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Biomedical subjects

D Georgopoulos

Publications and source records attributed to D Georgopoulos.

At least 55 records · Page 3Linked to original sources
PubMed1991

How is maximal expiratory flow reduced in canine postpneumonectomy lung growth?

Six dogs underwent left pneumonectomy (P) at 10 wk of age, while four littermates had a sham operation (C). All dogs were studied at 26 wk of age. Pressure capsules were placed on the right lung to measure lobar alveolar pressures and flows, and a Pitot-static tube was used to measure dynamic intrabronchial pressures. Vital capacity and lung elastic recoil did not differ between P and C. At all lung volumes studied, maximum expiratory flows (Vmax) in P were substantially lower than in C. Choke points in P were located more peripherally than in C. In central airways subjected to the same distending pressure, calculated cross-sectional area was significantly lower in P than in C, indicating different bronchial area-pressure behavior. In P, frictional resistances of the right lower, middle, and cardiac lobes were significantly higher than those in C. These results indicate that the reduction in Vmax in P was greater than would have been expected on the basis of reductions in central airway diameter alone. We calculated that, in the middle vital capacity range, approximately 60% of the decrease in Vmax was due to changes in dynamic central airways properties, and approximately 40% was due to increased lobar frictional resistance related to compensatory growth.

Airway Resistance↗
PubMed1990

Effect of dichloroacetate on ventilatory response to sustained hypoxia in normal adults.

In adult humans, the ventilatory response to acute sustained hypoxia is biphasic, characterized by an initial brisk increase followed by a decline to an intermediate plateau. Recently, it has been shown that hypoxic lactate formation in the brain depresses ventilation in peripherally chemodenervated animals, and postulated that this formation might mediate the hypoxic ventilatory decline observed in adult humans. To investigate this hypothesis, the ventilatory response to 25 min of acute isocapnic hypoxia (SaO2 = 80%) was evaluated in adult humans after pretreatment with intravenous dichloroacetate (DCA), a drug that crosses the blood-brain barrier and reduces lactate formation. Ten subjects were pretreated with DCA (50 mg.kg-1.h-1) or normal saline infusion on two days in a double blind manner. The infusion started 35 min before the institution of hypoxia and continued throughout the experiment. Independent of pretreatment, the ventilatory response to acute sustained hypoxia was biphasic; an increase followed by a decline. Ventilation during hypoxia declined significantly and the magnitude of the decline did not differ between the DCA and placebo pretreatments, averaging 3.32 +/- 0.45 and 3.17 +/- 0.58 L/min, respectively (mean +/- SE). With and without DCA infusion the hypoxic ventilatory decline was due to significant decrease in tidal volume and mean inspiratory flow without changes in breathing frequency. We conclude that brain lactic acidosis is unlikely to be involved in the ventilatory response to sustained hypoxia of adult humans, at least in the range of hypoxia studied.

Adult↗
PubMed1990

Continuous oxygen therapy for the chronically hypoxemic patient.

The effects of long-term continuous O2 therapy on chronically hypoxemic patients are well established. Such therapy remains the most important means of improving survival and quality of life of these patients. The mechanism by which O2 induces these beneficial effects is not well understood, and several factors probably are involved. Patients who show stable hypoxemia are candidates for long-term continuous O2 therapy. O2 should be administered at least 19 hours per day, including sleep hours, and in a dose sufficient to raise arterial PO2 to 65-80 mm Hg. Continuous O2 therapy virtually eliminates hypoxemic episodes during sleep or exercise. Nasal prongs are the usual method for delivering O2 on long-term basis, and portable O2 supply systems permit patients to use O2 continuously without significant restriction of their activities.

Chronic Disease↗
PubMed1990

Effect of sustained hypoxia on ventilatory response to CO2 in normal adults.

In adult humans the ventilatory response to sustained hypoxia is biphasic, characterized by an early increase followed by a decline to an intermediate plateau. Recently, we have shown that this decrease in hypoxic sensitivity is long lasting, because up to 1 h of room air breathing is required for complete recovery of the initial hypoxic response (J. Appl. Physiol. 64: 521-528, 1988). It is not known whether this posthypoxia decrease in ventilatory response is general or specific only to hypoxic stimuli. We therefore examined responses to CO2 before and after hypoxia. The ventilatory response to 5 min of normoxic CO2 breathing was evaluated in eight normal adults on 2 days: 5 min before and after 25 min of normocapnic hypoxia (arterial O2 saturation +/- 80%) and 5 min before and after 25 min of room air breathing (control day). During hypoxia, ventilation (VI), after an initial increase, declined significantly. At the end of hypoxia, abrupt exposure to room air transiently dropped VI to values that were significantly below base line. On each experimental day, the first and second exposure to CO2 increased ventilation by a similar amount, averaging, respectively, 8.46 +/- 0.9 and 8.84 +/- 0.92 (SE) l/min on the hypoxic day and 8.24 +/- 0.96 and 7.65 +/- 0.94 l/min on the control day. All the hypercapnic increases of VI were accomplished through similar changes of breathing pattern with similar time courses. We conclude that sustained hypoxia does not affect the ventilatory response to CO2, but it selectively depresses hypoxic sensitivity.

