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[Consequences of short term fluctuations of environmental temperatures in calves--Part 1: Immediate reactions of the respiratory system, the cardiovascular system, metabolism and thermal regulation].

Clinically healthy calves (aged 3-6 weeks) were exposed to defined ambient temperature for 4 hours (cold: 5 degrees C, 60% humidity, n = 12; warm: 35 degrees C, 60% humidity, n = 11). During the exposure of each animal in a climatic chamber, certain parameters of lung function, respiratory mechanics, blood gas analysis, circulation, metabolism and thermal regulation were registered simultaneously in order to study immediate physiological consequences of different environmental conditions. In comparison to control calves (18-20 degrees C, 60% humidity, n = 13) an insufficient adaptation of these young calves was noticed in both cold and warm conditions. At 5 degrees C, marked changes in lung function were observed, i.e. airway constriction, pulmonary hypertension, and ventilation-perfusion-mismatching leading to hypoxemia and hypercapnia. Due to compensation by the circulatory system, a sufficient O2-consumption of the organism as well as an unchanged body temperature were maintained. At 35 degrees C, the respiratory pattern changed to panting and a higher dead space ventilation. No changes were observed in pulmonary gas exchange and blood arterialisation. Due to hyperventilation, the partial pressure for CO2 decreased in blood. Since the body temperature increased continuously, thermal regulation was insufficient. This situation would have led to animals collapsing after a period of heat stress lasting longer than 4 hours. In conclusion, young calves up to the age of 6 weeks were not able to tolerate acute changes in ambient temperature. This was true for cold conditions (5 degrees C) as well as for hot conditions (35 degrees C). The results of this study should be taken into account in order to optimise transport and farming conditions.

Adaptation, Physiological↗

Menstrual cycle effects on the neurohumoral and autonomic nervous systems regulating the cardiovascular system.

Gonadal hormones may affect homeostatic mechanisms regulating the cardiovascular system. We investigated this relationship at five different crucial hormonal time points along the menstrual cycle. Eight eumenorrheic healthy subjects underwent a battery of autonomic tests, hemodynamics, and volume-regulatory hormone measurements. Fluid-regulatory hormones, plasma renin activity, and aldosterone increased along the luteal phase (P = 0.003 and 0.02, respectively), whereas rest supine-corrected hematocrit declined in the course of the menstrual cycle (P = 0.001). Plasma norepinephrine decreased from 1.4 +/- 0.2 to 0.95 +/- 0.1 nmol/liter (P < 0.02) [early follicular (EF) to late follicular]. Thereafter, concentrations gradually returned to EF levels. Lf to Hf domain ratio (spectral analysis of electrocardiogram) showed a difference from that of norepinephrine. The cardiovagal baroreflex sensitivity increased significantly along the luteal phase (P = 0.04). The dose of isoproterenol required to increase heart rate (HR) 15 beats per minute was 0.19 +/- 0.04 microg during the EF time point, and it increased to 0.39 +/- 0.06 microg during the late luteal time point (P = 0.05). However, blood pressure, HR, and their responses to orthostatic stress remained unchanged. Fluctuations in the ovarian hormones along the menstrual cycle are associated with unchanged blood pressure and HR, despite the significant variations in the different homeostatic mechanisms regulating the cardiovascular system.

Adrenergic beta-Agonists↗

Gender differences in the neurohumoral control of the cardiovascular system.

The cardiovascular system is regulated by many complex neurohumoral mechanisms which ensure the cardiac, cerebral and renal functions. The nervous control of the heart is mainly mediated by the vagal and sympathetic systems and by their interaction, known as the sympatho-vagal balance. An increased sympathetic tone is found in many abnormal situations, such as arterial hypertension, diabetes, chronic heart failure and myocardial infarction, and is associated with an increase in over-all mortality. The hormonal control of the cardiovascular system is mediated by various substances such as renin-angiotensin, catecholamines, insulin and estrogens, that are themselves correlated with the autonomic nervous system. In contrast to men, fertile women show a predominant vagal tone. Sex-related differences in the neurohumoral control of the cardiovascular system have been demonstrated during physical effort and in the hemodynamic adaptation to orthostatism. They have been postulated to explain the lower mortality in women compared to men among hypertensive or chronic heart failure patients. Prospective studies are needed to better define the gender differences in the pathophysiological mechanisms underlying cardiovascular diseases, in order to refine prevention and therapy.

Autonomic Nervous System↗

Identification and role of aldosterone receptors in the cardiovascular system.

The cardiovascular system is now recognized as an important mineralocorticoid target. All -components required for specific and selective aldosterone effects are present in the cardiovascular system. Mineralocorticoid receptors (MR) are expressed in the heart and large blood vessels together with the 11 B-hydroxysteroid dehydrogenase type II, which ensures the enzymatic protection of MR against glucocorticoids. The recent description of local vascular and cardiac aldosterone biosynthesis strongly supports an autocrine/paracrine hormonal action. Establishment of transgenic mice models of targeted overexpression of the mineralocorticoid receptor should facilitate new insights into the molecular and cellular mechanisms of aldo-sterone actions in the cardiovascular system.

