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Biomedical subjects

A T Gray

Publications and source records attributed to A T Gray.

30 records · Page 2Linked to original sources
PubMed1997

Neuromuscular blocking drugs do not alter the pupillary light reflex of anesthetized humans.

OBJECTIVE: To test the hypothesis that systemically administered neuromuscular blocking drugs acutely alter resting pupil size or the direct reflex response to light in anesthetized humans. DESIGN: Patients were randomized to receive an intravenous injection of saline (0.15 mL/kg), pancuronium bromide (0.1 mg/kg), or vecuronium bromide (0.15 mg/kg) after induction of general anesthesia and tracheal intubation. SETTING: The University of California, San Francisco, Moffitt-Long Hospitals. PATIENTS: Healthy adults (American Society of Anesthesiologists physical status I or II) of either sex scheduled for elective surgery requiring general anesthesia, tracheal intubation, and muscle relaxation of an anticipated duration of 2 or more hours. MAIN OUTCOME MEASURES: Measurements of resting pupil size, direct reflex response to light, and constriction velocity were obtained in double-blinded fashion using infrared pupillometry. RESULTS: Pupillary size, reflex amplitude, and constriction velocity were not altered by the presence of either vecuronium or pancuronium. Tetanic stimuli and concomitant isoflurane administration respectively increased and decreased pupillary light reflex amplitude, indicating that pupillary responses were not fixed. CONCLUSIONS: We conclude that systemically administered neuromuscular blocking drugs (vecuronium and pancuronium) do not acutely affect the pupillary light reflex in healthy, anesthetized patients.

Adult↗
PubMed1997

Anesthesia for combined cesarean section and extra-adrenal pheochromocytoma resection: a case report and literature review.

Pheochromocytoma during pregnancy is unusual, with approximately 250 cases now reported in the literature. The current case describes the anesthetic management of a patient with a large extra-adrenal pheochromocytoma who underwent a combined cesarean section and tumor removal in which perioperative hemodynamic control was difficult despite high-dose a-adrenergic blockade. In this case it is believed that difficulty in perioperative hemodynamic management was related to mechanical stimulation of the tumor by the gravid uterus. Review of published case reports since 1980 reveals that a pheochromocytoma during pregnancy may be diagnosed in an extra-adrenal location relatively more commonly compared to non-pregnant patients. Established criteria exist for the adequacy of alpha- and beta-adrebergic blockade for the management of pheochromocytoma in the non-pregnant patient. We discuss how these criteria apply to pregnant patients with pheochromocytoma, and suggest possible modifications to the criteria.

Journal Article↗
PubMed1997

Interactive effects of pH and temperature on N-methyl-D-aspartate receptor activity in rat cortical brain slices.

Low extracellular pH decreases the activity of the N-methyl-D-aspartate (NMDA) glutamate receptor, and may thus limit neuronal calcium overload during cerebral ischemia. During induced hypothermia, alkaline pH ("alphastat regulation") is often used to preserve cardiac and enzymatic function. The purpose of this study is to measure the functional activity of cerebral cortex NMDA receptors over the range of temperatures used in profound hypothermic cardiopulmonary bypass (20-37 degrees C). Extracellular pH was varied over a broad range relevant to both alphastat and pH stat acid-base management (7.0-7.8). Change in cytosolic free calcium evoked by 50 microM NMDA in brain slices was used as an index of NMDA receptor activity. Cortical slices (300 microns thick) were loaded with fura-2 Aspartate Methyl for study in a fluorometer. At 37 degrees C, a change in extracellular pH from 7.1 to 7.8 increased the NMDA-evoked change in cytosolic calcium in brain slices by a factor of 4 (p < 0.05). In contrast, at 20 degrees C there was minimal effect of changing extracellular pH from 7.1 to 7.8 (27% increase). We conclude that hypothermia results in decreased pH sensitivity of the NMDA receptor. The results predict that different strategies of pH management during induced hypothermia may have limited impact on NMDA receptor-mediated processes, such as neuronal calcium overload.

Adenosine Triphosphate↗
PubMed1997

Cloning and functional expression of a human liver organic cation transporter.

