Transport of nitrite from large arteries modulates regional blood flow during stress and exercise.

Background: Acute cardiovascular stress increases systemic wall shear stress (WSS)-a frictional force exerted by the flow of blood on vessel walls-which raises plasma nitrite concentration due to enhanced endothelial nitric oxide synthase (eNOS) activity. Upstream eNOS inhibition modulates distal perfusion, and autonomic stress increases both the consumption and vasodilatory effects of endogenous nitrite. Plasma nitrite maintains vascular homeostasis during exercise and disruption of nitrite bioavailability can lead to intermittent claudication. Hypothesis: During acute cardiovascular stress or strenuous exercise, we hypothesize enhanced production of nitric oxide (NO) by vascular endothelial cells raises nitrite concentrations in near-wall layers of flowing blood, resulting in cumulative NO concentrations in downstream arterioles sufficient for vasodilation. Confirmation and implications: Utilizing a multiscale model of nitrite transport in bifurcating arteries, we tested the hypothesis for femoral artery flow under resting and exercised states of cardiovascular stress. Results indicate intravascular transport of nitrite from upstream endothelium could result in vasodilator-active levels of nitrite in downstream resistance vessels. The hypothesis could be confirmed utilizing artery-on-a-chip technology to measure NO production rates directly and help validate numerical model predictions. Further characterization of this mechanism may improve our understanding of symptomatic peripheral artery occlusive disease and exercise physiology.

Method for estimating pulsatile wall shear stress from one-dimensional velocity waveforms.

Wall shear stress (WSS)-a key regulator of endothelial function-is commonly estimated in vivo using simplified mathematical models based on Poiseuille's flow, assuming a quasi-steady parabolic velocity distribution, despite evidence that more rapidly time-varying, pulsatile blood flow during each cardiac cycle modulates flow-mediated dilation (FMD) in large arteries of healthy subjects. More exact and accurate models based on the well-established Womersley solution for rapidly changing blood flow have not been adopted clinically, potentially because the Womersley solution relies on the local pressure gradient, which is difficult to measure non-invasively. We have developed an open-source method for automatic reconstruction of unsteady, Womersley-derived velocity profiles, and WSS in conduit arteries. The proposed method (available online at https://doi.org/10.5281/zenodo.7576408) requires only the time-averaged diameter of the vessel and time-varying velocity data available from non-invasive imaging such as Doppler ultrasound. Validation of the method with subject-specific computational fluid dynamics and application to synthetic velocity waveforms in the common carotid, brachial, and femoral arteries reveals that the Poiseuille solution underestimates peak WSS 38.5%-55.1% during the acceleration and deceleration phases of systole and underestimates or neglects retrograde WSS. Following evidence that oscillatory shear significantly augments vasodilator production, it is plausible that mischaracterization of the shear stimulus by assuming parabolic flow leads to systematic underestimates of important biological effects of time-varying blood velocity in conduit arteries.

Hemodynamic modeling of the circle of Willis reveals unanticipated functions during cardiovascular stress.

The circle of Willis (CW) allows blood to be redistributed throughout the brain during local ischemia; however, it is unlikely that the anatomic persistence of the CW across mammalian species is driven by natural selection of individuals with resistance to cerebrovascular disease typically occurring in elderly humans. To determine the effects of communicating arteries (CoAs) in the CW on cerebral pulse wave propagation and blood flow velocity, we simulated young, active adult humans undergoing different states of cardiovascular stress (i.e., fear and aerobic exercise) using discrete transmission line segments with stress-adjusted cardiac output, peripheral resistance, and arterial compliance. Phase delays between vertebrobasilar and carotid pulses allowed bidirectional shunting through CoAs: both posteroanterior shunting before the peak of the pulse waveform and anteroposterior shunting after internal carotid pressure exceeded posterior cerebral pressure. Relative to an absent CW without intact CoAs, the complete CW blunted anterior pulse waveforms, although limited to 3% and 6% reductions in peak pressure and pulse pressure, respectively. Systolic rate of change in pressure (i.e., ∂P/∂t) was reduced 15%-24% in the anterior vasculature and increased 23%-41% in the posterior vasculature. Bidirectional shunting through posterior CoAs was amplified during cardiovascular stress and increased peak velocity by 25%, diastolic-to-systolic velocity range by 44%, and blood velocity acceleration by 134% in the vertebrobasilar arteries. This effect may facilitate stress-related increases in blood flow to the cerebellum (improving motor coordination) and reticular-activating system (enhancing attention and focus) via a nitric oxide-dependent mechanism, thereby improving survival in fight-or-flight situations.NEW & NOTEWORTHY Hemodynamic modeling reveals potential evolutionary benefits of the intact circle of Willis (CW) during fear and aerobic exercise. The CW equalizes pulse waveforms due to bidirectional shunting of blood flow through communicating arteries, which boosts vertebrobasilar blood flow velocity and acceleration. These phenomena may enhance perfusion of the brainstem and cerebellum via nitric oxide-mediated vasodilation, improving performance of the reticular-activating system and motor coordination in survival situations.

