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Biomedical subjects

J A Dempsey

Publications and source records attributed to J A Dempsey.

At least 181 records · Page 10Linked to original sources
PubMed1980

Effects of prolonged N2O and barbiturate anesthesia on brain metabolism and pH in the dog.

The brain acid-base status and metabolites were measured in 17 mongrel dogs that were anesthetized with pentobartital (20-25 mg/kg initially and 2-4 mg/kg every 2 h thereafer), or initially anesthetized with sodium pentothal (20 mg/kg) and placed on nitrous oxide (70% N2O-30% 02) for 5-51/2 h under normoxic, normocapnic conditions. In comparison with the awake, unrestrained state, both anesthetics caused a significant metabolic acidosis in both plasma and cisternal CSF. No significant differences between anesthetics were found with: (1) acid-base status in plasma or brain ECF and ICF; (2) cerebral tissue energy charge potential; or (3) creatine and phosphocreatine levels and the creatine to phosphocreatine ratios. No differences were found in the ATP to ADP ratios, but lactate to pyruvate ratios were significantly lower. Within pentobarbital anesthesia, citrate levels were higher, while other TCA metabolites measured were lower. Further, the citrate to alpha-ketoglutarate and malate to oxaloacetate ratios were significantly increased. We propose that pentobarbital anesthesia lowers metabolic activity in brain tissue and the primary site of 'crossover' inhibition is between citrate and alpha-ketoglutarate.

Acid-Base Equilibrium↗
PubMed1980

Problems with the gas-calibrated PCO2 electrode.

The PCO2 of tonometered human blood was measured with three different Radiometer PCO2 electrodes mounted in three different blood gas analysis systems. When the PCO2 electrode was calibrated with humidified gases it measured the PCO2 of gases accurately but showed a consistent error measuring the PCO2 of human blood. This error was reduced but not abolished by calibrating the electrodes over a wide range of PCO2 and by measuring each sample repeatedly. The PCO2 of human blood was measured accurately by electrodes calibrated with tonometered human blood or buffer. The electrode responded differently to gas and human blood. This could not be explained by an electrode memory effect or by exchange of CO2 between the sample and the electrode. When human, rat, dog and goat blood were tonometered and measured under identical conditions, the difference between gas and blood PCO2 varied. The error of measurement in all species was greatest at high PCO2.

Animals↗
PubMed1980

Determinants of chronic carbon dioxide retention and its correction in humans.

17 patients with chronic ventilatory failure (including 14 with chronic obstructive pulmonary disease) were studied to determine the causes of carbon dioxide retention and the chronic effect of medroxyprogesterone acetate on ventilatory drive and acid-base status. Carbon dioxide retention in patients with high mechanical loads occurred concomitantly with a higher than normal inspiratory effort (mouth occlusion pressure) and normal minute ventilation to carbon dioxide production ratio (Ve/Vco(2)); but with shortened inspiratory time (1.3+/-0.1 vs. 1.8+/-3 s), increased breathing frequency (17+/-1 vs. 14+/-1 breaths/min), low tidal volume (0.57+/-0.03 vs. 0.88+/-0.04 L), and high dead space to tidal volume ratio (0.63+/-0.02 vs. 0.39+/-0.07). Using a randomized application of treatment and placebo conditions, it was shown that 4 wk of medroxyprogesterone acetate caused significant reductions in Paco(2) (from 51+/-1 to 42+/-1 mm Hg) in 10 of 17 patients. This "correction" of Paco(2) in these patients was associated with increases in mouth occlusion pressure (14%), tidal volume (11%), and alveolar ventilation (15%) compared to placebo, although inspiratory time remained shortened. Arterial and lumbar cerebrospinal fluid pH was alkaline compared to placebo in patients who "corrected" Paco(2). No change was noted in lung mechanics or core temperature. Common prerequisites for correction of Paco(2) with medroxyprogesterone acetate treatment were the ability to significantly lower Paco(2) upon acute voluntary hyperventilation and to increase tidal volume rather than breathing frequency in response to the drug. We attribute chronic CO(2) retention in these patients to alterations in respiratory cycle timing and to a neuromuscular inspiratory effort which is adequate for the level of tissue CO(2) production, but inadequate in the presence of mechanical and ventilation-perfusion abnormalities to normalize arterial blood gases.

Acid-Base Equilibrium↗
PubMed1980

Pulmonary control systems in exercise.

