Rapid and Efficient Computation of Cell Paths During Ultrasonic Focusing.

This biophysical analysis explores the first-principles physics of movement of white blood cell sized particles, suspended in an aqueous fluid and experiencing progressive or standing waves of acoustic pressure. In many current applications the cells are gradually nudged or herded toward the nodes of the standing wave, providing a degree of acoustic focusing and concentration of the cells in layers perpendicular to the direction of sound propagation. Here the underlying biomechanics of this phenomenon are analyzed specifically for the viscous regime of water and for small diameter microscopic spheroids such as living cells. The resulting mathematical model leads to a single algebraic expression for the creep or drift velocity as a function of sound frequency, amplitude, wavelength, fluid viscosity, boundary dimensions, and boundary reflectivity. This expression can be integrated numerically by a simple and fast computer algorithm to demonstrate net movement of particles as a function of time, providing a guide to optimization in a variety of emerging applications of ultrasonic cell focusing.

A compact theory of magnetic nerve stimulation: predicting how to aim.

BACKGROUND: A compact theory that predicts quantitatively when and where magnetic neurostimulation will occur is needed as a guide to therapy, ideally providing a single equation that defines the target volume of tissue excited by single or dual coils. METHODS: A first-principles analysis of magnetic stimulation incorporating a simplified description of electromagnetic fields and a simplified cable theory of the axon yields a mathematical synthesis predicting how to aim. RESULTS: Nerve stimulation produced by a single circular coil having one or more closely packed turns occurs in donut shaped volume of tissue beneath the coil. Axons spanning several millimeters are the sites of magnetic stimulation. The sites of maximal transmembrane depolarization in nerve fibers correspond to points where the axons enter or exit this volume of magnetically induced voltage and current. The axonal membrane at one end is depolarized locally during the rising phase of current in the coil. The axonal membrane at the opposite end is depolarized locally during the falling phase of current in the coil. Penetration depths of several centimeters from the skin surface or approximately one to two coil radii are practical. With two coils placed in a figure-of-eight configuration the separate clockwise and counterclockwise currents generate magnetic fields that add, producing maximal stimulation of a spindle shaped volume, centered at a depth of one-third to one-half coil radius from the body surface. CONCLUSIONS: This condensed synthesis of electromagnetic theory and cable theories of axon physiology provides a partial solution to the targeting problem in peripheral and in transcranial magnetic stimulation.

Noninvasive measurement of cardiac stroke volume using pulse wave velocity and aortic dimensions: a simulation study.

BACKGROUND: Concerns about the cost-effectiveness of invasive hemodynamic monitoring in critically ill patients using pulmonary artery catheters motivate a renewed search for effective noninvasive methods to measure stroke volume. This paper explores a new approach based on noninvasively measured pulse wave velocity, pulse contour, and ultrasonically determined aortic cross sectional area. METHODS: The Bramwell-Hill equation relating pulse wave velocity to aortic compliance is applied. At the time point on the noninvasively measured pulse contour, denoted th, when pulse amplitude has fallen midway between systolic and diastolic values, the portion of stroke volume remaining in the aorta, and in turn the entire stroke volume, can be estimated from the compliance and the pulse waveform. This approach is tested and refined using a numerical model of the systemic circulation including the effects of blood inertia, nonlinear compliance, aortic tapering, varying heart rate, and varying myocardial contractility, in which noninvasively estimated stroke volumes were compared with known stroke volumes in the model. RESULTS: The Bramwell-Hill approach correctly allows accurate calculation of known, constant aortic compliance in the numerical model. When nonlinear compliance is present the proposed noninvasive technique overestimates true aortic compliance when pulse pressure is large. However, a reasonable correction for nonlinearity can be derived and applied to restore accuracy for normal and for fast heart rates (correlation coefficient > 0.98). CONCLUSIONS: Accurate estimates of cardiac stroke volume based on pulse wave velocity are theoretically possible and feasible. The precision of the method may be less than desired, owing to the dependence of the final result on the square of measured pulse wave velocity and the first power of ultrasonically measured aortic cross sectional area. However, classical formulas for propagation of random errors suggest that the method may still have sufficient precision for clinical applications. It remains as a challenge for experimentalists to explore further the potential of noninvasive measurement of stroke volume using pulse wave velocity. The technique is non-proprietary and open access in full detail, allowing future users to modify and refine the method as guided by practical experience.