A comparison of feature selection methods for the detection of breast cancers in mammograms: adaptive sequential floating search vs. genetic algorithm.

This paper presents a comparison of feature selection methods for a unified detection of breast cancers in mammograms. A set of features, including curvilinear features, texture features, Gabor features, and multi-resolution features, were extracted from a region of 512x512 pixels containing normal tissue or breast cancer. Adaptive floating search and genetic algorithm were used for the feature selection, and a linear discriminant analysis (LDA) was used for the classification of cancer regions from normal regions. The performance is evaluated using Az the area under ROC curve. On a dataset consisting 296 normal regions and 164 cancer regions (53 masses, 56 spiculated lesions, and 55 calcifications), adaptive floating search achieved Az = 0.96 with comparison to Az = 0.93 of CHC genetic algorithm and Az = 0.90 of simple genetic algorithm.

Consensus evidence evaluation in resuscitation research: analysis of Type I and Type II errors.

OBJECTIVE: This paper addresses the following statistical question: 'if genuine improvements in cardiopulmonary resuscitation (CPR) were discovered that doubled the probability of resuscitation success in a series of randomized clinical trials, would they be recognized and incorporated into consensus guidelines?'. METHODS: Statistical powers for hypothetical individual clinical trials comparing experimental and control CPR were computed as a function of the study N when the true probabilities for immediate survival, 24 h survival, and discharge survival in the experimental group were twice those in the control group. Next, the binomial distributions describing the numbers of statistically significant studies in a series of equally powered trials of the same intervention were determined. These were compared with varying criteria for consensus among expert reviewers, expressed in terms of the number of 'positive' studies showing a statistically significant difference that reviewers would require before approving the experimental method. RESULTS: False-negative evaluations (i.e. failures to approve a technique that actually doubled survival) were extremely common under a wide range of realistic assumptions and consensus criteria, especially when simulated long-term survival data were considered. Similar methods showed that false-positive evaluations would be extremely rare, provided that at least two of the clinical trials in a series showed a statistically significant benefit of the experimental method. CONCLUSIONS: Optimization of evidence evaluation can and should be carried out to make better use of available data in creating resuscitation guidelines. One simple approach is the 'two and one quarter test': if at least two well-conducted studies in a series are significantly positive (P<0.05) comprising at least one-quarter of all studies in the series, a positive effect can be inferred with small Type I and Type II errors. In addition, greater reliance on modern, unbiased methods such as cumulative meta-analysis is needed to increase the sensitivity of evidence evaluation for detecting useful innovations in resuscitation.

Biomechanics of heading a soccer ball: implications for player safety.

To better understand the risk and safety of heading a soccer ball, the author created a set of simple mathematical models based upon Newton's second law of motion to describe the physics of heading. These models describe the player, the ball, the flight of the ball before impact, the motion of the head and ball during impact, and the effects of all of these upon the intensity and the duration of acceleration of the head. The calculated head accelerations were compared to those during presumably safe daily activities of jumping, dancing, and head nodding and also were related to established criteria for serious head injury from the motor vehicle crash literature. The results suggest heading is usually safe but occasionally dangerous, depending on key characteristics of both the player and the ball. Safety is greatly improved when players head the ball with greater effective body mass, which is determined by a player"s size, strength, and technique. Smaller youth players, because of their lesser body mass, are more at risk of potentially dangerous headers than are adults, even when using current youth size balls. Lower ball inflation pressure reduces risk of dangerous head accelerations. Lower pressure balls also have greater "touch" and "playability", measured in terms of contact time and contact area between foot and ball during a kick. Focus on teaching proper technique, the re-design of age-appropriate balls for young players with reduced weight and inflation pressure, and avoidance of head contact with fast, rising balls kicked at close range can substantially reduce risk of subtle brain injury in players who head soccer balls.

