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Biomedical subjects

G G Weinmann

Publications and source records attributed to G G Weinmann.

11 recordsLinked to original sources

Use of collateral airways to assess airway reactivity.

We investigated the correlation between collateral airway reactivity and other indexes of lung reactivity in response to aerosol and intravenous (iv) challenges. In four anesthetized mongrel dogs, we measured the peripheral airway resistance (Rp) to gas flow out of a wedged lung segment in different lobes on multiple occasions. We obtained dose-response curves of peripheral airways challenged with iv histamine or aerosols through the bronchoscope. During the same iv bolus challenge, whole lung airway pressure (Paw) responses to histamine were also measured. On separate occasions, changes in lung resistance (RL) were measured after the whole lung was challenged with a histamine aerosol. Reactivity was assessed from the dose-response curves for Rp and RL as the PD50 (dose required to produce a 50% increase); for changes in Paw we calculated the PD15 (dose required to produce a 15% increase over baseline). Results for Rp showed considerably more variability among different lobes in a given animal with the aerosol challenge through the bronchoscope than with the iv challenge. With aerosol challenge there were no significant differences in the mean PD50 for Rp among any of the animals. However, with the iv challenge two of the dogs showed significant differences from the others in reactivity assessed with Rp (P less than 0.01). Moreover, the differences found in the peripheral airways with iv challenge reflected differences found in whole lung reactivity assessed with either iv challenge (Paw vs. Rp, r2 = 0.96) or whole lung aerosol challenge (RL vs. Rp, r2 = 0.84). We conclude that the measurement of the collateral resistance response to iv challenge may provide a sensitive method for assessing airway reactivity.

Aerosols

In vitro tracheal responses from mice chosen for in vivo lung cholinergic sensitivity.

We selected two inbred strains of mice based on their different in vivo lung responses to intravenous acetylcholine for studies on the in vitro tracheal responses to contractile and relaxing agents. In addition, we studied the role of cyclooxygenase products on the in vitro responses. Tracheal rings were contracted with increasing concentrations of carbachol and KCl and relaxed with increasing concentrations of isoproterenol after contraction with carbachol at the concentration that produced 30, 50, and 70% of the maximal contraction (EC30, EC50, and EC70, respectively) and KCl at the EC50. Half the tracheae simultaneously underwent the same protocols after pretreatment with indomethacin (3 X 10(-6) M). Despite a severalfold difference in the maximal response to cholinergic agents in vivo, there were no significant differences between the strains in the tracheal responses to carbachol (P = 0.78) or KCl (P = 0.13) in vitro. Both strains showed inhibition of the isoproterenol relaxation by carbachol (P less than 0.0001). Multiple linear regression analysis showed that the strain that was more sensitive to carbachol in vivo was also more sensitive to isoproterenol in vitro after carbachol contraction (P = 0.014). The greater isoproterenol sensitivity of the tracheae from this strain was not present after contraction with KCl, nor were these tracheae more sensitive to relaxation with sodium nitroprusside. Indomethacin pretreatment of the tissues in vitro augmented the maximal response and the sensitivity to carbachol (P less than 0.001) and KCl (P = 0.0006), and this effect was similar in both strains. Evaluation of isoproterenol relaxation after indomethacin pretreatment was confounded by the lower concentrations of carbachol needed for contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Succinylcholine potentiates responses to intravenous acetylcholine in the canine lung periphery.

Using the wedged bronchoscope technique to measure collateral resistance (Rcs), we evaluated the effect of succinylcholine (SCh) on the response to acetylcholine (ACh) and methacholine (MCh) in the lung periphery in six mongrel dogs. Dogs were anesthetized, intubated, and mechanically ventilated. After a stable baseline Rcs was obtained, responses to intravenous ACh (25-200 micrograms), intravenous MCh (3-30 micrograms), and aerosolized ACh (30-100 micrograms/ml for 15 s) were measured. We compared the Rcs responses with 1) ACh alone, 2) ACh 2 min after SCh (0.5 mg/kg), 3) ACh 2 min after SCh and during hexamethonium infusion (5 mg/kg + 10 mg.kg-1.h-1), 4) MCh 2 min after SCh, and 5) ACh aerosol 2 min after SCh. SCh did not significantly alter baseline airway tone. SCh increased the Rcs response to ACh by 48 +/- 17% (SE) (P less than 0.01). SCh in the presence of hexamethonium increased the Rcs response by 10 +/- 3% (P less than 0.05), while hexamethonium itself increased the response to ACh by 69 +/- 27%. Because SCh did not increase the Rcs response to intravenous MCh or to aerosolized ACh, SCh probably enhances airway reactivity to intravenous ACh by competing for pseudocholinesterase in plasma. We conclude that the level of muscle relaxant must be taken into account in interpreting studies of airway reactivity when intravenous ACh is employed.

