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A theoretic analysis of the effect of pulmonary vasodilation on pulmonary venous pressure: implications for inhaled nitric oxide therapy.

BACKGROUND: Although the use of inhaled nitric oxide offers certain advantages over more traditional pulmonary vasodilators, concerns have emerged because of reports of acute pulmonary edema during nitric oxide administration in patients with chronic heart failure. It is unclear whether the pulmonary vasodilating action of nitric oxide could, by itself, cause venous pressures to rise in the lung and why patients with preexisting chronic heart failure are at greatest risk for the development of pulmonary edema during inhaled nitric oxide therapy. METHODS: The cardiovascular system was modeled as time-varying elastances; the pulmonary and systemic vascular systems were each modeled as a series of resistive and compliance elements. Protocols were devised to examine the effects of a decrease in pulmonary vascular resistance on pulmonary venous pressure under different conditions of contractile state and volume status. RESULTS: Under all conditions studied, pulmonary venous pressure increased as pulmonary vascular resistance decreased. Increases in pulmonary venous pressure were caused by volume shifts between pulmonary arterial and venous compartments. These volume shifts were accentuated by high volume status. The impact of alterations in contractile state was minimal. CONCLUSIONS: Pulmonary vasodilation by itself can lead to an increase in pulmonary venous pressure that is mediated by shifts of blood between arterial and venous compartments of the pulmonary bed. Furthermore, impairment in ventricular contractile state by itself has relatively little effect on pulmonary venous pressure. The magnitude of the increase in pulmonary venous pressure is largely determined by the volume status and the initial value of pulmonary vascular resistance.

Administration, Inhalation↗

In vivo interaction of endotoxin and recombinant bactericidal/permeability-increasing protein (rBPI23): hemodynamic effects in a human endotoxemia model.

The cardiovascular derangement that results from the administration of endotoxin in healthy subjects is qualitatively similar to what is observed in patients in septic shock. The biological response to endotoxin is attributed in part to cytokine release. In experimental endotoxemia, recombinant bactericidal/permeability increasing protein (rBPI(23)) has shown a protective effect by binding endotoxin with the subsequent inhibition of the endotoxin-induced cytokine release and of neutrophil activation. In a controlled, blinded crossover study the early cardiovascular effects of rBPI(23) were investigated in an experimental endotoxemia model in humans. The beat-to-beat changes in arterial pressure and cardiac output following infusion of endotoxin (40 EU/kg body weight) and rBPI(23) (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg) were studied for 2 hours in 8 healthy male adults. Endotoxin or rBPI(23) alone did not induce significant cardiovascular changes. Endotoxin following rBPI(23) infusion elicited a fall in total peripheral resistance with its nadir after 4 minutes to 40% (range 16-53; P <.001) of control level. Mean arterial pressure showed little change, and the fall in total peripheral resistance was associated with a reflex increase in heart rate and cardiac output (32%; range 43-106). Changes in cardiovascular variables in the subsequent 2 hours were not significant. In vitro activation of the contact system by, respectively, rBPI(23), LPS, and LPS-rBPI(23) complexes was assessed. Following incubation with rBPI(23), LPS, and LPS-rBPI(23) complexes, complex levels were generated at levels comparable to those observed in the buffer control. The rapid vasodilatation by endotoxin administered concomitantly with rBPI(23) is not mediated by complement or contact system activation. The early vasodilatation is compensated by an increase in cardiac output, which therefore does not result in arterial hypotension. The monitoring of continuous cardiac output allows for the detection of rapid effects on systemic flow and conductance that go unnoticed in a recording of arterial pressure.

Adult↗

A mathematical model of the fetal cardiovascular system based on genetic algorithms as identification technique.

The development of fetal cardiac surgery, considered the ultimate goal in the treatment of congenital cardiac malformations, needs to be supported by detailed knowledge of the blood circulation in the fetal cardiovascular system. The hemodynamic behavior in distal territories is usually inferred from vessel resistance indices, which give limited physiological information. This study presents a mathematical model of the human fetal global cardiovascular system, developed to clarify the relationships and differences existing between upper and lower body circulation. We modelled the heart with two time-varying capacitances, each representing the respective ventricle's pressure-volume relationship. The fetal vascular system was represented using two six-element Windkessel models, for the upper and lower body respectively. We obtained the identification of the set of circuital and elastance function parameters of the model using Genetic Algorithms (GAs), which follow the laws of evolutionary theory. We compared the results of our numerical study on the model identified with data collected from measurements and literature, to validate the proposed global cardiovascular system model of the human fetus. This model is intended as an instrument to investigate the differences in blood distribution between the different vascular districts in the upper and lower fetal body and the role of the aortic isthmus, the small tract of vessel connecting upper and lower fetal vascular beds; it may also represent a useful tool in the assessment of dynamic balance during mechanical assistance of circulation.

Algorithms↗

A collaborative model for hospital-based cardiovascular secondary prevention.