Efficacy of interposed abdominal compression-cardiopulmonary resuscitation (CPR), active compression and decompression-CPR and Lifestick CPR: basic physiology in a spreadsheet model.

This study was undertaken to understand and predict results of experimental cardiopulmonary resuscitation (CPR) techniques involving compression and decompression of either the chest or the abdomen. Simple mathematical models of the adult human circulation were used. Assumptions of the models are limited to normal human anatomy and physiology, the definition of compliance (volume change/pressure change), and Ohm's law (flow = pressure/resistance). Interposed abdominal compression-CPR, active compression and decompression of the chest, and Lifestick CPR, which combines interposed abdominal compression and active compression and decompression, produce, respectively, 1.9-, 1.2-, and 2.4-fold greater blood flow than standard CPR and systemic perfusion pressures of 45, 30, and 58 mm Hg, respectively. These positive effects are explained by improved pump priming and are consequences of fundamental principles of cardiovascular physiology.

CPR techniques that combine chest and abdominal compression and decompression: hemodynamic insights from a spreadsheet model.

BACKGROUND: This study was done to elucidate mechanisms by which newer cardiopulmonary resuscitation (CPR) techniques, including interposed abdominal compression (IAC), active compression-decompression (ACD), and Lifestick CPR, augment systemic perfusion pressure and forward flow and to compare the 3 techniques in the same test system. METHODS AND RESULTS: Mathematical models describing hemodynamics of the adult human circulation during cardiac arrest and CPR were created and exercised by use of spreadsheet software. Assumptions of the models are limited to normal human anatomy and physiology, the definition of compliance (volume change/pressure change), and Ohm's law (flow=pressure/resistance). Standard CPR generates 1.3 L/min forward and 25 mm Hg systemic perfusion pressure. In otherwise identical models, IAC-CPR generates 2.4 L/min and 45 mm Hg; ACD-CPR, 1.6 L/min and 30 mm Hg; and Lifestick CPR, which combines IAC and ACD, 3.1 L/min and 58 mm Hg. Augmented CPR techniques work by enhanced priming of either chest or abdominal pump mechanisms. CONCLUSIONS: Adjunctive maneuvers, combined with conventional chest compression, can produce substantial hemodynamic benefit in CPR by credible physiological mechanisms.

Ventricular defibrillating threshold: strength-duration and percent-success curves.

The term defibrillation threshold is usually understood to mean the shock intensity just enough to defibrillate a specified cardiac chamber (atria or ventricles). With the advent of so many different types of defibrillator, it is important to be able to specify the defibrillation threshold, which has frequently been described by the classical strength-duration curve. Another method of representing defibrillation plots the percent-successful defibrillation against shock-strength area. The mechanism of defibrillation is discussed, and the concepts of the strength-duration curve and percent-success against shock-strength curves are compared. Because defibrillation is associated with a time-varying spectrum of cellular excitability, a given shock strength will not always achieve defibrillation, and this produces the sigmoid shape for the curve that relates percent-successful defibrillation to shock strength. Therefore it is important to recognise two concepts: first, there is a family of strength-duration curves for defibrillation, each curve representing a given percent-successful defibrillation, and, secondly, there is a family of percent-success against shock-strength curves, one for each pulse duration. Canine ventricular defibrillation data are used to bring these two concepts together. Most importantly, the concepts adduced in the paper apply to transventricular, intracardiac and transchest defibrillation; the only difference in these applications is a scale factor that represents electrode location with respect to the heart.

Maintenance of atrial fibrillation in anesthetized and unanesthetized sheep using cholinergic drive.

