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PubMed2004

Hypertension management in primary care: standard care and attitude towards a disease management model.

INTRODUCTION: Cardiovascular risk control has become one of the hallmarks in the treatment of diabetes and coronary heart disease, yet assessment of individual risk factors is suboptimal. We have designed a new Hypertension Screening Facility (HSF) for the evaluation of cardiovascular risk in hypertensive patients, based on 1) systematic, protocol-driven (WHO/ISH-based) analysis by nurse practitioners, 2) computer-assisted reporting of results and advice, 3) risk assessment using a Decision Support System (DSS), 4) maintenance of the autonomy of the GP. In a pilot study we wanted to investigate this HSF. METHODS: Survey 1 addressed a. how general practitioners deal with hypertension, b. whether they intend to and do use existing clinical guidelines, c. what their opinions are towards changes in the current process of care. In survey 2, we evaluated the attitude of GPs using the HSF. Responses were 43% (51 out of 120) to the first survey and 100% (20 out of 20) to the second. RESULTS: The majority of physicians included lifestyle in their assessment of risk factors and management of hypertension. Consideration of age and a positive family history was extremely high. In contrast, vision disturbances, ECG and microalbuminuria were not often considered. In the absence of additional risk factors, drug treatment was initiated in patients with a mean systolic blood pressure of 162+/-6 over 99+/-4 mmHg. In the presence of risk factors (obesity, smoking and a positive family history of cardiovascular disease) treatment is started at an average blood pressure of 154+/-8 over 96+/-4 mmHg. Opinions towards a change in management of hypertensive patients were generally positive. The opinions about the new HSF and the cardiovascular risk were reported to the general practitioner and considered useful or very useful by 79%. CONCLUSION: The present study thus confirms that cardiovascular risk evaluation by GPs is suboptimal, but there is a positive attitude towards an improvement in their assessment by HSF. The novelty of the HSF is that it respects the autonomy of the GP and brings the expertise to the GP.

Attitude of Health Personnel↗
PubMed2002

Cardiovascular response to dynamic aerobic exercise: a mathematical model.

An original mathematical model of the cardiovascular response to dynamic exercise is presented. It includes the pulsating heart, the pulmonary and systemic circulation, a separate description of the vascular bed in active tissues, the local metabolic vasodilation in these tissues and the mechanical effects of muscular contractions on venous return. Moreover, the model provides a description of the ventilatory response to exercise and various neural regulatory mechanisms working on cardiovascular parameters. These mechanisms embrace the so-called central command, the arterial baroreflex and the lung inflation reflex. All parameters in the model have been given in accordance with physiological data from the literature. In this work, the model has been used to simulate the steady-state value of the main cardiorespiratory quantities at different levels of aerobic exercise and the temporal pattern in the transient phase from rest to moderate exercise. Results suggest that, with suitable parameter values the model is able accurately to simulate the cardiorespiratory response in the overall range of aerobic exercise. This response is characterised by a moderate hypertension (10-30%) and by a conspicuous increase in systemic conductance (80-130%), heart rate (64-150%) and cardiac output (100-200%). The transient pattern exhibits three distinct phases (lasting approximately 5s, 15s and 2 min), that reflect the temporal heterogeneity of the mechanisms involved. The model may be useful to improve understanding of exercise physiology and as an educational tool to analyse the complexity of cardiovascular and respiratory regulation.

Baroreflex↗
PubMed1975

Use of artificial heart for basic cardiovascular research.

Improved technology in artificial heart development and implantation studies in unanesthetized calves have stimulated a new model for cardiovascular research. Independent control of the left and right ventricles, replacement of the natural right atrium with an artificial atrium (with a compliant inner diaphragm) are illustrated as examples of new methods to study the cardiovascular system. Preliminary results in three calves suggest that synchronous ventricular pumping is not required for total circulatory maintenance. In four calves a passive artificial right atrium was shown to decrease outflow obstruction to the right ventricle. A compliant inner deiapragm demonstrated a reduction in the amplitude of the atrial C and V waves. The effects of volume and drug infusion on peripheral vascular response in the presence of controlled artificial heart pumping (which does not respond to direct neural or hormonal influences) further illustrate the efficacy of this preparation as a new model for cardiovascular research.

Animals↗
PubMed1997

Transgenic animal models: new avenues in cardiovascular physiology.