This article presents a collaborative model for hospital-based cardiovascular secondary prevention. The model employs a stake holder consortium to provide hospitals with a unified approach to improve care and conform to regulatory requirements. Hospital teams use a Web-based tool that embeds data collection in the process of care and supports rapid cycle improvement. Recognition of participation and achievement by the American Heart Association helps to obtain administrative support for the program.

Cardiology Service, Hospital↗

Modeling human hematopoietic and cardiovascular diseases in zebrafish.

Zebrafish have emerged as a useful vertebrate model system in which unbiased large-scale screens have revealed hundreds of mutations affecting vertebrate development. Many zebrafish mutants closely resemble known human disorders, thus providing intriguing prospects for uncovering the genetic basis of human diseases and for the development of pharmacologic agents that inhibit or correct the progression of developmental disorders. The rapid pace of advances in genomic sequencing and map construction, in addition to morpholino targeting and transgenic techniques, have facilitated the identification and analysis of genes associated with zebrafish mutants, thus promoting the development of zebrafish as a model for human disorders. This review aims to illustrate how the zebrafish has been used to identify unknown genes, to assign function to known genes, and to delineate genetic pathways, all contributing valuable leads toward understanding human pathophysiology.

Anemia↗

Effect of dietary n-3 fatty acids on atherosclerosis prone JCR:LA-corpulent rats.

Corpulent male rats of the atherosclerosis prone JCR:LA-corpulent strain were fed diets supplemented with 10% by weight of olive oil or red fish oil. These rats are obese, with VLDL hyperlipidemia and marked insulin resistance. The diets were maintained to 9 months of age. Olive oil-fed rats had a 45% reduction in triglyceride concentrations with no significant changes in cholesterol or phospholipids. Red fish oil caused significant reduction in all lipid classes, with a 65% reduction in triglycerides and 35% reduction in cholesterol concentrations. Olive oil caused increases in the relative concentrations of oleic acid-containing triglycerides, while red fish oil preferentially enriched the longer chain fatty acids. There were no significant changes in insulin or glucose metabolism. The incidence of myocardial lesions, characteristic of the JCR:LA-cp strain, was unaltered by either oil-supplemented diet. These results, in a spontaneous animal model for cardiovascular disease, are consistent with other studies showing that diets rich in n-3 fatty acids do not, in themselves, confer protection against cardiovascular disease in animal models with genetically or experimentally induced lipid disorders.

Animals↗

Echocardiographic characterization of the cardiovascular phenotype in rodent models.

Echocardiographic techniques are commonly utilized to describe the rodent cardiovascular phenotype. These approaches are contrasted with other in vivo methods and are positioned in the assay selection process by a review of studies from our laboratory and others. Although not conventionally considered a biomarker, the technique has the potential to be exploited as a marker of intentional or unanticipated toxic biological effects in the preclinical development of drugs and chemicals.

Animals↗

A forward model-based validation of cardiovascular system identification.

We present a theoretical evaluation of a cardiovascular system identification method that we previously developed for the analysis of beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure, and instantaneous lung volume. The method provides a dynamical characterization of the important autonomic and mechanical mechanisms responsible for coupling the fluctuations (inverse modeling). To carry out the evaluation, we developed a computational model of the cardiovascular system capable of generating realistic beat-to-beat variability (forward modeling). We applied the method to data generated from the forward model and compared the resulting estimated dynamics with the actual dynamics of the forward model, which were either precisely known or easily determined. We found that the estimated dynamics corresponded to the actual dynamics and that this correspondence was robust to forward model uncertainty. We also demonstrated the sensitivity of the method in detecting small changes in parameters characterizing autonomic function in the forward model. These results provide confidence in the performance of the cardiovascular system identification method when applied to experimental data.

Autonomic Nervous System↗

[An analysis of the cardiovascular responses under hyper- and hypo-gravity environments using a mathematical model].

Gravity affects cardiovascular control system remarkably. Internal control mechanism responsible for such cardiovascular changes under hypo- and hyper-gravity have not yet been fully understood, although many biological and physiological measurements as to cardiovascular system have been conducted since man's first exploration to space. One reason for this arises from the difficulty in continuous and simultaneous measurements of hemodynamics of many parts of the body. To overcome this difficulty, a mathematical model was constructed based on animal and human physiological evidence in our previous study. In the present study, the model is used for explaining hemodynamics during hyper- and hypo-gravity environments obtained during parabolic flight. The parabolic flight experiment was conducted by a small rear-jet MU300. Three university male students volunteered as subjects. Five to eleven parabolic flights per day were performed for 6 days. The subjects sat on a chair either in an upright position or a 45 degree reclining position. Electrocardiogram and finger blood pressure were measured continuously during the flights. Variable parameters of the model were adjusted so that heart rate and blood pressure of the model fit to those of the experiment. It was shown that the model can quantitatively reproduce and predict experimental heart rate and blood pressure during a parabolic flight. Analysis of internal property of the model revealed hemodynamics of the human cardiovascular system during a parabolic flight which explains the mechanisms of cardiovascular responses under hyper- and hypo-gravitational environments.

Blood Pressure↗

Effectiveness of aggressive management of dyslipidemia in a collaborative-care practice model.

