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Biomedical subjects

R L Carpenter

Publications and source records attributed to R L Carpenter.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effect of epinephrine on central nervous system and cardiovascular system toxicity of bupivacaine in pigs.

To determine what effect the addition of epinephrine has on bupivacaine toxicity, toxic doses of bupivacaine were administered to awake spontaneously breathing pigs. Twenty animals were randomized to one of two groups. One group received an infusion of bupivacaine with epinephrine (5 micrograms/ml) at a rate of 2 mg.kg-1.min-1; the other received an infusion of plain bupivacaine at the same rate. Bupivacaine infusion was continued until cardiovascular collapse. Following cardiovascular collapse we attempted to resuscitate the animals via open chest cardiac massage and a standardized resuscitation protocol. The addition of epinephrine to bupivacaine significantly increased blood pressure and systemic vascular resistance but not heart rate or cardiac output early in the bupivacaine infusion. Epinephrine had no effect on the dose of bupivacaine that caused cardiovascular collapse (P = 0.1), on the plasma concentration of bupivacaine at collapse (P = 0.9), or on the ability to resuscitate animals following cardiovascular collapse. The addition of epinephrine decreased the dose of bupivacaine required to initiate cardiac dysrhythmias (P = 0.003). The first dysrhythmia experienced by the epinephrine group was second degree heart block, which contrasts with the premature ventricular and atrial dysrhythmias experienced by the plain group. The dose of bupivacaine that produced seizures was also reduced by the addition of epinephrine (P = 0.006). The addition of epinephrine to bupivacaine did not alter the dose of bupivacaine that caused cardiovascular collapse in awake spontaneously breathing pigs but did decrease the dose of bupivacaine that caused seizures and dysrhythmias.

Animals↗
PubMed1989

Accuracy of laser Doppler capillary flow measurements for predicting blood loss from skin incisions in pigs.

This study assesses the clinical applicability of laser Doppler capillary flow measurements for predicting blood loss from a surgical incision. To produce a wide range of blood flows, we injected lidocaine 1%, lidocaine 1% plus octapressin (0.03 IU.ml-1), and lidocaine 1% plus epinephrine (5 micrograms.ml-1) subcutaneously into three separate sites on the flank of each animal (N = 6). Laser Doppler flow measurements were made before and 10 minutes after injection Subcutaneous injection of lidocaine tended to increase cutaneous blood flow (96 +/- 13 to 153 +/- 30 mV, mean +/- SE, P = 0.09). Blood flow tended to decrease after injection of lidocaine with epinephrine (101 +/- 13 to 57 +/- 10 mV, P = 0.03) or octapressin (108 +/- 20 to 58 +/- 11 mV, P = 0.08). Laser Doppler measurements were higher after the injection of plain lidocaine than after that of lidocaine with either epinephrine or octapressin (P = 0.004). A standard incision was performed at each site and blood loss measured over the subsequent 10 minutes. Laser Doppler measurements correlated with the amount of bleeding from the surgical incision (R = 0.69, P less than 0.001). We conclude that the laser Doppler is a useful tool for evaluating the ability of subcutaneously injected local anesthetics (vasodilators) or vasoconstrictors to alter bleeding from skin incisions.

Animals↗
PubMed1988

Comparative inhalation toxicity of nickel sulfate to F344/N rats and B6C3F1 mice exposed for twelve days.

