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Biomedical subjects

W D Voorhees

Publications and source records attributed to W D Voorhees.

At least 19 recordsLinked to original sources

The chronaxie for myocardium and motor nerve in the dog with chest-surface electrodes.

The chronaxie (i.e., the duration for a stimulating current having twice the rheobasic, or minimum, value) was determined for ventricular myocardium in 12 pentobarbital-anesthetized dogs. Current was applied transthoracically via chest-surface electrodes located at the optimal axillary site for producing inspiration by stimulation of the phrenic nerve (electroventilation). In four dogs the chronaxie for motor-nerve was determined using electrodes at the same location. After using hand-held electrodes to identify the optimal stimulation site for electroventilation, 4.1 cm diameter electrodes were applied bilaterally to the optimal site on the thorax. In 12 dogs, the threshold current for producing ventricular ectopic beats was determined for single rectangular current pulses ranging from 0.1-10 ms in duration. From these data, strength-duration curves were determined and the average chronaxie for ventricular myocardium was found to be 1.82 ms. In four dogs the relationship between inspired volume and maximum stimulus intensity was determined using a 0.8 s burst of stimuli (60/s) with pulse durations ranging from 20-500 microseconds. From these data, strength-duration curves for current were constructed and the average chronaxie for motor-nerve was found to be 0.17 ms. The results of this study show that, because of the differing chronaxies, the current required to produce inspiration with short-duration stimuli is much less than that required to evoke an ectopic heart beat.

Animals

Ventricular fibrillation produced by stimulation of external transthoracic electrodes--an experimental study.

The threshold for ventricular fibrillation was determined in 12 pentobarbital anesthetized dogs using transthoracic electrodes located at the optimal axillary electroventilation sites. Electroventilation is the name used to designate inspiration produced by stimuli applied to body surface electrodes. The optimal stimulation site for electroventilation was first determined using hand-held electrodes. Then electrodes, 4.1 cm in diameter, were sutured bilaterally to the optimal anterior axillary stimulation site. The threshold current for producing ventricular fibrillation was determined using single pulses ranging from 0.1-10 msec in duration delivered during the vulnerable period of the cardiac cycle. Fibrillation was produced in all dogs with the 10- and 5-msec pulse durations, in 11 dogs with 0.3-msec, in 6 dogs with 0.2-msec, and in 1 dog with 0.1-msec pulse duration. In all dogs, the current required to produce ventricular fibrillation increased greatly as the pulse duration was decreased. The current required for fibrillation was much in excess of that required to produce one tidal volume. With the longer duration pulses, the ratio was about 80. With the 8 microseconds duration pulses used for electroventilation the estimated ratio is about 800.

Animals

Correlation of motor-evoked potential response to ischemic spinal cord damage.

The prevalence of morbidity is a major deterrent to the success of aortic aneurysm replacement operations. We have developed a model of spinal cord ischemia, based on the amplitude reduction of the motor-evoked potential, which produces approximately a 90% prevalence of paraplegia. Regional blood flow was studied with the use of radioactive microspheres, and results showed that there was a significant decrease in flow to the lumbar cord (85% reduction) during aortic occlusion, followed by a twofold to threefold hyperemia that persisted for 24 hours. Histopathologic examination of the cord revealed that the greater portion of microgliosis, spongiosis, and neuronal damage was confined to the gray matter of the cord, and its severity increased as one progressed caudally. The somatosensory-evoked potential disappeared before the motor-evoked potential L-2 signal in all dogs, with a mean disappearance time of 10.9 +/- 5.6 minutes, compared with 21 +/- 6.6 minutes for the motor-evoked potential. Both the sensory-evoked potential and the motor-evoked potential cord signal were present 24 hours later in all dogs tested. The peripheral nerve motor-evoked potential disappeared within 1 minute of cord ischemia, was not present 24 hours later, and hence appears to be too sensitive to use as an indicator of spinal cord damage. Plotting spinal cord motor-evoked potential amplitude reduction versus both histopathologic damage and regional blood flow revealed a positive correlation between motor-evoked potential amplitude reduction, decreased cord perfusion, and increased histopathologic damage. In addition, it may be possible to make inferences about the neurologic status of a subject based on the magnitude and time-course of the motor-evoked potential's amplitude reduction and wave morphology.