Optimizing electrode placement for hemodynamic benefit in cardiac resynchronization therapy.

BACKGROUND: Research is needed to explore the relative benefits of alternative electrode placements in biventricular and left ventricular (LV) pacing for heart failure with left bundle branch block (LBBB). METHODS: A fast computational model of the left ventricle, running on an ordinary laptop computer, was created to simulate the spread of electrical activation over the myocardial surface, together with the resulting electrocardiogram, segmental wall motion, stroke volume, and ejection fraction in the presence of varying degrees of mitral regurgitation. Arbitrary zones of scar and blocked electrical conduction could be modeled. RESULTS: Simulations showed there are both sweet spots and poor spots for LV electrode placement, sometimes separated by only a few centimeters. In heart failure with LBBB, pacing at poor spots can produce little benefit or even reduce pumping effectiveness. Pacing at sweet spots can produce up to 35% improvement in ejection fraction. Relatively larger benefit occurs in dilated hearts, in keeping with the greater disparity between early and late activated muscle. Sweet spots are typically located on the basal to midlevel, inferolateral wall. Poor spots are located on or near the interventricular septum. Anteroapical scar with conduction block causes little shift in locations for optimal pacing. Hearts with increased passive ventricular compliance and absence of preejection mitral regurgitation exhibit greater therapeutic gain. The durations and wave shapes of QRS complexes in the electrocardiogram can help predict optimum electrode placement in real time. CONCLUSIONS: Differences between poor responders and hyperresponders to cardiac resynchronization therapy can be understood in terms of basic anatomy, physiology, and pathophysiology. Computational modeling suggests general strategies for optimal electrode placement. In a given patient heart size, regional pathology and regional dynamics allow individual pretreatment planning to target optimal electrode placement.

Oscillometric measurement of systolic and diastolic blood pressures validated in a physiologic mathematical model.

BACKGROUND: The oscillometric method of measuring blood pressure with an automated cuff yields valid estimates of mean pressure but questionable estimates of systolic and diastolic pressures. Existing algorithms are sensitive to differences in pulse pressure and artery stiffness. Some are closely guarded trade secrets. Accurate extraction of systolic and diastolic pressures from the envelope of cuff pressure oscillations remains an open problem in biomedical engineering. METHODS: A new analysis of relevant anatomy, physiology and physics reveals the mechanisms underlying the production of cuff pressure oscillations as well as a way to extract systolic and diastolic pressures from the envelope of oscillations in any individual subject. Stiffness characteristics of the compressed artery segment can be extracted from the envelope shape to create an individualized mathematical model. The model is tested with a matrix of possible systolic and diastolic pressure values, and the minimum least squares difference between observed and predicted envelope functions indicates the best fit choices of systolic and diastolic pressure within the test matrix. RESULTS: The model reproduces realistic cuff pressure oscillations. The regression procedure extracts systolic and diastolic pressures accurately in the face of varying pulse pressure and arterial stiffness. The root mean squared error in extracted systolic and diastolic pressures over a range of challenging test scenarios is 0.3 mmHg. CONCLUSIONS: A new algorithm based on physics and physiology allows accurate extraction of systolic and diastolic pressures from cuff pressure oscillations in a way that can be validated, criticized, and updated in the public domain.

Heart rate and age modulate retinal pulsatile patterns.

Theoretical models of retinal hemodynamics showed the modulation of retinal pulsatile patterns (RPPs) by heart rate (HR), yet in-vivo validation and scientific merit of this biological process is lacking. Such evidence is critical for result interpretation, study design, and (patho-)physiological modeling of human biology spanning applications in various medical specialties. In retinal hemodynamic video-recordings, we characterize the morphology of RPPs and assess the impact of modulation by HR or other variables. Principal component analysis isolated two RPPs, i.e., spontaneous venous pulsation (SVP) and optic cup pulsation (OCP). Heart rate modulated SVP and OCP morphology (pFDR < 0.05); age modulated SVP morphology (pFDR < 0.05). In addition, age and HR demonstrated the effect on between-group differences. This knowledge greatly affects future study designs, analyses of between-group differences in RPPs, and biophysical models investigating relationships between RPPs, intracranial, intraocular pressures, and cardiovascular physiology.