Groups of F344/N rats and B6C3F1 mice were exposed to aerosols of nickel sulfate hexahydrate (NiSO4.6H2O) 6 hr/day for 12 days to determine the short-term inhalation toxicity of this compound. Target exposure concentrations were 60, 30, 15, 7, 3.5, and 0 mg NiSO4.6H2O/m3. Endpoints evaluated included clinical signs, mortality, quantities of Ni in selected tissues, effect on mouse resistance to tumor cells, and pathological changes in tissues of both rats and mice. All mice exposed to 7 mg NiSO4.6H2O/m3 or greater and 10 rats exposed to 15 mg NiSO4.6H2O/m3 or greater died before the termination of exposures. Quantities of Ni remaining in lungs of rats at the end of the exposure were independent of exposure concentration. Lung burdens of Ni in mice were approximately one-half that in lungs of rats. Exposure of female mice to 3.5 mg NiSO4.6H2O/m3 had no effect on resistance to tumor cells as determined by spleen natural killer cell activity. Histopathological changes were seen in tissues of rats and mice exposed to as low as 3.5 mg NiSO4.6H2O/m3. Lesions related to NiSO4.6H2O exposure occurred in lung, nose, and bronchial and mediastinal lymph nodes. Results indicated that exposure of rats and mice to amounts of NiSO4.6H2O aerosols resulting in Ni exposure concentrations only eight times greater than the current threshold limit value for soluble Ni (0.1 mg/m3) for as little as 12 days can cause significant lesions of the respiratory tract.

Administration, Inhalation↗
PubMed1988

Isoflurane elimination via a bubble oxygenator during extracorporeal circulation.

It has been suggested that inhalational anesthetics should be discontinued at least 15 minutes prior to termination of extracorporeal circulation (ECC) to avoid myocardial depression. However, data regarding elimination of inhalation agents via a bubble oxygenator from hypothermic, hemodiluted patients have not been previously reported. The washout of isoflurane (ISF) from ten cardiac surgical patients using mass spectrometry was studied. The mean baseline oxygenator exhaust concentration of ISF was 0.85% prior to termination of ECC. Oxygenator concentration of ISF decreased to less than 0.05% in 8.8 +/- 2.5 minutes. Eight of ten patients had ISF washout curves best characterized by a one-compartment model, with a mean time constant of 1.94 minutes. Therefore, 95% washout of ISF should occur in 5.8 minutes (three time constants). It is suggested that ISF may be used closer to the termination of ECC than previously recommended without fear of significant myocardial depression.

Aged↗
PubMed1987

Toxicant distribution in the Thomas Domes.

Measurement of test article concentration distribution for light gases have been made in the Thomas Dome inhalation chambers at Wright-Patterson Air Force Base, using propane as a test agent. The method used to analyze for inhomogeneities in test article spatial distribution deliberately varies the dome operational parameters rather than requiring extreme operational stability. The variation in test article concentration is analyzed by regression to determine which operational parameters most influence the test agent distribution. Unaccounted concentration variability is assumed to be the inherent spatial variation of the test article in the dome. The propane studies indicated that the spatial variation within the dome was 6.4% of the mean and that room air temperature at the top of the dome, propane analyzer baseline stability, and dome pressure were (listed in order of decreasing importance) the variables influencing the test article distribution.

Air Pressure↗
PubMed1987

Comparative inhalation toxicity of nickel subsulfide to F344/N rats and B6C3F1 mice exposed for 12 days.

Groups of F344/N rats and B6C3F1 mice were exposed to aerosols of nickel subsulfide (Ni3S2) 6 hr/day for 12 days not including weekends. Actual exposure concentrations were within 3% of target (target = 10.0, 5.0, 2.5, 1.2, 0.6, and 0.0 mg Ni3S2/m3). Nickel lung burdens of exposed rats and mice increased linearly with exposure concentration. Two male rats and all mice exposed to 10.0 mg Ni3S2/m3 died before the end of the exposures. Exposure to Ni3S2 had no effect on the natural killer cell activity of mouse spleen cells. Lesions in rats and mice related to inhalation of Ni3S2 were found in the nasal epithelium, lung, and bronchial lymph nodes. The most extensive lesions were found in the lung and included necrotizing pneumonia. Emphysema developed in rats exposed to 5.0 or 10.0 mg Ni3S2/m3, while fibrosis developed in mice exposed to 5.0 mg Ni3S2/m3. Degeneration of the respiratory epithelium and atrophy of the olfactory epithelium of the nose occurred in rats exposed to as low as 0.6 mg Ni3S2/m3 and mice exposed to 1.2 mg/m3. Results indicate that inhalation exposure of rats and mice to Ni3S2 aerosol concentrations near the current threshold limit value (TLV) for nickel compounds (1 mg/m3 for Ni metal and roasting fume and dust and 0.1 mg/m3 as Ni for soluble compounds) can produce lesions in the respiratory tract. Atrophy of lymphoid tissues (spleen, thymus, and bronchial lymph nodes) was found in animals of the highest exposure concentration. Degeneration of the testicular germinal epithelium was also observed in mice and rats that survived 5.0 or 10.0 mg/m3 exposure concentrations.

