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Matriarchal model for cardiovascular prevention.

Family patterns of cardiovascular risk behavior are well documented. Significant correlation exists between spouse-spouse, parent-child, and sibling-sibling for cholesterol, high- and low-density lipoprotein, diet, physical activity, and smoking. Family/environmental influences are important in how/if risk and/or preventive behavior is learned. The family matriarch commonly functions as gatekeeper, controlling eating behavior, access to health care, and other patterns. She often acts as menu planner, shopper, and preparer of meals for all family members. She provides information and verbal reinforcement about food and is a powerful model concerning dietary practices. In fact, the mother, as head of household in most single-parent families, may be the only adult model for many children. Because relevance and credibility are the most important characteristics of a behavioral model, parents (especially mothers) are strong models for observational learning by children. Risk factor information and risk reduction activities adopted by the matriarch can be generalized to the entire family if she learns the skills to act as a change agent. Initiation of this process of education and training the matriarch lies with primary care providers for women (Ob-Gyns see most women). By teaching risk reduction to the matriarch as a component of primary care, physician interaction can have a rippling effect.

Adult↗

Haemodynamic effects of a new dihydropyridine calcium entry blocker, S-12968-(-), in a rat model of cardiovascular calcium overload.

1. The haemodynamic effects of S-12968-(-), a new dihydropyridine calcium entry blocker (enantiomer of S-11568), were compared with those of the stereoisomer, S-12967-(+), nifedipine, and sodium nitroprusside. 2. A first experiment was performed in conscious, young male rats chronically implanted with femoral artery and vein cannula and repeated in rats previously treated with vitamin D3 and nicotine. Such treatment produces marked vascular calcium overload, especially of the compliance arteries, with no overt sign of toxicity as far as can be judged from the plasma profile. 3. In conscious rats the hypotensive effects of S-12968-(-), nifedipine and sodium nitroprusside were of similar potency. The falls in blood pressure produced by nifedipine and sodium nitroprusside were accompanied by reflex tachycardia which was less marked in the vascular calcium overload model. S-12968-(-) did not induce reflex tachycardia. S-12967-(+) increased blood pressure in both models. 4. A second experiment was performed in open-chest pentobarbitone-anaesthetized rats with electromagnetic flowprobes on the ascending aorta. In controls the falls in blood pressure produced by low doses (0.1 and 0.3 mg kg-1, i.v.) of S-12968-(-) were accompanied by falls in total peripheral resistance. The higher dose (1 mg kg-1, i.v.) of S-12968-(-) produced no change in total peripheral resistance, and in rats pretreated with vitamin D3 and nicotine, cardiac output fell. 5. In conclusion, S-12968-(-) appears to have a dual action and to lower blood pressure at higher doses at least in part by a cardiac effect. This phenomenon is more pronounced in rats pretreated with vitamin D3 and nicotine.6. S-12967-(+) resembles a calcium channel activator in this model.

Animals↗

Genetically modified mice: tools to decode the functions of connexins in the heart-new models for cardiovascular research.

It has long been known that gap junctions are required for the propagation of electrical impulse in the heart. A good deal later, the connexins (Cxs), which are probably exclusive components of the junctional channels that constitute the gap junctions, were identified. More recently, the in vivo functions of cardiac Cxs have been investigated by the analysis of genetically modified mice. These studies have confirmed that Cxs are involved in cardiac impulse conduction, and, unexpectedly, in heart morphogenesis. In addition, cardiac abnormalities described in mice genetically modified for Cx genes, and those observed in certain human cardiac diseases, have been proven to be similar.

Animals↗

Long-term results after aortic valve replacement with the Bravo 400 stentless xenograft.

