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Biomedical subjects

J W Fanton

Publications and source records attributed to J W Fanton.

At least 37 records · Page 2Linked to original sources

Evaluation of dual-tip micromanometers during 21-day implantation in goats.

Investigative research efforts using a cardiovascular model required the determination of central circulatory haemodynamic and arterial system parameters for the evaluation of cardiovascular performance. These calculations required continuous beat-to-beat measurement of pressure within the four chambers of the heart and great vessels. Sensitivity and offset drift, longevity, and sources of error for eight 3F dual-tipped micromanometers were determined during 21 days of implantation in goats. Subjects were instrumented with pairs of chronically implanted fluid-filled access catheters in the left and right ventricles, through which dual-tipped (test) micromanometers were chronically inserted and single-tip (standard) micromanometers were acutely inserted. Acutely inserted sensors were calibrated daily and measured pressures were compared in vivo to the chronically inserted sensors. Comparison of the pre- and post-gain calibration of the chronically inserted sensors showed a mean sensitivity drift of 1.0 +/- 0.4% (99% confidence, n = 9 sensors) and mean offset drift of 5.0 +/- 1.5 mmHg (99% confidence, n = 9 sensors). Potential sources of error for these drifts were identified, and included measurement system inaccuracies, temperature drift, hydrostatic column gradients, and dynamic pressure changes. Based upon these findings, we determined that these micromanometers may be chronically inserted in high-pressure chambers for up to 17 days with an acceptable error, but should be limited to acute (hours) insertions in low-pressure applications.

Animals↗

Evidence for increased cardiac compliance during exposure to simulated microgravity.

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Animals↗

Effect of hyperbaric oxygenation on peripheral nerve regeneration in adult male rabbits.

Oxygen environments were used to study the regenerative effects of hyperbaric oxygen on crushed sciatic nerves in 30 adult male rabbits. Six different oxygen environments were used, and treatments were initiated 4 days post injury. Transmission electron microscopy and light microscopy were used to evaluate the regenerative morphology of crushed nerves. The morphology of crushed nerves after 7 wk of treatment with compressed oxygen at 202, 242, and 303 kPa resembled normal uncrushed nerves, with nerve fibers uniformly distributed throughout the section. The treatment groups receiving 202 kPa compressed air, 100% normobaric oxygen, or ambient air did not display morphologies similar to normal uncrushed nerve. The nerves in these animals were edematous and contained disarrayed nerve fibers. Myelination in the animals receiving 100% O2 at high pressures resembled undamaged nerves. Collagen and blood vessels were more evident in the lower pressure/oxygen tension treatments than in the animals receiving 100% O2 at higher pressures. The neurofilamentous material inside the crushed control axons was dense, whereas in the axons of animals treated with compressed O2 it was loosely packed. These differences in morphology suggest that treatments consisting of 100% O2 under pressure can accelerate a peripheral nerve's recovery from a crush injury.

Animals↗

Total and regional cerebral blood flow during recovery from G-LOC.

INTRODUCTION: This study measured total and regional cerebral blood flow (BF) in baboons during +Gz-induced loss of consciousness (G-LOC) and during recovery from G-LOC. METHODS: Flowprobes (Transonic Inc., T201, Ithaca, NY) were placed on the common carotid and internal carotid arteries of five male baboons for continuous measurement of total cephalic and cerebral BF, respectively. Radiolabeled microspheres were used to measure regional central nervous system BF at discrete timepoints. G-LOC was determined from visual observations of the animals and from EEG recordings. RESULTS: Cerebral blood flow was maintained and animals remained conscious during 60 s exposure to +4 Gz. In contrast, G-LOC was observed during the first 16-25 s (mean = 20.3 +/- 3.7 s) of exposure to +8 Gz in all five animals. Internal and common carotid artery BF decreased rapidly to zero during the first few seconds of +8 Gz. BF always appeared to cease prior to the occurrence of G-LOC. During early recovery from G-LOC there was no hyperemic response recorded with flowprobes, whereas a hyperemic response was recorded following 60 s exposures to +4 Gz in which the animals did not experience G-LOC. Microsphere measurements of the regional distribution of BF are consistent with the hypothesis of a +Gz-induced differential perfusion deficit throughout the brain and central nervous system during G-LOC. CONCLUSIONS: We conclude that G-LOC is preceded by cessation of cerebral BF. The fact that the hyperemic response following +Gz exposure is less when G-LOC occurs than when G-LOC does not occur suggests CNS energy conservation during G-LOC.

Acceleration↗

Database created from magnetic resonance images of a Sprague-Dawley rat, rhesus monkey, and pigmy goat.