We reviewed the response and regulation of alveolar ventilation, chest wall mechanics, and alveolar-to-arterial gas exchange to the demands imposed by increases in tissue metabolic rate. The primary mediator of iso-capnic exercise hyperpnea remains a dilemma--with conflicting evidence presented on both sides of a "CO2 flow" humoral hypothesis versus a "neurogenic" non-humoral hypothesis. The increased expiratory flows and tidal volumes at any given level of hyperpnea are achieved at a "minimum" of increased mechanical work exerted on the lung and chest wall, owing to a control system that has multiple levels of nervous integration (from cortex to spinal motor neuron) readily accessible to a wide variety of sensory information concerning the mechanical status of the lung and respiratory muscles. The maintenance of arterial PO2 in the face of a falling CVO2 during exercise was attributed to a precise regulation over factors that limit diffusion equilibrium and intra- and interregional ventilation: perfusion distributions in the lung. Finally, we noted that the near-optimal nature of these responses and their control during exercise had many exceptions in the real world of physical exercise outside of the laboratory.

Carbon Dioxide↗
PubMed1979

Hodgkin's disease: evaluation of staging procedures for abdominal involvement.

Results of preoperative assessment procedures and subsequent staging laparotomy are evaluated in 32 consecutive patients who presented with extra-abdominal Hodgkin's disease which was not already known to be in an advanced stage. Disease was found in the abdominal cavity of 10 of the 27 patients who presented with disease above the diaphragm, and of two of the five patients in whom disease presented in the inguinal nodes. In patients who initially presented with disease above the diaphragm, the spleen was involved in all 10 cases where abdominal disease was detected. Lymphography was not found to be reliable as a diagnostic aid in doubtful cases. Neither liver nor spleen scans were found to be helpful in assessment of these patients.

Abdominal Neoplasms↗
PubMed1979

Human pulmonary resistance: effect of frequency and gas physical properties.

We have investigated a new technique that could be specific for detecting small airway diseases. We measured resistance in nine subjects, evaluating the effect of breathing 80% He-20%O2, air, and 80% SF6-20% O2 at different flow rates (0.25--1.01 l/s) and frequencies (4--12 Hz). To test the sensitivity and specificity of this new technique, we used intravenous histamine infusion to cause peripheral constriction. During histamine infusion six of nine subjects showed the following changes: 1) dynamic compliance decreased; 2) subjects developed frequency dependence of compliance, and 3) there was no significant change in pulmonary resistance or Rrs (respiratory resistance) at 4 Hz. These data suggested a time-constant discrepancy in the periphery due to histamine infusion. These six subjects also developed frequency dependence of resistance (delta Rrs from 4 to 12 Hz), which was significant when breathing air (-22 +/- 6%) and maximal when we used He-O2 (-32 +/- 3%). We conclude that He-O2 can improve the specificity of frequency dependence of Rrs for detecting events occurring in the peripheral airways.

Adult↗
PubMed1979

Role of cerebrospinal fluid [H+] in ventilatory deacclimatization from chronic hypoxia.

Once ventilatory acclimatization begins in sea level residents sojourning at high altitude, abrupt restoration of normal oxygen tensions will not restore ventilation to normal. We have investigated the role of cerebrospinal fluid (CSF) [H(+)] in this sustained hyperventilation by measuring CSF acid-base status in seven men (lumbar) and five ponies (cisternal) in normoxia, first at sea level and then periodically over 13-24 h of "deacclimatization" after 3-5 d in hypoxia (P(B) = 440 mm Hg). After 1 h deacclimatization, hyperventilation continued at a level only slightly less than that obtained in chronic hypoxia (+1-2 mm Hg Pa(CO2)), whereas CSF pH was either equal (in man) or alkaline (in pony, +0.02, P < 0.01) to sea level values. Between 1 and 12-13 h deacclimatization in all humans and ponies Va fell progressively (Pa(CO2) increased 4-7 mm Hg) and CSF pH became increasingly more acid (-0.02 to -0.05, P < 0.01). Between 12 and 24 h of normoxic deacclimatization in ponies, Pa(CO2) rose further toward normal, coincident with an increasing acidity in CSF (-0.02 pH). Similar negative correlations were found between changes in arterial pH and Va throughout normoxic deacclimatization. We conclude that [H(+)] in the lumbar or cisternal CSF is not the mediator of the continued hyperventilation and its gradual dissipation with time during normoxic deacclimatization from chronic hypoxia. These negative relationships of Va to CSF [H(+)] in normoxia are analogous to those previously shown during acclimatization to hypoxia.

Acclimatization↗
PubMed1979

Serotonin and the control of ventilation in awake rats.

In awake, unrestrained, intact rats, reserpine, para-chlorophenylalanine, 6-fluorotryptophan, and para-chloroamphetamine depleted whole brain serotonin and produced a substantial and sustained hyperventilation as evidenced by a 5--9 torr drop in PaCO2. Administration of 5-hydroxytryptophan to rats treated with para-chlorophenylalanine partially alleviated the hyperventilation. No change in ventilation was observed after alpha-methyltyrosine. 5,7-Dihydroxytryptamine produced contradictory results. On the basis of these pharmacological studies, we propose that some serotonin-mediated nerve transmissions might function under physiological conditions to inhibit the central nervous system output which controls normal breathing.

5,7-Dihydroxytryptamine↗
PubMed1979

The brain's role in exercise hyperpnea.