BACKGROUND: This study was undertaken to evaluate the long-term clinical and echocardiographic outcome after aortic valve replacement with the Bravo Cardiovascular Model 400 stentless xenograft. METHODS: Between February 1992 and January 1994, 67 patients underwent aortic valve replacement with the Bravo 400 bioprosthesis. The valvular pathology was aortic stenosis in 36 patients (53.7%), aortic insufficiency in 17 patients (25.4%), and mixed lesion in 14 patients (20.9%). Mean follow-up time was 9.8 +/- 2.73 years and median follow-up time was 11 years. Cumulative follow-up time was 659 patients-years and was 94% complete. RESULTS: No early deaths were observed. Overall survival estimates at 11 years were 74.71% +/- 5.47%. The actuarial freedom from valve-related death at 11 years was 91.04% +/- 3.84%; from cardiac-related death at 11 years it was 87.95% +/- 4.29%; and from noncardiac death at 11 years it was 85.14% +/- 4.58%. Eleven-year Kaplan-Meier survival of patients younger than 65 years was 90.91% +/- 6.13% versus 66.08% +/- 7.38% for older patients (p = 0.0307, log-rank test). The actuarial freedom from all valve-related morbidity and mortality at 11 years was 80.3% +/- 5.4%. The mean transvalvular gradient decreased significantly after aortic valve replacement with a corresponding increase in effective orifice area. Left ventricular mass index at 10-year follow-up was 68.5% of the preoperative value. CONCLUSIONS: The Bravo Cardiovascular Model 400 stentless xenograft has provided good clinical and hemodynamic results up until 11 years of follow-up.

Adult↗

QRAR models for cardiovascular system drugs using biopartitioning micellar chromatography.

The capability of biopartitioning micellar chromatography (BMC) to describe and estimate pharmacological parameters of cardiovascular system drugs has been studied. The retention of cardiovascular system drugs was studied using different pH of Brij-35 as micellar mobile phase in modified C(18) stationary phase. Quantitative retention-activity relationships (QRAR) in BMC were investigated for these compounds. An adequate correlation between the retention factors (log k) and the toxicity (LD(50)) of cardiovascular system drugs was obtained.

Cardiovascular Agents↗

Prenatal cocaine exposure to the fetus: a sheep model for cardiovascular evaluation.

Transplacental passage of cocaine in response to maternal administration of intravenous (IV) cocaine in doses of 1.0 and 2.0 mg/kg was studied in 6 pregnant ewes and fetuses and correlated with maximum changes in maternal and fetal blood pressures (BP), heart rates (HR) and fetal arterial blood gas values. Certain animals were given larger doses (3.0 and 5.0 mg/kg) of cocaine to examine cocaine-related cardiopulmonary and neurologic sequelae. Cocaine was extracted on C-18 sorbent columns and analyzed by gas chromatography. At 1.0 and 2.0 mg/kg, cocaine produced dose-dependent increases in maternal HR and BP which were maximum by 1 minute. The fetal response was characterized by maximum increases in BP and decreases in PO2 by 3 minutes and increases in HR by 15 minutes. Cocaine rapidly appeared in the fetal circulation, was approximately 15% of maternal concentrations by 5 minutes, and was undetectable in both circulations by 60 minutes. At cocaine doses of 3.0 and 5.0 mg/kg significant maternal cardiopulmonary and neurologic complications were encountered including bradyarrhythmias, respiratory distress, seizure and death. These data indicate that cocaine exerts direct drug actions upon maternal cardiovascular and neurologic function. In addition, cocaine affects fetal cardiovascular function directly via transplacental passage and indirectly by fetal hypoxemia from cocaine-induced uterine artery vasoconstriction. (NIDA 04415)

Animals↗

Head down tilt combined with breathing assistance by the "IRON LUNG." A new simulation model for cardiovascular deconditioning, skin, and kidney function in weightlessness?

In 1951 Gauer, Henry and Sieker proposed that "central hyper-volemia" might produce a diuresis that serves to reduce blood volume, a postulated negative-feedback system for the control of blood volume. Recent surprising results from human spaceflight indicate that although a central hyper-volemia takes place in weightlessness, an increase in salt and urine excretion cannot be observed. We hypothesised that on earth the mediastinum is shaped by gravity because of the gravity dependent hydrostatic gradient in the blood filled cavities and that its unloading by weightlessness reduces the wall stretch in the atria, thus resulting in reduced sodium and urine excretion. Therefore we have applied the principle of the "Iron Lung" (lung pressure manipulator LPM) in combination with a simulation method of weightlessness, head down tilt bed rest (HDT), to test this hypothesis. We found that similar to weightlessness, not only urinary excretion, but also evaporative water loss was reduced and that diastolic blood pressure increased.

Journal Article↗

Swine models for cardiovascular research: a low stress transport and restraint system for large swine.

