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1.
J Appl Physiol (1985) ; 90(3): 889-96, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11181597

ABSTRACT

Because abnormalities in cerebrovascular reactivity (CVR) in subjects with long-term diabetes could partly be ascribed to autonomic neuropathy and related to central chemosensitivity, CVR and the respiratory drive output during progressive hypercapnia were studied in 15 diabetic patients without (DAN-) and 30 with autonomic neuropathy (DAN+), of whom 15 had postural hypotension (PH) (DAN+PH+) and 15 did not (DAN+PH-), and in 15 control (C) subjects. During CO(2) rebreathing, changes in occlusion pressure and minute ventilation were assessed, and seven subjects in each group had simultaneous measurements of the middle cerebral artery mean blood velocity (MCAV) by transcranial Doppler. The respiratory output to CO(2) was greater in DAN+PH+ than in DAN+PH- and DAN- (P < 0.01), whereas a reduced chemosensitivity was found in DAN+PH- (P < 0.05 vs. C). MCAV increased linearly with the end-tidal PCO(2) (PET(CO(2))) in DAN+PH- but less than in C and DAN- (P < 0.01). In contrast, DAN+PH+ showed an exponential increment in MCAV with PET(CO(2)) mainly >55 Torr. Thus CVR was lower in DAN+ than in C at PET(CO(2)) <55 Torr (P < 0.01), whereas it was greater in DAN+PH+ than in DAN+PH- (P < 0.01) and DAN- (P < 0.05) at PET(CO(2)) >55 Torr. CVR and occlusion pressure during hypercapnia were correlated only in DAN+ (r = 0.91, P < 0.001). We conclude that, in diabetic patients with autonomic neuropathy, CVR to CO(2) is reduced or increased according to the severity of dysautonomy and intensity of stimulus and appears to modulate the hypercapnic respiratory drive.


Subject(s)
Carbon Dioxide/metabolism , Cerebrovascular Circulation/physiology , Diabetes Mellitus/physiopathology , Diabetic Neuropathies/physiopathology , Middle Cerebral Artery/physiopathology , Respiratory Mechanics/physiology , Adult , Autonomic Nervous System Diseases/blood , Autonomic Nervous System Diseases/physiopathology , Blood Flow Velocity , Blood Pressure , Carbon Dioxide/blood , Diabetic Neuropathies/blood , Epinephrine/blood , Heart Rate , Humans , Hypotension, Orthostatic , Lung Volume Measurements , Male , Middle Aged , Middle Cerebral Artery/physiology , Norepinephrine/blood , Partial Pressure , Reference Values , Respiratory Function Tests
2.
Chest ; 112(1): 145-53, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9228370

ABSTRACT

To investigate the effects of the autonomic nervous system on control of breathing, the neuromuscular (mouth occlusion pressure at 0.1 s after onset of inspiration [P0.1]) and ventilatory (minute ventilation [VE]) response to progressive hyperoxic hypercapnia was assessed in diabetic patients with autonomic dysfunction of different severity. Eighteen diabetics with autonomic neuropathy, nine with parasympathetic damage (DANp), and nine with parasympathetic and sympathetic damage (DANp+s), as indicated by marked postural hypotension, low increment of diastolic BP during sustained handgrip, and lowest resting catecholamine plasma levels, were studied together with a group of 10 diabetic patients without autonomic neuropathy (D) and a group of 10 normal subjects (C). All subjects had pulmonary function tests, including maximal voluntary ventilation and diffusion of carbon monoxide, measurements of respiratory muscle strength as maximal inspiratory mouth pressure (MIP) and maximal expiratory mouth pressure (MEP), and a CO2 rebreathing test (Read's method). Although in the normal range, lung volumes and FEV1 and forced expiratory flows were lower in the DANp and DANp+s groups than in the D and C groups, MIP and MEP were similar among C and diabetic groups, as well as resting P0.1, VE, tidal volume (VT), and respiratory rate (RR). The slope of the linear relationship between P0.1 and end-tidal PCO2 (PETCO2) was higher in DANp+s (0.63+/-0.07 cm H2O/mm Hg) than in C (0.45+/-0.06 cm H2O/mm Hg; p<0.05) and three times greater in DANp+s than in D (0.26+/-0.03 cm H2O/mm Hg; p<0.001) and DANp (0.24+/-0.03 cm H2O/mm Hg; p<0.001), who in turn showed a lower deltaP0.1/deltaPETCO2 than C. The VE increase with increasing PETCO2 was greater in DANp+s (3.70+/-0.85 L/min/mm Hg) than in DANp (2.13+/-0.20 L/min/mm Hg; p<0.05) and D (2.37+/-0.40 L/min/mm Hg; p=0.07), but not significantly higher from that of C (3.17+/-0.36 L/min/mm Hg). No differences were found for deltaVT/deltaPETCO2 among the groups, whereas the deltaRR/deltaPETCO2 relationship was steeper in DANp+s than in DANp (p<0.05) and D (p=0.055). These data reflect a depressed CO2 response both in D and DANp. The presumable decrease of the sympathetic nerve traffic in DANp+s appears to reverse this abnormality. DANp+s, however, exhibit an enhanced CO2 neuromuscular response even in respect to C, suggesting that the sympathetic nervous system might modulate the output of the respiratory centers to hypercapnic stimulus.