Animals

Methylene blue as an inhibitor of superoxide generation by xanthine oxidase. A potential new drug for the attenuation of ischemia/reperfusion injury.

Tissue oxidases, especially xanthine oxidase, have been proposed as primary sources of toxic oxygen radicals in many experimental models of disease states. Among these, ischemia-reperfusion injury may be of the greatest clinical interest. In this paper we propose the use of methylene blue as a means of suppressing the production of superoxide radicals O2- by acting as an alternative electron acceptor for xanthine oxidase. Previous work has indicated that methylene blue accepts electrons from xanthine oxidase at the iron-sulfur center. Initial experiments in our laboratory demonstrated that (1) pairs of electrons from each enzymatic oxidation are transferred to methylene blue, (2) the reduction of methylene blue can be achieved by model iron-sulfur centers, similar to the iron-sulfur center of xanthine oxidase, (3) reduced methylene blue auto-oxidizes to produce H2O2 directly, rather than O2-, and (4) methylene blue is effective at non-toxic levels (2-5 mg/kg) in preventing free radical damage to liver and kidney tissues in an in vitro model of ischemia and reoxygenation. Accordingly, we propose that methylene blue may represent a new class of antioxidant drugs that competitively inhibit reduction of molecular oxygen to superoxide by acting as alternative electron acceptors for tissue oxidases. We have termed these agents "parasitic" electron acceptors.

Animals

The effects of soman poisoning in combination with hypovolemic shock.

Hemorrhage is a cause of death in both combat and civilian injuries. The specific objectives of this research were: (1) to determine the pathophysiologic effects of combined injuries from sublethal amounts of an organophosphate (soman) along with hypovolemic shock, and (2) to determine the efficacy of atropine sulfate and pralidoxime (2-PAM) therapy for organophosphate poisoning when combined injuries occur. Four groups of six beagle dogs/group were used: Group V/H, vehicle administration followed by hemorrhage; Group S/H, soman administration followed by hemorrhage; Group S/A/H, soman followed by antidote (atropine and 2-PAM) and then hemorrhage; and Group S, soman only. Acetylcholinesterase (AChE) activity, hemodynamic parameters, regional blood flow, plasma enzyme, and hematological changes were monitored. Soman rapidly decreased AChE activity in RBCs, plasma, and brain tissue. Treatment with atropine and 2-PAM resulted in only slight reactivation of AChE; they helped maintain blood gases, cortisol, plasma enzymes, inspiratory volume, and blood pressure nearer baseline values. The effects of combined injuries appear to be greater than those of either injury alone. This was indicated by increased plasma lactate, plasma enzymes indicative of tissue damage (aspartate amine transferase and creatine kinase), and increased lethality in dogs subjected to both soman and hemorrhage (5/12 died). All dogs subjected to only one insult survived the 6-hr experiment.

Acetylcholinesterase

Impedance cardiography by use of a spot-electrode array to track changes in cardiac output in anesthetized dogs.

Transthoracic impedance cardiography is a noninvasive method to determine changes in cardiac output on the basis of the cardiac-induced impedance change measured across the thorax. In this report, we describe a new, easily applied, tetrapolar spot-electrode configuration for use in canine transthoracic impedance cardiography. The array is a convenient alternative to use of the traditional circumferential band-electrode array which, in the dog, is prohibitive because of the extensive skin preparation required. The spot-electrode array was used to compare changes in cardiac output measured by transthoracic impedance cardiography, with changes measured by a reference indicator-dilution technique. A spot-electrode array, composed of 4 standard ECG electrodes, was used to measure transthoracic impedance in 10 anesthetized dogs. Variations in cardiac output were produced by controlled hemorrhage (200- to 250-ml increments). Simultaneous reference measurements of cardiac output were made before hemorrhage (control) and at each level of hemorrhage, using the saline-dilution method. The beat-by-beat impedance changes were measured by use of a Minnesota impedance cardiograph, which also recorded the first derivative of impedance (dZ/dt). An index of cardiac output was defined as the product of the maximal value of the first time derivative of impedance, ejection time, and heart rate for each beat during inscription of a saline-dilution curve. The average of the beat-by-beat indices was calculated and then normalized relative to the initial control value. Linear regression analysis was performed to evaluate the correlation of the index of cardiac output with the reference cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia

Optimum stimulus frequency for contracting the inspiratory muscles with chest-surface electrodes to produce artificial respiration.

Electroventilation is the term used to describe the production of inspiration by applying a train of short-duration pulses to chest-surface electrodes. Studies were conducted in the dog to determine the optimum frequency to produce a smooth air flow in the trachea. It was found that a stimulus frequency of 25/sec or slightly higher meets this criterion. To illustrate that electroventilation can be carried out for a prolonged period using these parameters, electroventilation was applied continuously for 5 hours in a dog without a noticeable change in blood pressure.

Animals

End-tidal carbon dioxide concentration, carbon dioxide production, heart rate, and blood pressure as indicators of induced hyperthermia.

In 4 spontaneously breathing, barbiturate-anesthetized dogs, hyperthermia was induced with 2,4-dinitrophenol while rectal temperature, heart rate, mean blood pressure, end-tidal carbon dioxide, and carbon dioxide production (milliliters per minute) were measured continuously. The latter was determined with a pneumotachygraph (to obtain respired volume) and an infrared carbon dioxide analyzer that measured inspired and expired carbon dioxide concentration. Of the five physiologic measurements, the increase in carbon dioxide production preceded the increase in rectal temperature by more than 120 seconds. End-tidal carbon dioxide was an unreliable indicator in the spontaneously breathing animal of approaching hyperthermia during spontaneous breathing due to a transient tachypnea, which decreased end-tidal carbon dioxide. The carbon dioxide production (milliliters per minute) increased immediately and reached three to five times the control value. Blood pressure and heart rate were insensitive indicators of approaching hyperthermia.

2,4-Dinitrophenol

Oxygen uptake and mean blood pressure as indicators of induced hyperthermia.

This dog study was designed to identify which of two measurements (oxygen consumption, mean blood pressure) tracked the onset of hyperthermia as reflected by rectal temperature. The animals were anesthetized, paralyzed, and mechanically ventilated. Hyperthermia was induced with 2,4-dinitrophenol (5 mg/kg) injected intravenously in 5 dogs. It was found that the best and earliest predictor of approaching hyperthermia was the increase in oxygen consumption, which increased 10% in 1.72 min. Mean blood pressure was an insensitive indicator of approaching hyperthermia. Rectal temperature, not surprisingly, was found to be a late and undependable early indicator of developing hyperthermia, requiring about 15 minutes to exhibit a definite increase. It is concluded that among these indicators, monitoring oxygen consumption (ml/min) is the most reliable way to identify a metabolic change such as incipient hyperthermia.

2,4-Dinitrophenol

The use of an electrically activated valve to control preload and provide maximal muscle blood flow with a skeletal-muscle ventricle.