Atrial fibrillation (AF) was induced electrically and the duration of AF was measured in six isoflurane-anesthetized sheep (weight range 54.5-72.7 kg), and in five unanesthetized sheep (weight range 60-75 kg). In the anesthetized sheep, AF was induced by direct electrical stimulation of the right atrium with a catheter electrode and the duration of AF was determined. Intravenous neostigmine (10 micrograms/kg IV) was administered and the duration of AF was again measured. Then cholinergic drive was increased by bilateral electrical vagal stimulation; AF was induced and the duration of AF was measured. In the anesthetized animals with no neostigmine or vagal stimulation, 34% of the episodes of AF lasted 10 seconds, 11% lasted 20 seconds, and only 1% lasted 200 seconds. However, in one anesthetized animal AF was sustained for 4,800 seconds with no drug or vagal support. The administration of neostigmine alone in 3 anesthetized animals more than doubled the average duration of AF. In the animals with vagal stimulation (after neostigmine), AF persisted throughout stimulation, but ceased shortly after vagal stimulation was terminated at 2,220, 4,500, and 3,840 seconds. The AF frequency ranged from 325-750/min. The unanesthetized sheep were lightly sedated with a small dose (200 micrograms/kg IM) of xylazine to make them less sensitive to environmental noise; then AF was induced and its duration was timed. After these measurements, neostigmine was administered (30 micrograms/kg IM) and cholinergic drive was produced reflexly by intravenous injection of 60-2,000 micrograms of phenylephrine. AF was electrically induced at the time of maximum reflex slowing in heart rate. For the control (no drug) studies, 64% of the AF episodes lasted 10 seconds, 20% lasted 20 seconds, and only 2% of the episodes lasted as long as 140 seconds. When phenylephrine was injected after neostigmine to provide increased cholinergic drive, the duration of fibrillation depended on the dose of phenylephrine. In a 60-kg sheep, the duration of AF increased from 1 second with an intravenous dose of 60 micrograms to 700 seconds with an intravenous dose of 2,000 micrograms. However, there was a considerable range in responsiveness to the reflex cholinergic drive provided by the intravenous phenylephrine; for example a single intravenous 500-micrograms dose produced AF ranging from 190-540 seconds among the sheep. The duration of AF was most controllable in the anesthetized sheep, following neostigmine administration and with bilateral vagal stimulation. In the unanesthetized sheep, AF could generally be sustained for more than the duration of the half-life (about 4 minutes) of phenylephrine following neostigmine. However, there was a large variation in the duration of AF among the animals for the same dose of phenylephrine. This study identifies two methods (direct vagal stimulation and reflex vagal stimulation) for providing the cholinergic drive needed to sustain AF in the adult sheep. The duration of AF is sufficiently long to enable the measurement of electrical atrial defibrillation threshold.

Theoretically optimal duty cycles for chest and abdominal compression during external cardiopulmonary resuscitation.

OBJECTIVE: To use an electronic model of human circulation to compare the hemodynamic effects of different durations of chest compression during external CPR, both with and without interposed abdominal compression (IAC). METHODS: An electrical analog model of human circulation was studied on digital computer workstations using SPICE, a general-purpose circuit simulation program. In the model the heart and blood vessels were represented as resistive-capacitive networks, pressures as voltages, blood flow as electric current, blood inertia as inductance, and cardiac and venous valves as diodes. External pressurization of the heart and great vessels, as would occur in IAC-CPR, was simulated by the alternate application of damped rectangular voltage pulses, first between intrathoracic vascular capacitances and ground, and then between intra-abdominal vascular capacitances and ground. With this model compression frequencies of 60, 80, and 100 cycles/min and duty cycles ranging from 10% to 90%, both with and without IAC, were compared. RESULTS: There was little difference in hemodynamics when the overall compression frequency was varied between 60 and 100 cycles/min, but the effects of duty cycle were substantial. During both standard CPR and IAC-CPR, total flow and coronary flow were greatest at chest compression durations equal to 30% of cycle time. Interposed abdominal compression substantially improved simulated systemic blood flow and perfusion pressure at all duty cycles, compared with standard CPR without abdominal compression. Mean arterial pressure > 75 mm Hg and artificial cardiac output > 2.0 L/min could be generated by 30% duty cycle compression with IAC. Coronary perfusion in the model is clearly optimized at 30% chest compression (i.e., high-impulse chest compression technique). CONCLUSION: Combined high-impulse chest compressions and IACs maximize blood flow during CPR in the electrical analog model of human circulation.