Adult↗
PubMed1990

Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans.

After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing.

Adult↗
PubMed1990

Tolerance to beta 2-agonists in patients with chronic obstructive pulmonary disease.

Eleven patients with severe COPD were examined to determine whether tolerance to beta 2-agonists developed after long-term inhalation therapy with these agents. Before the study all patients were on regular treatment with inhaled salbutamol for six months. At the beginning of the study, response of FEV1 to inhaled salbutamol was measured. Dose-response curves were measured after three weeks of treatment with ipratropium bromide and again after a three-week course of inhaled salbutamol. After ipratropium bromide treatment, responses to low doses of salbutamol tended to be larger than after salbutamol treatment, but differences were not significant. Three hours after the last inhalation of salbutamol the FEV1 was lower on days 1 and 42 than on day 21. We conclude that long-term inhalation therapy with beta 2-agonists in patients with COPD decreases the duration of the bronchodilation produced by the same agents but does not affect the peak response.

Administration, Inhalation↗
PubMed1989

Effects of CO2 breathing on ventilatory response to sustained hypoxia in normal adults.

The relationship between CO2 and ventilatory response to sustained hypoxia was examined in nine normal young adults. At three different levels of end-tidal partial pressure of CO2 (PETCO2, approximately 35, 41.8, and 44.3 Torr), isocapnic hypoxia was induced for 25 min and after 7 min of breathing 21% O2, isocapnic hypoxia was reinduced for 5 min. Regardless of PETCO2 levels, the ventilatory response to sustained hypoxia was biphasic, characterized by an initial increase (acute hypoxic response, AHR), followed by a decline (hypoxic depression). The biphasic response pattern was due to alteration in tidal volume, which at all CO2 levels decreased significantly (P less than 0.05), without a significant change in breathing frequency. The magnitude of the hypoxic depression, independent of CO2, correlated significantly (r = 0.78, P less than 0.001) with the AHR, but not with the ventilatory response to CO2. The decline of minute ventilation was not significantly affected by PETCO2 [averaged 2.3 +/- 0.6, 3.8 +/- 1.3, and 4.5 +/- 2.2 (SE) 1/min for PETCO2 35, 41.8, and 44.3 Torr, respectively]. This decay was significant for PETCO2 35 and 41.8 Torr but not for 44.3 Torr. The second exposure to hypoxia failed to elicit the same AHR as the first exposure; at all CO2 levels the AHR was significantly greater (P less than 0.05) during the first hypoxic exposure than during the second. We conclude that hypoxia exhibits a long-lasting inhibitory effect on ventilation that is independent of CO2, at least in the range of PETCO2 studied, but is related to hypoxic ventilatory sensitivity.

Adult↗
PubMed1989

Aminophylline effects on ventilatory response to hypoxia and hyperoxia in normal adults.

In 10 normal young adults, ventilation was evaluated with and without pretreatment with aminophylline, an adenosine blocker, while they breathed pure O2 1) after breathing room air and 2) after 25 min of isocapnic hypoxia (arterial O2 saturation 80%). With and without aminophylline, 5 min of hyperoxia significantly increased inspiratory minute ventilation (VI) from the normoxic base line. In control experiments, with hypoxia, VI initially increased and then declined to levels that were slightly above the normoxic base line. Pretreatment with aminophylline significantly attenuated the hypoxic ventilatory decline. During transitions to pure O2 (cessation of carotid bodies' output), VI and breathing patterns were analyzed breath by breath with a moving-average technique, searching for nadirs before and after hyperoxia. On placebo days, at the end of hypoxia, hyperoxia produced nadirs that were significantly lower than those observed with room-air breathing and also significantly lower than when hyperoxia followed normoxia, averaging, respectively, 6.41 +/- 0.52, 8.07 +/- 0.32, and 8.04 +/- 0.39 (SE) l/min. This hypoxic depression was due to significant decrease in tidal volume and prolongation of expiratory time. Aminophylline partly prevented these alterations in breathing pattern; significant posthypoxic ventilatory depression was not observed. We conclude that aminophylline attenuated hypoxic central depression of ventilation, although it does not affect hyperoxic steady-state hyperventilation. Adenosine may play a modulatory role in hypoxic but not in hyperoxic ventilation.