The Cardiovascular Risk Identification and Treatment Center was established in 1997, adopting a collaborative-care clinic model for the purpose of improving the management of high-risk patients with dyslipidemia. This was a retrospective analysis of 417 high-risk patients with > or =1 year of follow-up laboratory data. Analysis included changes in total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, triglycerides, and total cholesterol to HDL ratio; lipoprotein goal achievement; Framingham risk score; liver function; and cardiovascular events. At baseline, 66% of patients had coronary heart disease (CHD) or equivalent risk, 45% were not receiving dyslipidemia therapy, and 29% were on statin monotherapy. After 3 years in the program, 56% were receiving combination therapy, 41% were on monotherapy, and 2% were not on therapy. The 3 most common treatment regimens were statin plus niacin (36%), statin alone (22%), and niacin alone (14%). All lipoproteins improved from baseline (p <0.001). Overall, 62% to 74% of patients reached singular lipid goals and 35% achieved combined lipid goals. Patients with Framingham 10-year CHD risk of >20% were reduced from 6% to <1%. Only 29 patients (7.0%) had a cardiovascular event, including 5 (1.0%) who experienced a myocardial infarction. Aspartate aminotransferase/alanine transferase elevation >3 times normal occurred in 1% of patients. In conclusion, a collaborative-care practice model adopting individualized, aggressive pharmacologic and nonpharmacologic treatment strategies is highly effective in achieving lipid goals, is sustainable, and is safe. Furthermore, this approach yields reduced projected 10-year CHD risk. A low rate of cardiovascular events was observed.

Adult↗

Computer modeling of non-adjacent regional ischemic zones on ventricular function.

Multiple regional myocardial ischemia that leads to depressed left ventricular (LV) function is commonplace. Quantitative analysis of the hemodynamic consequences, however, has been limited. We investigated this aspect using a novel computer model of the cardiovascular system. The model consists of an LV with two ischemic zones (IZs) and a normal zone (NZ), the preload, and the arterial system afterload. The IZ size and activation timing could be altered. Results show that the greater the size and activation asynchronization between NZ and IZ, the more severe the LV dysfunction. Increased preload during ischemia improved LV function. This computer model predicts features that agree well with reported experimental observations and is particularly useful for myocardial ischemic function analysis.

Animals↗

Theoretical analysis of rest and exercise hemodynamics in patients with total cavopulmonary connection.

The objective of this study was to determine the impact of a total cavopulmonary connection on the main hemodynamic quantities, both at rest and during exercise, when compared with normal biventricular circulation. The analysis was performed by means of a mathematical model of the cardiovascular system. The model incorporates the main parameters of systemic and pulmonary circulation, the pulsating heart, and the action of arterial and cardiopulmonary baroreflex mechanisms. Furthermore, the effect of changes in intrathoracic pressure on venous return is also incorporated. Finally, the response to moderate dynamic exercise is simulated, including the effect of a central command, local metabolic vasodilation, and the "muscle pump" mechanism. Simulations of resting conditions indicate that the action of baroreflex regulatory mechanisms alone can only partially compensate for the absence of the right heart. Cardiac output and mean systemic arterial pressure at rest show a large decrease compared with the normal subject. More acceptable hemodynamic quantity values are obtained by combining the action of regulatory mechanisms with a chronic change in parameters affecting mean filling pressure. With such changes assumed, simulations of the response to moderate exercise show that univentricular circulation exhibits a poor capacity to increase cardiac output and to sustain aerobic metabolism, especially when the oxygen consumption rate is increased above 1.2-1.3 l/min. The model ascribes the poor response to exercise in these patients to the incapacity to sustain venous return caused by the high resistance to venous return and/or to exhaustion of volume compensation reserve.

Blood Pressure↗

Subband modeling of the human cardiovascular system: new insights into cardiovascular regulation.

We present a new approach to cardiovascular analysis based on a well-known signal processing technique, namely, the frequency subband decomposition. The subbands are chosen in accordance with physiological standards: (1) 0-0.04 Hz, (2) 0.04-0.15 Hz, (3) 0.15-0.4 Hz. It is shown that such a pre-processing drastically improves the accuracy of the analysis and introduces a new direction in the understanding of the relationships between cardiovascular signals.

Adult↗

Correspondence between laboratory and ambulatory measures of cardiovascular reactivity: a multilevel modeling approach.

We examined the correspondence between laboratory measures of cardiovascular reactivity (CVR) and within-person changes in cardiovascular activity during the challenges of daily life, after adjustment for posture, activity, and other effects. Healthy adults (n = 335) were administered laboratory measures of CVR along with 6 days of ambulatory blood pressure monitoring and electronic diary reports. Compared with low reactors, high laboratory systolic blood pressure (SBP) reactors showed larger increases in SBP during periods of high task demand or low decisional control in daily life. High diastolic blood pressure (DBP) reactors showed larger increases in ambulatory DBP during situations rated as both low control and high demand. This multilevel modeling approach may enhance our ability to detect the correspondence between laboratory and ambulatory measures of CVR, and to identify the circumstances under which it may be most clearly observed.

Aged↗