Behavior of a viscoelastic valveless pump: a simple theory with experimental validation.

BACKGROUND: A valveless pump generates a unidirectional net flow of fluid around a closed loop of soft viscoelastic tubing that is rhythmically compressed at one point. The tubing must have at least two sections with two different stiffnesses. When a short segment of the tube is squeezed asymmetrically at certain frequencies, net flow of fluid around the loop can occur without valves. METHODS: Partial differential equations for the pressures, volumes, and flows define a simple one-dimensional model of such a pump, based upon elementary physical principles. Numerical computations on a personal computer can predict measured net flows. RESULTS: Net flow varies with the frequency and waveform of compression used to excite the pump, as well as with the site of compression and the stiffness and viscosity of the tubing. Net flows on the order of 1 ml/sec are obtained in a water-filled loop including 46 cm of stiffer plastic (Tygon) laboratory tubing and 70 cm of softer latex rubber tubing. CONCLUSIONS: The heretofore mysterious phenomenon of valveless pumping can be described in terms of classical Newtonian physics, in which viscous damping in the walls of the pump is included. Studying valveless pumps in the laboratory and modeling their behavior numerically provides a low-cost, engaging, and instructive exercise for research and teaching in biomedical engineering.

High expression of obesity-linked phosphatase SHIP2 in invasive breast cancer correlates with reduced disease-free survival.

SH2-containing 5'-inositol phosphatase (SHIP2) is a known regulator of insulin function. Genetic knockout of SHIP2 in mice causes mild insulin hypersensitivity and prevents high-fat-diet-induced obesity. SHIP2 also regulates actin remodeling and epidermal growth factor receptor (EGFR) turnover and supports breast cancer; and metastatic growth. To determine the clinical significance of SHIP2 expression in breast cancer and its relationship to relevant oncogenic molecules, SHIP2 expression was determined immunohistochemically in 285 primary breast cancers; 140 ductal carcinomas in situ (DCIS) and 145 invasive carcinomas. Forty-five percent of the specimens showed high SHIP2 levels in cancer cells while only 15% of adjacent normal cells expressed high SHIP2 levels (p < 0.0001). In cancer cells, the risk of SHIP2 overexpression is elevated (a) in women aged < or =50 years (relative risk, RR = 4.13; 95% confidence interval, CI, 2.5-6.9) compared to women aged >50 years (RR = 2.37; 95% CI 1.6-3.5; p = 0.0003), and (b) in invasive carcinomas (RR = 3.52; 95% CI 2.3-5.5) compared with DCIS (RR = 2.22; 95% CI 1.5-3.5; p = 0.0009). Patients with higher SHIP2 levels in invasive carcinomas had significantly reduced disease-free (p = 0.0025) and overall survival periods (p = 0.0228). In invasive carcinomas, SHIP2 correlated with estrogen receptor absence (p = 0.003) and EGFR presence (p = 0.0147). In conclusion, SHIP2 is an important biomarker for breast cancer.

Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway.

Skeletal muscle atrophy results from an imbalance in protein degradation and protein synthesis and occurs in response to injury, various disease states, disuse, and normal aging. Current treatments for this debilitating condition are inadequate. More information about mechanisms involved in the onset and progression of muscle atrophy is necessary for development of more effective therapies. Here we show that expression of the mouse ether-a-go-go related gene (Merg1a) K+ channel is up-regulated in skeletal muscle of mice experiencing atrophy as a result of both malignant tumor expression and disuse. Further, ectopic expression of Merg1a in vivo induces atrophy in healthy wt-bearing mice, while expression of a dysfunctional Merg1a mutant suppresses atrophy in hindlimb-suspended mice. Treatment of hindlimb-suspended mice with astemizole, a known Merg1a channel blocker, inhibits atrophy in these animals. Importantly, in vivo expression of Merg1a in mouse skeletal muscle activates the ubiquitin proteasome pathway that is responsible for the majority of protein degradation that causes muscle atrophy, yet expression of a dysfunctional Merg1a mutant decreases levels of ubiquitin-proteasome proteolysis. Thus, expression of Merg1a likely initiates atrophy by activating ubiquitin-proteasome proteolysis. This gene and its product are potential targets for prevention and treatment of muscle atrophy.