Subject(s)
Autonomic Nervous System Diseases/physiopathology , Diabetic Neuropathies/physiopathology , Hypercapnia/physiopathology , Respiration/physiology , Adult , Case-Control Studies , Death, Sudden/etiology , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Hemodynamics/physiology , Humans , Male , Middle Aged , Pulmonary Ventilation/physiology , Respiratory Center/physiopathology , Respiratory Function Tests , Respiratory Mechanics/physiology , Sleep Apnea Syndromes/etiology
3.
Monaldi Arch Chest Dis ; 52(2): 130-7, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9203809

ABSTRACT

In a randomized, double-blind, placebo-controlled study, the acute and long-term effects of the reduction of thromboxane A2 (TxA2) synthesis on airway sensitivity and maximal airway narrowing in response to methacholine was evaluated in 12 subjects with mild-to-moderate stable asthma, using imidazole salycilate (IS), an anti-inflammatory drug which selectively inhibits the TxA2 synthetase. Dose-response curves with methacholine (MCh) were performed in basal conditions (baseline); 1-1.5 h after administration of 1,500 mg of IS or placebo (acute); at 15 and 30 days of treatment with 750 mg t.i.d. of IS or placebo; and after a 2 week period of run-off (45 days). The serum levels of thromboxane B2 (TxB2) were measured at the same time points, except after acute administration, in five patients from each group. Baseline forced expiratory volume in one second (FEV1) was 78 +/- 7 and 85 +/- 8% of predicted in the IS and control group, respectively (NS). Throughout the study FEV1 remained unchanged in both groups, indicating that IS did not caused substantial modification of resting bronchial calibre. The initial provocative dose of methacholine causing a 20% fall in FEV1 (PD20) amounted to 27.0 +/- 1.5 micrograms in the IS group and 41.7 +/- 1.5 micrograms in the control group (geometric mean +/- GSEM) (NS). Despite a reduction of TxB2 serum levels with IS vs placebo at 15 days (24.9 +/- 8.5 vs 45.5 +/- 3.4 pg.mL-1; p < 0.05) and 30 days (27.0 +/- 6.3 vs 45.0 + 3.2 pg.mL-1; p < 0.05), MCh-induced bronchoconstriction, evaluated either as PD20 or maximal airway narrowing, did not change significantly during active treatment compared to placebo. These results show that prolonged reduction of thromboxane A2 synthesis does not improve airway sensitivity and limit maximal bronchoconstriction in asthmatic subjects, suggesting that thromboxane A2 per se does not play a substantial role in the pathogenesis of the airway hyperresponsiveness in human asthma.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Asthma/physiopathology , Bronchial Hyperreactivity/drug therapy , Enzyme Inhibitors/therapeutic use , Imidazoles/therapeutic use , Thromboxane-A Synthase/antagonists & inhibitors , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Asthma/drug therapy , Bronchial Provocation Tests , Bronchoconstrictor Agents , Dose-Response Relationship, Drug , Double-Blind Method , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Female , Forced Expiratory Volume , Humans , Imidazoles/administration & dosage , Imidazoles/adverse effects , Male , Methacholine Chloride , Middle Aged , Treatment Failure
4.
J Appl Physiol (1985) ; 81(5): 1978-86, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8941519