A new method for optimally loading a skeletal muscle-wrapped pouch to act as a blood pump is described. The method takes advantage of the fact that the high preload pressure required for a forceful contraction needs to be present for only a short time. By using an electrically controlled valve to delay pouch filling until just before muscle contraction, pouch diastolic pressure can be kept low, which in turn maintains a high muscle capillary blood flow. The intrapouch precontraction pressure can be controlled by selecting the appropriate valve-open time (VOT). The pumping capabilities of untrained rectus abdominis and latissimus dorsi muscles were evaluated using a hydraulic circulatory system in a ten dog study (weight range 20-32.7 kg). The afterload was constant at 100 mmHg, and the pouch precontraction pressure, selected by choice of the VOT, was the test variable. It was found that for maximum pouch output, a precontraction pressure of 60-100 mmHg was required, being attained in this hydraulic model with a VOT of 400-500 msec. Typical pouch outputs were 400-600 mL/min with a muscle contraction rate of 40/min. Muscle capillary blood flow, measured with a periarterial electromagnetic flowmeter, varied inversely with pouch diastolic pressure and was near zero during tetanic muscle contraction. In one animal, a pouch output of 200 mL/min or more was maintained for more than 20 hours of continuous pumping without fatigue. In a related experiment, the method was applied to pump blood in a 32.7 kg dog, in which the muscle-wrapped pouch was connected between the descending thoracic aorta and the abdominal aorta. A pouch output of about 400 mL/min was obtained when the muscle was contracted 30 times/min and the VOT was 400 msec. This flow represented about 20% of the animal's cardiac output. This study demonstrates that by delaying pouch filling until just before the muscle is to be contracted, a low pouch diastolic pressure can be maintained, thereby maximizing muscle capillary blood flow and, in turn, providing the best opportunity for prolonged pumping.

Animals

Tracking cardiac output by a saline dilution technique using esophageal catheter electrodes.

This paper presents preliminary results of a study in which saline indicator dilution curves were obtained by measuring impedance dilution curves using a tetrapolar catheter-based electrode placed in the esophagus of anesthetized dogs. Cardiac output (CO) was calculated from the area under the impedance-derived saline dilution curve, and compared to CO calculated from the saline dilution curve obtained by a cylindrical external conductivity cell placed in an arterio-venous shunt. The results revealed an approximately two-third overestimation in CO determined using the esophageal electrodes. However, the esophageal impedance CO tracked CO determined by the conventional indicator dilution method very well. When the data were pooled, a cumulative correlation coefficient of 0.96 was obtained. Although the esophageal impedance CO method overestimates CO, it tracks changes in CO well. Further investigation is indicated to determine an optimal electrode configuration for the tetrapolar esophageal electrode.

Animals

Cardiac assistance with electrically stimulated skeletal muscle.

This study examined the ability of a skeletal muscle-powered assist ventricle (SMV) to augment cardiac output in ten dogs with pharmacologically induced heart failure under acute conditions. An SMV was surgically constructed in each dog by wrapping the untrained rectus abdominis muscle around a compressible pouch that was inserted into a left ventricular apex-to-aortic vascular conduit. The multiple motor nerves to the rectus muscle were then stimulated during ventricular diastole at a rate which equalled a ratio of 1:2, 1:3, or 1:4 with the natural ventricular beat. There was an increased cardiac output during SMV assistance compared with preassistance values in all ten dogs at each stimulation ratio with a mean increase of 46 +/- 4 per cent with a ratio of 1:2, 25 +/- 4 per cent with a ratio of 1:3, and 31 +/- 7 per cent with a ratio of 1:4 (p less than 0.01 for all values). The diastolic blood pressure and mean blood pressure were both increased (p less than 0.01 and p less than 0.05, respectively) during SMV stimulation at ratios of 1:2 and 1:3, but not 1:4. We have shown that untrained rectus abdominis muscle, when used as the power supply for a SMV in an apico-aortic conduit, can temporarily augment cardiac output in dogs with pharmacologically induced heart failure.

Abdominal Muscles

A skeletal muscle ventricle made from rectus abdominis muscle in the dog.

