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Biomedical subjects

C F Babbs

Publications and source records attributed to C F Babbs.

At least 109 records · Page 6Linked to original sources

Theoretical advantages of abdominal counterpulsation in CPR as demonstrated in a simple electrical model of the circulation.

Recent animal studies and preliminary clinical observations suggest that the addition of interposed abdominal compressions (IAC) to ventilation and chest compression of standard cardiopulmonary resuscitation (CPR) augments blood flow, blood pressures, and immediate survival. To investigate the physical basis for enhanced circulation during IAC-CPR, we developed an electrical model of the circulation. Heart and blood vessels were modeled as resistive-capacitive networks, pressures as voltages, blood flow as electric current, blood inertia as inductance, and the cardiac and venous valves as diodes. External pressurization of the heart and great vessels, as would occur in CPR, was simulated by application by half-sinusoidal voltage pulses between vascular capacitances and ground. Closed-chest CPR was simulated by pressurization of all intrathoracic capacitances. IAC was simulated by similar pressurization of the inferior vena cava and abdominal aorta, 180 degrees out of phase with chest compression. During simulation of CPR, IAC improved cranial and myocardial perfusion at all levels of chest compression pressure by amounts linearly related to peak abdominal pressure, suggesting that the abdomen can function as a second, independent blood pump during CPR. Brain and heart flow were improved further during simulated vasoconstriction in kidneys, abdominal viscera, and extremities. Based on the fundamental properties of the cardiovascular system represented in the model, abdominal counterpulsation provides a rational basis for flow augmentation during CPR.

Blood Circulation↗

Regional blood flow during cardiopulmonary resuscitation with abdominal counterpulsation in dogs.

The addition of abdominal counterpulsation to standard cardiopulmonary resuscitation (AC-CPR) during ventricular fibrillation has been shown to improve cardiac output, oxygen uptake, and central arterial blood pressure in dogs. The present study was performed to determine the effect of AC-CPR on regional blood flow. Regional blood flow was measured with radioactively labeled microspheres during sinus rhythm and during alternate periods of AC-CPR and standard CPR (STD-CPR) in nine dogs anesthetized with pentobarbital. Blood pressures and oxygen uptake were measured continuously. As in previous studies, diastolic arterial pressure was higher (30.8%) during AC-CPR than during STD-CPR, as were cardiac output (24.5%) and oxygen uptake (37.5%). Whole brain and myocardial blood flow increased 12.0% and 22.7%, respectively, during AC-CPR. Blood flow to abdominal organs was not changed appreciably in response to abdominal compression, and postmortem examination revealed no gross trauma to the abdominal viscera. The AC-CPR technique is simple and is easily added to present basic life support procedures. In light of the improvements observed in myocardial and cerebral blood flow, AC-CPR could significantly improve the outcome of CPR attempts.

Abdomen↗

Abnormal response of tumor vasculature to vasoactive drugs.

The effects of the vasoconstrictor phenylephrine and the vasodilator hydralazine on blood flow to tumor were studied and compared to those on blood flow to normal tissues in vivo. Regional blood flow and cardiac output were measured with the use of radioactive microspheres in 150- to 250-g inbred Harlan F344 rats bearing subcutaneous nodules of two types of transplantable carcinoma ("hard" and "soft") with microscopically different vascular patterns. Three groups of rats were treated with hydralazine, saline, or phenylephrine, and regional blood flow was determined at the time of maximum blood pressure response. Results were correlated with quantitative morphometric analysis of arteriolar and capillary wall thickness in tumor and normal tissue. Phenylephrine decreased and hydralazine increased normal tissue perfusion as indicated by cardiac output. Tumor blood flow remained low and was not significantly influenced by drug treatment, except for the phenylephrine effect on hard tumors. Histologic study of tumor vessel walls revealed an absence of smooth muscle capable of responding to the vasoactive drugs by constriction or dilation. Evidently, by their selective action on normal vessels, vasoactive drugs can change the ratio of tumor:normal tissue perfusion. In particular, the increase of normal tissue: tumor blood flow by vasodilator drugs may enhance the selectivity of local heat therapy.

Animals↗

Safety factor for precordial pacing: minimum current thresholds for pacing and for ventricular fibrillation by vulnerable-period stimulation.