A restraint and transport system was developed for handling large swine during cardiovascular research studies. The major design criteria provided for comfortable, low stress restraint of the swine, safety for laboratory personnel and ability to perform a wide variety of hemodynamic and echocardiographic measurements in the standing, supported standing and sedated, or in Panepinto sling positions. A head gate is provided for venipuncture procedures, and an auxiliary feeding and watering front panel can replace the head gate for use of the system as a post-operative "recovery room". Using this system animals weighing 22 to 150 kg can be easily managed.

Animals↗

A public health model for cardiovascular risk reduction. Impact of cholesterol screening with brief nonphysician counseling.

To examine the impact of cholesterol screening with brief nonphysician counseling on cardiovascular risk factors, 886 employees at a large financial services firm underwent fingerstick screening followed by brief (3- to 5-minute) counseling by a registered nurse. At the 6-month follow-up, there were significant declines in total cholesterol levels (5.9 to 5.5 mmol/L [228 to 213 mg/dL]), weight (78 to 75 kg), blood pressure (119/78 to 115/75 mm Hg), and number of people reporting smoking (16.8% to 14.5%) among participants with a baseline cholesterol value of 5.2 mmol/L (200 mg/dL) or greater. A randomized experiment was conducted on 137 participants initially classified as having a "borderline-high blood cholesterol" level (5.2 to 6.2 mmol/L [200 to 239 mg/dL]) to test the impact of frequency of follow-up. Those receiving frequent follow-up (cholesterol measurement and brief counseling at 2, 4, and 6 months) reported significantly greater dietary change and demonstrated a trend toward greater declines in total cholesterol compared with those receiving follow-up at 6 months only. The results of this study support the feasibility and efficacy of cholesterol screening utilizing brief nonphysician counseling on multiple cardiovascular risk factors and suggest an enhanced effect when patients receive more frequent follow-up.

Adult↗

Spontaneous hypertension in the fawn-hooded rat: a cardiovascular disease model.

The fawn-hooded (FH) rat develops hypertension spontaneously. Systolic blood pressure is already elevated at 5 weeks of age, increases with age, and the final range is 180-240 mmHg at the age of 1 year. Concomitantly with the rise in blood pressure proteinuria occurs and increases with age. Fawn-hooded rats reaching the accelerated phase of the hypertension are characterized by blood pressure values exceeding 220 mmHg, heavy proteinuria and increased heart, kidney, liver, adrenal and spleen weights. Those prone to malignant hypertensive disease show a period of increased water turnover for several weeks after weaning; during this period, they do not show the pronounced decrease in water intake upon fasting for 24 h as observed in FH rats of the same age prone to a milder form of hypertension, i.e. diuresis and drinking continue even when no food is consumed. The major cause of death for FH rats is malignant nephrosclerosis with the nephrotic syndrome and/or cardiac failure with chronic pulmonary congestion. Some animals die of bleeding from mesenteric vessels with periarteritis nodosa. In FH rats with malignant hypertension, heart, kidney, liver and spleen weights are significantly increased compared with FH rats of the same age with mild hypertension. Histopathology shows myocardial fibrosis and myocardial infarctions. Generalized arteriolosclerosis is common, sometimes accompanied with local fibrinoid degeneration and (peri)arteritis. Some major arteries show intimal proliferation. It is concluded that the FH rat provides an interesting model for the study of hypertension and its consequences.

Animals↗

Anesthetic interaction in cardiovascular research models: effects of xylazine and pentobarbital in cats.

The effects of xylazine given to cats before anesthetization was induced with pentobarbital were determined. Cardiac hemodynamic variables and regional blood flow rates in the heart and other organs were measured, using radiolabeled microspheres. Two groups, each of 10 cats, were included in the study: one group (group 1) was anesthetized with pentobarbital given intraperitoneally and subsequently given xylazine; the other group (group 2) was first given 1 mg of xylazine/kg, IM, and then anesthetized with pentobarbital given IV. Anesthesia was maintained in both groups with nitrous oxide. The preanesthetic administration of xylazine decreased the amount of pentobarbital used for surgical anesthesia by approximately 50%. It also resulted in decreased heart rate, cardiac contractility, and cardiac output and increased left ventricular end-diastolic pressure, compared with those values in cats given pentobarbital (group 1). After the latter cats (anesthetized with pentobarbital) were given xylazine, heart rate, cardiac contractility, and cardiac output decreased and left ventricular end-diastolic pressure increased to values similar to those found in group 2 (given xylazine before anesthetization). Myocardial tissue blood flow rates in the left and right ventricles were lower in the cats of group 2. In group 1 cats, myocardial blood flow rates decreased when xylazine was subsequently added. Blood flow rates in the kidneys and gastrointestinal tract were generally decreased by xylazine. Xylazine profoundly changed cardiac hemodynamic function and perfusion in the heart, as well as several other organ systems, because of marked cardiodepression.