ABSTRACT

We have used diabetic autonomic neuropathy as a model of chronic pulmonary denervation to study the ventilatory response to incremental exercise in 20 diabetic subjects, 10 with (Dan+) and 10 without (Dan-) autonomic dysfunction, and in 10 normal control subjects. Although both Dan+ and Dan- subjects achieved lower O2 consumption and CO2 production (VCO2) than control subjects at peak of exercise, they attained similar values of either minute ventilation (VE) or adjusted ventilation (VE/maximal voluntary ventilation). The increment of respiratory rate with increasing adjusted ventilation was much higher in Dan+ than in Dan- and control subjects (P < 0.05). The slope of the linear VE/VCO2 relationship was 0.032 +/- 0.002, 0.027 +/- 0.001 (P < 0.05), and 0.025 +/- 0.001 (P < 0.001) ml/min in Dan+, Dan-, and control subjects, respectively. Both neuromuscular and ventilatory outputs in relation to increasing VCO2 were progressively higher in Dan+ than in Dan- and control subjects. At peak of exercise, end-tidal PCO2 was much lower in Dan+ (35.9 +/- 1.6 Torr) than in Dan- (42.1 +/- 1.7 Torr; P < 0.02) and control (42.1 +/- 0.9 Torr; P < 0.005) subjects. We conclude that pulmonary autonomic denervation affects ventilatory response to stressful exercise by excessively increasing respiratory rate and alveolar ventilation. Reduced neural inhibitory modulation from sympathetic pulmonary afferents and/or increased chemosensitivity may be responsible for the higher inspiratory output.


Subject(s)
Autonomic Nervous System Diseases/physiopathology , Diabetic Neuropathies/physiopathology , Exercise/physiology , Respiratory Mechanics/physiology , Adult , Anaerobic Threshold/physiology , Blood Glucose/metabolism , Carbon Dioxide/metabolism , Electrocardiography , Humans , Lactic Acid/blood , Male , Oxygen Consumption/physiology , Pulmonary Gas Exchange/physiology , Respiratory Function Tests
5.
Int J Clin Pharmacol Ther ; 34(10): 438-43, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8897082

ABSTRACT

Measurements of bronchial caliber and airway sensitivity were performed 4 times during the day (at 9, 11, 16, and 22 hr) at basal conditions (baseline), following the first inhalation of 50 micrograms salmeterol (acute) and at the 21st, 90th and 150th day after the initiation of an uninterrupted long-term treatment with inhaled salmeterol (50 micrograms b.i.d., at 10 and 22 hr). In each period of the protective effect was assessed by computing the increase of the methacholine dose able to induce a 20% fall of the forced expiratory volume in the first second (PD20FEV1) in terms of doubling dose (DD), either against the respective 9-hour PD20FEV1 value (DD9hr) or against the corresponding baseline PD20FEV1 value (DDbaseline). After the first dose of salmeterol the forced expiratory volume in the first second (FEV1) increased significantly as compared with the 9-hour FEV1 and the corresponding baseline FEV1 at each observation time (p < 0.01). During regular treatment FEV1 was higher than baseline at the 21st and 90th day at each observation time (p < 0.05), whereas at the 150th day no significant FEV1 increments were observed at 9 hr and 22 hr. The acute protective effect exerted by salmeterol amounted to about 2 DD9hr (p < 0.05) and 2 DDbaseline (p < 0.05) at each observation time. At the 21st, 90th, and 150th day, however, no significant increase of DD9hr was found, although a mild decrease of airway sensitivity of 1 DDbaseline of magnitude was observed for all periods at each observation time. We conclude that in mild to moderate asthma salmeterol appears to rapidly lose its ability to improve bronchial responsiveness while it is effective in maintaining a well-sustained bronchodilation despite a small degree of tachyphylaxis.