Temporary cardiac pacing by means of rapidly applied, precordial electrodes can be of great value in selected patients suffering cardiac arrest or profound bradycardia, post-defibrillation atrioventricular block, or digitalis intoxication. This study provides data pertaining to the safety of precordial pacing measured as the ratio of the minimum current required to induce ventricular fibrillation (VF) to the minimum current required to pace the ventricular myocardium. Single rectangular pulse stimuli having durations of 1-50 ms were evaluated. In 6 anesthetized dogs, a cutaneous electrode was centered over the shaved apex beat area of the left chest and paired with a larger electrode sutured to the right chest wall. Using a specially fabricated, synchronized, high-energy pulse generator, the "most vulnerable" time in the cardiac cycle at which the least current was required to induce VF with a single shock was identified. This current was compared to the much lower current required to pace the heart in the diastolic interval. While the current required to produce either fibrillation or pacing decreased as pulse duration increased, the safety factor (i.e., the ratio of fibrillation current to pacing current) remained nearly constant, averaging 12.6 for all pulse durations examined. That is, on the average, a stimulus of any given duration between 1 and 50 ms required at least 12 times the current required for pacing to produce ventricular fibrillation. We conclude that in normal canine hearts, the risk of inducing VF during precordial pacing is small.

Animals↗

Precordial pacing windows.

The threshold peak current for cardiac pacing with 10 ms rectangular pulses applied to precordial electrodes was determined in 18 anesthetized dogs (average weight 20.8 kg). The entire left and right precordium was mapped with a 1 cm diameter (cathode) electrode, paired with a 10 cm diameter reference electrode on the opposite chest. It was found that the lowest current required for pacing corresponded to the region of the apex beat on the left chest. At this site the average pacing threshold with the 1 cm electrode was 34.3 mA (peak). No sharply defined low pacing current area was found on the right chest, indicating that the location for the right chest electrode is not critical. The term "pacing window" is introduced to identify the region on the precordium where the pacing threshold is lowest. Studies were also performed to determine the manner in which the pacing current increased as electrode diameter was increased beyond the diameter of the pacing window. It was determined that little is to be gained with a left chest electrode larger than 5 cm in diameter in this animal study.

Animals↗

Functional cardiac depression caused by defibrillator shocks. Quantitation of the safety factor for electrical defibrillation.

The overdose shock strengths required to depress ventricular contraction were determined for damped sinusoidal current in 7 metabolically supported, isolated contracting canine hearts. Each heart was suspended in an isoresistive and isotonic solution-through which the defibrillating shocks were delivered. Defibrillation thresholds were determined with standard damped sine wave shocks of 4.4-5.5 msec duration. Then overdose shocks were delivered and the depressant effect on systolic left ventricular pressure was measured for shocks of 3-12 times threshold current. The minimum (threshold) current and energy densities required to defibrillate were 59.5 +/- 4.6 mA/cm2 (average) and 3.12 +/- 0.2 mJ/cm3. Increasing the shock strength above threshold produced a concomitant reduction of postshock left ventricular systolic pressure. The current and energy densities required to produce 50% depression (TD50) of left ventricular systolic pressure were 5.0 and 24.1 times the threshold current and energy densities respectively, indicating a wide safety margin using this criterion.

Animals↗

Irradiation-hyperthermia in canine hemangiopericytomas: large-animal model for therapeutic response.

Results of irradiation-hyperthermia treatment in 11 dogs with naturally occurring hemangiopericytoma were reported. Similarities of canine and human hemangiopericytomas were described. Orthovoltage X-irradiation followed by microwave-induced hyperthermia resulted in a 91% objective response rate. A statistical procedure was given to evaluate quantitatively the clinical behavior of locally invasive, nonmetastatic tumors in dogs that were undergoing therapy for control of local disease. The procedure used a small sample size and demonstrated distribution of the data on a scaled response as well as transformation of the data through classical parametric and nonparametric statistical methods. These statistical methods set confidence limits on the population mean and placed tolerance limits on a population percentage. Application of the statistical methods to human and animal clinical trials was apparent.

Animals↗

Improved preferential tumor hyperthermia with regional heating and systemic blood cooling: a balanced heat transfer method.