Animals↗
PubMed1987

Comparative lung immunotoxicity of inhaled quartz and coal combustion fly ash.

Some inhaled particles that are deposited in the terminal airways and alveoli clear to the lung-associated lymph nodes, and insoluble particles have a long half-life in these tissues. Because the lung-associated lymph nodes are essential in the induction of immunity after lung immunization, the accumulation of inhaled particles in these tissues could alter immune responses that develop after lung immunization. This study evaluated the effects of inhaled insoluble fly ash particles or alpha quartz on the immune functions of lung-associated lymph nodes. F344 rats were exposed for 20 days by inhalation of fly ash from a fluidized bed combustor (FBC) or a pulverized coal combustor (PCC). Rats were similarly exposed to quartz particles (Min-U-Sil). Control rats were exposed to filtered air. Groups of ten exposed and ten control rats from each group were immunized by intratracheal instillation of 10(8) sheep red blood cells at 4, 6, 40, and 52 weeks after the start of exposures. The cellularity of the lung-associated lymph nodes and antibody-mediated immunity were evaluated at 7 days after immunization. Tissues from lung and lung-associated lymph nodes were taken for histopathology. The inhalation of FBC fly ash, PCC fly ash, and quartz particles all significantly increased the number of lymphoid cells in the lung-associated lymph nodes at each of the sacrifice times. However, FBC fly ash had no significant effect on antibody immunity, while both PCC fly ash and quartz caused suppression of antibody responses at 52 weeks after the start of exposure. Histopathology data showed that exposure to quartz and PCC fly ash caused significant cellular changes in lungs and lung-associated lymph nodes, while FBC fly ash had less effect. These data indicate that an acute exposure (20 days) to relatively insoluble particles significantly increased the cellularity of the lung-associated lymph nodes for up to 52 weeks after the start of the exposure, but the pulmonary toxicity of the particles inhaled appeared to influence the effects of the exposure on antibody immune responses.

Animals↗
PubMed1987

Effects of inhaled nitrogen dioxide and diesel exhaust on developing lung.

This study examined age-related differences in the physiological responses of rats to inhaled automotive emissions. Previous reports suggested that lung development of animals exposed to oxidant gases early in life might be impaired, or that developing lungs might be more susceptible than adult lungs to inhaled toxicants. There were no previous comparisons in developing and adult lungs of the effects of atmospheres containing particles. The hypothesis tested in this study was that rats exposed to chronically inhaled nitrogen dioxide (NO2) or diesel exhaust during lung development were more susceptible to lung injury than rats that were exposed to these atmospheres as adults. Rats were exposed either throughout the period of lung development or as adults, and health effects in the two groups were compared at the end of exposure. Rats were exposed seven hours per day, five days per week for six months to NO2 at 9.5 ppm, to whole diesel exhaust diluted to a soot concentration of 3.5 mg/m3, or to filtered air as controls. These concentrations were selected to produce mild effects in adults. The younger group (developing) was conceived in the exposure atmospheres and exposed during gestation and through the age of six months, and the older group (adult) was exposed between six and twelve months of age. Health effects were evaluated at the end of six months' exposure and some measurements were repeated six months after the cessation of exposure. Measurements included respiratory function, pulmonary immune responses, lung clearance of radiolabeled particles, airway fluid enzymes, protein and cytology, lung tissue collagen and proteinases, lung burdens of diesel soot, lung morphometry and histopathology. Nitrogen dioxide slightly reduced body weight and altered airway fluid enzymes of both age groups, with a greater number of statistically significant differences detectable in the enzyme levels of animals exposed as adults. Normal lung development, as reflected in the size and functional efficiency at adulthood, was not affected by NO2 in this study. Diesel exhaust altered the airway fluid constituents as well as lung tissue collagen and proteinases of both age groups. Particularly striking was an almost sixfold increase in the percentage of neutrophils, a class of highly phagocytic leukocytes, in the airway fluids of adults after six months of exposure. Exhaust-exposed adults had increased numbers of cells in pulmonary lymph nodes, delayed clearance of both diesel soot and 134Cs-labeled particles, and increased lung weight. These changes did not occur in the rats exposed during development.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗
PubMed1987