Adenosine↗
PubMed1989

Increased chemoreceptor output and ventilatory response to sustained hypoxia.

In adult humans the ventilatory response to sustained hypoxia (VRSH) is biphasic, characterized by an initial brisk increase, due to peripheral chemoreceptor (PC) stimulation, followed by a decline attributed to central depressant action of hypoxia. To study the effects of selective stimulation of PC on the ventilatory response pattern to hypoxia, the VRSH was evaluated after pretreatment with almitrine (A), a PC stimulant. Eight subjects were pretreated with A (75 mg po) or placebo (P) on 2 days in a single-blind manner. Two hours after drug administration, they breathed, in succession, room air (10 min), O2 (5 min), room air (5 min), hypoxia [25 min, arterial O2 saturation (SaO2) = 80%], O2 (5 min), and room air (5 min). End-tidal CO2 was kept constant at the normoxic base-line values. Inspiratory minute ventilation (VI) and breathing patterns were measured over the last 2 min of each period and during minutes 3-5 of hypoxia, and nadirs in VI were assessed just before and after O2 exposure. Independent of the day, the VRSH was biphasic. With P and A pretreatment, early hypoxia increased VI 4.6 +/- 1 and 14.2 +/- 1 (SE) l/min, respectively, from values obtained during the preceding room-air period. On A day the hypoxic ventilatory decline was significantly larger than that on P day, and on both days the decline was a constant fraction of the acute hypoxic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effect of salbutamol, ipratropium bromide and cromolyn sodium on prostaglandin F2 alpha-induced bronchospasm.

We studied the effects of salbutamol, ipratropium bromide and cromolyn sodium on PGF2 alpha-induced bronchospasm in ten patients with asthma. Initially, the bronchial reactivity to IC-PGF2 alpha and the DP20-PGF2 alpha were determined. Recalculations were made two days later and again 1 h after administration of various drugs given on different days. Salbutamol and ipratropium bromide induced significant bronchodilation and of similar magnitude 1 h after administration. On the day salbutamol was given, surface area under the dose-response curve to PGF2 alpha was significantly higher and the final drop of FEV1 significantly lower than those observed on days when placebo, ipratropium bromide and cromolyn sodium were given. No differences among these values were found for placebo, ipratropium bromide and cromolyn sodium. Thus, beta 2 stimulants attenuate significantly PGF2 alpha-induced bronchospasm, while ipratropium bromide and cromolyn sodium do not have protective effect.

Adolescent↗
PubMed1988

Effects of captopril in patients with chronic obstructive pulmonary disease and secondary pulmonary hypertension.

Ten patients with chronic obstructive pulmonary disease (COPD) with normal left ventricular function were given a single dose of captopril (0.25 mg/kg). Mean systemic arterial pressure, heart rate and coronary flow to the right ventricle were reduced significantly after captopril. In contrast captopril did not cause a significant fall in pulmonary arterial pressure or pulmonary vascular resistance. We conclude that captopril fails to produce haemodynamic benefits in such hypoxic patients and that angiotensin II is not playing a significant role in maintaining pulmonary vasoconstriction.

Aged↗
PubMed1988

Interactive effects of systemically administered salbutamol and aminophylline in patients with chronic obstructive pulmonary disease.

It has been previously shown that inhaled salbutamol (S) and intravenous aminophylline (A) have an additive effect as bronchodilators in patients with chronic obstructive pulmonary disease (COPD). This additive effect could be due to different modes of action or different distributions of drug. In order to investigate the additive effect of S and A when administered by the same route, we studied eight patients 63.4 +/- 1.84 yr of age (mean +/- SEM), with long-standing COPD (FEV1, 0.96 +/- 0.12 L) by giving them intravenous A and S. A double-blind, cross-over study was performed on two separate days by administering either A followed by S or vice versa. Each drug when given alone increased the FEV1 significantly (p less than 0.01). The mean increase was 0.17 +/- 0.06 L (18% of baseline) for S and 0.15 +/- 0.05 L (17% of baseline) for A. The FEV1 increased 0.07 +/- 0.02 L when S was added to A (95% confidence interval, 0.02 to 0.12, 7% of baseline), and when A was added to S 0.05 +/- 0.03 L (95% confidence interval, -0.02 to 0.12, 6% of baseline). Neither change was significant. Heart rate (HR) was increased significantly (p less than 0.01) by S (22 +/- 3.4%), but not by A when it was given first. However, addition of the second drug increased HR significantly (p less than 0.01) from HR with one drug alone; the mean increase was 31 +/- 8.5% of baseline with the addition of S, and 19 +/- 4.06% of baseline with the addition of A.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗
PubMed1986

Influence of pindolol on asthmatics and effect of bronchodilators.