Subject(s)
Adrenergic beta-Agonists/pharmacology , Albuterol/analogs & derivatives , Asthma/physiopathology , Bronchial Hyperreactivity/chemically induced , Bronchodilator Agents/pharmacology , Circadian Rhythm/drug effects , Administration, Inhalation , Adrenergic beta-Agonists/administration & dosage , Adult , Albuterol/administration & dosage , Albuterol/pharmacology , Analysis of Variance , Asthma/metabolism , Bronchoconstrictor Agents/administration & dosage , Bronchoconstrictor Agents/pharmacology , Bronchodilator Agents/administration & dosage , Drug Interactions , Female , Humans , Male , Methacholine Chloride/administration & dosage , Methacholine Chloride/adverse effects , Middle Aged , Peak Expiratory Flow Rate/drug effects , Salmeterol Xinafoate
6.
Mult Scler ; 2(3): 161-7, 1996 Oct.
Article in English | MEDLINE | ID: mdl-9345381

ABSTRACT

In 10 patients (five females) suffering from multiple sclerosis with mild degree of disability, (EDSS ranging from 0 to 2) and in 10 age and sex matched control subjects we investigated lung function, respiratory muscles strength and cardiorespiratory response to incremental exercise in order to assess the metabolic cost of exercise. In the absence of any impairment of lung volumes and flows and in- and expiratory maximal mouth pressures, at peak of exercise oxygen consumption (VO2max = 1886 +/- 145 ml/min) and workload (Wmax = 137 +/- 9.8 watts) were slightly diminished in patients, as compared with controls (VO2max = 2246 +/- 196 ml/min and Wmax = 164 +/- 14.7 watts). These findings were associated with an increased heart rate (HR) and reduced oxygen pulse (VO2/HR) at the same workloads. During the whole exercise, however, the slope of the linear relationship between VO2 and work exhibited by the patients, amounting to 9.9 +/- 0.6 ml/min/watt, was similar to that of the controls (10.9 +/- 0.42 ml/min/watt). Incidentally, both at rest and during exercise, the patients showed a significantly greater minute ventilation (VE) due to a faster respiratory rate, associated with an augmented dead space (P < 0.05). We conclude that an increase of metabolic cost of exercise does not occur in multiple sclerosis patients with mild disability, suggesting a lack or a low degree of spasticity and/or ataxia elicited by the effort. Thus, their exertional capacity appears to be limited mainly by a poor training. The tachypnea observed in these patients at rest and during exercise was unexpected and the reason for adopting such a pattern of breathing is unclear.


Subject(s)
Energy Metabolism , Fatigue/etiology , Multiple Sclerosis/complications , Multiple Sclerosis/metabolism , Physical Exertion/physiology , Adult , Disability Evaluation , Fatigue/metabolism , Fatigue/physiopathology , Female , Heart Rate , Humans , Male , Multiple Sclerosis/physiopathology , Oximetry , Oxygen Consumption , Respiratory Function Tests
7.
Diabetologia ; 38(2): 244-50, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7713321

ABSTRACT

We investigated cardiovascular function and plasma catecholamine response during incremental exercise and recovery in diabetic patients with (DAN+) and without autonomic neuropathy (DAN-). The former group was divided according to the presence of parasympathetic (DAN+PH-) or associated parasympathetic and sympathetic (DAN+PH+) damage to the autonomic nervous system. A group of healthy volunteers was studied as a control group. All the patients and control subjects underwent a submaximal or symptom-limited incremental exercise test using a cycle-ergometer. Air flow and respiratory gas fractions were sampled at the level of the mouth allowing a breath-by-breath analysis of oxygen consumption (VO2). Heart rate and systolic blood pressure were recorded and venous blood samples were obtained from the patients at rest and during each minute of exercise and recovery to measure norepinephrine and epinephrine plasma levels. Haemodynamic parameters and plasma catecholamines were computed at rest and at 25, 50, 75 and 100% of the peak VO2 (VO2max). The breath-by-breath relationships among VO2, heart rate and VO2/heart rate against work were assessed during exercise for patients and control subjects. While VO2max in absolute values was not significantly different among the diabetic groups, VO2 max was much less in diabetic patients than in control subjects (p < 0.01). During exercise the rate of heart rate, systolic blood pressure, norepinephrine and epinephrine increase was different among the diabetic groups, being significantly blunted in DAN+PH+. The VO2/work relationship of the three diabetic groups was similar but markedly reduced in respect to that of control subjects (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Autonomic Nervous System Diseases/physiopathology , Diabetic Neuropathies/physiopathology , Exercise/physiology , Hemodynamics/physiology , Adult , Blood Pressure/physiology , Case-Control Studies , Diabetes Mellitus/physiopathology , Epinephrine/blood , Heart Rate/physiology , Humans , Male , Middle Aged , Norepinephrine/blood , Oxygen Consumption/physiology , Physical Exertion/physiology
8.
Chest ; 105(4): 1163-70, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8162744

