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PubMed2000

Assessment of arterial and cardiopulmonary baroreflex gains from simultaneous recordings of spontaneous cardiovascular and respiratory variability.

OBJECTIVES: In usual models of cardiovascular regulation, arterial pressure drives RR interval through a simple baroreflex, and the influence of respiration is dismissed. We examined the applicability of a trivariate autoregressive model to obtain separate values of the gain of the arterial and non-arterial, i.e. cardiopulmonary, components of the lumped baroreflex, employing spontaneous RR interval, systolic arterial pressure and respiration variability. DESIGN: We studied 30 normal subjects (age 37 +/- 1 years), both at rest and during standing, a condition known to enhance sympathetic activity while reducing venous return. Electrocardiogram was obtained by telemetry, arterial pressure by Finapres and respiration with a piezoelectric respiratory belt Data were acquired with a PC and processed with an ad hoc Windows program. METHODS: We employed an additive and a linear multivariate approach to approximate overall gain of the arterial pressure-heart beat period baroreflex (alphalumped) and of its arterial (alphaart) and non-arterial, i.e. cardiopulmonary (alphacp), components, from continuous beat-by-beat series of RR interval, systolic arterial pressure variability and respiration, without using any non-physiological intervention. RESULTS: The overall baroreflex gain at rest (alphalumped = 23.7 +/- 3.4 ms/mmHg) was subdivided into arterial (alphaart = 5.2 +/- 1.0 ms/mmHg) and cardiopulmonary (alphacp = 18.5 +/- 3.2ms/mmHg) components. During active orthostatism, alphaluumped was diminished to 10.0 +/- 2.2 ms/ mmHg. In addition, standing selectively reduced alphacp to 4.8 +/- 1.3 ms/mmHg, while alphaart was not significantly changed. CONCLUSIONS: A trivariate autoregressive model, that considers explicitly the influence of respiration, can subdivide overall, lumped, arterial pressure-heart period baroreflex gain, into two separate components, alphaart and alphacp. Only the latter is reduced by active orthostatism.

Adult↗
PubMed1992

Effect of age on autonomic and cardiac responses in a rat stroke model.

The cardiovascular system and its responses change with increasing age. This has seldom been considered in experimental models of stroke, although most strokes occur in the elderly. We studied 57 male Wistar rats in three age groups: 47 to 70 days old (juvenile), 110 to 152 days old (young adult), and 186 to 245 days old (mature adult), each group being subdivided into experimental and sham operation groups. All rats underwent occlusion or sham occlusion of the left middle cerebral artery and monitoring of the mean arterial blood pressure, heart rate, sympathetic nerve activity, plasma catecholamine levels, and electrocardiogram. Eight of the 12 rats in the oldest group died within 6 hours of the middle cerebral artery occlusion; of these, the youngest was 186 days old. The mature adult rats that died before completion of the experiment showed the highest level of sympathetic nerve activity and the only significant increase in the QT interval of the electrocardiogram. Following middle cerebral artery occlusion, sympathetic nerve activity increased in the young adult rats but most strikingly in the mature adult rats that died before the end of the 6-hour experiments. Plasma norepinephrine levels were significantly elevated at 4 and 6 hours after middle cerebral artery occlusion in the oldest group and only at 6 hours in the juvenile rats. The results of this study are consistent with impaired sympathetic and cardiovascular regulation in the mature adult rat. High sympathetic activity may represent one mechanism leading to fatal cardiac arrhythmias. Age-related impairment of sympathetic regulation may contribute to the higher mortality seen among elderly patients with stroke.

Aging↗
PubMed1997

Promoting wellness by delaying age of cardiovascular disease onset: development of a model.

Studies promoting wellness and prevention of cardiovascular disease have primarily dealt with identifying risk factors rather than factors that influence the age at which the cardiovascular disease develops. The purpose of this study was to determine whether selected risk factors affect the age when cardiovascular disease develops. Using a nonexperimental design, all 800 subjects who developed cardiovascular disease were selected from the Framingham Heart Study. A structural equation model for age of cardiovascular disease development was tested. Gender, smoking, entry age, antihypertensive medication use, hemoglobin, body mass index, systolic blood pressure, and diastolic blood pressure were significant determinants of the age at which cardiovascular disease develops. The model accounted for 72% of the variance in age of cardiovascular disease development. The results of this study suggest that in assisting individuals to modify cardiovascular disease risk, cardiovascular nurses and other professionals must address smoking, body mass index, and blood pressure as a package to delay onset of cardiovascular disease symptoms.