Acetylcholine

Peripheral lung resistance in normal and asthmatic subjects.

In obstructive lung disease, peripheral airways are a major site of pathologic abnormalities. However, resistance to airflow in small airways in the periphery of the lung accounts for only a small fraction of total airway resistance. Consequently, abnormalities of small airway function may not be readily detected using routine pulmonary function testing. In the present study, resistance of the peripheral lung was examined directly in six normal subjects and nine mildly asthmatic subjects. There were no significant differences between the normal and asthmatic groups in pulmonary function assessed by spirometry (FEV1, FVC) and body plethysmography (specific airway conductance). Direct measurements of peripheral lung function were made using a fiberoptic bronchoscope wedged into a subsegmental, right upper lobe bronchus. Using a double-lumen catheter inserted into the instrument channel of the bronchoscope, pressures (PB) produced by three or more different levels of gas flow (V) (5% CO2 in air) between 50 and 500 ml/min were measured. All pressure measurements were made at a constant lung volume (i.e., functional residual capacity) confirmed by monitoring transpulmonary pressure with an esophageal balloon. The pressure-flow relationship in both normal and asthmatic subjects could be approximated by a straight line through the origin, demonstrating these airways to be relatively nondistensible. Peripheral lung resistance (Rp) was defined by PB/V and averaged for three or more levels of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance

Effect of tidal volume and frequency on the temporal fall in lung compliance.

In this study we have investigated how changes in respiratory frequency and tidal volume in anesthetized dogs affect the fall in dynamic compliance (Cdyn) that occurs with time after a hyperinflation. Results showed that increasing frequency [at controlled arterial (PaCO2)] PCO2 from 16 to 32 breaths/min had no effect on either the rate of fall or the magnitude of the fall up to 1 h after the hyperinflation. However, increasing the tidal volume from 300 to 750 ml abolished the fall in Cdyn from 10 to 50 min after the hyperinflation; the fall within the first 10 min remained unchanged. We also examined the effect of a simulated "hyperinflation" on the compliance of strips of parenchymal tissue in vitro. This result indicated that in the absence of surface forces, parenchymal tissue demonstrates a fall in compliance, which is complete within 10 min. Overall our findings are consistent with the hypothesis that the fall in Cdyn after hyperinflation is a two-phase process. The initial rapid fall in Cdyn (i.e., within 10 min) may simply represent a passive recovery process from the hyperinflation stress on the parenchymal tissue. The slower fall occurring after 10 min likely results from progressive increases in surface tension, and this increase can apparently be blocked by increases in tidal volume.

Animals

Interaction between high frequency jet ventilation and cardiovascular function.

We have studied the interaction of high frequency jet ventilation with cardiovascular pressures and flows. Results in dogs show that the amplitude of all intrathoracic pressures and flows fluctuate with a frequency equal to the difference between the heart rate and ventilator rate. The magnitude of this amplitude variation may be sufficient to obliterate periodically the pulsations in pulmonary artery and right atrial pressures. It is also shown that these cardiovascular beats can occur when the ventilator rate is close to integral multiples of the heart rate. Direct measurement of pleural pressure and the observation that the beats are markedly reduced when the chest is open support the hypothesis that the primary mechanism responsible for these beats is the interaction of the respiratory fluctuations in pleural pressure with the cardiac-generated pressure pulsations.

Animals

Absence of changes in airway responsiveness during the menstrual cycle.

The effect of sex hormones on airway function has not been well studied in spite of much evidence to suggest that they are important. We asked if the normal physiologic variation in hormone levels during the menstrual cycle resulted in changes in airway responsiveness and pulmonary function that were not clinically apparent. Nine women with asthma and with normal menstrual cycles but not taking systemic asthma medication were asked to chart temperatures, asthma attacks, and use of asthma medication for four menstrual cycles. We measured baseline spirograms, skin and airway responsiveness to histamine, and serum levels for estradiol, progesterone, and testosterone on approximately day 7 and day 24 of two consecutive cycles. None of the women reported cyclic asthma symptoms, and review of subjects' charts demonstrated no menstrual variation in asthma attacks or use of asthma medications. We found no differences in forced vital capacity or FEV1 early compared to late in the menstrual cycle. Neither did we find a change in airway responsiveness, as indicated by the histamine dose causing a 15% fall in FEV1 or a 35% fall in specific airway conductance. Skin responsiveness as indicated by the wheal response to intradermal histamine was also unchanged. We conclude that physiologic changes in hormone levels during the menstrual cycle are not in themselves associated with changes in airway or skin responsiveness to histamine.

Adrenal Cortex Hormones

Effect of high-frequency ventilation on lung mechanics at high transpulmonary pressure.

