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Biomedical subjects

J Cerrina

Publications and source records attributed to J Cerrina.

At least 73 records · Page 4Linked to original sources

Relaxation of isolated human pulmonary muscle preparations with prostacyclin (PGI2) and its analogs.

The effects of PGI2 and two analogs Iloprost and ZK 96480 were examined on isolated human pulmonary muscle preparations. High concentrations of these agents reduced the basal tone in all types of preparations. In addition, they relaxed tissues which had been maximally contracted with histamine (50 microM). PGI2 was more potent on pulmonary arterial muscle preparations (pD2 value: 6.33, n = 3) than on bronchial muscles. The relaxations induced by PGI2 in bronchial preparations were quite variable, that is, some tissues relaxed while others did not. The analogs also relaxed arterial preparations and the pD2 values were approximately the same (Iloprost: 7.42, n = 4 and ZK 96480: 7.48, n = 4). The isolated human pulmonary vascular preparations were approximately 10-fold more sensitive to the analogs than bronchial muscle preparations. In bronchial tissues we noted that the PGI2 relaxant effect was spontaneously reversed with time, an activity not observed with both analogs. A pretreatment of the bronchial tissues with indomethacin (1.7 microM) did not reduce the variations observed with PGI2 nor modify the transient relaxation observed with this agent. These data demonstrate that vascular tissues from the human lung are considerably more sensitive to these relaxant agonists than bronchial preparations.

Bronchi↗

Recurrence of pulmonary embolism during anticoagulant treatment: a prospective study.

The risk of early recurrence of pulmonary embolism in patients with venous thromboembolic disease treated by anticoagulants is not well established. To determine the risk linked to contemporary proximal deep venous thrombosis, a prospective study was organised to give clinical and scintigraphic surveillance to 50 patients with angiographically proved pulmonary embolism plus phlebographically proved proximal deep vein thrombosis during the first 15 days of anticoagulant treatment. Perfusion lung scans were performed initially and on days 3, 7, and 15. Only two patients had a recurrence of pulmonary embolism during this period; both episodes were revealed by new symptoms, and one recurrence was fatal. The systematic performance of angiography in four patients found to have new scintigraphic defects led to the diagnosis of "spurious scintigraphic recurrence" in three of them. It is concluded that (a) adjusted anticoagulant treatment showed an effectiveness of 96% for preventing early recurrence of pulmonary embolism in this group of supposed high risk patients, and (b) in patients with recent pulmonary embolism new defects on systematic perfusion lung scans are not specific indicators of recurrent pulmonary embolism.

Adult↗

[Heart-lung transplantation].

The combined transplantation of heart and lungs, first done successfully by the Stanford Team (USA) in 1982, at present seems to be superseding lung transplantation alone, and has broadened the indications of heart transplantation to include terminal heart failure with fixed pulmonary arterial hypertension. After reviewing the causes for failure in lung transplants, the authors stress the superiority of heart-lung transplants compared to isolated lung transplantations: healing of the tracheal anastomosis, ease of detection of rejects by endomyocardial biopsy and the lack of inhomogeneity of the ventilation/perfusion ratios. This operation still poses problems of surgical technique as the mediastinal nerves need to be preserved and the risk of haemorrhage linked to the mediastinal dissection or to the eventual pulmonary separation under cardiopulmonary bypass is important. Donor subjects for cardiopulmonary transplantation are rare as they ought to have a thoracic cage of matching size to the recipient and to be free of pulmonary infection and trauma. The post-operative complications are essentially those of immediate haemorrhage, graft rejection, pulmonary oedema and infection. The late complications are coronary atherosclerosis and bronchiolitis obliterans. The indications of such a transplant are currently reserved for primary or secondary pulmonary hypertension and to respiratory failure with a normal thoracic cage and ventilatory mechanics.

Heart Transplantation↗

Comparison of human bronchial muscle responses to histamine in vivo with histamine and isoproterenol agonists in vitro.

In an effort to explain the large variation of airway reactivity to histamine in human subjects in vivo, we have examined the relationship between histamine responses in vivo and isoproterenol in vitro. The bronchial reactivity in patients with lung carcinoma was assessed prior to surgery by measuring the provocative concentration of histamine that resulted in a 20 or a 40% reduction in either forced expiratory volume in one second or specific airway conductance (SGaw). We also determined the pD2 value (-Log EC50 molar) to histamine and isoproterenol in isolated bronchial muscle preparations from these subjects. A wide range of histamine responsiveness was observed in vivo for the 17 patients (PC40 SGaw: 1.3 to greater than 64 mg/ml of histamine). There was no correlation between this latter parameter and the bronchial histamine sensitivity in vitro. However, isolated bronchial muscle preparations from asthmatic subjects were less sensitive to isoproterenol than were those preparations from nonasthmatic subjects.

Adult↗

Histamine contraction of isolated human airway muscle preparations: role of prostaglandins.

Histamine concentration-effect curves were obtained using either an individual or cumulative dosing method. The maximal response to histamine in bronchial preparations using the individual dosing protocol was 0.25 +/- 0.03 g/mm2 and similar results were obtained using the cumulative method (0.24 +/- 0.03 g/mm2). The sensitivity (pD2 value) of isolated human bronchial muscle preparations was comparable for both the individual and cumulative methods (5.71 and 5.16, respectively). Prostaglandin (PG) E2 and PGF2 alpha contracted isolated human bronchial muscle preparations and the pD2 values were 5.64 and 5.59, respectively. PGE2 did not relax bronchial muscle preparations contracted with histamine (50 microM). At high concentrations prostacyclin (3 microM) relaxed histamine-contracted bronchial tissues but this effect was quite variable. Indomethacin (1.7 microM) did not affect basal tone in bronchial tissues. Isolated human bronchial preparations which were contracted maximally with histamine always released measurable quantities of PGs. In some experiments the rat stomach strip was used to detect the presence of these substances before and subsequent to the indomethacin (1.7 microM) treatment. The use of radioimmunoassay for PGE2 and PGF2 alpha confirmed these bioassay results. In a large number of experiments (18 preparations from 9 individual lung samples) the baseline production of PGs was PGE2, 22.9 +/- 2.8 pg/mg of tissue and PGF2 alpha, 11.9 +/- 2.5 pg/mg of tissue. Subsequent to histamine stimulation the quantities of PGs released were PGE2, 72.4 +/- 7.6 pg/mg of tissue and PGF2 alpha, 40.9 +/- 7.3 pg/mg of tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗

Hypercapnic acidosis induced by nutrition in mechanically ventilated patients: glucose versus fat.

Total parenteral nutrition (TPN) increases CO2 production (VCO2) in patients on intermittent positive-pressure ventilation who cannot match their CO2 excretion to the CO2 load, leading to an increase in PaCO2. We studied gas exchange and blood gas values in six patients with chronic respiratory failure, who were ventilated at low (6 +/- .7 L/min) and high (10 +/- 2 L/min) minute ventilation during three randomized nutritional regimens: control (255 kcal/day), glucose TPN (2550 kcal/day), and lipid TPN (3000 kcal/day). At the two levels of ventilation, TPN compared to control increased VCO2 and PaCO2 (p less than .01) and decreased pH (p less than .001). At low minute ventilation, the increase in VCO2 and the hypercapnic acidosis were less with lipid than with glucose TPN (p less than .05 and p less than .01, respectively). These results indicate that the risk of TPN-induced CO2 retention is lower if minute ventilation is increased before beginning TPN. Conversely, in patients with compromised ventilatory function, this risk could be higher during intermittent mandatory ventilation or weaning from the ventilator.

Acidosis↗

Response and sensitivity of guinea-pig airway muscle preparations to 5-hydroxytryptamine during ontogenesis.

Responsiveness (g mm-2) and sensitivity (pD2 value) to 5-hydroxytryptamine (5-HT) were markedly reduced in isolated tracheal and bronchial tissues from guinea-pigs during ontogenesis. Responsiveness of the trachea to 5-HT was depressed much more than that to histamine. Airway preparations from young guinea-pigs of either sex always contracted when exposed to 5-HT, an effect that was blocked by methysergide. Airway muscle preparations from old animals exhibited a wide range of responses to 5-HT, namely, no effect, relaxation or contraction. The contractile effect of 5-HT in tracheal and bronchial preparations from old animals was always blocked by methysergide, whereas, the relaxant effect was not. These results indicate that there are significant alterations in the response to 5-HT receptor stimulation in airway muscle preparations from guinea-pigs during ontogenesis.