To obtain a database of accurate anatomical images onto which dosimetry data of electromagnetic fields could be mapped, a healthy Sprague-Dawley rat, rhesus monkey, and pigmy goat were scanned using magnetic resonance imaging (MRI). Axial sections throughout the length of the animals were collected. Sections were 3 mm thick for the rat and 5 mm thick for the monkey and goat. Sagittal sections (2 mm thick) of the rat head were also scanned. Images were recorded on magnetic tape and transferred to computer disk for image enhancement and network distribution. Images are available in 16 bit Big Endian signed or 8 bit TIFF formats. This is the first database of contiguous MRI axial scans of rat, monkey, and goat available for distribution via magnetic tape (4 mm DDS) or Internet file transfer protocol. Digital transfer of the data was selected to preserve the integrity of each image, circumventing the need for the user to scan the images back into a digital format for use with their software. These images should be useful to physiologists, neuroscientists, veterinarians, anatomists, and teachers. Reconstructing these 2-dimensional images into 3-dimensional structures is an effective media for conveying spatial anatomical information in a quick and comprehensive manner.

Animals↗

Gastrin levels and gastric emptying times in rhesus monkeys with a history of acute gastric dilatation.

Abnormal gastric motility has been suggested as a possible causative factor for acute gastric dilatation observed in nonhuman primates. To evaluate gastric motility in a colony, fasting serum gastrin immunoreactivity and gastric emptying times were assessed in rhesus monkeys that had survived single episodes of acute gastric dilatation. These were paired with age- and weight-matched control monkeys from the same colony. Neither gastric emptying times nor gastrin assays were significantly different between the acute gastric dilatation and control groups.

Acute Disease↗

Acute behavioral toxicity of pyridostigmine or soman in primates.

Effects of a peripherally active carbamate (pyridostigmine bromide) and a centrally active organophosphate (OP) nerve agent (soman) on performance by rhesus monkeys of a compensatory tracking (primate equilibrium platform, or PEP) task were measured using a balanced Latin-square design to determine the ED50 for pyridostigmine (0.66 mg/kg) and the up-and-down (titration) method to determine the ED50 for soman (2.50 micrograms/kg). We concluded that the PEP performance model is a sensitive and reliable indicator of anticholinesterase (anti-ChE) behavioral toxicity. We also found that soman, an irreversible inhibitor of acetylcholinesterase (AChE), is more than 100 times more behaviorally disruptive than the reversible peripheral inhibitor pyridostigmine, as indicated by the difference in ED50 doses expressed in molar terms. Soman's behavioral toxicity is severe at levels of serum cholinesterase inhibition (70-80%) at which pyridostigmine does not significantly affect performance. As a prophylactic treatment for OP agent poisoning, pyridostigmine has a substantial safety factor, since behavioral toxicity becomes significant only at approximately four times the proposed therapeutic dose.

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Central hemodynamics in a baboon model during microgravity induced by parabolic flight.

We developed a chronically instrumented nonhuman primate model (baboon) to evaluate the central cardiovascular responses to transient microgravity induced by parabolic flight. Instrumentation provided simultaneous recording of high fidelity (Ao) and pulmonary artery (PA) pressures, right and left ventricular and atrial pressures, Ao and PA blood flow velocities and vessel dimensions, ECG and pleural pressures. Four daily flights in 1991 and five in 1992 were flown with forty parabola per flight. Animals flown in 1991 were not controlled for volume status. Animals flown in 1992 were studied in one of three conditions: 1) volume depleted by furosemide (DH), 2) volume expanded by saline infusion (VE), and 3) euvolemic (EU, no intervention, used for echo only). Mean right atrial pressures (RAP) during 1991 flights had a variable early microgravity response: increases in n=3 and decrease in n=3 (supine) and increases in n=5, decreases in n=2 (upright). In 1992 flights, DH, upright and supine, changed -10 +/- 4.1 mmHg, -3.2 +/- 2.2 mmHg, respectively (p < .05) compared to the pull-up phase. In contrast, VE changed (from pull-up to microgravity) +13 +/- 1.5 mmHg and +4.25 +/- 2.9 mmHg (upright and supine, respectively, p < .05). EU increased with microgravity +6.9 +/- .9 mmHg (upright only). LAP responses were similar, but more variable. Finally, heart chamber areas paralleled pressure changes. Thus, right and left heart filling pressure changes with sudden entry into microgravity conditions were dependent on initial circulatory volume status and somewhat modified by position (supine vs upright).

Animals↗

The influence of the AGSM, PBG, and anti-G suit inflation on thoracic hemodynamics during +Gz in swine.