Animals↗

A modular numerical model of the cardiovascular system for studying and training in the field of cardiovascular physiopathology.

A modular numerical model of the cardiovascular system has been developed to reproduce the most important circulatory phenomena in terms of pressure and volume relationships. It is an easy tool to use, designed to be used with a friendly approach on any IBM or compatible personal computer: it offers a wide selection of graphical and numerical outputs and can be rearranged easily for a particular experiment. A set of subroutines related to different circulatory phenomena has been developed; they can be assembled easily together and communicate with each other by two variables. A full description of the existing subroutines is presented in this paper with three different application examples resulting from the rearrangement of the existing software modules: the first concerns the behaviour of the natural ventricle model itself and can be regarded as a ventricle stand-alone characterization test in terms of preload and afterload sensitivities, the second is related to the use of a pneumatic ventricle instead of the model of the natural ventricle, and the third is a full model of the cardiocirculatory system.

Cardiology↗

Development of a numerical simulation model of the cardiovascular system.

A numerical simulation model of the cardiovascular system has been developed. It consists of a model of the left atrium, the left ventricle, the coronary vascular system, the aorta, the arterial system, and the venous system. The input of the complete model is the elastance (pressure/volume ratio) developed by the left ventricle. The shape of this elastance is constant in different circumstances. Left ventricular (LV) myocardial oxygen consumption and the amount of oxygen offered to the left ventricle can be calculated with the model. The model has been validated using data from a patient suffering from coronary artery disease. The measured clinical hemodynamical waveforms could be fitted to those generated by the model. With the numerical simulation model, it is possible to predict the functioning of the left ventricle under different circumstances. This makes it possible to study in vitro various pathological clinical situations.

Aorta↗

Mathematical modeling of human cardiovascular system for simulation of orthostatic response.

This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

Blood Pressure↗

Computer-controlled heart rate increase by isoproterenol infusion: mathematical modeling of the system.

The purpose of this study was mathematical modeling of the heart rate (HR) response to isoproterenol (Iso) infusion. We developed a computerized system for the controlled increase of HR by Iso, based on a modified proportional-integral controller. HR was measured in conscious, freely moving rats. We found that the steady-state HR can be described as a hyperbolic power function of the steady-state Iso flow rate. This dependence was coupled with a first-order difference equation to form a pharmacodynamic model that reliably describes the relationship between HR and Iso flow for any arbitrary form of Iso flow function. In simulation studies, we showed that the model continued to follow the HR curve from real-time experiments far beyond the initial "learning interval" from which its parameters were calculated. Our results suggest that the predictive ability and the simplicity of calculating the parameters render this pharmacodynamic model appropriate for use within future advanced, model-based, adaptive control systems and as a part of larger cardiovascular models.

Animals↗

Computer simulation of the baroregulation in response to moderate dynamic exercise.

A baroregulation model, based on a previous pulsatile non-linear multielement cardiovascular model, is extended and used to study short-term regulation mechanisms. Using this model, the responses of several cardiovascular variables to different exercise levels are simulated and compared with the experimental data reported in the literature. The impact of physiological or pathological changes on the short-term regulation of arterial pressure under the stimulus of moderate dynamic exercise is then studied. The simulation results indicate that baroreflex feedback plays a critical role in the short-term regulation of arterial pressure. When the baroreflex gain decreases to one-third of the normal value, the response of the mean arterial pressure to moderate dynamic exercise and post-exercise recovery time increases by factors of 1.7 and 2.3, respectively. Clinical data from 36 subjects (two groups: normal and hypertensive) are collected to validate the model. Computer simulations for the hypertensive group show that the elastic modulus of the arterial vessel wall is increased by 1.5 times, and peripheral resistance is increased by 1.3 times the normal value, and the baroreflex gain decreases from 0.55 (for the normal group) to 0.40. The simulation results for normal and hypertensive groups agree well with the clinical data.

Adult↗