Does the duration of anesthetic administration affect the pharmacokinetics or metabolism of inhaled anesthetics in humans?

To define the effect of anesthetic duration on the pharmacokinetics of inhaled anesthetics, we determined the pharmacokinetics of isoflurane, enflurane, halothane, and methoxyflurane given simultaneously to seven healthy subjects for exactly 30 min and compared the results with data from a previous study in which these four anesthetics were administered for 120 min. End-tidal and mixed-expired anesthetic concentrations were measured during washin of anesthetic and for 3-9 days of washout. Multiexponential (multicompartment) models were fit by least squares to the alveolar washin and washout curves. We estimated the percentage of anesthetic that was metabolized from total uptake and recovery of anesthetic. Alveolar washout was more rapid after the shorter period of anesthetic administration. However, duration of administration did not affect the time constants determined, the number of compartments identified (i.e., five compartments were identified in both studies), or the percentages of anesthetic metabolized.

Adult↗
PubMed1986

Effects of sulfuric acid mist inhalation on mucous clearance and on airway fluids of rats and guinea pigs.

The responses of guinea pigs and rats to inhaled sulfuric acid aerosols were compared to define species differences and to determine the small-animal model most relevant to human exposures. Rats were exposed for 6 h to 1, 10, and 100 mg H2SO4/m3. Guinea pigs were exposed for 6 h to 1, 10, and 27 mg H2SO4/m3. Tracheal mucous clearance of guinea pigs was slowed 1 d after exposures to 1 mg H2SO4/m3. A tendency toward faster clearance was observed at high concentrations of H2SO4 for both guinea pigs and rats (statistically significant only for the rats). The speeding of mucous clearance was correlated with increases in airway sialic acid and also with the appearance of excess tracheal secretions, detected using scanning electron microscopy in both rats and guinea pigs. The responses of guinea pigs to sulfuric acid exposures were more similar to those reported for humans than were those of rats.

Aerosols↗
PubMed1986

Studies of the temporal and spatial distribution of aerosols in multi-tiered inhalation exposure chambers.

Two multi-tiered whole body inhalation exposure chambers with nominal volumes of 1 m3 (H-1000) and 2 m3 (H-2000) were evaluated for their performance in terms of the temporal and spatial distribution of test aerosols within the chamber. Parameters investigated included chamber type, single-chamber-single-aerosol generator versus two-chamber-single-aerosol generator systems, chamber air supply and exhaust systems, particle size, and aerosol diluter type. Results indicated that: 1) particle size has an effect on chamber aerosol concentration distribution, with the larger particle resulting in a higher variation; 2) the single-chamber-single-generator system is more stable than the two-chamber-single-generator system; 3) the H-2000 chamber has a lower aerosol spatial variability than the H-1000 chamber; and 4) the aerosol distribution within the chamber could be improved with the use of a newly designed diluter.

Aerosols↗
PubMed1986

The extent of metabolism of inhaled anesthetics in humans.