Age Factors↗
PubMed2007

Gene therapy and stem cell therapy for cardiovascular diseases today: a model for translational research.

Clinical trials looking at ways to promote myocardial regeneration have reported that the administered therapies have either neutral effects or modest benefits of questionable impact. These somewhat disappointing results should emphasize the need for translational research, with bidirectional feedback between the basic research laboratory and the clinical arena. Such a translational pathway is illustrated by the quest to find an effective therapy for restenosis, which culminated in the development of sirolimus. At this point a move away from the bedside and a return to the bench seems necessary to better understand the mechanisms of action of progenitor cells and stimulating factors. Without such basic knowledge research might be prematurely discouraged and the opportunity to fully understand the true potential of cardiovascular regenerative therapy might be missed.

Cardiovascular Diseases↗
PubMed2005

Laguerre-model blind system identification: cardiovascular dynamics estimated from multiple peripheral circulatory signals.

This paper presents a method for comparing multiple circulatory waveforms measured at different locations to improve cardiovascular parameter estimation from these signals. The method identifies the distinct vascular dynamics that shape each waveform signal, and estimates the common cardiac flow input shared by them. This signal-processing algorithm uses the Laguerre function series expansion for modeling the hemodynamics of each arterial branch, and identifies unknown parameters in these models from peripheral waveforms using multichannel blind system identification. An effective technique for determining the Laguerre base pole is developed, so that the Laguerre expansion captures and quickly converges to the intrinsic arterial dynamics observed in the two circulatory signals. Furthermore, a novel deconvolution method is developed in order to stably invert the identified dynamic models for estimating the cardiac output (CO) waveform from peripheral pressure waveforms. The method is applied to experimental swine data. A mean error of less than 5% with the measured peripheral pressure waveforms has been achieved using the models and excellent agreement between the estimated CO waveforms and the gold standard measurements have been obtained.

Algorithms↗
PubMed1993

Mathematical modelling of the human cardiovascular system in the presence of stenosis.

This paper reports a theoretical study on the distribution of blood flow in the human cardiovascular system when one or more blood vessels are affected by stenosis. The analysis employs a mathematical model of the entire system based on the finite element method. The arterial-venous network is represented by a large number of interconnected segments in the model. Values for the model parameters are based upon the published data on the physiological and rheological properties of blood. Computational results show how blood flow through various parts of the cardiovascular system is affected by stenosis in different blood vessels. No significant changes in the flow parameters of the cardiovascular system were found to occur when the reduction in the lumen diameter of the stenosed vessels was less than 65%.

Blood Circulation↗
PubMed2004

A thermal analogy for modelling drug elution from cardiovascular stents.

Restriction of blood flow by the narrowing or occlusion of arteries is one of the most common presentations of cardiovascular disease. One treatment involves the introduction of a metal scaffold, or stent, designed to prevent recoil and to provide structural stability to the vessel. On the occasions that this treatment is ineffective, failure is usually associated with re-invasion of tissue. This can be prevented by local delivery of drugs which inhibit tissue growth. The drug might be delivered locally in a polymer coating on the stent. This paper develops and explores the use of a thermal analogue of the drug delivery process and the associated three-dimensional convection-diffusion equation to model the spatial and temporal distribution of drug concentration within the vessel wall. This allows the routine use of commercial finite element analysis software to investigate the dynamics of drug distribution, assist in the understanding of the treatment process and develop improved delivery systems. Two applications illustrate how the model might be used to investigate the effects of controllable or measurable parameters on the progression of the process. It is demonstrated that the geometric characteristics of the stent can have significant impact on the homogeneity of the dosing in the vessel wall.

Animals↗
PubMedDate not supplied

Model-based estimation of cardiovascular repolarization features: ischaemia detection and PTCA monitoring.

