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Biomedical subjects

A S Menon

Publications and source records attributed to A S Menon.

At least 37 records · Page 2Linked to original sources
PubMed1990

Control of expiratory duration by arterial CO2 oscillations in vagotomized dogs.

The role of respiratory oscillations of PaCO2 (CO2 oscillations) in the regulation of expiratory duration (TE) was examined in eight anesthetized dogs by measuring instantaneous changes of arterial pH during the respiratory cycle with a catheter-tip ISFET (ion-sensitive field effect transistor) pH electrode. Steady-state changes in arterial pH oscillation were induced by vagotomy, which increased the amplitude of pH oscillation from 0.014 +/- 0.002 (mean +/- SEM) to 0.058 +/- 0.006 units (P less than 0.001), and prolonged TE from 5.12 +/- 0.56 to 9.99 +/- 1.11 sec (P less than 0.005) with little change in average pH (0.021 +/- 0.011 units, P = 0.12). Vagotomy also reversed the phase relationship between arterial pH oscillation at the carotid bodies and tidal ventilation, such that pH rose during early expiration, rather than falling as occurred in the intact state. When the within-breath oscillation of arterial pH was transiently reduced by having the vagotomized dogs inspire a single breath of CO2 enriched air, TE of the same breath was shortened in proportion to the reduction in amplitude of pH oscillation (r = 0.72, P less than 0.001), rather than in proportion to changes in the average pH of the test breath (r = 0.44). The results indicate that the profile of within-breath oscillation of PaCO2 (phase relationship and amplitude) can exert an important influence on TE, and may in part account for the prolongation of TE following vagotomy.

Animals↗
PubMed1990

Mechanisms of gas exchange with different gases during constant-flow ventilation.

To investigate the mechanisms responsible for the difference in gas exchange during constant-flow ventilation (CFV) when using gases with different physical properties, we used mixtures of 70% N2-30% O2 (N2-O2) and 70% He-30% O2 (He-O2) as the insufflating gases in 12 dogs. All dogs but one had higher arterial PCO2 (PaCO2) with He-O2 compared with N2-O2. At a flow of 0.37 +/- 0.12 l/s, the mean PaCO2's with N2-O2 and He-O2 were 41.3 +/- 13.9 and 53.7 +/- 20.3 Torr, respectively (P less than 0.01); at a flow rate of 0.84 +/- 0.17 l/s, the mean PaCO2's were 29.1 +/- 11.3 and 35.3 +/- 13.6 Torr, respectively (P less than 0.01). The chest was then opened to alter the apposition between heart and the lungs, thereby reducing the extent of cardiogenic oscillations by 58.4 +/- 18.4%. This intervention did not significantly alter the difference in PaCO2 between N2-O2 and He-O2 from that observed in the intact animals, although the individual PaCO2 values for each gas mixture did increase. When the PaCO2 was plotted against stagnation pressure (rho V2), the difference in PaCO2 between N2-O2 and He-O2 was nearly abolished in both the closed- and open-chest animals. These findings suggest that the different PaCO2's obtained by insufflating gases with different physical properties at a fixed flow rate, catheter position, and lung volume result mainly from a difference in the properties of the jet.

Animals↗
PubMed1988

Influence of phasic afferent information on phrenic neural output during hypercapnia.

We measured the moving time average (MTA) of the phrenic neurogram before and after removal of phasic afferent information from the lungs, chest wall, and oscillations in blood gases by using constant-flow ventilation (CFV). Anesthetized dogs were studied at various levels of steady-state and progressive hypercapnia during spontaneous breathing and during CFV. When steady-state and progressive hypercapnia were compared, the frequency and height of the MTA phrenic neurogram were independent of the rate of induction of hypercapnia during each mode of ventilation. During spontaneous ventilation, the response to hypercapnia comprised mainly an increase in frequency with only a slight increase in the amplitude of the MTA phrenic waveform. During muscular paralysis and CFV, the responses were similar to those observed after vagotomy with mainly an increase in the amplitude and only a small increase in frequency. For both spontaneous breathing and CFV, increases in frequency were achieved mainly by a shortening in expiratory time with the inspiratory time remaining relatively constant. Our data support the concept of a centrally patterned respiratory generator, whose inherent pattern is modified by phasic feedback from peripheral receptors mainly of vagal origin.

Afferent Pathways↗
PubMed1988

Mechanisms mediating the heart rate response to hypoxemia.