ABSTRACT

In 11 patients with moderately severe multiple sclerosis, lasting 11.2 +/- 7.3 years, in stable condition, and in 10 age- and sex-matched control subjects, we investigated lung function, respiratory muscle strength, and ventilatory control system. Respiratory muscle strength was assessed by measuring maximal inspiratory and expiratory mouth pressures (Pimax and Pemax, respectively). Respiratory central drive was evaluated in terms of neuromuscular (P0.1) and ventilatory (Ve) output, breathing room air and during CO2 rebreathing. In the absence of any significant impairment of lung function, patients showed a reduction of Pimax and Pemax amounting to about 40 percent and 60 percent of the predicted value at functional residual capacity (FRC), respectively; a significant, inverse correlation was found between both Pimax and Pemax at FRC and the severity score of the disease. While at rest Ve was similar to that of control subjects, baseline P0.1 was significantly higher in patients (1.97 +/- 0.79 vs 0.97 +/- 0.20 cm H2O, p < 0.005). Compared with the control group, during CO2 rebreathing P0.1/PetCO2 slope, although less steep, was not dissimilar in patients (0.34 +/- 0.13 vs 0.46 +/- 0.19 cm H2O/mm Hg, NS); on the other hand, Ve/PetCO2 slope was much lower in the patient group (1.93 +/- 0.91 vs 3.27 +/- 1.11 L/min/mm Hg, p < 0.01) and was significantly related to the functional stage of disease and to Pimax and Pemax values at FRC. These results indicate that in patients with clinically stable, moderately severe multiple sclerosis, the respiratory muscle function is abnormal. Moreover, the inspiratory drive at rest is increased and the drive response to CO2 appears normal, while the ventilatory response to CO2 is significantly impaired. Respiratory muscle weakness (and/or lack of coordination) could explain, at least in part, the lower ventilatory response in these patients, whereas the mechanism of increased rate of the initial inspiratory force generation remains unclear.


Subject(s)
Multiple Sclerosis/physiopathology , Respiration/physiology , Respiratory Muscles/physiopathology , Adult , Carbon Dioxide/physiology , Female , Humans , Male , Middle Aged , Respiratory Mechanics
10.
Am Heart J ; 120(2): 467-72, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2200257

ABSTRACT

Cardioselectivity of a single oral dose of metoprolol oral osmotic (OROS) (14/190 mg) and atenolol (100 mg) was compared in 12 patients with reversible obstructive airway disease by assessing the dose-response curve to increasing doses of inhaled salbutamol. The beta-blocking activity of the two drugs, which was determined by measuring heart rate, blood pressure, and derived indexes at peak plasma drug levels, was similar. Both metoprolol and atenolol significantly reduced forced vital capacity and peak expiratory flow, with no difference between drugs. Atenolol but not metoprolol also significantly reduced forced expiratory volume in 1 second and specific airway conductance. Both metoprolol and atenolol shifted the dose-response curve of specific airway conductance to the right. The results indicate that the new OROS delivery system for metoprolol, which produces a relatively constant plasma drug level, provides a cardioselectivity comparable to or greater than that of atenolol at maximum plasma levels.


Subject(s)
Atenolol/therapeutic use , Heart/drug effects , Metoprolol/administration & dosage , Adolescent , Adult , Aged , Airway Resistance/drug effects , Albuterol , Atenolol/blood , Clinical Trials as Topic , Double-Blind Method , Forced Expiratory Volume , Heart Rate/drug effects , Humans , Lung Diseases, Obstructive/drug therapy , Lung Diseases, Obstructive/physiopathology , Metoprolol/blood , Metoprolol/therapeutic use , Middle Aged , Organ Specificity , Peak Expiratory Flow Rate
11.
Int J Clin Pharmacol Res ; 10(3): 183-9, 1990.
Article in English | MEDLINE | ID: mdl-1977709