Polyspecific organic cation transporters in the liver mediate the elimination of a wide array of endogenous amines and xenobiotics. In contrast to our understanding of the mechanisms of organic cation transport in rat liver, little is known about the mechanisms of organic cation transport in the human liver. We report the cloning, sequencing, and functional characterization of the first human polyspecific organic cation transporter from liver (hOCT1). hOCT1 (554 amino acids) is 78% identical to the previously cloned organic cation transporter from rat, rOCT1 [Nature (Lond.) 372:549-552 (1994)]. In Xenopus laevis oocytes injected with the cRNA of hOCT1, the specific uptake of the organic cation 3H-1-methyl-4-phenylpyridinium (3H-MPP+) was significantly enhanced (8-fold) over that in water-injected oocytes. Uptake of 3H-MPP+ was saturable (K(m) = 14.6 +/- 4.39 microM) and sensitive to membrane potential. Both small monovalent organic cations such as tetraethylammonium and N1-methylnicotinamide and bulkier organic cations (e.g., vecuronium and decynium-22) inhibited the uptake of 3H-MPP+. In addition, the bile acid taurocholate inhibited the uptake of 3H-MPP+ in oocytes expressing hOCT1. Northern analysis demonstrated that the mRNA transcript of hOCT1 is expressed primarily in the human liver, whereas the mRNA transcript of rOCT1 is found in rat kidney, liver, intestine, and colon [Nature (Lond.) 372:549-552 (1994)]. In comparison to rOCT1, hOCT1 exhibits notable differences in its kinetic characteristics and tissue distribution. The functional expression of hOCT1 will provide a powerful tool for elucidation of the mechanisms of organic cation transport in the human liver and understanding of the mechanisms involved in the disposition and hepatotoxicity of drugs.

Amino Acid Sequence↗
PubMed1991

Predicting chemically induced duodenal ulcer and adrenal necrosis with classification trees.

Binary tree-structured statistical classification algorithms and properties of 56 model alkyl nucleophiles were brought to bear on two problems of experimental pharmacology and toxicology. Each rat of a learning sample of 745 was administered one compound and autopsied to determine the presence of duodenal ulcer or adrenal hemorrhagic necrosis. The cited statistical classification schemes were then applied to these outcomes and 67 features of the compounds to ascertain those characteristics that are associated with biologic activity. For predicting duodenal ulceration, dipole moment, melting point, and solubility in octanol are particularly important, while for predicting adrenal necrosis, important features include the number of sulfhydryl groups and double bonds. These methods may constitute inexpensive but powerful ways to screen untested compounds for possible organ-specific toxicity. Mechanisms for the etiology and pathogenesis of the duodenal and adrenal lesions are suggested, as are additional avenues for drug design.

Adrenal Gland Diseases↗
PubMed1991

The effects of D/Q and D/VA inequalities on pulmonary oxygen diffusing capacity estimates.

Bohr-integrated estimates of steady-state pulmonary diffusing capacity for oxygen (DLO2) were calculated using lung compartments with different VA/Q ratios. Compartmental diffusing capacity was distributed in proportion to either ventilation or blood flow. This method was applied to 115 gas exchange data sets previously collected from healthy human subjects during normoxic (PIO2 = 148 Torr) or acute hypoxic (PIO2 = 80 Torr) exercise. Ventilation-weighted estimates of oxygen diffusing capacity exceeded blood flow-weighted estimates by 10 and 78% during hypoxia and normoxia, respectively. While blood flow-weighted DLO2 estimates during heavy exercise were greater in hypoxia than in normoxia (mean +/- SEM of 87.1 +/- 4.4 vs 53.0 +/- 3.1 ml.min-1.Torr-1), ventilation-weighted estimates were not significantly different (93.2 +/- 5.5 vs 96.3 +/- 9.4 ml.min-1.Torr-1). These results show that the effect of D/Q inequality on DLO2 estimates is greater at higher levels of inspired oxygen. Furthermore, a D/Q mismatch of similar magnitude as the VA/Q mismatch that is observed during heavy exercise can account for a previously observed discrepancy between normoxic and hypoxic oxygen diffusing capacity estimates.

Humans↗
PubMed1990

Temperature and the oxygen-hemoglobin dissociation curve of the harbor seal, Phoca vitulina.