Statistical analysis of joint short-term and long-term survival in resuscitation research.

OBJECTIVE: To develop statistical tools that use combined initial survival data and post-resuscitation survival data to test the null hypothesis that true, population-wide outcomes following experimental CPR interventions are not different from control. METHOD: A new test statistic, d(2), for evaluating Type 1 error is derived from a bivariate, two-dimensional analysis of categorical initial resuscitation and post-resuscitation survival data, which are statistically independent because they are obtained during non-overlapping periods of time. The d(2) test statistic, which is distributed as a chi-squared distribution, is derived from first principles and validated using Monte Carlo methods of computer simulation for thousands of clinical trials. RESULTS: Under the null hypothesis, the normalized difference in the proportions of patients surviving the initial resuscitation period and the normalized difference in the proportions of such short-term survivors that also survive the post-resuscitation period are jointly distributed in a two-dimensional space as a bivariate standard normal distribution, against which observed intervention and control outcomes can be compared in a test of statistical significance. Typically this two-dimensional approach has greater statistical power to detect true differences, compared to conventional one-dimensional tests. Smaller group sizes (Ns) are usually required to reach statistical significance when both initial survival and post-resuscitation survival are considered together. Such two-dimensional analysis is easily extended to meta-analysis of multiple trials. CONCLUSIONS: A straightforward, easy-to-use bivariate test for Type I errors in statistical inference can be done for resuscitation studies reporting both short-term and long-term survival data. Acceptance of such two-dimensional tests of the null hypothesis, as proposed by Hallstrom, can save time, money, effort, and disappointment in the difficult and sometimes frustrating field of resuscitation research.

Sustained abdominal compression during CPR raises coronary perfusion pressures as much as vasopressor drugs.

OBJECTIVES: This study investigated sustained abdominal compression as a means to improve coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) and compared the resulting CPP augmentation with that achieved using vasopressor drugs. METHOD: During electrically induced ventricular fibrillation in anesthetized, 30kg juvenile pigs, Thumper CPR was supplemented at intervals either by constant abdominal compression at 100-500mmHg using an inflated contoured cuff or by the administration of vasopressor drugs (epinephrine, vasopressin, or glibenclamide). CPP before and after cuff inflation or drug administration was the end point. RESULTS: Sustained abdominal compression at >200mmHg increases CPP during VF and otherwise standard CPR by 8-18mmHg. The effect persists over practical ranges of chest compression force and duty cycle and is similar to that achieved with vasopressor drugs. Constant abdominal compression also augments CPP after prior administration of epinephrine or vasopressin. CONCLUSIONS: During CPR noninvasive abdominal compression with the inflatable contoured cuff rapidly elevates the CPP, sustains the elevated CPP as long as the device is inflated, and is immediately and controllably reversible upon device deflation. Physical control of peripheral vascular resistance during CPR by abdominal compression has some advantages over pharmacological manipulation and deserves serious reconsideration, now that the limitations of pressor drugs during CPR have become better understood, including post-resuscitation myocardial depression and the need for intravenous access.

A novel open field activity detector to determine spatial and temporal movement of laboratory animals after injury and disease.

The wide range of tests for laboratory animal behavior after neurological injury or disease each have their benefits and detriments. The varied behavior an animal exhibits makes it difficult to decide which test to use. However, a fundamental instinct for the laboratory animal is to explore when placed in a new environment. A way to test exploratory behavior is in the open field. Here, we introduce a simple activity box without the use of video equipment to determine the exploratory movement of a rat after traumatic brain injury. The activity box is an open field and the rat explores its surroundings when placed inside. Four infrared beams were placed in both the X and Y-axis inside the box. Using a novel system to determine which beam the rat breaks, we describe where the rat is in space and time while in the activity box. Other models can show the number of beams broken, but here we elucidate the methods to additionally determine the amount of area explored, the total distance traveled by the rat and percent time exploring.

Design of near-optimal waveforms for chest and abdominal compression and decompression in CPR using computer-simulated evolution.

OBJECTIVE: To discover design principles underlying the optimal waveforms for external chest and abdominal compression and decompression during cardiac arrest and cardiopulmonary resuscitation (CPR). METHOD: A 14-compartment mathematical model of the human cardiopulmonary system is used to test successive generations of randomly mutated external compression waveforms during cardiac arrest and resuscitation. Mutated waveforms that produced superior mean perfusion pressure became parents for the next generation. Selection was based upon either systemic perfusion pressure (SPP = thoracic aortic minus right atrial pressure) or upon coronary perfusion pressure (CPP = thoracic aortic pressure minus myocardial wall pressure). After simulations of 64,414 individual CPR episodes, 40 highly evolved waveforms were characterized in terms of frequency, duty cycle, and phase. A simple, practical compression technique was then designed by combining evolved features with a constant rate of 80 min(-1) and duty cycle of 50%. RESULTS: All ultimate surviving waveforms included reciprocal compression and decompression of the chest and the abdomen to the maximum allowable extent. The evolved waveforms produced 1.5-3 times the mean perfusion pressure of standard CPR and greater perfusion pressure than other forms of modified CPR reported heretofore, including active compression-decompression (ACD)+ITV and interposed abdominal compression (IAC)-CPR. When SPP was maximized by evolution, the chest compression/abdominal decompression phase was near 70% of cycle time. When CPP was maximized, the abdominal compression/chest decompression phase was near 30% of cycle time. Near-maximal SPP/CPP of 60/21 mmHg (forward flow 3.8 L/min) occurred at a compromise compression frequency of 80 min(-1) and duty cycle for chest compression of 50%. CONCLUSIONS: Optimized waveforms for thoraco-abdominal compression and decompression include previously discovered features of active decompression and interposed abdominal compression. These waveforms can be used by manual (Lifestick-like) and mechanical (vest-like) devices to achieve short periods of near normal blood perfusion non-invasively during cardiac arrest.

Biophysics of cardiopulmonary resuscitation with periodic z-axis acceleration or abdominal compression at aortic resonant frequencies.

UNLABELLED: Periodic z-axis acceleration (pGz)-CPR involves an oscillating motion of a whole patient in the head-to-foot dimension on a mechanized table. The method is able to sustain blood flow and long-term survival during and after prolonged cardiac arrest in anesthetized pigs. However, the exact mechanism by which circulation of blood is created has remained unknown. OBJECTIVES: To explain the hemodynamic mechanism of pGz-CPR and to suggest some theoretically useful improvements. METHOD: Computer modeling using a hybrid analytical-numerical approach, based upon Newton's second law of motion for fluid columns in the aorta and vena cavae, Ohm's law for resistive flow through vascular beds, and a 10-compartment representation of the adult human circulation. This idealized 70-kg human model is exercised to explore the effects upon systemic perfusion pressure of whole body z-axis acceleration at frequencies ranging from 0.5 to 5 Hz. The results, in turn, suggested studies of abdominal compression at these frequencies. RESULTS AND CONCLUSIONS: Blood motion induced in great vessels by periodic z-axis acceleration causes systemic perfusion when cardiac valves are competent. Blood flow is a function of the frequency of oscillation. At 3.5 Hz, periodic acceleration using +/-0.6G and +/-1.2 cm oscillations induces forward blood flow of 2.1L/min and systemic perfusion pressure of 47 mmHg. A form of resonance occurs at the frequency for peak-flow, in which the period of oscillation matches the round-trip transit time for reflected pulse waves in the aorta. For +/-1.0 G acceleration at 3.5 Hz, systemic perfusion pressure is 80 mmHg and forward flow is 3.8L/min in the adult human model with longitudinal z-axis motion of only +/-2 cm. Similar results can be obtained using abdominal compression to excite resonant pressure-volume waves in the aorta. For 20 mmHg abdominal pressure pulses at 3.8 Hz, systemic perfusion pressure is 7 mmHg and forward flow is 2.8L/min. pGz-CPR and high-frequency abdominal CPR are the physically realistic means of generating artificial circulation during cardiac arrest. These techniques have fundamental mechanisms and practical features quite different from those of conventional CPR and the potential to generate superior systemic perfusion.