ABSTRACT

The ventilatory and gas-exchange effects of broxaterol, a new selective beta 2-adrenoceptor agonist, were investigated in ten asthmatics following intravenous administration of a single dose of 200 mcg. Broxaterol elicited a prompt and marked bronchodilating effect (increase in forced expiratory volume in one second and specific conductance), maintained at least up to the sixtieth minute. Minute ventilation and the mean expiratory flow did not increase significantly, the pattern of breathing showing a reduction of expiratory time, without modification of inspiratory time. On the other hand, occlusion pressure did not show any significant rise at all times of observation. Furthermore, the partial arterial oxygen and carbon dioxide pressures and alveolar-arterial difference in oxygen and physiological dead space remained unchanged, when measured at 20 min. The results demonstrated that broxaterol was an effective bronchodilating agent, also when rapidly injected, causing a prompt relief of bronchospasm. With respect to other beta 2-adrenoceptor agonists, this compound did not appear to increase minute ventilation or to induce an impairment of ventilation/perfusion ratio, at least after 20 min, when the bronchodilation was still evident. Finally, no side-effects or alterations of heart rate or blood pressure were reported.


Subject(s)
Adrenergic beta-Agonists/pharmacology , Asthma/physiopathology , Intermittent Positive-Pressure Breathing , Isoxazoles/pharmacology , Pulmonary Gas Exchange/drug effects , Adrenergic beta-Agonists/administration & dosage , Adult , Aged , Asthma/drug therapy , Female , Humans , Injections, Intravenous , Isoxazoles/administration & dosage , Male , Middle Aged , Respiratory Function Tests
12.
Pain ; 29(3): 273-286, 1987 Jun.
Article in English | MEDLINE | ID: mdl-3614964

ABSTRACT

Twelve patients with intense or very intense pain of the non-incident type, secondary to neoplasia, were divided at random into two groups and treated with an epidural dose of 3 mg of morphine in 10 ml of glucose solution (6 patients = group M) or with 0.3 mg of buprenorphine in the same vehicle (6 patients = group B). None of the patients had previously been treated with opioids by any route. After first determining basal values, the following assessments were carried out: (1) evaluation of the analgesic effect of the drugs with checks at 30 min and at 1, 2, 3, 4, 6 and 18 h after administration, using a visual analogue scale, a numerical rating scale and a simple descriptive scale; and (2) evaluation of effects on respiration by means of checks at 30 and 90 min and at 6 and 18 h, on control of breathing indices (P0.1; VE; VA; Ti/Ttot; VT/Ti; RR), gas exchange indices (delta(A-a)O2; VD/VT; pAO2; R) and blood gas and acid-base indices (paO2; paCO2; pH; HCO3-). The data obtained were analyzed statistically using analysis of variance and Student's t test. The study results showed very similar analgesic efficacy for both treatments at a single dosage level of morphine (3 mg) compared to buprenorphine (0.3 mg), which was approximately 3 times greater than an equivalent parenteral dose of morphine (10 mg). Analysis of the results revealed statistically, though not clinically, significant changes in respiratory function indices, only in the buprenorphine-treated group. The effects of buprenorphine on respiratory function, when administered epidurally at the above dosage, are less favourable than those of morphine in the early measurements, probably because of its greater systemic absorption; nevertheless, the risk of delayed respiratory depression appears to be less after buprenorphine than after morphine.


Subject(s)
Buprenorphine/administration & dosage , Morphine/administration & dosage , Pain/drug therapy , Respiration/drug effects , Aged , Buprenorphine/adverse effects , Double-Blind Method , Female , Humans , Injections, Epidural , Male , Middle Aged , Morphine/adverse effects , Neoplasms/physiopathology , Pain/blood , Prospective Studies , Pulmonary Gas Exchange/drug effects , Random Allocation
15.
Eur J Respir Dis Suppl ; 146: 671-6, 1986.
Article in English | MEDLINE | ID: mdl-3536560

ABSTRACT

The authors refer to a double-blind versus placebo multicentric study, carried out in Italy on 128 hypoxaemic patients suffering from COLD, with Almitrine bismesylate, a new chemoreceptor stimulant drug, given by mouth for a period of two months. Almitrine induced significant changes (p less than 0.001) of PaO2, with a mean increase of 7.6 mmHg, and of PaCO2, with a mean decrease of 4.1 mmHg, without variations of lung volumes and caliber of large and/or small airways. Almitrine, well tolerated within the time limits of this trial, seems an effective oral respiratory drug, acting through a favourable effect on V/Q mismatching due mainly to a reduction of the shunt effect, but also to an improvement of the ventilatory pattern.


