Biomedical subjects

Charles F Babbs

Publications and source records attributed to Charles F Babbs.

16 recordsLinked to original sources

PubMed2006

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.

Blood Circulation↗

PubMed2006

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.

Animals↗

PubMed2006

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.

Animals↗

PubMed2006

Optimal strategy for cardiopulmonary resuscitation with continuous chest compression.

OBJECTIVES: To apply the mathematical techniques of optimal control theory (OCT) to a validated model of the human circulation during cardiopulmonary resuscitation (CPR), so as to discover improved waveforms for chest compression and decompression that maximize the coronary perfusion pressure (CPP). METHODS: The human circulatory system is represented by seven difference equations that describe the pressure changes in systemic vascular compartments that are caused by chest compression. The forcing term is the intrathoracic pressure that is generated by the external chest compression, which is taken as the control variable for the system. The optimum waveform of this forcing pressure as a function of time, determined from OCT, is that which maximizes the calculated CPP between the thoracic aorta and the superior vena cava over a period of 13.3 seconds of continuous chest compression. RESULTS: The optimal waveform included both compression and decompression of the chest to the maximum allowable extent. Compression-decompression waveforms were rectangular in shape. The frequency of optimal compression-decompression that was found by OCT was 90 per minute. The optimal duty cycle (compression duration per cycle time) was 40%. The CPP for the optimum control waveform was 36 mm Hg vs. 25 mm Hg for standard CPR. CONCLUSIONS: Optimal control theory suggests that both compression and decompression of the chest are needed for best hemodynamics during CPR.

Cardiopulmonary Resuscitation↗

PubMed2006

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.

Abdomen↗

PubMed2006

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.

Abdomen↗

PubMed2005

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.

Abdomen↗

PubMed2005

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.

Cardiopulmonary Resuscitation↗

PubMed2005

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.

Animals↗

PubMed2004

Optimizing chest compression to rescue ventilation ratios during one-rescuer CPR by professionals and lay persons: children are not just little adults.

OBJECTIVE: To estimate the optimum ratio of chest compressions to ventilations for one-rescuer CPR that maximizes systemic oxygen delivery in children. METHOD: Equations describing oxygen delivery and blood flow during CPR as functions of the number of compressions and the number of ventilations delivered over time were adapted from the former work of Babbs and Kern. These equations were solved explicitly as a function of body weight, using scaling algorithms based upon principles of developmental anatomy and physiology. RESULTS: The optimal compression to ventilation (C/V) ratios for infants and younger children increase sharply as a function of body weight. Optimal C/V ratios are lower for professional rescuers, who take less time to deliver a rescue breath, than for lay rescuers, who interrupt chest compressions for longer to perform ventilations. For professional rescuers the optimal C/V ratio, x*, is approximately 1.6 square root W where the W is the patient's body weight in kg. For lay rescuers the optimum C/V ratio is approximately 2.8 square root W. These values can be approximated for children and teens by the following rules of thumb, based upon the age of the victim: "5 + one half the age in years" for professional rescuers and "5 + age in years" for lay rescuers. CONCLUSIONS: Compression to ventilation ratios in CPR should be smaller for children than for adults and gradually increase as a function of body weight. Optimal CPR in children requires relatively more ventilation than optimal CPR in adults. A universal compression/ventilation ratio of 50:2, targeted to optimize adult resuscitation, would not be appropriate for infants and young children.

Adult↗

PubMed2003

Simplified meta-analysis of clinical trials in resuscitation.

OBJECTIVE: To present and demonstrate a new simplified method for synthesizing results of multiple clinical trials in resuscitation research. METHODS: The mean difference across studies in the proportion of favorable outcomes between experimental and control groups is calculated. This difference is shown to have a t-distribution. Its significance can be ascertained with a simple t-test. The analysis can be implemented in a one-page computer spreadsheet. RESULTS: Simplified meta-analysis provides high sensitivity and can be extended to include weighting of studies according to size or quality, comparison of subgroups of studies, tests for outliers, and calculation of the power of the meta-analysis. Sample analyses are presented for two experimental forms of cardiopulmonary resuscitation (CPR): interposed abdominal compression (IAC) CPR and active compression-decompression (ACD) CPR. CONCLUSIONS: Traditional narrative reviews, taking note of the proportion of individual studies with statistically significant results, can lead to erroneous conclusions and unnecessary delays in the clinical use of research findings. Simplified meta-analysis can provide rapid, quantitative, and accurate estimates of the amount of benefit or harm from an experimental intervention and can further empower physicians to practice evidence-based medicine.

Cardiopulmonary Resuscitation↗

PubMed2003

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.

Animals↗

PubMed2002

Optimum compression to ventilation ratios in CPR under realistic, practical conditions: a physiological and mathematical analysis.