Application of molecular genetic tools to inherited cardiovascular disorders has provided important insights into the molecular mechanisms underlying cardiomyopathies, arrhythmias, blood pressure regulation, and atherosclerosis. In addition, alteration of gene expression has been observed under common cardiovascular conditions such as cardiac hypertrophy and heart failure. Recent advances in transgenic and gene-targeting approaches allow a sophisticated manipulation of the mouse genome by gene addition, gene deletion, or gene modifications. These transgenic models enable the dissection of in vivo pathways responsible for these complex disease phenotypes. This review describes tissue-specific promoters suitable for targeting candidate genes to the cardiovascular system as well as a number of valuable transgenic animal models of blood pressure regulation, atherogenesis, defects in the coagulation system, cardiac hypertrophy, myocarditis, cardiomyopathies, and heart failure. Limitations and difficulties associated with these transgenic approaches are discussed. Animal models which may provide a basis for future gene therapy of cardiovascular diseases are introduced. Finally, methods are described to regulate the spatial and temporal expression level of a transgene, to inactivate a target gene in a tissue-specific manner, and to introduce specific mutations into the genome. These recent advances in transgenic technology are expected to have a considerable impact on cardiovascular research in the near future.

Animals↗
PubMed2000

Physiological requirements of cricket.

Despite its long history and global appeal, relatively little is known about the physiological and other requirements of cricket. It has been suggested that the physiological demands of cricket are relatively mild, except in fast bowlers during prolonged bowling spells in warm conditions. However, the physiological demands of cricket may be underestimated because of the intermittent nature of the activity and the generally inadequate understanding of the physiological demands of intermittent activity. Here, we review published studies of the physiology of cricket. We propose that no current model used to analyse the nature of exercise fatigue (i.e. the cardiovascular-anaerobic model, the energy supply-energy depletion model, the muscle power-muscle recruitment model) can adequately explain the fatigue experienced during cricket. A study of players in the South African national cricket team competing in the 1999 Cricket World Cup revealed that, in a variety of measures of explosive ('anaerobic') power and aerobic endurance capacity, they were as 'fit' as South African national rugby players competing in the 1999 Rugby World Cup. Yet, outwardly, the physiological demands of rugby would seem to be far greater than those of cricket. This poses the question: 'Why are these international cricketers so fit if the physiological demands of cricket are apparently so mild?' One possibility is that this specific group of athletes are unusually proficient in a variety of sports; many achieved high standards of performance in other sports, including rugby, before choosing to specialize in cricket. Hence their apparently high fitness may simply reflect a superior genetic physical endowment, necessary to achieve success in modern international sports, including cricket. Alternatively, it could be hypothesized that superior power and endurance fitness may be required to cope with the repeated eccentric muscle contractions required in turning and in bowling and which may account for fatigue and risk of injury in cricket. If this is the case, the fitness of cricketers may be increased and their risk of injury reduced by more specific eccentric exercise training programmes.

Anaerobic Threshold↗
PubMed1989

Neurogenic mechanisms initiating essential hypertension.

Evidence for increased sympathetic drive, as assessed both by measurements of plasma norepinephrine and by studies of tritiated norepinephrine kinetics, is most frequently obtained in young hypertensive patients. During the initial phases of hypertension, the increased sympathetic drive may persistently elevate arterial pressure through effects on the heart, the blood vessels, and the kidneys. In some patients, signs of a hyperkinetic circulation--including elevated heart rate and, less often, high cardiac output--predominate. In others, elevated vascular resistance, reflecting increased alpha-adrenergic tone, is the principal hemodynamic aberration. Even in patients with high cardiac output, a relative increase of vascular alpha-adrenergic tone accounts for their higher blood pressure. Increased sympathetic drive to the kidneys diminishes the efficiency of pressure diuresis, which is designed to restore normal arterial pressure. Although increased plasma norepinephrine levels are not consistently observed among older hypertensive patients compared with age-matched controls, neurogenic hypertension is not only a temporary event. In fact, tachycardia, which is neutrogenically mediated, doubles the risk of sustained hypertension later in life. The precise sequence of events in the transition from a principally neurogenic hypertension early in life to a predominantly nonneurogenic hypertension later in life is not known, although it likely includes decreased beta-receptor sensitivity with consequently reduced tachycardia and beta-mediated vasodilation. Functional diminution in endothelium-dependent vasodilation may augment sensitivity to vasoconstrictors such as norepinephrine and serotonin. Moreover, structural vascular changes nonspecifically enhance vascular reactivity to all vasoactive compounds and may provide a more permanent basis for altered pressure diuresis. Thus, hypertension initiated predominantly by neurogenic mechanisms could be sustained later without excessive sympathetic drive.