Bronchospasm is a known side effect of the administration of beta-blockers to asthmatics. The purpose of this study was to investigate the frequency of bronchospasm caused by the administration of relatively low doses (2.5-7.5 mg) of pindolol, a beta-blocker with intrinsic sympathetic activity (ISA) to asthmatics, the severity of the bronchospasm and its reversibility and the probable correlations of bronchial asthma (BA) characteristics (severity, duration, allergy and airway hyperreactivity) with existing or nonexisting bronchospasm. Seventeen asthmatic patients: 10 men and 7 women, with a mean age of 44 +/- 10 years, participated in this study. The duration and severity of BA, the presence of allergy determined by skin tests and the bronchial hyperreactivity to methacholine inhalation challenge were observed on the first day of study. On the following days, the respiratory function parameters forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), and the pulse rate were measured before and 30, 60 and 90 min after the administration of placebo and pindolol. Then salbutamol was administered by a dosimetric aerosol (DA) at the usual dosage (200 micrograms) and the change in FEV1 was observed at 60 min; thereafter 40 micrograms of ipratropium bromide (IB) were administered by DA and FEV1 was measured after 60 min. Pindolol was administered gradually by mouth (2.5 mg every 30 min), the maximal total dose being 7.5 mg. Administration of pindolol caused a significant fall of FEV1 of 12 +/- 11% compared to placebo. A significant total decrease of FEV1 (greater than or equal to 20% of baseline) was observed in 9 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Effect of ipratropium bromide on repeated methacholine challenges.

The purpose of this study was to trace the protective effect of ipratropium bromide (IB) during methacholine inhalation challenge (MIC) at the first and fourth hour after its administration. IB-inhaler contains 0.02 mg IB in each puff and it was used in the usual dosage of two puffs (0.04 mg). In 20 asthmatic patients, the dose of methacholine caused a drop in FEV1 of 20% (PD20-FEV1). It was concluded that IB protected patients significantly one hour after its administration and showed a significant bronchodilating effect in comparison to placebo. IB protected 19 of the 20 patients one hour after administration during MIC while placebo protected none. IB protected 13 of the 20 patients, after the second PD20-FEV1 with methacholine, four hours after its administration.

Adult↗
PubMedDate not supplied

Effect of different levels of pressure support and proportional assist ventilation on breathing pattern, work of breathing and gas exchange in mechanically ventilated hypercapnic COPD patients with acute respiratory failure.

BACKGROUND: Proportional assist ventilation (PAV) has been shown to maintain better patient-ventilator synchrony than pressure support ventilation (PSV); however, its clinical advantage regarding invasive ventilation of COPD patients has not been clarified. OBJECTIVES: To compare the effect of PAV and PSV on respiratory parameters of hypercapnic COPD patients with acute respiratory failure (ARF). METHODS: Nine intubated hypercapnic COPD patients were placed on the PAV or PSV mode in random sequence. For each mode, four levels (L1-L4) of support were applied. At each level, blood gases, flow, tidal volume (VT), airway pressure (Paw), esophageal pressure (Pes) (n = 7), patient respiratory rate (fp), ventilator rate (fv), missing efforts (ME = fp - fv) were measured. RESULTS: We found increases in ME with increasing levels of PSV but not with PAV. PO2 and VT increased whereas PCO2 decreased significantly with increasing levels of PSV (p < 0.05). With PAV, PCO2 decreased and VT increased significantly only at L4 whereas PO2 increased from L1 to L4. Runaways were observed at L3 and L4 of PAV. The pressure-time product (PTP) was determined for effective and missing breaths. The mean total PTP per minute (of effective plus missing breaths) was 160 +/- 57 cm H2O/s.min in PSV and 194 +/- 60 cm H2O/s.min in PAV. CONCLUSION: We conclude that in COPD patients with hypercapnic ARF, with increasing support, PSV causes the appearance of ME whereas PAV develops runaway phenomena, due to the different patient-ventilator interaction; however, these do not limit the improvement of blood gases with the application of both methods.

Acute Disease↗