The different tidal volumes and frequencies of high-frequency ventilation (HFV) compared with conventional mechanical ventilation (CMV) may have different effects on lung mechanics. To test this hypothesis, we compared the effects of 3 h of HFV and CMV on total lung capacity (TLC), functional residual capacity (FRC), the shape of the pressure-volume (PV) curve (%V10), and dynamic compliance (Cdyn), as well as venous admixture and alveolar-arterial O2 gradient. We studied a total of 12 dogs at lung inflations equivalent to 15 cmH2O positive end-expiratory pressure (PEEP) (group I) and 8 dogs at lung inflations equivalent to 0 cmH2O PEEP (group II). For CMV, we used a standard-volume ventilator at a mean tidal volume of 13.8 ml/kg. For HFV, we used an oscillator-type ventilator at 15 Hz and an average tidal volume of 4.3 ml/kg. Our results showed that ventilation with 3 h of PEEP raised lung volume, and lung volumes on HFV were higher than those on CMV in both groups. Specifically, in group I, the volume during ventilation rose on both CMV (150 ml) and HFV (250 ml). These volume changes persisted beyond the ventilation period, such that TLC was unchanged on CMV but had risen 200 ml on HFV. FRC also rose 200 and 300 ml after HFV and CMV, respectively. In group II, the volume during ventilation fell 100 ml on CMV and rose slightly (40 ml) on HFV. TLC and FRC both tended to fall more on CMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Nifedipine overdose.

A 59-year-old man ingested 900 mg of nifedipine. Profound hypotension, sinus and atrioventricular node dysfunction, and hyperglycemia resulted. The patient's condition responded favorably to aggressive treatment with intravenous fluids, calcium, and dopamine. Similar effects and response to therapy have been reported in 17 cases of verapamil overdose and are briefly summarized. The effects of nifedipine overdose are discussed, and preliminary recommendations about its management are offered. With increasing use of nifedipine and other calcium channel blockers, more incidents of overdose can be expected.

Atropine

Effect of high-frequency ventilation on histamine-induced lung injury in dogs.

We compared the effects of high-frequency oscillation (HFO) and conventional mechanical ventilation (CMV) on dynamic lung compliance (Cdyn), venous admixture (Qsp/Qt), cardiac output, and total lung resistance (RL) in seven mongrel dogs with histamine-induced lung injury. Baseline measurements during CMV were followed by iv infusion of histamine at 100 micrograms/min. Cdyn, Qsp/Qt, cardiac output, and RL were measured in triplicate during CMV and then during HFO. Subsequently, at least one complete set of measurements was recorded again on CMV. During HFO, animals were ventilated at 15 Hz with a tidal volume of 70 to 80 ml. CMV was delivered at 15 to 18 breath/min with a tidal volume of 15 ml/kg. Histamine infusion produced a marked fall in Cdyn, a variable rise in RL, an inconsistent but usually progressive rise in Qsp/Qt, and hypotension. A period of ventilation with HFO made no difference in the Cdyn, Qsp/Qt, or cardiac output changes produced by histamine infusion.

Animals

Tonic beta-sympathetic activity in the lung periphery in anesthetized dogs.

The present study was undertaken to determine whether beta-adrenoceptors could be physiologically detected in the lung periphery and whether they were under tonic stimulation in the resting state in anesthetized dogs. A fiberoptic bronchoscope was wedged in a sublobar segment of lung in anesthetized male mongrel dogs for measurement of resistance through the collateral system (Rcs). beta-Agents were delivered locally as aerosols through the bronchoscope, and the response was evaluated by changes in Rcs. Distilled water alone produced a mean increase of 8.5 +/- 2.43% (SE) in Rcs at 2 min in six dogs, whereas dl-isoproterenol produced a mean decrease of 8.9 +/- 2.10% (P less than 0.03), thus demonstrating the presence of submaximally stimulated beta-receptors. To test whether the beta-receptors were under tonic stimulation, we compared the effect of aerosolized d- and dl-propranolol in 5 dogs. d-Propranolol that lacks significant beta-blocking activity and dl-propranolol both produced large transient increases in Rcs. However, with d-propranolol, Rcs had returned to base line at 15 min, whereas with dl-propranolol Rcs remained elevated at a mean of 20% above base line for greater than 2 h (P less than 0.01). Local timolol aerosol also produced a sustained increase in Rcs. After pretreatment with reserpine or after bilateral adrenalectomy, both d- and dl-propranolol still produced large transient increases in Rcs, but dl-propranolol no longer produced a sustained increase. Neither isoproterenol nor atropine affected Rcs in the presence of dl-propranolol, nor did pretreatment with atropine affect the response of Rcs to dl-propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy