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.

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.

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.

Choosing inclusion criteria that minimize the time and cost of clinical trials.

AIM: To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria. METHODS: We consider a two treatment, dichotomous outcome trial that includes a proportion of patients who are strong responders to the tested intervention. Patients are screened for inclusion using an arbitrary number of test results that are combined into an aggregate suitability score. The screening score is regarded as a diagnostic test for the responsive phenotype, having a specific cutoff value for inclusion and a particular sensitivity and specificity. The cutoff is a measure of stringency of inclusion criteria. Total cost is modeled as a function of the cutoff value, number of patients screened, the number of patients included, the case occurrence rate, response probabilities for control and experimental treatments, and the trial duration required to produce a statistically significant result with a specified power. Regression methods are developed to estimate relevant model parameters from pilot data in an adaptive trial design. RESULTS: The patient numbers and total cost are strongly related to the choice of the cutoff for inclusion. Clear cost minimums exist between 5.6 and 6.1 on a representative 10-point scale of exclusiveness. Potential cost savings for typical trial scenarios range in millions of dollars. As the response rate for controls approaches 50%, the proper choice of inclusion criteria can mean the difference between a successful trial and a failed trial. CONCLUSION: Early formal estimation of optimal inclusion criteria allows planning of clinical trials to avoid high costs, excessive delays, and moral hazards of Type II errors.

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.

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.

Subtle paranodal injury slows impulse conduction in a mathematical model of myelinated axons.

This study explores in detail the functional consequences of subtle retraction and detachment of myelin around the nodes of Ranvier following mild-to-moderate crush or stretch mediated injury. An equivalent electrical circuit model for a series of equally spaced nodes of Ranvier was created incorporating extracellular and axonal resistances, paranodal resistances, nodal capacitances, time varying sodium and potassium currents, and realistic resting and threshold membrane potentials in a myelinated axon segment of 21 successive nodes. Differential equations describing membrane potentials at each nodal region were solved numerically. Subtle injury was simulated by increasing the width of exposed nodal membrane in nodes 8 through 20 of the model. Such injury diminishes action potential amplitude and slows conduction velocity from 19.1 m/sec in the normal region to 7.8 m/sec in the crushed region. Detachment of paranodal myelin, exposing juxtaparanodal potassium channels, decreases conduction velocity further to 6.6 m/sec, an effect that is partially reversible with potassium ion channel blockade. Conduction velocity decreases as node width increases or as paranodal resistance falls. The calculated changes in conduction velocity with subtle paranodal injury agree with experimental observations. Nodes of Ranvier are highly effective but somewhat fragile devices for increasing nerve conduction velocity and decreasing reaction time in vertebrate animals. Their fundamental design limitation is that even small mechanical retractions of myelin from very narrow nodes or slight loosening of paranodal myelin, which are difficult to notice at the light microscopic level of observation, can cause large changes in myelinated nerve conduction velocity.

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.

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.

Predicting success or failure of immunotherapy for cancer: insights from a clinically applicable mathematical model.

The objective of this study was to create a clinically applicable mathematical model of immunotherapy for cancer and use it to explore differences between successful and unsuccessful treatment scenarios. The simplified predator-prey model includes four lumped parameters: tumor growth rate, g; immune cell killing efficiency, k; immune cell signaling factor, λ; and immune cell half-life decay, µ. The predator-prey equations as functions of time, t, for normalized tumor cell numbers, y, (the prey) and immunocyte numbers, ×, (the predators) are: dy/dt = gy - kx and dx/dt = λxy - µx. A parameter estimation procedure that capitalizes on available clinical data and the timing of clinically observable phenomena gives mid-range benchmarks for parameters representing the unstable equilibrium case in which the tumor neither grows nor shrinks. Departure from this equilibrium results in oscillations in tumor cell numbers and in many cases complete elimination of the tumor. Several paradoxical phenomena are predicted, including increasing tumor cell numbers prior to a population crash, apparent cure with late recurrence, one or more cycles of tumor growth prior to eventual tumor elimination, and improved tumor killing with initially weaker immune parameters or smaller initial populations of immune cells. The model and the parameter estimation techniques are easily adapted to various human cancers that evoke an immune response. They may help clinicians understand and predict certain strange and unexpected effects in the world of tumor immunity and lead to the design of clinical trials to test improved treatment protocols for patients.

