Angelo M. Taveira Da Silva

Cardiorespiratory effects produced by application ofl-glutamic and kainic acid to the ventral surface of the cat hindbrain

The purpose of our study was to determine the cardiorespiratory effects of exciting cell bodies at the rostral (area M), intermediate (area S), and caudal (area L) chemosensitive sites on the ventral surface of the medulla. To do this, L-glutamic and kainic acid were applied bilaterally to each chemosensitive site while monitoring tidal volume (VT), respiratory rate (f), mean arterial pressure (BP), and heart rate (HR) in chloralose-anesthetized cats. Application of solutions (5 microliter) of L-glutamic acid ranging from 62.5 to 2000 mM to the intermediate area produced concentration-dependent increases in VT (from 2.0 +/- 0.6 ml to 14 +/- 1.1 ml) and BP (from 2.0 +/- 1.7 mm Hg to 39 +/- 5.3 mm Hg). No significant changes in f and HR were noted. Similar effects were observed with application of kainic acid. Application of L-glutamic acid to the caudal area produced hypotension (-24 +/- 5.4 mm Hg) with no accompanying changes in VT and f. No responses were observed after application of L-glutamic acid to the rostral area. These data suggest that activation of cell bodies on the intermediate area produces simultaneous stimulatory effects on BP and VT, whereas activation of cell bodies at the caudal area produces selective depressant effects on BP.

Chemical stimulation of the area postrema induces cardiorespiratory changes in the cat

The purpose of our study was to determine the cardiorespiratory effects of exciting cell bodies of the area postrema of the cat. This was accomplished by local application of L-glutamic acid (bilateral application of 5 microliter of a 250-1000 mM solution) and kainic acid (bilateral application of 5 microliter of a 40 mM solution) to the area postrema of chloralose-anesthetized cats while monitoring arterial pressure, heart rate, tidal volume and respiratory rate. These excitatory amino acids activate neuronal cell bodies but not axons of passage. L-Glutamic acid produced a dose-dependent increase in arterial pressure, decreases in respiratory rate and minute volume and, occasionally, ventricular tachyarrhythmias. Kainic acid produced effects similar to those seen with L-glutamic acid except the changes in respiratory activity were more pronounced with each animal exhibiting respiratory arrest. In artificially respired animals, kainic acid produced similar cardiovascular changes as those occurring in spontaneously breathing animals (i.e. increases in arterial pressure of 61 +/- 5.7 mm Hg, and in heart rate of 32 +/- 8.3 beats/min). Finally, application of kainic acid to the area postrema abolished the pressor and tachycardic responses to bilateral occlusion of the carotid arteries. These results suggest that activation of cell bodies in the area postrema can result in pronounced cardiorespiratory changes.

Reversible Respiratory Failure Due to Intravascular Leukostasis in Chronic Myelogenous Leukemia Relationship of Oxygen Transfer to Leukocyte Count

In a 49 year old man with blast crisis and massive leukocytosis due to chronic myelogenous leukemia, severe hypoxic respiratory failure developed despite a normal chest film. Correction of hypoxemia was observed after reduction of the white blood cell count by hydroxy-urea therapy. A similar episode occurred prior to death, and necropsy examination revealed extensive plugging of the pulmonary vasculature by leukemic blast cells but no infection or pulmonary edema. An inverse linear correlation was demonstrated between the peripheral white blood cell count and the efficiency of oxygen transfer in the lung as determined by the arterial to alveolar oxygen tension ratio. We postulate that mechanical obstruction and/or leukocyte mediated capillary endothelial injury caused the severe leukocyte mediated capillary endothelial injury caused the severe hypoxemia. Abnormalities of pulmonary gas exchange may be common in leukemic patients with markedly increased leukocyte counts.

Respiratory and cardiovascular effects of intraventricular cholecystokinin

Cholecystokinin (1-300 ng) was administered into the lateral brain ventricle of chloralose-anesthetized cats while monitoring tracheal airflow, arterial blood pressure, and heart rate. Dose-related increases in respiratory activity occurred in each animal tested, and were due to an increase in tidal volume. When 300-1000 ng of cholecystokinin was administered intravenously, no respiratory stimulant effect was observed. These results indicate that cholecystokinin acts in the brain to stimulate respiration.

Airways Response to Inhaled Tobacco Smoke: Time Course, Dose Dependence and Effect of Volume History

We have measured puff by puff the effect of smoking three brands of cigarettes with different composition on airways resistance (Raw) thoracic gas volume (TGV) and the maximal expiratory flow volume (MEFV) curve. Raw increased significantly with all three brands of cigarettes after one puff. The maximum effect was reached after three puffs. Instantaneous flow at 50% of vital capacity (FEF50) decreased significantly with cigarettes high in nicotine content, but not so after smoking a low nicotine (0.31 mg) cigarette. Instantaneous flow at 75% of vital capacity out (FEF75) increased significantly 30 min after the low nicotine cigarette was smoked. A deep inspiration prior to Raw determination reduced by approximately one third the bronchoconstrictor effect of cigarette smoke. All effects were reversible within 30 min, except the delayed effect of the low nicotine cigarette on the FEF75. We conclude that the probable site of action of tobacco smoke is in the large and central airways. The bronchoconstrictor effect rapidly reaches a plateau. A delayed bronchodilation of the small airways observed after smoking the low nicotine cigarette might represent a response usually masked by other long-acting components in smoke. We suggest that the airway response to tobacco smoke is complex and probably a result of several components present in smoke which still have to be identified.

Respiratory depression produced by centrally administered taurine in the cat

The effects of taurine (0.8-64.8 mumol) were studied on respiratory activity following intracisternal (cisterna magna) and intracerebroventricular (lateral ventricle) injections in cats anesthetized with alpha-chloralose. Respiratory activity was measured by using a Fleisch pneumotachograph and monitoring tracheal airflow. The flow signal was integrated to obtain tidal volume (VT) and respiratory rate (f) was obtained by counting the number of VT excursions over one minute. Inspiratory (TI), expiratory (TE) and total (TTOT) cycle durations were also determined during this time period. In addition, end-tidal CO2 was continuously monitored. Associated changes in arterial pressure (femoral artery cannula) and heart rate were also determined. After injections into the cisterna magna, taurine caused dose-related decreases in minute ventilation (VE). The maximal decrease in VE was from 495 +/- 59 to 64 +/- 14 ml/min (p less than 0.05), and was due to both decreases in VT (from 27 +/- 3 to 5 +/- 1 ml; p less than 0.05) and f (from 18 +/- 1 to 12 +/- 2 breaths/min; p less than 0.05). TE and TTOT were increased from 2.4 +/- 0.4 to 4.5 +/- 0.6 sec (p less than 0.05) and from 3.7 +/- 0.4 to 6.4 +/- 0.8 sec (p less than 0.05), respectively. Mean inspiratory flow (VT/TI), a measure of inspiratory drive, was decreased from 21 +/- 4 to 4 +/- 2 ml/sec (p less than 0.05). Apnea occurred in 5 of 6 animals after the 64.8 mumol dose. This respiratory depression occurred without any significant change in arterial pressure. After lateral ventricle injections, taurine also caused dose-related, but not as pronounced, decreases in respiratory activity. In addition, taurine caused significant decreases (p less than 0.05) in arterial pressure in doses that decreased VE. Taurine administered intravenously had no significant cardiorespiratory depressant effects. These data indicate that centrally administered taurine produces respiratory depression and, depending on the route of CNS administration, also produces hypotension.

Aspirin and exercise-induced asthma☆

In four subjects with exercise-induced asthma, aspirin and placebo were administered prior to exercise in a double blind study. Pulmonary function tests did not reveal any difference between the response after aspirin or placebo. We conclude that in these four subjects aspirin did not prevent the bronchoconstrictor response. This might suggest that prostaglandins have no significant role in exercise-induced asthma.

Respiratory depression produced by glycine injected into the cisterna magna of cats

Glycine (0.8-64.8 mumol) was administered into the cisterna magna of alpha-chloralose anesthetized cats to determine its effect on ventilation. Glycine caused a dose-related decrease in respiratory minute volume with the highest dose resulting in a decrease from 454 +/- 35 to 159 +/- 44 ml/min (p less than 0.05). This decrease was due primarily to a reduction in tidal volume which decreased from 31 +/- 2 to 12 +/- 2 ml (p less than 0.05). The two largest doses tested (21.6 and 64.8 mumol) also produced a decrease in respiratory rate from 14 +/- 1 to 11 +/- 1 and from 15 +/- 1 to 12 +/- 1 breaths/min (p less than 0.05), respectively. Apnea occurred in 2 of 7 animals given 64.8 mumol of glycine. No consistent dose-related changes in inspiratory and expiratory durations were observed. Intravenous administration of glycine (64.8 mumol) did not affect respiratory activity. These results indicate that glycine causes respiratory depression by an action in the central nervous system.

The effect of prostaglandin F2β on expiratory flow rates

Prostaglandin F2beta (PGF2beta), a stereoisomer of F2alpha was administered by ultrasonic nebulization to eight patients with bronchial asthma and four normal subjects in increasing doses up to 200 mug maximum dose. Maximum expiratory flow (MEF) and forced vital capacity (FVC) were analyzed at 5, 15, 30, 60 and 120 minutes after administration of aerosol. All expiratory flow rates were reduced after 5 minutes. Some increase in terminal flow rates was observed after 60 minutes. We conclude that PGF2beta in not an effective bronchodilator at this dose level.

Effect of smoking a cigarette on the density dependence of maximal expiratory flow.

We have shown that tobacco smoke causes an increase in airways resistance and a drop in expiratory flow at 50% of the vital capacity (FEF50). To better define the nature and site of this bronchoconstrictive effect we measured maximal expiratory flow while breathing air and a low-density gas mixture (helium-oxygen), in 12 healthy volunteers, before and after smoking a cigarette. There was a significant drop in FEF50 while breathing air (FEF50Air) (5.52 +/- 1.83--5.05 +/- 1.86 liters/s; p less than 0.001). No changes were observed in the helium-oxygen FEF50 (FEF50 He) after smoking. The increase in FEF50 after breathing the low-density gas as a percentage of FEF50Air (delta Vmax50) increased from 47.1 +/- 11.4% before smoking to 57.0 +/- 13.3% after smoking (p less than 0.05). There were no changes in forced vital capacity (FVC), flow at 75% FVC and volume of isoflow. We discuss these observations in light of the equal pressure points (EPP) analysis and wave speed theory of flow limitation. We conclude that after smoking flow becomes more density dependent because there is constriction of a flow-limiting segment downstream from the EPP, located in lobar and segmental bronchi. No acute effect of tobacco smoke on the small airways could be demonstrated.