The ST-T segment of the surface ECG reflects cardiac repolarization, and is quite sensitive to a number of pathological conditions, particularly ischaemia. ST-T changes generally affect the entire waveshape, and are inadequately characterized by single features such as depression of the ST segment at one particular point. Metrics which represent overall waveshape should provide more sensitive indicators of ST-T wave abnormalities, particularly when they are subtle, intermittent or periodic. This study discusses a Karhunen-Loève transform (KLT) technique for the analysis of the ST-T waveform. The KL technique was used to analyse the ST-T complexes in the ESC ST-T database. KL coefficients were plotted as a function of time, and were effective in detection of transient ischaemic episodes. Twenty per cent of the records showed bursts of periodic ischaemia suggesting local vascular instability. A comparison between kl and ST depression series has shown the KL technique as more appropriate to the study of ST-T complex variations. Using the kl series, an ischaemia detector has been developed based on a resampled, filtered, and differentiated KL series. This technique demonstrates a sensitivity of 65% and a specificity of 54%. These low values can be due to shifts of the electrical axis which are detected as ischaemic changes, real ischaemic episodes that were not annotated with the protocol used at the European ST-T database, or erroneous detections. An increase in sensitivity can be obtained at the expense of a decrease in the positive predictive value and thus becomes a useful technique for previous scanning of the ECG record and subsequent review by the expert. The technique has also been used to monitor patients during a PTCA process, demonstrating that this technique allows us to monitor PTCA-induced ischaemia. A detailed analysis has shown that in some cases a repetitive oscillatory behaviour appears, lasting for a period of around 20 s, and highly related to the oscillatory behaviour of the HR. In other cases, transient changes in KL series with salves behaviour associated with the injection of contrast are shown on the ST-T waveform. We conclude that the KL-based analysis of the ST-T segment is a robust and sensitive technique, with considerable advantages over single feature measures in characterizing the subtle waveform changes which may be of importance in clinical risk detection.

Angioplasty, Balloon, Coronary↗
PubMed1995

[A transgenic animal model: new possibilities for cardiovascular research].

By means of molecular biology and genetic research the influence of genetic factors on a great variety of human diseases could be shown. In the field of cardiovascular research the genetic defects of a few monogenetic disorders, such as Marfan's syndrome and hypertrophic cardiomyopathy, have been characterized. In addition, candidate genes for polygenetic diseases, such as arterial hypertension and atherosclerosis, have been cloned. However, the identification of a candidate gene or its mutation does not prove its influence on the phenotype or the final cause of a particular disease. Only a targeted manipulation of a defined candidate gene in a transgenic animal model helps to understand the role of the gene and its product in the whole organism. Transgenic experiments can be divided into gene-addition and gene-deletion models. In a gene-addition experiment a fusiongene is microinjected into a fertilized oocyte. The fusiongene itself consists at least of a regulatory element promoter and of a DNA sequence coding for the gene product (protein) of intended overproduction. The choice of the right promoter is important for obtaining tissue-specific gene expression. The cardiac myosin light chain-2 promoter for example leads to a ventricle-specific gene expression in cardiomyocytes from early embryogenesis through adulthood. In a gene-deletion experiment on the other hand, the target gene is selectively knocked out by homologous recombination in embryonic stem (ES) cells. The selected ES-cells are then injected into blastocysts. If the ES-cells are integrated into the germ line and transmitted to the progeny, a transgenic line is established. This review article describes planning and development of transgenic animals and discusses established transgenic animal model systems with regard to cardiovascular physiology. In addition, animal models which may provide a basis for future gene therapy will be introduced.

Animals↗
PubMed1999

Model based classification of cardiovascular response patterns.

A comprehensive analysis of cardiovascular control (CVC) patterns with multiple subjects is presented. It became feasible by recent methodological advances. Simple computer models were generated automatically, reproducing only factors of the true model that are relevant to the focus if investigation. These models--named aspect-models--could in turn be used in model individualization, thus reducing the necessary computational amount. The achieved speedup by a factor of more than three thousand and the high numerical stability of the resulting method allows the unsupervised identification of a large body of experimental data. The analysis of tilt table experiments of 18 subjects revealed a remarkable variety of reaction patterns. Closer examination yielded different classes of subjects. Two main groups corresponding to basic types of CVC were observed. Three outliers could be assigned to the specific situation of some subjects.