Absorption of power in large body volumes can occur with some approaches used for hyperthermia treatment of cancer. A systemic heat absorption rate exceeding the heat dissipation rate can lead to systemic temperature elevation that limits the magnitude and duration of application of power and hence the degree of preferential tumor temperature rise. We describe a hyperthermia approach consisting of regional electromagnetic power absorption and extracorporeal blood cooling with regulation of both systemic heat absorption and dissipation rates ("balanced heat transfer"). A test of this approach in five dogs with nonperfused tumor models demonstrated intratumoral temperatures greater than 42 degrees C, while systemic temperature remained at 33 degrees C and visceral temperatures within the heated region equilibrated between 33 and 42 degrees C. Solutions of the bioheat transfer equation were obtained for a simplified model with a tumor perfusion rate lower than surrounding normal tissue perfusion rate. In this model, the use of arterial blood temperatures less than 37 degrees C allowed higher power densities to be used, for given normal tissue temperatures, than when arterial temperature was greater than or equal to 37 degrees C. As a result, higher intratumoral temperatures were predicted. Control of arterial blood temperature using extracorporeal cooling may thus (1) limit systemic temperature rise produced by regional heating devices and (2) offer a means of improving intratumoral temperature elevations.

Animals↗

Simple methods for determining the accuracy of tumor blood flow measurements using radioactive microspheres in rats.

Two simple methods are presented which allow positive identification of the accuracy and precision of the microsphere technique and a quick verification of sphere entrapment in tumor vessels. A known flow of Ringer's solution from a motor-driven syringe is perfused through the rat's isolated systemic circulation from left ventricle to right atrium and collected in a funnel. Using this preparation, total blood flow in rats measured with radioactive microspheres injected into the left ventricle was 97% of actual flow. The coefficient of variation (standard deviation/mean) of the microsphere measurements was 0.22. In the same preparation, nonentrapment of microspheres in subcutaneous tumor nodules grown on a hind limb could be measured from the difference in counts collected in venous effluent before and after placement of a tourniquet proximal to the tumor. For example, in two types of transplantable carcinoma, we found nonentrapment of less than 0.1% of the injected microspheres. Such a shunt would correspond to less than 10% of microspheres entering a typical tumor nodule and, in turn, less than 10% underestimation of true flow to the tumor. These two techniques may be helpful to other investigators in testing the accuracy of microsphere methods in various small animal tumor models.

Animals↗

Relationship of blood pressure and flow during CPR to chest compression amplitude: evidence for an effective compression threshold.

This study was conducted to investigate the importance of the depth of chest compression in producing effective cardiopulmonary resuscitation (CPR) in animals, as indicated by cardiac output and mean arterial blood pressure. Cardiac output was measured by a modified indicator dilution technique in 8 anesthetized dogs, 6 to 12 kg body weight, during repeated 2-minute episodes of electrically induced ventricular fibrillation and CPR provided by a mechanical chest compressor and ventilator (Thumper). Chest compression exceeding a threshold value (xo) between 1.5 and 3.0 cm was required in each animal to produce measurable cardiac output. In particular, cardiac output (CO) was linearly related to chest compression depth (x) by an expression of the form CO = a(x-xo) for x greater than xo. The mean value of xo was 2.3 cm. A similar threshold for measurable blood pressure was observed in 7 of the 8 dogs, with a mean value of 1.8 cm. For chest compression of 2.5 cm or greater, relatively modest increases in chest compression depth caused relatively large changes in cardiac output.

Animals↗

Improved oxygen delivery during cardiopulmonary resuscitation with interposed abdominal compressions.