To determine the percentage of anesthetic metabolized and to assess the role of metabolism in the total elimination of inhaled anesthetics, the authors administered isoflurane, enflurane, halothane, and methoxyflurane simultaneously, for 2 h, to nine healthy patients. Total anesthetic uptake during the 2 h of washin and total recovery of unchanged anesthetic in exhaled gases during 5 to 9 days of washout were measured, and from these the per cent of anesthetic uptake that was recovered was calculated. Of the isoflurane taken up, 93 +/- 4% (mean +/- SE) was recovered. To compensate for factors other than metabolism that limit complete recovery of unchanged anesthetic, the percentage recovery of each anesthetic was normalized to the percentage recovery of isoflurane (which it was assumed undergoes no metabolism). Deficits in normalized recovery were assumed to be due to metabolism of the anesthetics. The resulting estimates of metabolism of anesthetic taken up were: enflurane 8.5 +/- 1.0%, halothane 46.1 +/- 0.9%, and methoxyflurane 75.3 +/- 1.6%. These results indicate that elimination is primarily via the lungs for isoflurane and enflurane, equally via the lungs and via metabolism for halothane, and primarily via metabolism for methoxyflurane.

Adult↗
PubMed1986

Edrophonium antagonizes combined lidocaine-pancuronium and verapamil-pancuronium neuromuscular blockade in cats.

The effects of lidocaine or verapamil on pancuronium neuromuscular blockade and the ability of anticholinesterase agents to antagonize these combined blockades were studied in 14 cats using a standard peroneal nerve-anterior tibialis muscle preparation. Pancuronium was infused at a constant rate to produce a stable 50% depression of single twitch tension. In nine cats, intravenous lidocaine boluses followed by a constant infusion produced serum lidocaine levels of 5.09 +/- 1.9 micrograms/ml (mean +/- SD) and resulted in an additional 20.0 +/- 5.5% depression of twitch tension. In the other five cats, intravenous injection of 0.15 mg/kg of verapamil produced an additional 12.8 +/- 8.0% twitch depression of pancuronium-induced neuromuscular blockade. For individual animals, edrophonium antagonism of the combined lidocaine-pancuronium-induced neuromuscular blockade or combined verapamil-pancuronium-induced neuromuscular blockade was not significantly different from antagonism of an equivalent twitch depression produced by pancuronium alone. It is concluded that lidocaine and verapamil augment neuromuscular blockade caused by pancuronium and that anticholinesterase antagonism of this augmented blockade can be expected to occur in a normal fashion.

Animals↗
PubMed1986

Pharmacokinetics of inhaled anesthetics in humans: measurements during and after the simultaneous administration of enflurane, halothane, isoflurane, methoxyflurane, and nitrous oxide.

To determine the relative washin and washout characteristics of isoflurane, enflurane, halothane, and methoxyflurane, we administered all four anesthetics simultaneously (total = 1.1 MAC) to nine healthy patients for 2 hr. Concentrations of anesthetics in end-tidal gases were measured during washin and for 5-9 days during washout. Multiexponential (multicompartment) models were fit to the washin and washout curves using least-squares analysis. Slowly equilibrating compartments could only be identified during washout. For 27 of the 36 data sets, five-compartment models fit the washout curves significantly better than four-compartment models. The time constant for our first compartment is consistent with that predicted for washout of the lungs. Time constants for the second, third, and fifth compartments were consistent with current data for blood flows and solubilities of vessel-rich, muscle, and fat tissue groups, respectively. The fourth compartment has a time constant that lies between the time constants predicted for muscle and fat.

Adult↗
PubMed1985

Method for determining the lung burden of talc in rats and mice after inhalation exposure to talc aerosols.