OBJECTIVE: To develop and evaluate a practical formula for the optimum ratio of compressions to ventilations in cardiopulmonary resuscitation (CPR). The optimum value of a variable is that for which a desired result is maximized. Here the desired result is assumed to be either oxygen delivery to peripheral tissues or a combination of oxygen delivery and waste product removal. METHOD: Equations describing oxygen delivery and blood flow during CPR as functions of the number of compressions and the number of ventilations delivered over time were developed from principles of classical physiology. These equations were solved explicitly in terms of the compression/ventilation ratio and evaluated for a wide range of conditions using Monte Carlo simulations. RESULTS: As the compression to ventilation ratio was increased from 0 to 50 or more, both oxygen delivery and the combination of oxygen delivery with blood flow increased to maximum values and then gradually declined. For variables typical of standard CPR as taught and specified in international guidelines, maximum values occurred at compression/ventilation ratios near 30:2. For variables typical of actual lay rescuer performance in the field, maximal values occurred at compression/ventilation ratios near 60:2. CONCLUSION: Current guidelines overestimate the need for ventilation during standard CPR by two to four-fold. Blood flow and oxygen delivery to the periphery can be improved by eliminating interruptions of chest compression for these unnecessary ventilations.

Blood Gas Analysis↗

PubMed2002

Circulatory adjuncts. Newer methods of cardiopulmonary resuscitation.

Principles of cardiovascular physiology tell us that during cardiac arrest and CPR, forward flow of blood can be generated by external compression or decompression of either the chest or the abdomen. Standard CPR utilizes only one of these modes--chest compression--and generates roughly 1 L/min forward flow in an adult human, which is 20% of normal cardiac output. IAC-CPR uses two of these modes--chest compression and abdominal compression--and generates roughly twice the forward flow, or 2 L/min in an adult human. ACD-CPR uses two of these modes--chest compression and chest decompression--and also generates roughly twice the forward flow as standard CPR, although the results are somewhat model dependent. The studies by Sack et al with IAC-CPR and by Plaisance et al with ACD-CPR suggest that when methods that double perfusion are employed methodically, resuscitation outcome in terms of short- and long-term survival are also roughly doubled. This state of affairs is fortunate, because it is possible that factors, such as severe underlying disease or the quality of postresuscitation care, could blunt or cancel positive effects of improved blood flow during the brief resuscitation period. Theoretically, full four-phase CPR, including active compression and decompression of both chest and abdomen, is capable of generating 4 L/min forward flow or greater, which is 80% of normal, and there is a reasonable prospect of achieving 100% of normal flow under conditions in which all four phases are optimized. Standard CPR is clearly not the ultimate form of external CPR. There is real, credible evidence that substantial improvements in resuscitation methods and results will be possible in the next decade.

Abdomen↗

PubMed2002

Self-sealing, large bore arterial punctures: a counterintuitive new phenomenon.

The human femoral artery can bleed dangerously following the removal of a catheter uring cardiac catheterization. In this study, a modified technique of needle insertion, simply inserting the needle bevel-down instead of the standard bevel-up approach, was tested as a means to reduce bleeding after catheter removal. Large bore needle punctures were made in surgically exposed arteries of anesthetized pigs using either a standard technique (45 degree approach, bevel up) or a modified technique (25 degree approach, bevel down). For half the punctures, topical phenylephrine solution (1 mg/ml) was applied to the adventitia of the artery to cause constriction. Median bleeding rates were reduced from 81 to less than 1 ml/min/100 mmHg intraluminal pressure by the modified technique with application of phenylephrine. In most cases zero bleeding, that is self-sealing, of the arteries occurred. It is postulated that a flap-valve of tissue created by the modified technique produced this self-sealing behavior. Sophisticated modeling studies are needed to fully understand this new phenomenon.

Animals↗

PubMedDate not supplied

Meta-analysis of 2-treatment clinical trials including both continuous and dichotomous results.

To expedite the timely creation of medical practice guidelines, a meta-analytic method was developed to combine both dichotomous survival data and continuous physiologic data from multiple studies of differing experimental design, which compare the same innovative clinical intervention to standard care. An aggregate ratio, R*, of the observed treatment effect to a clinically optimal treatment effect for studies in a series is computed and compared to the 95% confidence limit for R* under the null hypothesis. Input data for continuous variables include sample means, standard errors, and sample sizes. Input data for dichotomous variables include group proportions and sizes. The analysis can be done using a simple, 1-page spreadsheet. It allows one to judge biological significance, to test for statistical significance, to compare subgroups of studies, to test for outliers, and to compute the power of the meta-analysis. These features are demonstrated for studies of interposed abdominal compression-cardiopulmonary resuscitation.

Abdomen↗