With the advent of pressure breathing for +Gz (head-to-foot inertial loading) protection (PBG) and the development of improved extended coverage anti-G suits (ECGS) it has become important to expand our knowledge of the cardiopulmonary physiologic interrelationships of pressure breathing, anti-G suit protection, and the anti-G straining maneuver (AGSM). Although high levels of pressure breathing have been previously investigated, there was continuing concern within the aeromedical community regarding the introduction of COMBAT EDGE, a PBG system. Some of the concerns were: barotrauma, pneumothorax, air embolism, excessive transmural vascular pressures, possible cardiac valvular damage, and possible overdilation of the right ventricle from a surge in venous return following +Gz. This study describes the experimental preparation and results of a hemodynamic investigation to address some of these concerns using chronically instrumented miniature swine (MS).

Animals↗

Cerebral and spinal cord blood flow dynamics during high sustained +Gz.

This study had two purposes. First, the use of Transonic flowprobes placed on the common carotid and internal carotid arteries of seven male baboons was evaluated for measuring cerebral blood flow (BF) during +Gz stress. The approach was to compare BF's obtained with these flowprobes to microsphere measurements of total cerebral BF. The second purpose was to measure regional variations in cerebral and spinal cord BF during +Gz to test the hypothesis that +Gz produces a differential perfusion deficit throughout the central nervous system so that BF's at the superior portion of the brain are decreased more than in areas of the brain that are nearer to the heart. The results indicate that internal carotid artery and microsphere measurements of total brain BF were related so that the relative decrease in internal carotid artery BF was consistently comparable to that measured with the labeled microsphere technique. Thus, Transonic flowprobes placed on the internal carotid artery of the baboon give reliable estimates of cerebral BF during +Gz stress. The microsphere BF data demonstrated that there were no regional differences in the relative decrease in BF measured in the brain or spinal cord during +Gz. We conclude that our results do not support the hypothesis of a gradient of BF deficit within the brain or spinal cord during +Gz.

Acceleration↗

Effect of upright tilt on ventricular/vascular coupling in chronically instrumented primates.

Studies of the hydraulic loading conditions on the heart in humans, especially pulsatile load, have primarily been limited to the supine state. Therefore, we have chosen a nonhuman primate model, the baboon, to assess left ventricular/vascular coupling in both supine and upright positions. Primate subjects were studied by catheterization under sedation and then after surgical implantation of transducers. This allowed the evaluation of postural stress in the chronically instrumented conscious baboon and then after light dissociative doses of ketamine. Basic hemodynamic variables were evaluated for baboons in supine and upright positions. Fourier analysis was applied to aortic pressure and flow to obtain input and characteristic impedance and the ratio of pulsatile (Wp) to total (Wt) left ventricular power (Wp/Wt). The aortic reflected, or backward, pressure was also calculated. Peripheral resistance increased (P = 0.01) and reflected pressure decreased (17.74 +/- 1.50 vs. 15.21 +/- 2 mmHg; P < 0.01) in upright subjects. Characteristic impedance and Wp/Wt were unchanged. Postoperatively, peripheral resistance increased (2,651 +/- 311 vs. 3,667 +/- 276; P < 0.05) and mean power and Wt decreased (P < 0.01) without changes in reflected pressure. All variables were unchanged after light dissociative doses of ketamine. Thus there is no significant change in efficiency of left ventricular/vascular coupling formulated in terms of Wp/Wt or input impedance with postural stress.

Animals↗

Transesophageal echocardiographic evaluation of baboons during microgravity induced by parabolic flight.

The central cardiovascular responses to transient microgravity are not well understood. Theoretically, entrance into microgravity results in the loss of the hydrostatic pressure head and an increase in central venous pressure (CVP) as a consequence of augmented venous return. However, controversy exists regarding the time course and magnitude of cephalad blood volume shifts and its relationship to central atrial filling pressures. On the June 1991 STS 40 shuttle mission, pre-launch echocardiograms suggested changes in cardiac dimensions occurred while the astronauts were in the supine, feet-up position. Furthermore, a CVP line in an astronaut (n=1) demonstrated an unexpected abrupt decrease in CVP during orbital insertion. In April 1991, our laboratory performed Doppler echocardiography in 6 normal human volunteers during parabolic flight. Increases in right ventricular velocities reflecting a central shift of blood volume was demonstrated in subjects examined in the sitting position. However, test subjects examined in the horizontal positions had no significant rise in Doppler velocities. In addition, Latham et al noted variable central cardiovascular responses in chronically instrumented baboons during early microgravity. Transthoracic echocardiography (TTE) is a feasible method to noninvasively examine cardiac anatomy during parabolic flight. However, transducer placement on the chest wall is very difficult to maintain during transition to microgravity. In addition, TTE requires the use of low frequency transducers (2.5 MHz) which limits resolution. Transesophageal echocardiography (TEE) is an established imaging technique which obtains echocardiographic information from the esophagus. It is a safe procedure and provides higher quality images of cardiac structures than obtained with TTE. Since there are no interposed structures between the esophagus and the heart, higher frequency transducers can be used and resolution is enhanced. With TEE, a flexible transducer tip permits contact with the esophageal mucosa, allowing for consistent imaging. This study was designed to determine whether TEE was feasible to perform during parabolic flight and to determine whether acute central volume responses occur in acute transition to zero gravity (0G) by direct visualization of the cardiac chambers.