Quantitative reappraisal of the helmholtz-guyton resonance theory of frequency tuning in the cochlea.

To explore the fundamental biomechanics of sound frequency transduction in the cochlea, a two-dimensional analytical model of the basilar membrane was constructed from first principles. Quantitative analysis showed that axial forces along the membrane are negligible, condensing the problem to a set of ordered one-dimensional models in the radial dimension, for which all parameters can be specified from experimental data. Solutions of the radial models for asymmetrical boundary conditions produce realistic deformation patterns. The resulting second-order differential equations, based on the original concepts of Helmholtz and Guyton, and including viscoelastic restoring forces, predict a frequency map and amplitudes of deflections that are consistent with classical observations. They also predict the effects of an observation hole drilled in the surrounding bone, the effects of curvature of the cochlear spiral, as well as apparent traveling waves under a variety of experimental conditions. A quantitative rendition of the classical Helmholtz-Guyton model captures the essence of cochlear mechanics and unifies the competing resonance and traveling wave theories.

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.

Anterior-posterior impedance cardiography: a new approach to accurate, non-invasive monitoring of cardiac function.

The conventional impedance cardiogram is a record of pulsatile changes in the electrical impedance of the chest with each heartbeat. The signal seems intuitively related to cardiac stroke volume. However doubts persist about the validity of stroke volume measurements based on electrical impedance. This paper presents a new electrical axis for impedance cardiography that is perpendicular to the conventional head-to-foot axis in an anterior-posterior direction. Dual chest and back electrodes are concentric, permitting tetrapolar technique. A relatively simple analytical model is developed, and this model is validated in a three-dimensional finite element model of current flow through the human chest. Three-dimensional simulations show predictable relationships between the fractional increase in anterior-posterior chest impedance and the ventricular ejection fraction (cardiac stroke volume/ventricular end-diastolic volume). Ejection fraction can be computed accurately with a roughly 30-fold increase in signal level compared to the conventional impedance cardiogram. Breathing causes only modest changes in the signal. When the axis of current flow is optimized, one can interpret the impedance changes during the cardiac cycle with greater confidence as noninvasive, beat-by-beat indicators of ventricular ejection fraction in a wide variety of clinical settings.

Neonatal CPR: room at the top--a mathematical study of optimal chest compression frequency versus body size.

OBJECTIVE: To explore in detail the expected magnitude of systemic perfusion pressure during standard CPR as a function of compression frequency for different sized people from neonate to adult. METHOD: A 7-compartment mathematical model of the human cardiopulmonary system - upgraded to include inertance of blood columns in the aorta and vena cavae - was exercised with parameters scaled to reflect changes in body weight from 1 to 70 kg. RESULTS: Maximal systemic perfusion pressure occurs at chest compression rates near 60, 120, 180, and 250/min for subjects weighing 70, 10, 3, and 1 kg, respectively. Such maxima are predicted by analytical models describing the dependence of stroke volume on pump-filling time in the presence of blood inertia. This mathematical analysis reproduces earlier experimental results of Fitzgerald et al. in 10 kg dogs. CONCLUSIONS: Fundamental geometry and physics suggest that the most effective chest compression frequency in CPR depends upon body size and weight. In neonates there is room for improvement at the top of the compression frequency scale at rates >120/min. In adults there may be benefit from lower compression frequencies near 60/min.

Methods for calculating coronary perfusion pressure during CPR.