This study examined the ability of a skeletal muscle-powered assist ventricle to augment cardiac output in 10 dogs with experimentally induced heart failure. Heart failure was induced with the use of the beta-blocking agents atenolol and propranolol. A "skeletal muscle ventricle" was then surgically constructed by wrapping the rectus abdominis muscle, with an intact neurovascular supply, around a double open-ended compressible pouch. The skeletal muscle ventricle was then interposed in a left ventricular apicoaortic conduit. The motor nerves to the skeletal muscle ventricle were stimulated by a custom designed pulse generator and caused tetanic contraction of the ventricle during diastole of every fourth natural heart beat. Stimulation was continued for 60 min. Cardiac output, systolic and diastolic blood pressures, mean blood pressure, left ventricular end diastolic pressure, and central venous pressure were then monitored prior to, during, and several times after skeletal muscle ventricle stimulation to evaluate assist ventricle function. There was an increased cardiac output in all 10 dogs at all recording times during skeletal muscle ventricle assistance compared to the cardiac output prior to stimulation of the assist ventricle. The mean increase in cardiac output after 30 min of assist ventricle stimulation was 31.0 +/- 14% (P less than 0.01), and at 60 min was 8.0 +/- 1% (P less than 0.05). The mean diastolic blood pressure after 1 and 30 min of skeletal muscle ventricle assistance (50.0 +/- 2.9 and 48.6 +/- 2.2 mm Hg, respectively) was increased (P less than 0.05) vs the preassistance value (44.9 +/- 2.8 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Changes in expired end-tidal carbon dioxide during cardiopulmonary resuscitation in dogs: a prognostic guide for resuscitation efforts.

Expired end-tidal carbon dioxide (PCO2) measurements made during cardiopulmonary resuscitation have correlated with cardiac output and coronary perfusion pressure when wide ranges of blood flow are included. The utility of such measurements for predicting resuscitation outcome during the low flow state associated with closed chest cardiopulmonary resuscitation remains uncertain. Expired end-tidal PCO2 and coronary perfusion pressures were measured in 15 mongrel dogs undergoing 15 min of closed chest cardiopulmonary resuscitation after a 3 min period of untreated ventricular fibrillation. In six successfully resuscitated dogs, the mean expired end-tidal PCO2 was significantly higher than that in nine nonresuscitated dogs only after 14 min of cardiopulmonary resuscitation (6.2 +/- 1.2 versus 3.4 +/- 0.8 mm Hg; p less than 0.05). No differences in expired end-tidal PCO2 values were found at 2, 7 or 12 min of cardiopulmonary resuscitation. A significant decline in end-tidal PCO2 levels during the resuscitation effort was seen in the nonresuscitated group (from 6.3 +/- 0.8 to 3.4 +/- 0.8 mm Hg; p less than 0.05); the successfully resuscitated group had constant PCO2 levels throughout the 15 min of cardiac arrest (from 6.8 +/- 1.1 to 6.2 +/- 1.2 mm Hg). Changes in expired PCO2 levels during cardiopulmonary resuscitation may be a useful noninvasive predictor of successful resuscitation and survival from cardiac arrest.

Animals

Correlation of Cu(PTSM) localization with regional blood flow in the heart and kidney.

In a dog model of myocardial ischemia, i.v. injection of [67Cu]Cu(PTSM) leads to an excellent linear correlation for both the heart and kidney between regional tissue radiocopper concentration and regional blood flow measured by radioactive micropheres. The 62Cu-labeled complex may serve as a generator-produced position-emitting perfusion tracer for these organs.

Animals

The safety factor for electroventilation measured by production of cardiac ectopy in the anesthetized dog.

The safety factor of electroventilation (ie, the ratio of the current required to produce an ectopic beat to the current required to produce an inspired volume of 225 ml, which is approximately twice tidal volume) was determined in 12 pentobarbital-anesthetized dogs using transthoracic electrodes positioned at the optimal electroventilation site. The optimal stimulation site for electroventilation was first determined using hand-held, stimulating electrodes. Then electrodes, 4.1 cm in diameter, were sutured bilaterally to the optimal stimulation site. The relationship between inspired volume and stimulus intensity was determined using a 0.8-s burst of stimuli (60/s) with a pulse duration of 0.1 ms. Using the same electrodes, the threshold current for producing ectopic beats was determined for single pulses ranging from 0.1 to 10 ms duration. In all dogs, the current required to produce an ectopic beat increased greatly as the pulse duration decreased. At 0.1 ms, the safety factor for electroventilation was calculated to be 25.8.

Anesthesia