Animals↗

Circulatory filling pressures during transient microgravity induced by parabolic flight.

Theoretical concepts hold that blood in the gravity-dependent portion of the body would relocate to more cephalad compartments under microgravity conditions. The result is an increase in blood volume in the thoracic and cardiac chambers. This increase in central volume shift should result in an increase in central atrial filling pressures. However, experimental data has been somewhat contradictory and nonconclusive to date. Early investigations of peripheral venous pressure and estimates of central venous pressure (CVP) from these data did not show an increase in CVP in the microgravity condition. However, CVP recorded in human volunteers during the parabolic flight by Norsk revealed an increase in CVP during the microgravity state. On the June 1991 STS 40 shuttle mission, a payload specialist wore a fluid line that recorded CVP during the first few hours of orbital insertion. These data revealed decreased CVP. When this CVP catheter was tested during parabolic flight in four subjects, two subjects had increased CVP recordings and two other subjects had decreased CVP measurements. In April 1991, our laboratory performed parabolic flight studies in several chronic-instrumented baboon subjects. It was again noted that centrally recorded right atrial pressure varied with exposure to microgravity, some animals having an increase and others having a decrease. Thus, data presently available has demonstrated a variable response in the mechanism not clearly defined. In April 1992, we determined a test hypothesis relating the possible mechanism of these variable pressure responses to venous pressure-volume relationships.

Animals↗

Diazepam as a treatment for nerve agent poisoning in primates.

Diazepam is known to decrease organophosphate nerve agent-induced convulsions, neuropathology, and lethality in rhesus monkeys. We report that, when added to the previously fielded treatment regimen (pyridostigmine, atropine, and pralidoxime chloride), diazepam significantly protects the performance of rhesus monkeys trained in an equilibrium task, the Primate Equilibrium Platform (PEP), against deficits induced by the nerve-agent soman. If administered soon enough to minimize the occurrence of convulsions, diazepam should increase the probability of mission accomplishment and eventual complete recovery from nerve agent poisoning. Diazepam was fielded by the United States military services during Operations Desert Shield and Storm for the treatment of possible organophosphate toxicity.

Animals↗

An attempt to eradicate Herpesvirus simiae from a rhesus monkey breeding colony.

In the fall of 1987 an attempt to establish a Herpesvirus simiae (B-virus)-negative rhesus monkey (Macaca mulatta) breeding colony was initiated at the Armstrong Laboratory. A serologic testing program was used to identify all monkeys into groups that were either positive or negative to B-virus based on serologic tests. Segregation of the groups allowed the creation of breeding harems that were exclusively seropositive or -negative to B-virus. Animals that were serologically positive were kept in breeding to maintain infant production levels not unlike those previous to segregation. Decreasing numbers of animals converted to a positive status during the first three serum tests for B-virus in the program. During 1990, an increase in the number of monkeys converting to positive status and the discovery of an indeterminate status demonstrated that latency of B-virus in the rhesus may have the potential to defeat an eradication attempt not conscientiously pursued.

Animal Husbandry↗

Radiation-induced endometriosis in Macaca mulatta.

Female rhesus monkeys received whole-body doses of ionizing radiation in the form of single-energy protons, mixed-energy protons, X rays, and electrons. Endometriosis developed in 53% of the monkeys during a 17-year period after exposure. Incidence rates for endometriosis related to radiation type were: single-energy protons, 54%; mixed-energy protons, 73%; X rays, 71%; and electrons, 57%. The incidence of endometriosis in nonirradiated control monkeys was 26%. Monkeys exposed to single-energy protons, mixed-energy protons, and X rays developed endometriosis at a significantly higher rate than control monkeys (chi 2, P less than 0.05). Severity of endometriosis was staged as massive, moderate, and minimal. The incidence of these stages were 65, 16, and 19%, respectively. Observations of clinical disease included weight loss in 43% of the monkeys, anorexia in 35%, space-occupying masses detected by abdominal palpation in 55%, abnormal ovarian/uterine anatomy on rectal examination in 89%, and radiographic evidence of abdominal masses in 38%. Pathological lesions were endometrial cyst formation in 69% of the monkeys, adhesions of the colon in 66%, urinary bladder in 50%, ovaries in 86%, and ureters in 44%, focal nodules of endometrial tissue throughout the omentum in 59%, and metastasis in 9%. Clinical management of endometriosis consisted of debulking surgery and bilateral salpingo-oophorectomy combined in some cases with total abdominal hysterectomy. Postoperative survival rates at 1 and 5 years for monkeys recovering from surgery were 48 and 36%, respectively.

Animals↗