To determine the effect of temperature and pH on oxygen-hemoglobin affinity of the harbor seal, we measured 61 biotonometric oxygen-hemoglobin dissociation curves on blood from 5 seals at 3 temperatures and a range of pH values. The average (+/- SEM) hemoglobin concentration was 3.44 +/- 0.15 mM, nearly 50% greater than found in normal humans. At pH 7.4 the P50 (partial pressure of O2 at 50% hemoglobin saturation) +/- SEM values were 22.4 +/- 0.6,25.3 +/- 0.5, and 28.5 +/- 0.4 Torr at 33, 37 and 41 degrees C, respectively. The effect of temperature on oxygen-hemoglobin affinity, (delta log P50/delta T) was 0.014 +/- 0.001 at pH 7.4, significantly lower than that observed in human and dog blood. This low temperature sensitivity may facilitate oxygen off-loading from hemoglobin when temperature gradients exist within the animal or as tissue temperature decreases during a dive. Temperature did not significantly affect the Hill coefficient 'n' (shape) of the dissociation curve which averaged 2.43 +/- 0.04 at 37 degrees C. The fixed-acid Bohr coefficient (delta log P50/delta pH) was -0.606 +/- 0.032 at 37 degrees C and increased with temperature. This relatively large value for the Bohr coefficient was similar to those previously reported for the Northern Elephant, Bladdernose, and Weddell Seals, and may facilitate oxygen off-loading as acidosis develops during a dive.

Animals↗
PubMed1990

Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood.

In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1989

Ventilation-perfusion relationships in alligators.

We measured V/Q distributions with the multiple inert gas elimination technique in five anesthetized artificially ventilated American alligators at 24 degrees C. The overall V/Q was relatively high (2.0 to 7.2) because of continuous artificial ventilation. The V/Q distributions were usually unimodal (log standard deviation of Q distribution averaged 0.47 +/- 0.09 [SD] and there was considerable shunt (28.5 +/- 10.3% of cardiac output). The data are consistent with a pulmonary, rather than central cardiovascular shunt. We also detected a molecular weight dependent limitation to inert gas elimination. The difference in error of fit to enflurane and cyclopropane retentions was significantly greater than predicted from experimental error. The estimated stratification diffusing capacity, a measure of this limitation, was 10% of the value estimated for mammals and similar to morphometric estimates of membrane diffusing capacity in alligators, which is comparatively low. Hence, even though the multicameral lungs of alligators are unevenly partitioned and have large gas phase diffusion spaces, V/Q matching and molecular weight dependent limitations are relatively small. Shunt, dead space and membrane diffusion resistances can be more important limitations of gas exchange.

Alligators and Crocodiles↗
PubMed1989

Protection against pulmonary O2 toxicity by N-acetylcysteine.

N-acetylcysteine (NAC) is a known antioxidant. We therefore investigated NAC as an agent protective against O2 toxicity in the lung. Twelve dogs were anaesthetized with sodium pentobarbital and ventilated with 100% O2 for 54 h. Five were given diluent and 7 intravenous NAC (loading dose prior to 100% O2 ventilation of 150 mg.kg-1 and maintenance dose of 20 mg.kg-1.h-1). Every 6 h, physiological evaluation of the pulmonary circulation, mechanical properties, and gas exchange was performed. Post-mortem evaluation consisted of gross examination and weighing followed by light and electron microscopy. By both functional and structural criteria, NAC protected against the effects of 100% O2. The NAC group developed significantly less increase in pulmonary vascular resistance, arterial carbon dioxide tension (PaCO2) and lung wet weight, while dynamic compliance was greater. NAC also delayed the development of abnormal ventilation-perfusion relationships and was associated with reduced pulmonary white cell accumulation, with less evidence of alveolar and interstitial oedema. NAC may well be worthy of evaluation as a therapeutic agent in human diseases characterized by oxidant damage.

Acetylcysteine↗
PubMed1988

Estimating steady-state DLO2 with nonlinear dissociation curves and VA/Q inequality.

A DLO2 estimate which accounts for the nonlinearity of the oxygen dissociation curve using the Kelman blood gas routines is presented here. The simultaneous differential equations that describe O2 and CO2 diffusion between alveolar gas and pulmonary capillary blood in lung compartments with different VA/Q ratios were solved numerically with a Runge-Kutta algorithm. These integrated estimates were compared to DLO2 estimates that assume the oxygen dissociation curve is linear. In 140 gas exchange data sets from 18 healthy male subjects previously collected at rest and during exercise it was found that DLO2 estimates based on linear dissociation curves exceeded integrated DLO2 estimates by 14, 31, and 55 percent when the PIO2 was 80, 100, and 148 Torr, respectively. We conclude that the linear approximation is accurate when PIO2 is less than 100 Torr but that comparisons of DLO2 estimates at different levels of inspired oxygen must allow for the difference in curvature of the oxygen dissociation curve as a function of PIO2.

Algorithms↗