Subject(s)
Lung Diseases, Obstructive/drug therapy , Piperazines/therapeutic use , Almitrine , Clinical Trials as Topic , Female , Humans , Hypoxia/drug therapy , Italy , Male , Middle Aged
16.
Int J Clin Pharmacol Ther Toxicol ; 23(10): 560-4, 1985 Oct.
Article in English | MEDLINE | ID: mdl-3905630

ABSTRACT

Pharmacokinetics and ventilatory response to Theodur (Th) was compared to that of Aminomal R (AR) in a randomized within-patient double-blind study, carried out in patients with chronic obstructive lung disease. Both slow-release preparations of theophylline were given every 12 hours for 14 days each at the end of a placebo wash-out period. Th and AR did not differ significantly in their bronchodilating effect at 3 and 12 hours after intake. Salbutamol consumption was not dissimilar in the 2 preparations. Mean serum theophylline levels remained within the therapeutic range at 2, 3 and 12 hours after sustained administration of both Th and AR, but were slightly lower and less fluctuating after Th. Gastrointestinal side effects such as epigastric discomfort, nausea, abdominal pain and diarrhea were more common after AR, a result likely due to its higher content of anhydrous theophylline per tablet (474 mg vs 300 mg in Th). In conclusion, we failed to detect differences between Th and AR in their bronchodilating effect after sustained treatment in patients with chronic obstructive lung disease. Th, however, although containing less theophylline per tablet, resulted in comparable theophylline levels with similar ventilatory response, in presence of a better gastrointestinal tolerability. These results suggest a better bioavailability of Th, likely accounted for by a more advanced pharmaceutical technology.


Subject(s)
Lung Diseases, Obstructive/drug therapy , Theophylline/blood , Albuterol/therapeutic use , Clinical Trials as Topic , Delayed-Action Preparations , Double-Blind Method , Female , Humans , Male , Middle Aged , Random Allocation , Respiratory Function Tests , Theophylline/administration & dosage , Theophylline/adverse effects , Time Factors
17.
Respiration ; 48(4): 296-302, 1985.
Article in English | MEDLINE | ID: mdl-3909277

ABSTRACT

The present study was carried out to test the hypothesis of a possible effectiveness of captopril--an enzymatic inhibitor of both angiotensin II formation and bradykinin degradation--on hypoxic pulmonary hypertension. In 6 patients with this clinical condition, captopril-induced changes in pulmonary hemodynamics were observed after the acute administration of the drug with and without a short period of oxygen therapy at a flow rate sufficient to keep the PaO2 over 60 mm Hg. In our patients, captopril significantly lowered pulmonary arterial pressure and vascular resistance only when combined with oxygen, suggesting that an increase in bradykinin availability and/or a decrease in angiotensin II synthesis might be important factors in reversing pulmonary arterial hypertension only after blunting of the hypoxic stimulus on pulmonary circulation. Moreover, the authors suggest that the employment of vasodilators in the setting of hypoxic pulmonary hypertension should be considered not only as a means of relieving vasoconstriction but also as a possible tool for maintaining cardiac output and, in turn, peripheral oxygen delivery.


Subject(s)
Captopril/pharmacology , Hemodynamics/drug effects , Hypertension, Pulmonary/physiopathology , Pulmonary Artery/drug effects , Aged , Blood Pressure/drug effects , Cardiac Output/drug effects , Drug Interactions , Heart Rate/drug effects , Humans , Hypertension, Pulmonary/complications , Hypoxia/blood , Hypoxia/physiopathology , Lung Diseases, Obstructive/complications , Middle Aged , Oxygen/blood , Oxygen/pharmacology , Partial Pressure , Vascular Resistance/drug effects , Vasoconstriction/drug effects
18.
Int J Clin Pharmacol Ther Toxicol ; 22(10): 570-5, 1984 Oct.
Article in English | MEDLINE | ID: mdl-6150902

