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Biomedical subjects

V Grassi

Publications and source records attributed to V Grassi.

At least 55 records · Page 3Linked to original sources
PubMed1988

Metabolic and hormonal effects of preferential beta 1 and beta 2-adrenoceptor stimulation in man.

The changes of blood glucose, serum potassium (K+), plasma non-esterified fatty acids (NEFA), plasma insulin and plasma renin activity (PRA) following the preferential stimulation of beta-1 and beta-2 adrenoceptors were studied in 7 healthy subjects during a 60-min infusion of prenalterol, a new, relatively beta-1 selective agonist and salbutamol, a well known, relatively beta-2 selective agonist. Two different high and low doses were used for both agents: 300 micrograms and 600 micrograms and 1 mg and 2 mg for salbutamol and prenalterol, respectively. The levels of PRA seemed equally increased by the two agents in proportion to the dose infused, thus suggesting an equally important role for beta-1 and beta-2 adrenoceptors in renin release. Blood glucose did not change during prenalterol infusions, while increased by 12 +/- 2 mg/100 ml (mean +/- SE; p less than 0.01) and 25 +/- 3 mg/100 ml (p less than 0.01) on salbutamol, at low and high dose, respectively. Similarly the decrement of serum K+ was significantly more pronounced (p less than 0.01) after salbutamol infusion (0.6 +/- 0.07 mEq/L and 1.0 less than 0.09 mEq/L, at low and high dose, respectively) than after prenalterol (0.1 +/- 0.07 mEq/L and 0.3 +/- 0.05 mEq/L). These metabolic effects should suggest a main beta-2 adrenoceptor involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Sympathetic activation on effort in patients with chronic heart failure. Long term effects of captopril.

Ten patients with congestive heart failure (CHF) (NYHA II-IV) on adjusted doses of digitalis and diuretics underwent a careful clinical assessment including an evaluation of exertion dyspnoea and the usual echocardiographic indices of cardiac performance. A cardiopulmonary exercise test with an increment of 20W every 3 minutes was prolonged until exhaustion. Systemic arterial pressure, ECG, VO2, VCO2 and VE were monitored throughout. Gas tensions, plasma catecholamines and lactate were measured in blood samples taken at the first and third minute of each exercise stage. The above measurements were carried out before and after 3 months of treatment with Captopril, 50 mg b.i.d. or t.i.d. A highly significant correlation between arterial lactate and plasma norepinephrine (NE) was observed in each patient during both exercise tests (r = 0.77 to 0.99; p less than 0.05 at least). Left ventricular end-diastolic dimensions were reduced by Captopril (from 69.9 +/- 1.7 to 65.2 +/- 1.4 mm, p less than 0.01) along with a concomitant increase in percent fractional shortening. Most of the patients were reclassified at a lower NYHA class and a significant decrease in dyspnoea score was observed. The exercise time was significantly increased (from 11.2 +/- 1.8 to 12.9 +/- 1.9 min; p less than 0.05), but the peak values of NE, arterial lactate and VO2 were not affected by the treatment. The predicted value of VE at a VCO2 of 1 L/min, regarded as an index of dyspnoea, was significantly decreased by Captopril (from 41.4 +/- 2.9 to 38.9 +/- 2.7 L/min; p less than 0.05). The positive effects of long-term treatment with Captopril on cardiac performance in CHF are confirmed. Sympathetic activity is linked to anaerobic muscular metabolism during exercise and seems to be independent of pharmacological ACE inhibition. The discrepancy between the exercise tolerance and the peak VO2 might be explained by a better utilization of the available energy.

Adult↗
PubMed1987

Buprenorphine vs. morphine via the epidural route: a controlled comparative clinical study of respiratory effects and analgesic activity.

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.

Aged↗
PubMed1987

Evaluation of the effectiveness and safety of a controlled-release theophylline in patients with reversible and stable bronchial obstruction.

In this study the effectiveness and safety of a new controlled-release theophylline formulation were evaluated. Twenty patients (12 male, 8 female) affected by bronchial asthma (mean age 45 years) or chronic obstructive lung disease (mean age 58 years) were given the drug. During the 30 days of controlled-release theophylline therapy, all patients reported a marked clinical improvement, confirmed by spirometric data (ventilation indexes, intrapulmonary air distribution, ventilation control, gas exchanges). Tolerability was excellent.

Adult↗
PubMed1987

Influence of the carotid body on gas exchange during exercise.

The role of the carotid body in the ventilatory changes of exercise is reviewed. Peripheral chemoreceptor function was studied in 20 patients with chronic airways obstruction. The patients were treated double-blind and randomly allocated to placebo and almitrine bismesylate 50 mg b.d. before undertaking an exercise programme at day 0 and after 30 and 60 days of therapy. Patients on almitrine therapy had an improved resting arterial oxygen tension (PaO2) which was maintained during exercise. A statistically significant improvement of effort tolerance was observed after 60 days treatment with almitrine.