Aldosterone↗

The water-tower analogy of the cardiovascular system.

The cardiovascular system is a complex arrangement of hydraulic, yet living, components. The complexity of this system may make it difficult for students to see the "forest" instead of the "trees." To better explain the dynamics of cardiovascular function and control, an analogy has been drawn to the operation of a city water supply. In cities that use a water tower, fresh water is pumped up into the tower from a river or other source. The tower serves as a pressure reservoir for providing water to homes through a largely parallel arrangement of distribution pipes. Local homeowners control their own water usage through faucets, whereas the city maintains water pressure by monitoring the level in the tower. Key analogous points with the cardiovascular system are the heart as the city pump, the aorta as the water tower, arteries as parallel distribution pipes, and arterioles as faucets. Baroreceptor reflex control is discussed as well as such features as the capacitance role of veins, the skeletal muscle pump, and the competition between locally mediated vasodilation and sympathetically mediated vasoconstriction. Subjective student and peer evaluations have indicated that this analogy is effective in improving student comprehension of the cardiovascular system.

Baroreflex↗

Mixed quantitative/qualitative modeling and simulation of the cardiovascular system.

The cardiovascular system is composed of the hemodynamical system and the central nervous system (CNS) control. Whereas the structure and functioning of the hemodynamical system are well known and a number of quantitative models have already been developed that capture the behavior of the hemodynamical system fairly accurately, the CNS control is, at present, still not completely understood and no good deductive models exist that are able to describe the CNS control from physical and physiological principles. The use of qualitative methodologies may offer an interesting alternative to quantitative modeling approaches for inductively capturing the behavior of the CNS control. In this paper, a qualitative model of the CNS control of the cardiovascular system is developed by means of the fuzzy inductive reasoning (FIR) methodology. FIR is a fairly new modeling technique that is based on the general system problem solving (GSPS) methodology developed by G.J. Klir (Architecture of Systems Problem Solving, Plenum Press, New York, 1985). Previous investigations have demonstrated the applicability of this approach to modeling and simulating systems, the structure of which is partially or totally unknown. In this paper, five separate controller models for different control actuations are described that have been identified independently using the FIR methodology. Then the loop between the hemodynamical system, modeled by means of differential equations, and the CNS control, modeled in terms of five FIR models, is closed, in order to study the behavior of the cardiovascular system as a whole. The model described in this paper has been validated for a single patient only.

Central Nervous System↗

Effects of the renin-angiotensin-aldosterone system on the cardiovascular system during 20-days bed rest.

Long term change of renin-angiotensin-aldosterone system (RAAS) induced by bed rest and its effects on cardiovascular system are still controversial. The purpose of this study was to obtain a general conclusion on these questions by analyzing our two 20-days horizontal bed rest experiments in past two years with 18 subjects. Plasma renin activity and aldosterone were consistently increased during the bed rest, but angiotensin II was increased only during the early days. Decrease in urinary sodium excretion and increase in urinary potassium excretion were observed during day 3-8 and day 7-12, respectively. Mean arterial pressure increased during day 3-8. Pulse pressure was returned to pre-bed rest level by day 10 after an initial decrease. All these results indicated an activated RAAS and its active effects on cardiovascular and overall fluid regulating systems during our horizontal bed rest studies. Direct effect of change in gravitational force on renal pressure-sensitive cells or effects related to physical inactivity may explain our results.

Adult↗

Immunocytochemical analysis of connexin expression in the healthy and diseased cardiovascular system.

Gap junctions play essential roles in the normal function of the heart and arteries, mediating the spread of the electrical impulse that stimulates synchronized contraction of the cardiac chambers, and contributing to co-ordination of activities between cells of the arterial wall. In common with other multicellular systems, cardiovascular tissues express multiple connexin isotypes that confer distinctive channel properties. This review highlights how state-of-the-art immunocytochemical and cellular imaging techniques, as part of a multidisciplinary approach in gap junction research, have advanced our understanding of connexin diversity in cardiovascular cell function in health and disease. In the heart, spatially defined patterns of expression of three connexin isotypes-connexin43, connexin40, and connexin45-underlie the precisely orchestrated patterns of current flow governing the normal cardiac rhythm. Derangement of gap junction organization and/or reduced expression of connexin43 are associated with arrhythmic tendency in the diseased human ventricle, and high levels of connexin40 in the atrium are associated with increased risk of developing atrial fibrillation after coronary by-pass surgery. In the major arteries, endothelial gap junctions may simultaneously express three connexin isotypes, connexin40, connexin37, and connexin43; underlying medial smooth muscle, by contrast, predominantly expresses connexin43, with connexin45 additionally expressed at restricted sites. In normal arterial smooth muscle, the abundance of connexin43 gap junctions varies according to vascular site, and shows an inverse relationship with desmin expression and positive correlation with the quantity of extracellular matrix. Increased connexin43 expression between smooth muscle cells is closely linked to phenotypic transformation in early human coronary atherosclerosis and in the response of the arterial wall to injury. Current evidence thus suggests that gap junctions in both their guises, as pathways for cell-to-cell signaling in the vessel wall and as pathways for impulse conduction in the heart, contribute to the initial pathogenesis and eventual clinical manifestation of human cardiovascular disease.

Cardiovascular Diseases↗

Basic safety pharmacology: the cardiovascular system.

The cardiovascular system is one of the primary vital functions which have to be examined during safety pharmacology studies. Cardiovascular system functioning is maintained by cardiac electrical activity and by pump-muscle function which contribute to haemodynamic efficacy. The aim of cardiovascular safety pharmacology is to evaluate the effects of test substances on the most pertinent components of this system, in order to detect potentially undesirable effects, before engaging in clinical trials. In the basic programme, a detailed haemodynamic evaluation is carried out in the anaesthetized dog. It is completed by cardiac and/or cellular electrophysiology investigations in order to assess the arrhythmogenic risk. The basic programme can be preceded by rapid and simple testing procedures, during the early drug discovery stage. It should be completed, if necessary, by specific supplementary studies, depending on the data obtained during the early clinical trials. The following article describes and presents an analytic strategy aimed at problems of cardiovascular risk.

Animals↗

Autonomic nervous system interaction with the cardiovascular system during exercise.

There is considerable recent evidence that parameters thought to reflect the complex interaction between the autonomic nervous system and the cardiovascular system during exercise testing can provide significant prognostic information. Specific variables of great importance include heart rate (HR) response to exercise (reserve), HR recovery after exercise, and multiple components of HR variability both at rest and with exercise. Poor HR response to exercise has been strongly associated with sudden cardiac death and HR recovery from a standard exercise test has been shown to be predictive of mortality. In addition, there are limited studies evaluating the components of HR variability at rest and during exercise and their prognostic significance. Research continues seeking to refine these exercise measurements and further define their prognostic value. Future findings should augment the power of the exercise test in risk-stratifying cardiovascular patients.

Autonomic Nervous System↗

The plasma and tissue kininogen-kallikrein-kinin system: role in the cardiovascular system.

Bradykinin and Lys-bradykinin are potent peptide mediators implicated in several physiopathological effects in mammals. They act through activation of G-protein-coupled constitutive B(2) or inducible kinin B(1) receptors linked to signaling pathways involving increased intracellular Ca(++) concentrations and/or release of mediators including arachidonic acid metabolites, NO and EDHF. In the cardiovascular system, the kallikrein-kinin system exerts a fine control of vascular smooth muscle tone and arterial blood pressure, and plays a significant cardioprotective effect. This has been lately confirmed in experimental studies employing transgenic mice overexpressing human tissue kallikrein and animals with knockout of kinin B(1) and B(2) receptor gene. Disturbances in this system are associated with arterial hypertension, myocardial ischaemia and other clinical complications. Inhibitors of kininase II (angiotensin-converting enzyme) have been prescribed successfully to patients with cardiovascular diseases, but there is still a great interest in developing drugs or pharmacological strategies that augment the activity of kininogen-kallikrein-kinin system in pathological conditions. Delivery of adenovirus vector containing the human tissue kallikrein gene (gene kallikrein therapy) has emerged as a great potential to satisfy these conditions. This review provides a summary of plasma and tissue kallikrein-kinin system, focusing on the pharmacological properties, kinin receptors and drugs reported to interfere with their actions. The modulatory effects of the kallikrein-kinin system on cardiovascular system, particularly in regulating smooth muscle tone and arterial blood pressure and in preventing myocardium ischaemia have also been explored in the review.

Angiotensin-Converting Enzyme Inhibitors↗

Tissue engineering of biological cardiovascular system surrogates.

Cardiovascular diseases are common in ageing communities globally. This fact is most striking in the industrialised world where the aged population makes up a large proportion of society. Elderly patients are frequently treated surgically with grafts to replace damaged tissues and vessels. The number of human-donated components is insufficient and synthetic surrogates are sought. These might be wholly mechanical, wholly biological, or tissue engineered complexes of cells and their products growing in a scaffold. At present, many such composites exist with potential for use as substitutes for specific blood vessels. The challenges of producing tissue engineered heart valves are now being widely explored. Neotissues must provide an effective, durable, non-thrombogenic and non-immunogenic substitute that will fulfil the purpose of the natural tissue. The aims and scope of this paper are to review current and novel concepts in the field of tissue engineering of biological cardiovascular system surrogates. Mechanical stresses and strains on cardiovascular cells in vitro have been recognised and can be measured by a culture force monitor. Physiological stresses can be generated by a tensioning culture force monitor and applied to engineered tissue, aligning the cells and mimicking arterial wall architecture. The hydrostatic forces a vessel experiences and mechanical parameters of blood vessels can be studied in the tubular culture system of a multi-cue bioreactor.

Journal Article↗