Adult↗
PubMed2006

Similar support for three different life course socioeconomic models on predicting premature cardiovascular mortality and all-cause mortality.

BACKGROUND: There are at least three broad conceptual models for the impact of the social environment on adult disease: the critical period, social mobility, and cumulative life course models. Several studies have shown an association between each of these models and mortality. However, few studies have investigated the importance of the different models within the same setting and none has been performed in samples of the whole population. The purpose of the present study was to study the relation between socioeconomic position (SEP) and mortality using different conceptual models in the whole population of Scania. METHODS: In the present investigation we use socioeconomic information on all men (N = 48,909) and women (N = 47,688) born between 1945 and 1950, alive on January, 1st,1990, and living in the Region of Scania, in Sweden. Focusing on three specific life periods (i.e., ages 10-15, 30-35 and 40-45), we examined the association between SEP and the 12-year risk of premature cardiovascular mortality and all-cause mortality. RESULTS: There was a strong relation between SEP and mortality among those inside the workforce, irrespective of the conceptual model used. There was a clear upward trend in the mortality hazard rate ratios (HRR) with accumulated exposure to manual SEP in both men (p for trend < 0.001 for both cardiovascular and all-cause mortality) and women (p for trend = 0.01 for cardiovascular mortality) and (p for trend = 0.003 for all-cause mortality). Inter- and intragenerational downward social mobility was associated with an increased mortality risk. When applying similar conceptual models based on workforce participation, it was shown that mortality was affected by the accumulated exposure to being outside the workforce. CONCLUSION: There was a strong relation between SEP and cardiovascular and all-cause mortality, irrespective of the conceptual model used. The critical period, social mobility, and cumulative life course models, showed the same fit to the data. That is, one model could not be pointed out as "the best" model and even in this large unselected sample it was not possible to adjudicate which theories best describe the links between life course SEP and mortality risk.

Adolescent↗
PubMed1994

Hydrodynamic simulation of arterial networks which include compliant and rigid bypass grafts.

The conditions required to produce an ideal bypass graft have not yet been determined. In order to understand the hemodynamic impact of bypass grafts on cardiovascular function, a hydrodynamic model for the part of the human arterial network below the renal arteries has been constructed. The results from this physical model were used to validate a digital computer model of the arterial network developed by the authors, that incorporated loops which occur due to bypass grafts. The hydrodynamic model was designed to study the interaction between an arterial stenosis and bypass graft and, in particular, the effect of the compliance of the graft on their function. In the model, similarity laws have been maintained with regard to geometry, viscosity, peripheral resistance, wall elastic properties, pulse shape, and blood flow rate. Measured and predicted pressure and flow wave-forms showed an increase in their mean and peak values for the healthy leg when the bypass graft was closed. There was also a severe pressure drop across the stenosis and a marked decrease in mean and pulsatile flow in the stenotic leg. The stenosis in the hydrodynamic model produced similar behaviour to published results obtained on animals. When the graft was open, the agreement between our experimental and theoretical model was within 5% and both the pressure and flow waves were almost similar at the maxima and minima in both legs. Although the arterial system is non-linear, the non-linearities are shown to be of insignificant magnitude and therefore, we have concluded that the pressure flow relationship is essentially linear. The effect of the degree of compliance of the graft and the 'steal' phenomenon due to the graft have been investigated. It was found that there were no significant differences in the flow delivery between the compliant graft and stiff graft. Also, there was no 'steal'. Thus the compliance of the graft is not a significant factor in promoting its patency.

Arteries↗
PubMedDate not supplied

Energetic parameter changes with mechanical ventilation in conjunction with BVAD assistance.

The aim was to assess the influence of a biventricular assist device (BVAD) on ventricular energetics parameters (external work, oxygen consumption, cardiac mechanical efficiency) for both ventricles, when mechanical ventilation was applied. The experiments were performed using a computer simulator of cardiovascular system (CARDIOSIM) after modelling a pathological state of the left ventricle (E(v)Left = 0. 9 mmHg cm(-3) and increasing pulmonary resistance (Rap = 0.3 mmHg cm(-3 s). The effect of mechanical ventilation was mean intrathoracic pressure changes from 0 to +5 mmHg. This simulation showed that application of BVAD for both ventricles reduces external work and that this effect is stressed by positive intrathoracic pressure, reduces cardiac mechanical efficiency that is quite insensitive to intrathoracic pressure and increases oxygen consumption, which is reduced by positive intrathoracic pressure. The increase of potential energy at the onset of BVAD evidences a rightwards shift of ventricular work cycle (unloading of the ventricles). In general, positive intrathoracic pressure during BVAD assistance adversely affects ventricular energetics.