Aged↗
PubMed1986

Acute on chronic comparative effects of a combination of fenoterol-ipratropium bromide and terbutaline in patients with chronic obstructive lung disease.

Twenty patients suffering from chronic obstructive lung disease (COLD) were examined in a randomized intra-individual single-blind study in order to compare the ventilatory response, tolerance and side-effects of a combination of 40 micrograms ipratropium bromide and 100 micrograms fenoterol (Duovent) with 250 micrograms terbutaline, both given by inhalation (2 puffs) three times a day. The ventilatory parameters FVC, FEV1, sGaw, RV and PaO2, tested on the 7th and 14th days at 0, 30, and 240 min after the morning administration of the two drugs, showed significant differences between treatments, revealing a greater persistence of bronchodilator effect and a more prolonged duration of action with Duovent than with terbutaline. We believe that the results obtained suggest the usefulness of a combination of anti-cholinergic and beta 2-agonist drugs in the treatment of reversible bronchial obstruction in COLD, where even the parasympathetic nervous system seems to play an important role. The observed clinico-functional effects (intensity and duration of bronchodilatation) together with the lack of side-effects permit us to affirm that Duovent is a rational pharmacologic combination which represents real progress in the difficult treatment of COLD patients.

Adult↗
PubMed1986

Oral beta 2-selective adrenergic bronchodilators.

Oral beta 2-agonists (carbuterol, pirbuterol, procaterol, bitolterol, clenbuterol) are drugs widely used as bronchodilators. The efficacy and selectivity of bronchodilators drugs depend on their intrinsic pharmacological properties and on the route of administration. The characteristics of the oral route are easy usage, precise dosage and assured effects. Consequently, disadvantages (delayed onset of action, more frequent side-effects) and the indications, (patients with severe chronic airways obstruction, nocturnal asthmatic attacks, and children and elderly subjects) are clearly evident. The most recent beta 2-agonists have an efficient and prolonged bronchodilating action with well-known side-effects. In order to control drug efficiency in a large population and identify type and degree of adverse reactions, a post-marketing surveillance study was programmed for clenbuterol. The results available confirms that long-term treatment with oral clenbuterol is an effective and safe therapeutical approach. During long-term treatment, tachyphylaxis (a diminished responsiveness) develops. This complex biological phenomenon can be studied, in several ways i.e. functional response of target-organ, appropriate biochemical-metabolical indices, and functional evaluation of the cellular beta-receptors in vitro. Also in the light of evaluation of serum levels of cyclic nucleotides (cyclic adenosine and guanosine monophosphates) it appears that the clinical importance of tachyphylaxis is mild and that chronic therapy with beta 2-agonists is safe and effective when used in selected patients.

Administration, Oral↗
PubMed1986

A review of clinical studies carried out in Italy with almitrine bismesylate.

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.

Almitrine↗
PubMed1985

Acute effects of captopril in hypoxic pulmonary hypertension. Comparison with transient oxygen administration.

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.

Aged↗
PubMed1985

[The first Italian clinical experience with almitrine bismesylate].

A double blind randomised multicentre clinical trial against placebo was performed in Italy on 128 patients with chronic airflow obstruction and hypoxaemia. On entry to the study all the patients were hypoxaemic (PaO2 less than or equal to 70 mmHg), 22 were normocapnic (PaCO2 less than or equal to 41 mmHg), 106 hypercapnic (PaCO2 greater than or equal to 43 mmHg). The patients (107 males and 21 females) with a mean age of 64 received oral Almitrine bismesylate for two months in a dose of 100 mg per day or placebo taken in two doses with the main meals. After inclusion in the study (TO), patients were reviewed after 30 and 60 days of treatment to evaluate pulmonary function and blood gases. The results were as follows: Almitrine bismesylate did not produce any significant variations in lung volumes, tests of airflow obstruction (for large or small airways) or the distribution of intra-pulmonary inspired air. The blood gas values at the end of treatment showed statistically significant changes (p less than 0.001: PaCO2 + 7.6 mmHg in patients overall and PaCO2 - 4.1 mmHg in those patients with hypercapnia.) The changes in arterial blood, already apparent after 30 days, were even more marked at the end of the study. These favourable blood gas changes might be the result (for the greater part) of the intra-pulmonary haemodynamic effect induced by Almitrine bismesylate (improved VA/QC ratios described in the literature) and (for a smaller part) a better ventilatory pattern with a reduction in the (A-a) DO2 and the functional dead space.(ABSTRACT TRUNCATED AT 250 WORDS)

Almitrine↗
PubMed1985

Serum theophylline and ventilatory function in chronic obstructive lung disease. Comparison between two slow-release formulations of theophylline.

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.

Albuterol↗
PubMed1984

Noninvasive assessment of chronotropic and inotropic response to preferential beta-1 and beta-2 adrenoceptor stimulation.

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)

Adrenergic beta-Agonists↗
PubMed1984

Ventilatory effects of selective beta 1-(prenalterol) or beta 2-(salbutamol) adrenoceptor agonism in man.

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)

Adrenergic beta-Agonists↗