Animals↗
PubMed2005

Physics-driven CFD modeling of complex anatomical cardiovascular flows-a TCPC case study.

Recent developments in medical image acquisition combined with the latest advancements in numerical methods for solving the Navier-Stokes equations have created unprecedented opportunities for developing simple and reliable computational fluid dynamics (CFD) tools for meeting patient-specific surgical planning objectives. However, for CFD to reach its full potential and gain the trust and confidence of medical practitioners, physics-driven numerical modeling is required. This study reports on the experience gained from an ongoing integrated CFD modeling effort aimed at developing an advanced numerical simulation tool capable of accurately predicting flow characteristics in an anatomically correct total cavopulmonary connection (TCPC). An anatomical intra-atrial TCPC model is reconstructed from a stack of magnetic resonance (MR) images acquired in vivo. An exact replica of the computational geometry was built using transparent rapid prototyping. Following the same approach as in earlier studies on idealized models, flow structures, pressure drops, and energy losses were assessed both numerically and experimentally, then compared. Numerical studies were performed with both a first-order accurate commercial software and a recently developed, second-order accurate, in-house flow solver. The commercial CFD model could, with reasonable accuracy, capture global flow quantities of interest such as control volume power losses and pressure drops and time-averaged flow patterns. However, for steady inflow conditions, both flow visualization experiments and particle image velocimetry (PIV) measurements revealed unsteady, complex, and highly 3D flow structures, which could not be captured by this numerical model with the available computational resources and additional modeling efforts that are described. Preliminary time-accurate computations with the in-house flow solver were shown to capture for the first time these complex flow features and yielded solutions in good agreement with the experimental observations. Flow fields obtained were similar for the studied total cardiac output range (1-3 1/min); however hydrodynamic power loss increased dramatically with increasing cardiac output, suggesting significant energy demand at exercise conditions. The simulation of cardiovascular flows poses a formidable challenge to even the most advanced CFD tools currently available. A successful prediction requires a two-pronged, physics-based approach, which integrates high-resolution CFD tools and high-resolution laboratory measurements.

Blood Flow Velocity↗
PubMed2000

Transgenic mouse models in angiogenesis and cardiovascular disease.

Novel gene technologies have allowed us to manipulate the genetic balance of candidate molecules in mice in a controllable manner. Homologous or site-specific recombination in embryonic stem cells allows us to study the consequences of deficiencies, mutations, and conditional or tissue-specific expression of gene products in transgenic mice. These technological breakthroughs have significantly advanced biomedical research and broadened our understanding of the pathophysiological role of candidate disease genes. In addition, gene transfer allows us to test the possible therapeutic use of gene products for gene therapy. A variety of assays have been miniaturized, allowing analysis of cardiovascular physiology in the mouse. With the advent of genome sequencing programmes, these gene technologies provide means of studying gene function in a conclusive manner. Furthermore, disease models can be generated which can be used as test models for (gene) therapy or for the discovery of novel genes using differential gene profiling techniques. The present review will focus on the molecular basis of how blood vessels form (angiogenesis and arteriogenesis) and how they become diseased. A selected number of molecules that have been studied in the authors' laboratory will be reviewed in more detail.

Animals↗
PubMed1996

[20 years of cardiovascular epidemiology. The epidemiologist's viewpoint].