Biomedical Engineering↗
PubMed1998

Combined oral contraceptives, smoking, and cardiovascular risk.

STUDY OBJECTIVE: To assess age specific incidence and mortality of stroke, acute myocardial infarction (AMI), and idiopathic venous thromboembolism (VTE) associated with use of modern low dose combined oral contraceptives (OCs) and the interaction with smoking. DESIGN: Hospital-based case-control study. SETTING: Hospitals in Oxford region in the United Kingdom, which covered a defined population, during the period 1989-1993. METHODS: Relative risk estimates from the WHO Collaborative Study and observed incidence rates from the Oxford region were used to estimate age specific incidence of each disease among women without cardiovascular risk factors and model total cardiovascular incidence and mortality. RESULTS: Among women who did not use OCs, smoke nor had any other cardiovascular risk factors, total incidence of stroke and AMI were less than 2 events per 100,000 woman years in those aged 20-24 years and rose exponentially with age to 8 events per 100,000 among women aged 40-44 years. Incidence of idiopathic VTE among women who did not use OCs rose linearly with age (from 3.3 per 100,000 at ages 20-24 years to 5.8 per 100,000 at ages 40-44 years). The increased risk of idiopathic VTE associated with OC use among non-smokers constituted over 90% of all cardiovascular events for women aged 20-24 years and more than 60% in those aged 40-44 years. Fatal cardiovascular events were dominated by haemorrhagic stroke and AMI, and among OC users who smoked these two diseases accounted for 80% of cardiovascular deaths among women aged 20-24 years, rising to 97% among those aged 40-44 years. Cardiovascular mortality associated with smoking was greater than that associated with OC use at all ages. Attributable risk associated with OC use was 1 death per 370,000 users annually among women aged 20-24 years, 1 per 170,000 at ages 30-34 years, and 1 per 37,000 at ages 40-44 years. Among smokers, the cardiovascular mortality attributable to OC use was estimated to be about 1 per 100,000 users annually among women aged less than 35 years, and about 1 per 10,000 users annually among those above the age of 35 years. CONCLUSION: The incidence of fatal cardiovascular events among women aged less than 35 years is low. The VTE risk associated with OC use is the largest contributor to OC induced adverse effects. The potentially avoidable excess VTE risk associated with the newer progestogens desogestrel and gestodene would account for a substantial proportion of total cardiovascular morbidity in this age group. For women over age 35 years the absolute risks associated with OC use and smoking are greater because of the steeply rising incidence of arterial diseases. The combination of smoking and OC use among such women is associated with particularly increased risks. Any potential reduction in AMI or stroke risk with use of third generation OCs would be a more important consideration among older compared with younger women, particularly if they smoke. However, the mortality associated with smoking is far greater than that associated with OC use (of any type) at all ages.

Adult↗
PubMed2005

Noninvasive assessment of vascular function.

Impaired arterial compliance contributing to increased blood pressure and cardiac workload is well accepted as a major factor in cardiovascular disease. Information on local arterial compliance is obtained when analyzing the deformation of selected arterial segments under stress. A more global measure of arterial compliance is obtained by analyzing the arterial pulse by so-called pulse wave analysis. The arterial pulse, even when measured locally, carries characteristic information from the whole arterial system because of reflection of waves at distinct sites of the arterial system. Pulse wave velocity and the transfer function for pulse transmission is obtained from the combined measurement of arterial pulses at proximal and distal measuring points. Both pulse wave velocity and transfer function importantly, but not exclusively, depend on arterial compliance. The reconstruction of the aortic pulse from peripheral pulse measurements using a population-based transfer function finally provides information on central effects of reduced arterial compliance and increased peripheral resistance which may help in the diagnosis and treatment of vascular disease.

Arteries↗