Coronary perfusion pressure (CPP) is a major indicator of the effectiveness of cardiopulmonary resuscitation in human and animal research studies, however, methods for calculating CPP differ among research groups. Here we compare the 6 published methods for calculating CPP using the same data set of aortic (Ao) and right atrial (RA) blood pressures. CPP was computed using each of the 6 calculation methods in an anesthetized pig model, instrumented with catheters with Cobe pressure transducers. Aortic and right atrial pressures were recorded continuously during electrically induced ventricular fibrillation and standard AHA CPR. CPP calculated from the same raw data set by the 6 calculation methods ranged from -1 (signifying retrograde blood flow) to 26 mmHg (mean +/- SD of 15 +/- 11 mmHg). The CPP achieved by standard closed chest CPR is typically reported as 10-20 mmHg. Within a single study the CPP values may be comparable; however, the CPP values for different studies may not be a reliable indicator of the efficacy of a given CPR method. Electronically derived true mean coronary perfusion pressure is arguably the gold standard method for representing coronary perfusion pressure.

Quantitative prediction of body surface potentials from myocardial action potentials using a summed dipole model.

This paper demonstrates quantitatively, using streamlined mathematics, how the transmembrane ionic currents in individual cardiac muscle cells act to produce the body surface potentials of the electrocardiogram (ECG). From fundamental principles of electrostatics, anatomy, and physiology, one can characterize the strength of apparent dipoles along a wavefront of depolarization in a local volume of myocardium. Net transmembrane flow of ionic current in actively depolarizing or repolarizing tissue induces extracellular current flow, which sets up a field of electrical potential that resembles that of a dipole. The local dipole strength depends upon the tissue cross section, the tissue resistivity, the resting membrane potential, the membrane capacitance, the volume fraction of intracellular fluid, the time rate of change of the action potential, and the cell radius. There are no unknown, "free" parameters. There are no arbitrary scale factors. Body surface potentials are a function of the summed local dipole strengths, directions, and distances from the measuring points. Calculations of body surface potentials can be made for the scenarios of depolarization (QRS complex), repolarization (T wave) and localized acute injury (ST segment shifts) and agree well with experimentally measured potentials. This simplified predictive dipole theory provides a solution to the forward problem of electrocardiography that explains from a physiological perspective how the collective depolarization and repolarization of individual cardiac muscle cells create body surface potentials in health and disease.

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.

A new paradigm for human resuscitation research using intelligent devices.

OBJECTIVES: To develop new methods for studying correlations between the performance and outcome of resuscitation efforts in real-world clinical settings using data recorded by automatic devices, such as automatic external defibrillators (AEDs), and to explore effects of shock timing and chest compression depth in the field. METHODS: In 695 records of AED use in the pre-hospital setting, continuous compression data were recorded using AEDs capable of measuring sternal motion during compressions, together with timing of delivered shocks and the electrocardiogram. In patients who received at least one shock, putative return of spontaneous circulation (P-ROSC) was defined as a regular, narrow complex electrical rhythm > 40 beats/min with no evidence of chest compressions at the end of the recorded data stream. Transient return of spontaneous circulation (t-ROSC) was defined as the presence of a post-shock organized rhythm > 40 beats/min within 60s, and sustained > or = 30 s. 2x2 contingency tables were constructed to examine the association between these outcomes and dichotomized time of shock delivery or chest compression depth, using the Mood median test for statistical significance. RESULTS: The probability of P-ROSC for first shocks delivered < 50 s (the median time) after the start of resuscitation was 23%, versus 11% for first shocks > 50 s (p=0.028, one tailed). Similarly, the probability of t-ROSC for shorter times to shock was 29%, compared to the 15% for delayed first shocks (p=0.016). For shocks occurring > 3 min after initiation of rescue attempts, the probability of t-ROSC with pre-shock average compression depth > 5 cm was more than double that with compression depth < 5 cm (17.7% vs. 8.3%, p=0.028). For shocks > 5 min, the effect of deeper compressions increased (23.4% versus 8.2%, p=0.008). CONCLUSIONS: Much can be learned from analysis of performance data automatically recorded by modern resuscitation devices. Use of the Mood median test of association proved to be sensitive, valid, distribution independent, noise-resistant and also resistant to biases introduced by the inclusion of hopeless cases. Efforts to shorten the time to delivery of the first shock and to encourage deeper chest compressions after the first shock are likely to improve resuscitation success. Such refinements can be effective even after an unknown period of preceding downtime.

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.