Aging↗

Response and sensitivity of isolated human pulmonary muscle preparations to pharmacological agents.

The responsiveness (grams per millimeter squared) and sensitivity (pD2 value) of various agonists were examined in isolated stored human bronchial and pulmonary arterial and venous preparations. In isolated bronchial muscles, large preparations (internal diameter about 6 mm) were less responsive (grams per millimeter squared) to contractile agents than smaller preparations (internal diameter approximately 2 mm). Noncumulative concentration-effect curves were produced in bronchial preparations using histamine, acetylcholine, carbachol and barium chloride. Histamine contracted both bronchial and vascular preparations whereas 5-hydroxytryptamine contracted only vascular tissues. The latter effect was always blocked by either methysergide or ketanserin. 5-hydroxytryptamine relaxed bronchial tissues that were contracted with either histamine, acetylcholine or prostaglandin E2. This relaxation was not antagonized by methysergide, ketanserin, propranolol or indomethacin. Dimaprit and 4-methyl histamine were without effect in isolated contracted bronchial preparations. Vasoactive intestinal peptide, Substance P and platelet-activating factor when added to preparations at resting tone failed to induce a contraction. These agents did not relax histamine-contracted isolated human pulmonary muscle preparations. Anti-immunoglobulin E antibody sometimes contracted isolated human bronchial muscle but not pulmonary vascular preparations. However, these data were difficult to assess because of the variations observed. Anti-immunoglobulin G antibody was inactive. Noradrenaline did not elicit a physiological response in isolated bronchial muscle preparations at concentrations which always induced a contraction in the pulmonary vascular preparations. In the presence of propranolol, noradrenaline neither contracted nor relaxed isolated human bronchial preparations. We also determined the sensitivity of isolated bronchial muscle preparations to isoproterenol, salbutamol and theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗

[Bronchodilators].

Bronchodilating drugs can be divided into three main groups: beta-adrenergic stimulants including specific beta-2 receptor agonists (salbutamol, terbutaline, fenoterol) which are the agents of this group used in everyday practice, theophylline and its derivatives, and atropine-like drugs (ipratropium bromide). Bronchodilators act chiefly upon the spasm observed at the bronchial level in reversible obstructive phenomena (mainly asthma), their effect upon inflammation and hypersecretion being slight or controversial. Beta-stimulants have a relatively specific mode of action at the bronchial level in the setting of use in pneumology; they exhibit cardiac effects only at high doses and when used by oral or parenteral routes. Relative to isoprenaline, they also have the advantage of being active orally and over a longer period of time. They are given in maintenance treatment of asthma, by parenteral or oral routes or as aerosols. Main side effects of adrenergic beta-stimulants are tremor with oral administration, and tachycardia with very high doses by parenteral or oral routes; when given as aerosols these agents may fail to control severe attacks. The bronchodilating properties of theophylline have been known for a long time; late advances concerning this drug result from better knowledge of its pharmacokinetics. Recent studies have discriminated between serum levels correlated with therapeutic effectiveness and those accompanied with mild or severe side effects; in addition, it has been clearly shown that the half life of this alkaloid varies from one person to another and with various physiopathologic (age, dietary habits, liver failure, heart failure...) or pharmacologic (drug interactions with enzyme inductors or inhibitors...) factors; these recent advances have led to improved individual adjustment of theophylline dosage using serum concentration assays if needed. Theophylline is used in acute attacks and in maintenance therapy of asthma. Main side effects are digestive intolerance and, with toxic doses, neurologic disorders. Atropine-like drugs inhibit the effects of the parasympathetic reflex which results from stimulation of receptors by irritation of the respiratory tract, through the action of mediators. In this group, ipratropium is the only drug given in aerosols; this, together with its pharmacologic specificity, contributes to its tolerance. In some instances, the bronchodilating effect of ipratropium bromide is comparable to that of sympathomimetics.