The author reviews the evolution of cardiovascular epidemiology during the twenty last years. The mortality from cardiovascular diseases with atherosclerosis as their pathological basis grew rapidly in the industrialised countries after World War II. This led to epidemiological research which started in 1950 with respectively the studies of Framingham in the United States and the Seven Countries Study, essentially in Europe. The concept of multifactorial origin of coronary heart disease was proposed during the 60s. Three major coronary risk factors besides age and gender, hypercholesterolemia, hypertension and cigarette smoking emerged systematically in epidemiological studies before 1975. The last twenty years have confirmed the importance of these three modifiable coronary risk factors which are long-term predictors in different ethnic groups, both in males and females. Other risk factors appeared in this period. Some polymorphisms of several genes as well as their phenotypic expression have been found to be related to an increased risk of coronary heart disease. Uni- and multifactorial primary and secondary prevention trials have confirmed the observations of analytical epidemiology. Moreover, the crucial role of nutrition within a metabolic hypothesis has been confirmed by experimental research. The concept of the strategy of prevention in higher risk subjects as well as in the whole population was proposed by international bodies following the publications by the English epidemiologist G. Rose. Both France and Belgium contributed to the development of cardiovascular epidemiology during the last twenty years. France is doing cutting-edge research on genetic predictors of cardiovascular diseases. Although the multifactorial causal model of cardiovascular diseases is robust, it is still a probabilistic one; it predicts however relative risks of about 15 to 1 according to the decile of the multilogistic function distribution. Environmental factors essentially related to lifestyles explain a great part of these differences. At the individual level, genetic factors most probably modulate these environmental influences and one can foresee in the future a more predictive model. In most medical schools, teaching of cardiovascular epidemiology and prevention has a low priority with clinicians putting the accent on the risk factors rather than on the risk profile of the individual. Secondary prevention is more in the realm of clinical medicine due to a large publicity given to the results of the large randomised trials. Consequently, in hospital mortality of acute myocardial infarction is decreasing as well as long-term mortality. Finally, prevention at the population level is connected to political decisions in public health which could have a major impact on the economy at the country level. Consequently, these political decisions are very slow to be taken both at the national and European Union level.

Cardiovascular Diseases↗
PubMed1987

Positive effects of ketamine v. metomidate anesthesia on cardiovascular function, oxygen delivery and survival. Studies with a porcine endotoxin model.

Pulmonary and cardiovascular function, oxygen delivery and mortality were compared in endotoxemic pigs spontaneously breathing air and with continuous i.v. infusion of ketamine anesthesia (n = 10) or the equianesthetic dose of metomidate (n = 10). Continuous 6-hour i.v. infusion of endotoxin caused profound pulmonary and cardiovascular derangement in both groups. Cardiac output, mean arterial blood pressure, oxygen delivery and base excess were significantly higher and pulmonary vascular resistance significantly lower from 2-3 hours onwards in the ketamine than in the metomidate group. Six-hour survival was 6/10 and 1/10 in the respective groups. Death was presumably due to insufficient oxygen delivery in relation to tissue demand, reflected in the metomidate group's low base excess values. Control, non-stressed pigs showed no notable physiologic changes with either anesthetic regimen. The study demonstrated the importance of the type of anesthesia in stressful endotoxemic animal models. Although extrapolation of animal data requires great caution, the results may favor use of ketamine over etomidate (the clinical analogue of metomidate) in septic shock states requiring surgical intervention.

Anesthesia, Intravenous↗
PubMed1991

Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flights.

The Extended Duration Orbiter (EDO) program aims to extend the capability of the Shuttle orbiter beyond its current 7-10 day limit on mission duration. This goal is to be accomplished in steps, partly due to our limited knowledge of the physiological changes resulting from long-term exposure to weightlessness and their likely influence on critical mission operations involved in EDO flights. Answers to questions related to physiologic adaptation to weightlessness are being actively sought at the present time to help implement the EDO program. In the cardiovascular area, the loss of orthostatic tolerance is a medical concern because of its potential adverse effects on crew performance and safety during reentry and following return to earth. Flight and ground-based physiologic studies are being planned to understand the mechanism and time course of spaceflight-induced orthostatic intolerance and to develop effective countermeasures for improving post-flight cardiovascular performance. Where feasible, these studies are aided by theoretical analyses using mathematical modeling and computer simulation of physiological systems. This paper is concerned with the application of proven models of circulatory and cardiovascular systems in the analysis of chronic cardiovascular changes under weightless conditions.

Cardiovascular Deconditioning↗
PubMed1985

Velocity profiles in the wake of two prosthetic heart valves using a new cardiovascular simulator.

In this paper we present a study of the post valvular flow field on a new cardiovascular simulator including an elastic model of the aortic arch. Transverse and vertical two-dimensional velocity measurements are performed with an ultrasonic velocimeter. Two prosthetic heart valves are tested in the aortic position. The behaviour of the velocity vectors patterns during one pulsatile cycle is one of the most striking features of the flow.

Aorta, Thoracic↗