ABSTRACT

We compared the ventilatory effects of prenalterol (beta 1-selective adrenoceptor agonist) with those of salbutamol (beta 2-selective adrenoceptor agonist) in 6 healthy volunteers. Two intravenous doses of prenalterol (1 mg/60 min, 2 mg/60 min) and of salbutamol (300 micrograms/60 min, 600 micrograms/60 min) were given in random order in 4 separate sessions of 60 minutes each. Pulmonary ventilation per minute (V'E) increased only on the high dose of salbutamol. Mouth occlusion pressure (P0.1) did not vary either on prenalterol or on salbutamol. Only the high dose of salbutamol induced (1) an increase in tidal volume (VT) without changes in respiratory rate (RR), (2) an increase in mean inspiratory flow (VT/Ti) without changes in the fraction of inspiratory time to total cycle duration (Ti/Ttot). During forced expiration, salbutamol elicited a small bronchodilating effect at the level of both large (FEV1, FEF25-75, FEF50) and small (FEV3, FEF75-85, FEF75) airways. Prenalterol induced a very small dilatation of the large airways, and a somewhat more pronounced effect at the level of the small airways. Neither the indexes of ventilatory pattern nor those of bronchial tone showed any statistical or biological differences between values on prenalterol and values on salbutamol. However, both the former and the latter indexes showed a trend to be higher on salbutamol than on prenalterol. Results suggest that salbutamol-induced increase in pulmonary ventilation per minute in subjects without bronchial obstruction is likely the result of a reduced bronchomotor tone at rest, leading to an increase in tidal volume because of the rise in the VT/Ti ratio.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Adrenergic beta-Agonists/pharmacology , Albuterol/pharmacology , Practolol/analogs & derivatives , Respiration/drug effects , Albuterol/adverse effects , Bronchodilator Agents , Forced Expiratory Volume , Humans , Male , Muscle Tonus/drug effects , Practolol/adverse effects , Practolol/pharmacology , Prenalterol
19.
Clin Pharmacol Ther ; 35(6): 776-81, 1984 Jun.
Article in English | MEDLINE | ID: mdl-6145533

ABSTRACT

The relative chronotropic and inotropic activity of preferential beta 1- and beta 2-adrenoceptor stimulation was investigated in seven healthy male subjects in a randomized within-subject, single-blind study. Two doses of beta 1-selective agonist prenalterol (1 mg/hr or 2 mg/hr) and of beta 2-selective agonist salbutamol (300 micrograms/hr or 600 micrograms/hr) were infused intravenously in four separate sessions, with intervals of at least 48 hr between sessions. At each session cuff blood pressure and heart rate (HR) were measured and some hemodynamic information on the inotropic state were derived by echocardiography. Both prenalterol and salbutamol induced increases in HR, but tachycardia was greater after salbutamol, whereas the positive inotropic response to beta-stimulation was greater after prenalterol. At comparable HR rises (prenalterol, from 66.0 +/- 5.5 to 72.2 +/- 4 bpm; salbutamol, from 64.6 +/- 6 to 70.0 +/- 7 bpm), inotropic response seemed to be greater after prenalterol than after salbutamol (systolic blood pressure [SBP]: 133.5 +/- 8 and 120.7 +/- 8 mm Hg; mean velocity of circumferential fiber shortening [Vcf]: 1.54 +/- 0.13 and 1.31 +/- 0.12 c/s; ejection fraction [EF]: 72.4% +/- 5% and 69.5% +/- 4%; stroke index: 47.4 +/- 4 and 41.7 +/- 3 ml/m2). In presence of a chronotropic effect (HR from 64.6 +/- 6 to 70.0 +/- 7 bpm), the low salbutamol dose did not induce any changes in the indices of inotropism (SBP: from 119.2 +/- 6 to 120.7 +/- 8 mm Hg; mean Vcf: from 1.28 +/- 0.11 to 1.31 +/- 0.12 c/s; EF: from 68.1% +/- 5% to 69.5% +/- 4%; stroke index: from 40.2 +/- 3 to 41.7 +/- 3 ml/m2.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Adrenergic beta-Agonists/pharmacology , Heart Rate/drug effects , Myocardial Contraction/drug effects , Adult , Albuterol/pharmacology , Blood Pressure/drug effects , Echocardiography , Humans , Male , Practolol/analogs & derivatives , Practolol/pharmacology , Prenalterol , Random Allocation , Smoking , Stimulation, Chemical , Stroke Volume/drug effects
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