Three aspects concerning the role of the central nervous system in the control of exercise hyperpnea are reviewed. First, the integration of sensory input stresses the concept of multiple sites of integration--with the end result that both adequate gas exchange and near-optimal mechanical response of the lung and chest wall are achieved during exercise. Secondly, the potential role of the "central" [H+] chemoreceptor is discussed--in terms of the mechanisms available for the protection of brain ECF [H+] and the stimulus-response characteristics of this important chemical sensor and a critical analysis of how it may be evaluated. Finally, the question of forebrain influences on exercise hyperpnea and the "sensation" of ventilatory effect is discussed, with particular emphasis on the multi-purpose regulation of breathing in athletic endeavors.

Brain↗
PubMed1978

Role of H1 and H2 receptors in increased small airways resistance in the dog.

The relative importance of H1 and H2 receptors to central and peripheral airways resistance in the anesthetized intact dog lung were determined through the use of pharmacologically specific antagonists during graded intravenous infusions of histamine. The indirect effects of infused histamine were also tested via alpha and beta adrenergic blockade (alpha + beta blk) and post-ganglionic parasympathetic blockade (vagal blk). We measured pulmonary resistance (RL), dynamic compliance (Cdyn), thoracic gas volume (Vtg), and partitioned oscillatory pulmonary resistance (RLosc) into a peripheral (Rp) and central component with an intrabronchial catheter. Infused histamine caused a significant increase in RL, primarily the result of the increase in Rp, with substantial dose-dependent reductions in Cdyn, and increases in Vtg. These effects were not altered by vagal blk, were increased by alpha + beta blk, and were completely prevented by H1 receptor blockade, but not by H2 receptor blockade. We conclude that histamine infusion causes bronchoconstriction in the canine lung, primarily in peripheral airways (less than 3 mm diameter), by its direct action on H1-type receptors.

Airway Resistance↗
PubMed1978

Rat as a model for humanlike ventilatory adaptation to chronic hypoxia.

Oxygen uptake (VO2), expired volume (VE), and arterial blood gases were studied in awake, unrestrained rats over 14 days of hypobaric hypoxia (4,300 m altitude) and upon return to acute normoxia. Control data (at 250 m) showed (mean +/- 95% confidence limits (CL)) arterial oxygen pressure (Pao2) = 85.5 +/- 1.1; arterial carbon dioxide pressure (PaCO2) = 39.8 +/- 0.5; arterial pH pHa) = 7.430 +/- 0.009; VE = 78 +/- 3; VO2 = 2.36 +/- 0.09 ml.min-1.100 g-1; and dead space volumetidal volume ratio (VD/VT) = 0.37 +/- 0.04. During 14 days at 4.300 m the rat showed: a) a constant PaO2 (50-52 Torr); b) a time-dependent hyperventilation (e.g., PaCO2 = 30.2 +/- 1.1 at 1 h of hypoxia, 24.7 +/- 1.3 at day and 21.9 +/- 1.0 at 14 days); c) an increase in VE (85% of control) due to both frequency (33%) and VT (40%); d) a continued but reduced hyperventilation upon acute return to normoxia after 5 h to 14 days at 4,300 m; e) a 24% fall in VO2 after 1 h of hypoxia which returned to control by 4 days at 4,300 m; and f) a rise in pHa to 7.52 after 5 h of hypoxia, which fell to 7.45 by 14-day hypoxia. The rat's marked ventilatory response and changing VO2 during acute hypoxia clearly differs from the human response to sojourn at 4,300 m. However, the progressive and sustained hypocapnia during hypoxic exposure and the continued hyperventilation with acute normoxia in the rat provided essential, perhaps unique characteristics for an animal model of human ventilatory acclimatization.

Adaptation, Physiological↗
PubMed1978

Ventilatory response to medroxyprogesterone acetate in normal subjects: time course and mechanism.

The time course of ventilatory adaptation to medroxyprogesterone acetate (MPA) and potential mediators of this response in plasma and lumbar CSF were determined in five healthy adult males. A significant decrease in arterial PCO2 (PACO2) at rest and exercise was noted within 48 h of drug administration with the maximum effect reached within 7 days and amounting to a 5-Torr decrement in PACO2. Blood and lumbar cerebrospinal fluid pH because significantly alkaline to control as soon as the ventilatory resporse was noted and remained alkaline during the treatment period. The ventilatory and dP/dt max response to exogenous CO2 was unchanged but their response to moderate exercise was increased after MPA. MPA-rlated materials were detected in both the plasma and CSF as soon as the ventilatory response was noted. The increase in CSF MPA-related materials approximated the unbound fraction determined in plasma. We conclude that [H+] in plasma and CSF is a function rather than a cause of ventilator acclimatization to MPA. MPA-related materials are capable of crossing the blood-brain barrier and could potentially exert their ventilatory stimulant effect by some central mechanism.

Adult↗