiovascular regulation. The paratrigeminal nucleus (Pa5), a small collection of medullary neurons in the dorsal lateral spinal trigeminal tract, like the NTS, receives primary somatosensory inputs of glossopharyngeal, vagal, and other nerves. Recent studies show that the Pa5 has efferent connections to the rostroventrolateral reticular nucleus (RVL), NTS, and ambiguous nucleus, suggesting that its structure may play a role in the baroreceptor reflex modulation. In the present study, simultaneous recording from multiple single neurons in freely behaving rats challenged with i.v. phenylephrine administration, showed that 83% of NTS units and 72% of Pa5 units were baroreceptor sensitive. Whereas most of the baroreceptor-sensitive NTS and Pa5 neurons (86 and 61%, respectively) increased firing rate during the ascending phase of the pressor response, about 16% of Pa5 and NTS baroreceptor-sensitive neurons had a decreased firing rate. On one hand, the decrease in firing rate occurred during the ascending phase of the pressor response, indicating sensitivity to rapid changes in arterial pressure. On the other hand, the increases in neuron activity in the Pa5 or NTS occurred during the entire pressor response to phenylephrine. Cross-correlational analysis showed that 71% of Pa5 and 93% of NTS baroreceptor-activated neurons possessed phasic discharge patterns locked to the cardiac cycle. These findings suggest that the Pa5, like the NTS, acts as a terminal for primary afferents in the medullary-baroreflex or cardiorespiratory-reflex pathways.

Animals↗
PubMed2005

[Genetic analysis of 32 microsatellite loci in 13 families of Wuzhishan pig by multiplex PCR and gene scanning technique].

Wuzhishan pig is one of the rare and endangered breeds in china. They have the following characteristics such as :light body weight and small size, early sexually maturity, high meat quality and genetic identification with 6 approximately 8 pares litter size,body weight of born 0.3 approximately 0.4 kg, 15 approximately 16 kg at 6 month old, 35 kg at 2 years old, and so on. They may be used for laboratory utilization, comparative studies on human medical model, embryonic engineering, nutrition metabolism, sensitivity test on virus and bacteria, skin brut and tranfer, removing lipid, teeth and mouth cavity diseases, studies on cardiovascular model and evaluation of new medicine products. The polymorphisms of 32 microsatellites in 13 families of Wuzhishan pig in Hainan were Analysed. Number of alleles in each family was counted, mean heterozygosity and polymorphism Information content(PIC) were calculated. The results showed that number of alleles was 13.66, mean heterozygosity was 0.559 while polymorphism information content was 0.731. This revealed that genetic diversity is abundant in Wuzhishan pig in Hainan. These results have instructional significance for preserving breeds, selection and breeding, development and utilization of Wuzhishan pig in Hainan.

Alleles↗