A dose-response curve for the negative bias pressure of an intrathoracic pressure regulator during CPR.

An intrathoracic pressure regulator (ITPR) is a device that can be added to the external end of a tracheal tube to create controlled negative airway pressure between positive pressure ventilations. The resulting downward bias of the airway pressure baseline promotes increased venous return and enhanced circulation during CPR and also during hypovolemic shock. In the present study, we exercised a mathematical model of the human cardiopulmonary system, including airways, lungs, a four chambered heart, great vessels, peripheral vascular beds, and the biomechanics of chest compression and recoil, to determine the relationship between systemic perfusion pressure during CPR and the value of baseline negative airway pressure in an ITPR. Perfusion pressure increases approximately 50% as baseline airway pressure falls from zero to -10 cm H2O. Thereafter perfusion pressure plateaus. Negative bias pressures exceeding -10 cm H2O are not needed in ITPR-CPR.

Intravenous polyethylene glycol inhibits the loss of cerebral cells after brain injury.

We have tested the effectiveness of polyethylene glycol (PEG) to restore the integrity of neuronal membranes after mechanical damage secondary to severe traumatic brain injury (TBI) produced by a standardized head injury model in rats. We provide additional detail on the standardization of this model, particularly the use and storage of foam bedding that serves to both support the animal during the impact procedure-and as a dampener to the acceleration of the brass weight. Further, we employed a dye exclusion technique using ethidium bromide (EB; quantitative evaluation) and horseradish peroxidase (HRP; qualitative evaluation). Both have been successfully used previously to evaluate neural injury in the spinal cord since they enter cells when their plasma membranes are damaged. We quantified EB labeling (90 microM in 110 microL of sterile saline) after injection into the left lateral ventricle of the rat brain 2 h after injury. At six h after injection and 8 h after injury, the animals were sacrificed and the brains were analyzed. In the injured rat brain, EB entered cells lining and medial to the ventricles, particularly the axons of the corpus callosum. There was minimal EB labeling in uninjured control brains, limited to cells lining the luminal surfaces of the ventricles. Intravenous injections of PEG (1 cc of saline, 30% by volume, 2000 MW) immediately after severe TBI resulted in significantly decreased EB uptake compared with injured control animals. A similar result was achieved using the larger marker, HRP. PEG-treated brains closely resembled those of uninjured animals.

Effects of an impedance threshold valve upon hemodynamics in Standard CPR: studies in a refined computational model.

UNLABELLED: An impedance threshold valve (ITV) is a new airway adjunct for resuscitation that permits generation of a small vacuum in the chest during the recoil phase of chest compression. OBJECTIVES: To explore in detail the expected magnitude and the hemodynamic mechanisms of circulatory augmentation by an ITV in Standard CPR. METHOD: A 14-compartment mathematical model of the human cardiopulmonary system--upgraded to include applied chest compression force, elastic recoil of the chest wall, anatomic details of the heart and lungs, and the biomechanics of mediastinal compression--is exercised to explore the conditions required for circulatory augmentation by an ITV during various modes of CPR. RESULTS: The ITV augments systemic perfusion pressure by about 5 mmHg compared to any particular baseline perfusion pressure without the ITV. When baseline perfusion is low, owing to either diminished chest compression force, the existence of a thoracic pump mechanism of blood flow, or the presence of an effective compression threshold, then the relative improvement produced by an ITV is significant. With an ITV the heart expands into soft pericardiac tissue, which makes the heart easier to compress. CONCLUSIONS: An ITV can augment perfusion during CPR. The observed effectiveness of ITVs in the laboratory and in the clinic suggests a thoracic pump mechanism for Standard CPR, and perhaps also an effective compression threshold that must be exceeded to generate blood flow by external chest compression.

Relative effectiveness of interposed abdominal compression CPR: sensitivity analysis and recommended compression rates.