Preclinical ROC studies of digital stereomammography.

Reports the diagnostic performance of observers in detecting abnormalities in computer-generated mammogram-like images. A mathematical model of the human breast is defined in which breast tissues are simulated by spheres of different sizes and densities. Images are generated by casting rays from a specified source, through the model, and onto an image plane. Observer performance when using two viewing modalities (stereo versus mono) is compared. In the stereo viewing mode, images are presented to the observer (wearing liquid-crystal display glasses), such that the left eye sees the left image only and the right eye sees the right image only. In this way, the images can be fused by the observer to obtain a sense of depth. In the mono viewing mode, identical images are presented to the left and right eyes so that no binocular disparities will be produced by the images. Observer response data are evaluated using receiver operating characteristic (ROC) analysis to characterize any difference in detectability of abnormalities (in either the density or the arrangement of simulated tissue densities) using the two viewing modes. The authors' experimental results indicate the clear superiority of stereo viewing for detection of arrangement abnormalities. For detection of density abnormalities, the performance of the two viewing modes is similar. These preliminary results suggest that stereomammography may permit easier detection of certain tissue abnormalities, perhaps providing a route to earlier tumor detection in cases of breast cancer.

The evolution of abdominal compression in cardiopulmonary resuscitation.

OBJECTIVE: To review the history of external abdominal compression as an adjunct to cardiopulmonary resuscitation (CPR), tracking the development of five major themes over the course of the 20th century: 1) augmentation of peripheral resistance by physical means, 2) risk of hepatic injury with abdominal compression, 3) counterpulsation vs sustained compression, 4) the abdominal pump mechanism, and 5) contact compression techniques. METHODS: Literature retrieved from successive MEDLINE English-language searches was received with a special emphasis on work and concepts highlighted by participants at the First Purdue Conference on Interposed Abdominal Compression-CPR, September 1992. RESULTS: External abdominal compression of one form or another has been studied as a means of resuscitation by many investigators throughout the 20th century. Experimental and clinical studies have shown generally consistent evidence of hemodynamic augmentation by abdominal compression during various forms of CPR. Recent advances include a modified theoretical understanding of hemodynamic mechanisms and demonstration of clinical potential in humans. Inconsistencies in published results may be due to differences in mechanical techniques of abdominal compression. Based on these studies, a modified manual technique for "contact compression" of the abdominal aorta is recommended. CONCLUSIONS: A technique for left-of-center, angled compression of the abdominal aorta against the crest of the spine is recommended. Further well-supervised and controlled clinical trials using this standardized technique are warranted as a prelude to more widespread clinical application of abdominal compression in CPR.

Interposed abdominal compression as an adjunct to cardiopulmonary resuscitation.

The addition of IAC to otherwise standard CPR provides for the application of external pressure over the abdomen in counterpoint to the rhythm of chest compression. Interposed abdominal compression is a simple manual technique that can supplement the use of adrenergic drugs to increase both coronary perfusion pressure and total blood flow during CPR. Mechanistically, manual abdominal compressions induce both central aortic and central venous pressure pulses. However, owing to differences in venous versus arterial capacitance, the former are usually greater than the latter, so that systemic perfusion pressure is enhanced. Moreover, practical experience and theoretical analysis have suggested subtle refinements in the hand position and technique for abdominal compression that may further improve the ratio of arterial to venous pressure augmentation. Clinical studies confirm that IAC-CPR can improve perfusion pressures and carbon dioxide excretion during CPR in humans. The incidence of abdominal trauma, regurgitation, or other complications is not increased by IAC. Recently, randomized trials have shown that short-term and long-term survival of patients resuscitated in the hospital by IAC-CPR are about twice that of control patients resuscitated by standard CPR. The technique of IAC has thus evolved to become a highly promising adjunct to normal CPR, which is likely to be implemented in an increasing number of clinical protocols in the 1990s.