The ability of a new modification of cardiopulmonary resuscitation (CPR) to deliver oxygen to tissues was evaluated. The method utilizes standard CPR techniques with the addition of manual abdominal compressions (congruent to 100 mm Hg) interposed between chest compressions, and is termed interposed abdominal compression-CPR (IAC-CPR). Oxygen delivery was measured by a spirometer in a closed circuit designed to permit positive-pressure ventilation synchronized with mechanical chest compression. Ventricular fibrillation was induced electrically in 10 anesthetized dogs. In each dog, trials of IAC-CPR and standard CPR were alternated every five minutes during a 30-minute period. Arterial and central venous blood pressures, oxygen consumption, and Fick cardiac output were monitored. The addition of interposed abdominal compression significantly (P less than .01) increased each of these hemodynamic indicators. Oxygen delivery increased from 4.12 +/- 0.39 ml O2/kg/min during standard CPR to 6.37 +/- 0.35 ml O2/kg/min during IAC-CPR. Arterial systolic blood pressure increased from 67 +/- 5 mm Hg to 90 +/- 5 mm Hg, while diastolic arterial blood pressure rose from 15 +/- 2 mm Hg to 33 +/- 3 mm Hg. Cardiac output increased from 19.9 +/- 2.6 ml/min/kg to 37.5 +/- 2.7 ml/min/kg.

Animals↗

Efficacy and safety of defibrillation with rectangular waves of 2- to 20-milliseconds duration.

The effect of suprathreshold defibrillator shocks on cardiac function was compared in 8 isolated, perfused, contracting canine hearts using 4 durations of rectangular electrical waveforms. Defibrillation threshold was first determined for each duration; then overdose shocks of 3, 4.5, 6, and 9 times threshold current density were delivered. Left ventricular isovolumic systolic pressure decreased immediately after the shocks in proportion to the overdose shock strength. The mean defibrillation current density thresholds for the 2-, 5-, 10-, and 20-msec durations were 101, 63, 47, and 39 mA/cm2, respectively. The corresponding energy density thresholds were 4.6, 3.5, 4.4, and 6.4 mJ/cm3, respectively. The safety factor for defibrillation was defined as the current overdose ratio (delivered current density/threshold current density) required to produce a 50% decrease in isovolumic systolic pressure immediately after the shock. This dose was determined by interpolation of the curve for depression versus overdose of shock strength. The mean current safety factors for the 2-, 5-, 10-, and 20-msec durations were 3.9, 5.1, 5.4, and 5.2, respectively. The corresponding mean energy safety factors were 15, 25, 28, and 27. The margin of safety for functional depression of the heart was significantly less (p less than 0.05) for the 2 msec rectangular wave then for the 5-, 10-, and 20-msec rectangular waves.

Animals↗

Theoretical feasibility of vasodilator-enhanced local tumor heating.

Normal arterioles, in contrast to the abnormal microvasculature of many solid tumors, provide a target for selective drug action which can enhance local heat treatment of the tumors. Measurements of tissue blood flow with radioactive microspheres and estimates of changes in blood flow with thermal clearance methods revealed that vasodilator drugs either decreased or did not alter blood flow in hamster melanoma, rat hepatoma and canine transmissible venereal tumor while increasing perfusion in adjacent normal tissues 2 to 4-fold. Solutions of the bio-heat transfer equation, which take into account such selective effects of vasodilators on blood flow in normal tissues, clearly demonstrate improved selective heating for spheroidal tumors over 2 cm in diameter. In the presence of vasodilator drug effect, steady-state center tumor temperatures of 45-50 degrees C can be achieved by increased power input, while surrounding normal tissues remain below 42 degrees C.

Animals↗

Hydralazine-enhanced selective heating of transmissible venereal tumor implants in dogs.

This study was designed to test the hypothesis that vasodilator drugs can enhance selective heating of solid tumors by producing a favorable redistribution of blood flow between tumor and normal tissues. Subcutaneous transmissible venereal tumor implants were heated by inductive diathermy using Helmholtz coils in 8 dogs. The temperature rise in tumor and adjacent muscle was measured before and after giving hydralazine (0.5 mg/kg i.v.). Blood flow to the tumors and underlying muscle was measured with radioactive tracer microspheres. Before hydralazine treatment mean muscle blood flow was about one-third tumor blood flow (0.11 +/- 0.02 vs 0.28 +/- 0.09 ml/min/g), and tumor and normal muscle temperatures were not significantly different (40.0 +/- 0.6 vs 39.7 +/- 0.1 degrees C). After hydralazine tumor blood flow decreased and muscle blood flow increased in every dog, and selective heating of the tumors became possible. Muscle blood flow averaged 0.67 +/- 0.13 ml/min/g, 17 times greater than tumor blood flow, which decreased to 0.04 +/- 0.02 ml/min/g. Core tumor temperature was 48.0 +/- 0.9 vs 38.5 +/- 0.5 degrees C for underlying muscle. Blood pressure was maintained at 80 +/- 5.7 mmHg. These results demonstrate that adjuvant treatment with vasodilators is a promising technique to increase the temperature difference between tumors and surrounding normal tissues during local heat therapy.