We studied the effect of phasic pulmonary afferent information on heart rate (HR) during a progressive reduction in oxygen saturation (SaO2). The Hering-Breuer reflex was evaluated with the use of the ratio of apnea duration after lung inflation to the preceding expiratory time (dT). Phasic afferent activity was stopped in anesthetized, paralyzed dogs by constant-flow ventilation (CFV), a technique that removes cyclic changes in lung volume. During normocapnic (PaCO2 = 36.4 +/- 1.1 mm Hg) spontaneous breathing, there was a wide variability in HR response, with a mean delta HR/delta SaO2 (+/- SE) of 0.62 +/- 0.27 beats/min/% (values greater than 0 indicate a tachycardiac response). There was a good correlation between delta HR/delta SaO2 and dT (r = .79). Mean delta HR/delta SaO2 for the combined normocapnic and hypercapnic studies during CFV was lower (-1.32 +/- 0.19 bpm/%) than that during spontaneous breathing (0.23 +/- 0.19, p less than .0001). We suggest that the HR response to hypoxemia is strongly related to the strength of the Hering-Breuer reflex, which may explain the large interdog variability in HR responses.

Animals↗
PubMed1988

Contribution of pulmonary receptors to the heart rate response to acute hypoxemia in rabbits.

We studied the effect of pulmonary afferent activity on the heart rate response to a progressive, isocapnic decrease in oxygen saturation (SaO2) in anesthetized rabbits. To abolish the effect of rapidly adapting receptors, we used inhaled bupivacaine aerosol, and to abolish the effect of slowly adapting stretch receptor activity, we used sulfur dioxide insufflation. The heart rate (HR) response (delta HR/delta SaO2) under control conditions was 0.39 +/- 1.29 beats/min/% (mean +/- SD, n = 11; values greater than 0 indicate a tachycardiac response to hypoxemia). After sulfur dioxide insufflation, all nine rabbits had a bradycardiac response (-2.02 +/- 1.13 beats/min/%), which was significantly less than control (p less than 0.0001). After bupivacaine inhalation, the heart rate response (0.27 +/- 1.04 beats/min/%) was unchanged from control. There were no significant differences in the percent increase of minute ventilation during hypoxemia in all runs. Our results indicate that in rabbits the receptors responsible for the increase in heart rate during progressive hypoxemia are the slowly adapting receptors.

Acute Disease↗
PubMed1988

Constant oxygen insufflation (COI) in a ventilatory failure model.

We examined the use of a constant insufflation of oxygen into the lungs to assist ventilation in a ventilatory failure model. The model consisted of 12 anesthetized dogs (17 to 32 kg) that were partially paralyzed using intermittent low doses of muscle relaxant; this produced a steady-state mean PaCO2 of 90 +/- 15.8 mm Hg (+/- SD). A catheter (1.5 mm ID) was inserted into each lung to the most distal position possible and withdrawn 1 to 2 cm. The effects of a constant insufflation of oxygen at rates of 5, 10, or 20 L/min were studied at this position (mean distance from the carina = 9 +/- 2 cm); at the carina; and using a single catheter located 2 cm above the carina. The changes in PaCO2 and minute ventilation (VE) due to the insufflation were calculated from the mean steady-state control values. Using the data for all catheter positions and flow rates, the insufflation was associated with a mean decrease in PaCO2 of 31 (+/- 7.6) mm Hg associated with a mean decrease in VE of 48 (+/- 12.9)%. The flow of 20 L/min caused a significantly greater drop in PaCO2 than the flow of 5 L/min (p = 0.02). This technique may prove beneficial for patients with various forms of ventilatory failure that are difficult to treat by conventional means.

Acute Disease↗
PubMed1987

Binding of nucleotides to the ATP-dependent protease La from Escherichia coli.

A critical enzyme in protein breakdown in Escherichia coli is the ATP-hydrolyzing protease La, the lon gene product. In order to clarify the role of ATP in proteolysis, we studied ATP and ADP binding to this enzyme using rapid gel filtration to separate free from bound ligands. In the presence of Mg2+ or Mn2+ and 10 microM ATP, two molecules of ATP were bound to the tetrameric enzyme, while at 100 microM ATP (or higher), four ATP molecules were bound, both at 0 and 37 degrees C. Protease La thus has two high affinity sites (S0.5 less than 10(-7) M) for ATP and two lower affinity sites (S0.5 = 12-15 microM). Binding was reversible. In the absence of a divalent ion, ATP bound to only two sites. However, much lower Mg2+ concentrations (50 microM) were required for maximal ATPase binding than for maximal proteolytic and ATPase activity (2 mM). Decavanadate, which is a potent inhibitor of proteolysis, also blocked ATP binding, but orthovanadate had neither effect. Different ATP analogs bind to these sites in distinct ways. Adenyl-5'-yl imidodiphosphate binds to only one high affinity site, while adenyl-5'-yl methylene monophosphonate binds to two. Nevertheless, both non-metabolizable analogs can activate oligopeptide hydrolysis as well as ATP. Although binding of a single nucleotide can activate peptide hydrolysis, occupancy of all four sites appears necessary for maximal protein breakdown. The ATP molecules on all four sites are hydrolyzed rapidly. The Pi is released, but ADP remains on the enzyme. ADP binds to the same four sites, but this process does not require divalent ions. Protease La shows higher affinity for ADP than for ATP. Therefore, in vivo, ADP should inhibit ATP binding and protease La function.

ATP-Dependent Proteases↗
PubMed1987

Protein substrates activate the ATP-dependent protease La by promoting nucleotide binding and release of bound ADP.

The interaction of protein substrates with protease La from Escherichia coli enhances its ability to hydrolyze ATP and peptide bonds. These studies were undertaken to clarify how unfolded proteins allosterically stimulate this ATPase activity. The tetrameric protease can bind four molecules of ATP, which activates proteolysis, or four molecules of ADP, which inhibits enzymatic activity. Protein substrates stimulate binding of the nonhydrolyzable ATP analog [3H] adenyl-5'yl imidodiphosphate, although they do not increase the net binding of [3H]ATP or [3H]ADP. Once bound, ATP is quickly hydrolyzed to ADP, which remains noncovalently associated with protease La even through repeated gel filtrations. Exposure to protein substrates (e.g. denatured bovine serum albumin at 37 degrees C) induces the release of all the bound ADP from the enzyme. Nonhydrolyzable ATP analogs bound to the enzyme were not released by these substrates. Proteins that are not degraded (e.g. native bovine serum albumin) and oligopeptides that only bind to the catalytic site do not induce ADP release. Thus, polypeptide substrates have to interact with an allosteric site to induce this effect. The protein-induced ADP release is inhibited by high concentrations of Mg2+ and is highly temperature-dependent. Protein substrates promoted [3H]ATP binding in the presence of ADP and Mg2+ (i.e. ATP-ADP exchange) and reduced the ability of ADP to inhibit the enzyme's peptidase and ATPase activities. These results indicate that: 1) ADP release is a rate-limiting step in protease La function; 2) bound ADP molecules inhibit protein and ATP hydrolysis in vivo; 3) denatured proteins interact with the enzyme's regulatory site and promote ADP release, ATP binding, and their own hydrolysis.

ATP-Dependent Proteases↗
PubMed1987

The energy utilized in protein breakdown by the ATP-dependent protease (La) from Escherichia coli.

A crucial enzyme in the pathway for protein degradation in Escherichia coli is protease La, an ATP-hydrolyzing protease encoded by the lon gene. This enzyme degrades various proteins to small polypeptides containing 10-20 amino acid residues. To learn more about its energy requirement, we determined the number of ATP molecules hydrolyzed by the purified protease for each peptide bond cleaved. The enzyme hydrolyzed about 2 molecules of ATP for each new amino group generated with casein, bovine serum albumin, glucagon, or guanidinated casein as substrates, even though these proteins differ up to 20-fold in size and 3-4 fold in rates of hydrolysis of peptide bonds. Similar values for the stoichiometry (from 1.9 to 2.4) were obtained using fluorescamine or 2,4,6-trinitrobenzene sulfonic acid to estimate the appearance of new amino groups. These values appeared lower at 1 mM than at 10 mM Mg2+. The coupling between ATP and peptide bond hydrolysis appeared very tight. However, when the protease was assayed under suboptimal conditions (e.g. at lower pH or with ADP present), many more ATP molecules (from 3.5 to 12) were consumed per peptide bond cleaved. Our data would indicate that the early steps in protein degradation consume almost as much energy (2 ATPs for each cleavage) as does the formation of peptide bonds during protein synthesis.

ATP-Dependent Proteases↗
PubMed1987

Catheter position and blood gases during constant-flow ventilation.

We studied the effect of catheter position and flow rate on gas exchange during constant-flow ventilation (CFV) in eight anesthetized, paralyzed dogs. The distal tips of the insufflation catheters were positioned 0.5, 2.0, 3.5, and 5.0 cm from the tracheal carina. Flow rates were varied between 10 and 55 l/min and steady-state arterial blood gases were measured. At a given flow rate, arterial CO2 pressure (PaCO2) decreased as CFV was administered further into the lung up to a distance of 3.5 cm from the carina; there were no significant differences in PaCO2 at 3.5 and 5.0 cm. For a given catheter position, PaCO2 decreased with increasing flow rate up to a flow rate of 40 l/min. Further increases in flow rate had no significant effect on PaCO2. Arterial O2 pressure (PaO2) was relatively constant at all flow rates and catheter positions. We conclude that, up to a point, CO2 elimination can be improved by positioning the catheters further into the lung; advancing the catheters further than 3.5 cm from the carina may cause over-ventilation of specific lung regions resulting in a relative plateau in CO2 elimination and relatively constant PaO2's. Positioning the catheters further into the lung permits the use of lower flow rates, thus potentially minimizing the risk of barotrauma.

Animals↗
PubMed1987

Contribution of cardiogenic oscillations to gas exchange in constant-flow ventilation.

The contribution of cardiogenic oscillations to gas exchange during constant-flow ventilation was examined in 11 dogs. With the use of two variations of cardiopulmonary bypass to maintain the systemic and pulmonary circulation, the influence of cardiogenic oscillations was removed by arresting the heart. Cardiac arrest by ventricular fibrillation was associated with a mean decrease in alveolar ventilation of 43% in five dogs on right and left heart bypass. However, successful defibrillation and return of the prearrest level of alveolar ventilation could not be achieved; thus we studied six dogs on left heart bypass. Alveolar ventilation decreased an average of 37% with cardiac arrest, and defibrillation resulted in a return of alveolar ventilation to 81% of the prearrest value. These results are consistent with previous predictions that cardiogenic oscillations are an important mechanism of gas transport during constant-flow ventilation.

Animals↗
PubMed1986

Velocity profiles in central airways with endotracheal intubation: a model study.

Steady inspiratory velocity profiles were measured at two flow rates in a 3:1 scale model of the human central airways in the presence of five modes of endotracheal intubation. The presence of an orifice or a short endotracheal tube had no significant effect on the velocity profiles distal to the carina. Long endotracheal tubes change the profiles in both main bronchi. A significant peak occurred in the frontal plane near the walls, and the maximum velocity in the airway was almost identical to the endotracheal tube center-line velocity. The flow impinging on the medial wall of the main bronchus was redirected up around the anterior and posterior walls yielding bipeak velocity profiles in the sagittal plane. A tube placed eccentrically in the trachea over the right main bronchus did not alter the velocity profiles in the left main bronchus, suggesting a redirection of flow over the carina into the left lung. An endobronchial tube at the mouth of the right main bronchus did change the shape of the velocity profiles in the left main bronchus. In the left upper lobar bronchus the presence of trachea intubation had no effect on the velocity profiles. However, in the right upper lobar bronchus, the long endotracheal tube flattened the velocity profiles from the strongly skewed ones seen in the absence of the endotracheal inserts. These results not only are relevant to distribution of ventilation and aerosol particle deposition, but also have strong implications in intrapulmonary gas mixing, especially when high-frequency low tidal-volume ventilation is involved.

Humans↗
PubMed1986

Constant-flow ventilation in pigs.

Constant-flow ventilation (CFV) is a ventilatory technique in which physiological blood gases can be maintained in dogs by a constant flow of fresh gas introduced via two catheters placed in the main-stem bronchi (J. Appl. Physiol. 53: 483-489, 1982). High-velocity gas exiting from the catheters can create uneven pressure differences in adjacent lung segments, and these pressure differences could lead to gas flow through collateral channels. To examine this hypothesis, we studied CFV in pigs, animals known to have a high resistance to collateral ventilation. In three pigs we examined steady-state gas exchange, and in six others we studied unsteady gas exchange at three flow rates (20, 35, and 50 l/min) and three catheter positions (0.5, 1.5, and 2.5 cm distal to the tracheal carina). During steady-state runs we were unable to attain normocapnia; the arterial CO2 partial pressure (PaCO2) was approximately 300 Torr at all flow rates and all catheter positions, compared with 20-50 Torr at similar flows and positions in dogs studied previously. The initial unsteady gas-exchange experiments indicated no consistent effect of catheter position or flow rate on the rate of rise of PaCO2. In three other pigs, the rates of rise of PaCO2 were compared with the rates observed with apneic oxygenation (AO). At the maximum flow and deepest position, the rate of rise of PaCO2 was lower during CFV than during AO. These data suggest that flow through collateral channels might be important in producing adequate gas transport during CFV; however, other factors such as airway morphometry and the effects of cardiogenic oscillations may explain the differences between the results in pigs and dogs.

Animals↗
PubMed1985

Purification and characterization of fermodulin, an Fe2+-dependent inhibitor protein of 3-hydroxy-3-methylglutaryl-CoA reductase.

The activity of 3-hydroxy-3-methylglutaryl-CoA (HMGCoA) reductase of rat liver microsomes was inhibited by the addition of FeSO4 and the cytosolic protein, fermodulin. Modulation of the activity was obtained only in the combined presence of Fe2+ and fermodulin. Using ammonium sulfate fractionation, heat treatment, and chromatography on CM-Sephadex and then on an Fe2+-Blue Sepharose affinity matrix, fermodulin was purified to homogeneity. The molecular weight of the purified protein, as determined by filtration through a Sephacryl S-200 column, was 58,000. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis the protein resolved into two subunits of Mr 43,000 and 28,000. Fermodulin showed ultraviolet absorption and fluorescence spectra typical of tryptophan-containing proteins, and addition of FeSO4 quenched the fluorescence. Using the Millipore filter assay the binding of 1.6 mol 55FeCl2/mol fermodulin was observed in the presence of Tris-HCl buffer. The inhibitory effect of fermodulin at nonsaturating concentrations was potentiated by bicarbonate, ATP.Mg, and ADP.Mg.

Adenine Nucleotides↗
PubMed1985

Salmonellae and pollution indicator bacteria in municipal and food processing effluents and the Cornwallis River.

A study was conducted to determine the incidence of fecal coliforms, fecal streptococci, Aeromonas hydrophilia, and Salmonella spp. in the waste discharges of seven sewage treatment plants, four fruit and vegetable canneries, a meat packing plant, a poultry processing plant, and a potato processing plant located along the Cornwallis River in Nova Scotia, Canada. Surface water samples were also collected from 13 locations in the river to assess the impact of these waste discharges on the receiving water quality. The results showed that the final effluents from most of the sewage treatment and processing plants were of very poor bacteriological quality, with the number of indicator bacteria comparable with those found in raw sewage. Salmonellae were isolated from the effluents of the meat and poultry plants and five of the seven sewage treatment plants surveyed. No salmonellae were detected in the effluents of the fruit and vegetable canneries. The impact of the discharge of untreated municipal and food processing wastes on the Cornwallis River water quality was evidenced by the recovery from river water of five Salmonella serotypes, and the high fecal coliform counts which exceeded recommended limit for bathing and shellfish harvesting.

Animals↗
PubMed1985

Effect of the larynx on oscillatory flow in the central airways: a model study.

Measurements were made of the effect of the larynx on the oscillatory flow profiles in a 3:1 scale model of the human central airways. A fixed glottic aperture corresponding to the shape and size at midinspiration was used. Oscillatory airflows at peak Reynolds numbers, similar to those obtained during spontaneous breathing and panting, were studied. The flow distribution to the five lobar bronchi was maintained by distally placed linear resistors. A hot-wire anemometer probe was used to measure the local velocity along two perpendicular diameters at six stations distributed through the model. Near the proximal end of the trachea, the flat velocity profiles at the beginning of the flow cycle peaked at maximum flow because of the jet created by the glottic aperture. This peaked structure was conserved during the latter half of the inspiratory cycle. Close to the carina, the jet had almost dissipated and the entry conditions into the main bronchi corresponded to those in the absence of the laryngeal model. The effect of the glottic aperture on the mean velocity was not felt beyond the carina, and the characteristic skewed profiles seen in oscillatory flows, in the absence of the larynx, were present in the main and lobar bronchi.

Humans↗