UNLABELLED: Interposed abdominal compression, IAC-CPR incorporates alternating chest and abdominal compressions to generate enhanced artificial circulation during cardiac arrest. The technique has been generally successful in improving blood flow and survival compared to standard CPR; however, some questions remain. OBJECTIVE: To determine "why does IAC-CPR produce more apparent benefit in some subjects than in others?" and "what is the proper compression rate, given that there are actually two compressions (chest and abdomen) in each cycle?" METHOD: Computer models provide a means to search for subtle effects in complex systems. The present study employs a validated 12-compartment mathematical model of the human circulation to explore the effects upon systemic perfusion pressure of changes in 35 different variables, including vascular resistances, vascular compliances, and rescuer technique. CPR with and without IAC was modeled. RESULTS AND CONCLUSIONS: Computed results show that the effect of 100 mmHg abdominal compressions on systemic perfusion pressure is relatively constant (about 16 mmHg augmentation). However, the effect of chest compression depends strongly upon chest compression frequency and technique. When chest compression is less effective, as is often true in adults, the addition of IAC produces relatively dramatic augmentation (e.g. from 24 to 40 mmHg). When chest compression is more effective, the apparent augmentation with IAC is relatively less (e.g. from 60 to 76 mmHg). The optimal frequency for uninterrupted IAC-CPR is near 50 complete cycles/min with very little change in efficacy over 20-100 cycles/min. In theory, the modest increase in systemic perfusion pressure produced by IAC can make up in part for poor or ineffective chest compressions in CPR. IAC appears relatively less effective in circumstances when chest pump output is high.

The origin of Korotkoff sounds and the accuracy of auscultatory blood pressure measurements.

This study explores the hypothesis that the sharper, high frequency Korotkoff sounds come from resonant motion of the arterial wall, which begins after the artery transitions from a buckled state to an expanding state. The motions of one mass, two nonlinear springs, and one damper, driven by transmural pressure under the cuff, are used to model and compute the Korotkoff sounds according to principles of classical Newtonian physics. The natural resonance of this spring-mass-damper system provides a concise, yet rigorous, explanation for the origin of Korotkoff sounds. Fundamentally, wall stretching in expansion requires more force than wall bending in buckling. At cuff pressures between systolic and diastolic arterial pressure, audible vibrations (> 40 Hz) occur during early expansion of the artery wall beyond its zero pressure radius after the outward moving mass of tissue experiences sudden deceleration, caused by the discontinuity in stiffness between bucked and expanded states. The idealized spring-mass-damper model faithfully reproduces the time-domain waveforms of actual Korotkoff sounds in humans. Appearance of arterial sounds occurs at or just above the level of systolic pressure. Disappearance of arterial sounds occurs at or just above the level of diastolic pressure. Muffling of the sounds is explained by increased resistance of the artery to collapse, caused by downstream venous engorgement. A simple analytical model can define the physical origin of Korotkoff sounds, suggesting improved mechanical or electronic filters for their selective detection and confirming the disappearance of the Korotkoff sounds as the optimal diastolic end point.

Interposed abdominal compression CPR: a comprehensive evidence based review.

Interposed abdominal compression (IAC)-CPR includes all steps of standard external CPR with the addition of manual mid-abdominal compressions in counterpoint to the rhythm of chest compressions. IAC-CPR can increase blood flow during CPR about 2-fold compared with standard CPR without IAC, as shown by six of six studies in computer models and 19 of 20 studies in various animal models. The addition of IAC has clinical benefit in humans, as indicated in 10 of 12 small to medium sized clinical studies. The technique increases the frequency of immediate return of spontaneous circulation for in-hospital resuscitations from roughly 25 to 50%. Improved survival to discharge is also likely on the basis of two small in-hospital trials. Possible harm from abdominal compression is minimal on the basis of 426 humans, 151 dogs and 14 pigs that received IAC in published reports. The complexity of performing IAC is similar to that of opening the airway and is less than that of other basic life support maneuvers. The aggregate evidence suggests that IAC-CPR is a safe and effective means to increase organ perfusion and survival, when performed by professionally trained responders in a hospital and when initiated early in the resuscitation protocol. Cost and logistical considerations discourage use of IAC-CPR outside of hospitals.