Animals↗

CPR with simultaneous compression and ventilation at high airway pressure in 4 animal models.

CPR with simultaneous chest compression and ventilation at high airway pressure (SCV-CPR) improves blood flow in some studies but not in others, perhaps because of differences in the animal models employed. To resolve such discrepancies, we compared SCV-CPR to standard CPR in 4 mechanically different canine models, using both small and large dogs and small and large compression pads. The 4 groups were: large dogs receiving chest compression through a large pad (model A), large dogs receiving chest compression through a small pad (model B), small dogs receiving chest compression through a large pad (model C), and small dogs receiving chest compression through a small pad (model D). Cardiac output (CO) during CPR was determined by a specially modified indicator dilution method. Models A, B, and C all had similar mean COs of 14 ml/min . kg body weight during standard CPR, and 27 ml/min . kg during SCV-CPR. However, in model D, there was no significant difference during standard vs. SCV-CPR, and the mean output was 33 ml/min . kg. We conclude that in models A, B, and C, little direct heart compression occurred and the higher intrathoracic pressure pulses produced by SCV-CPR improved blood flow. However it seems likely that there was effective cardiac compression in model D. In the absence of direct cardiac compression, SCV-CPR provides an alternative means of generating satisfactory flow in a mechanically appropriate animal model.

Animals↗

High-pressure ventilation during CPR with 95% O2:5% CO2.

The effects of two different breathing-gas mixtures on blood flow, blood pressure, and arterial blood pH and PCO2 were measured in dogs during 2 different modes of CPR with high-pressure ventilation (50 cm H2O). Ventilation was either applied simultaneously with every compression (1:1) or interposed after every fifth compression (1:5). Ventilation with pure oxygen under either condition caused severe arterial alkalemia with hypocarbia after 2-min episodes of cardiac arrest and resuscitation (pH = 7.63, PCO2 = 5.0 after 1:1; pH = 7.63, PCO2 = 5.4 after 1:5). Ventilation with 5% CO2-enriched oxygen during CPR maintained acid/base status near prearrest values (pH = 7.22, PCO2 = 30.3 after 1:1; pH = 7.26, PCO2 = 28.0 after 1:5). Values obtained with radioactive microspheres for cardiac output (CO) and regional blood flow to brain, heart, and kidney were not significantly different under the 4 conditions. Electrical ventricular defibrillation was easily accomplished despite arterial alkalemia and hypocarbia. Ventilation at high pressures with CO2-enriched oxygen does not alter hemodynamics during CPR, but does prevent severe arterial alkalemia.

Alkalosis↗

Cardiopulmonary resuscitation with interposed abdominal compression in dogs.

This study was conducted to evaluate the hemodynamic effectiveness of a new modification of cardiopulmonary resuscitation (CPR), termed interposed abdominal compression-CPR (IAC-CPR). IAC-CPR utilizes all the steps of standard CPR with the addition of abdominal compressions interposed during the release phase of chest compression. Ventricular fibrillation was induced electrically in 10 anesthetized dogs, and either IAC-CPR or standard CPR was initiated while arterial and venous blood pressures and cardiac output were monitored. The two CPR methods were alternated every 3 minutes over a period of 30 minutes. The addition of interposed abdominal compressions to standard CPR improved arterial pressures and perfusion in 10 of 10 dogs. Brachial arterial blood pressure averaged 87/32 mm Hg during IAC-CPR vs 58/16 mm Hg during standard CPR. Cardiac output (+/- SE) averaged 24.2 +/- 5.7 ml/min/kg during IAC-CPR vs 13.8 +/- 2.6 ml/min/kg during standard CPR. IAC-SPR requires no extra mechanical equipment, and, if proven effective in human trials, may improve resuscitation success in the field and in the hospital.

Abdomen↗