A method has been developed to quantitate talc lung burdens in rats and mice after inhalation exposure to talc aerosols. The method is based on acid-insoluble magnesium (Mg) determination by flame atomic absorption. Precipitating protein from homogenates of lungs of unexposed rodents with 5% perchloric acid and washing with 5% trichloroacetic acid removed the soluble and naturally occurring Mg. This resulted in residual Mg content averaging 0.43 micrograms Mg per g lung in rats and less than 0.1 microgram Mg per g lung in mice for young rodents less than 12 weeks old. Rodents 12-18 months old had residual mean (+/- SD) Mg contents of 3.4 +/- 2.0 micrograms Mg per g rat lung (n = 17) and 6.5 +/- 2.9 micrograms Mg per g mouse lung (n = 12). Thus, the background residual acid-insoluble Mg content in rodent lungs appears to increase with age. Negligible quantities of Mg were extracted directly from the talc treated by these procedures. Adding 50-2000 micrograms talc to lungs from unexposed rodents, followed by the sample treatment, gave mean (+/- SD) Mg recoveries of 89 +/- 12% (n = 19) for rat lungs and 96 +/- 26% (n = 15) for mouse lungs. The lung burden of talc in rodents exposed to talc aerosols for 6 h per day, 5 days per week for 4 weeks was determined. Mean lung burdens in rats were 77, 187, and 806 micrograms talc per g lung (n = 10) for exposures at 2.3, 4.3, and 17 mg talc m-3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1983

Deposition of Crocidolite asbestos and glass microfibers inhaled by the Beagle dog.

The respiratory tract deposition of neutron activated Crocidolite asbestos and glass microfibers was determined in two groups of four Beagle dogs. The dogs were given 60-minute, nose-only inhalation exposures to an aerosol of either asbestos or glass fibers. The radioactivity in tissues and excreta four days after exposure was used to determine the fraction of inhaled fibers deposited in the upper respiratory tract and the deep lung. The activity median aerodynamic diameter (AMAD), count median diameter (CMD) and count median length (CML) were determined from fibers sampled during exposure. Crocidolite asbestos fibers (obtained from the Union Internationale Contre le Cancer) had an AMAD of 1.8 microns, a CMD of 0.25 micron and a CML less than 5 microns. The fraction of inhaled mass deposited in deep lung was 13-19 percent, while total deposition in the respiratory tract was 54-72 percent. Glass microfibers had an AMAD of 2.5 microns, a CMD of 0.15 microns and a CML of 5.4 microns. Five to 17 percent of the mass of glass fiber was deposited in the deep lung; total respiratory tract deposition was 45-64 percent. The deposition patterns were similar for these small asbestos and glass fibers inhaled by dogs and in good agreement with previous predictions made for man.

Aerosols↗
PubMed1983

In vitro and in vivo response after exposure to man-made mineral and asbestos insulation fibers.

The relative in vitro and in vivo toxicity of several types of manufactured fibrous glass insulation and crocidolite asbestos was investigated to aid in selection of a suitable glass fiber for subsequent use in inhalation exposures. The in vitro cytotoxicity to pulmonary alveolar macrophages of small glass fibers from microfiber insulation (count median diameter (CMD) approximately 0.1-0.2 micrometer) was greater than that of the larger fibers from household insulation (CMD approximately 2.4 micrometers). To screen for in vivo pulmonary toxicity, 2-21 mg of glass or asbestos fibers were administered in divided doses to male Syrian hamsters by intratracheal instillation. Animals were sacrificed at 1, 3.5 and 11 months following initial administration of material. One type of glass microfiber [count median diameter (CMD) approximately 0.1 micrometer] caused deaths from pulmonary edema at early times after instillation. High levels of asbestos, a second glass microfiber (CMD approximately 0.2 micrometer) and one type of household insulation fiber (CMD 2.3 micrometers) all resulted in increase in total collagen and mild pulmonary fibrosis at later times after instillation, although microfiber insulation produced a greater response than household insulation. Asbestos insulation produced the greatest response. A five-day inhalation exposure to a high level of glass microfibers deposited in lung less than 10 percent of the lowest instilled amount which elicited indications of lung injury. This amount did not produce significant biological changes at 1 to 12 months after exposure.

Animals↗