Animals↗

Inhibition of rat mast cell degranulation by verapamil.

Calcium antagonists, e.g. verapamil, prevent exercise-induced asthma. This protective effect may proceed from inhibition of contraction of bronchial smooth muscle, release of mediators by primary effector cells, e.g. mast cells, or both. Therefore, we studied the inhibitory effect of increasing concentrations of verapamil on both in vitro antigen-induced degranulation and ionophore A23187-induced release of labelled serotonin by rat peritoneal mast cells. There was a dose-dependent inhibition by verapamil of both ovalbumin-induced degranulation of mast cells passively sensitized by incubation with mice IgE-rich serum and ionophore-induced release of tritiated serotonin by mast cells previously incubated with (3H)-5HT; the 50% inhibiting concentration was 1.4 X 10(-4) mol I-1 and 5.2 X 10(-5) mol I-1, respectively. An attractive explanation of our results is that verapamil inhibits the antigen-induced release of mediators by mast cells through its calcium antagonist effect. Our results also suggest that the preventing effect of calcium antagonists on asthma may be multi-factorial since other authors have clearly shown that these drugs inhibit contraction of guinea-pig tracheal smooth muscle in vitro.

Animals↗

Effects of five different organic calcium antagonists on guinea-pig isolated trachea.

The relaxant effects of five organic calcium antagonists (nicardipine, diltiazem, PY 108068, verapamil and bepridil) on guinea-pig isolated trachea were tested against contractions induced by acetylcholine, histamine, 5-hydroxytryptamine, potassium chloride (KCl) and tetraethylammonium (TEA) in a medium containing the normal amount of calcium and against calcium dose-response curves in a calcium-free, potassium-enriched medium. These effects were compared with those of spasmolytic or specific acetylcholine or histamine antagonists. In contrast to the other drugs tested, organic calcium antagonists exerted a specific inhibitory effect on KCl- and TEA-induced contractions. Their degree of activity was in the order: nicardipine greater than diltiazem greater than PY 108068 greater than verapamil greater than bepridil. All calcium antagonists inhibited calcium dose-response curves at similar concentrations. Organic calcium antagonists therefore seem to exert a specific inhibitory effect on depolarizing agents in the guinea-pig isolated trachea, unlike other tissues, notably some vascular smooth muscles.

Animals↗

Effects of a single bolus of urokinase in patients with life-threatening pulmonary emboli: a descriptive trial.

To evaluate hemodynamic, angiographic, and biological effects of a single bolus of urokinase, an open descriptive trial was conducted in a homogeneous group of 14 patients with acute life-threatening pulmonary emboli and without prior cardiopulmonary disease. For every patient the efficacy of the treatment was evaluated by comparing control and posttherapeutic values after the bolus injection of 15,000 IU/kg body weight urokinase (urinary source) administered in 10 min in the right atrium, followed by continuous intravenous full-dose heparin therapy. In two patients clinical status, hemodynamics, vascular obstruction, and biological (fibrinogen and plasminogen levels) parameters remained unchanged. One of these two patients died, making the mortality rate for the whole group 7%. Twelve of 14 patients showed rapid clinical improvement. Evaluation at 12 hr demonstrated significant decreases in pulmonary vascular obstruction (Miller index, 34%), total pulmonary vascular resistances (37%), and fibrinogen and plasminogen levels (41% and 40%, respectively), without any significant change in cardiac index. The hemodynamic sequential measurements performed (1,3, 6, and 12 hr) in seven of the 12 improved patients showed that the greatest percentage of the total hemodynamic improvement occurred within the first 3 hr after bolus administration of urokinase. No severe hemorrhagic complications were observed. Because of its rapid efficacy and its low cost, the bolus technique appeared particularly useful in the treatment of patients with acute life-threatening pulmonary emboli.

Aged↗

Effects of diltiazem and other Ca2+ antagonists on guinea-pig tracheal muscle.

The effects of diltiazem and 3 other Ca2+ antagonists (verapamil, nicardipine, bepridil) were studied on isolated guinea-pig tracheal preparations which were contracted with several agonists. Assessment of the contractile agonists was performed under physiological conditions as well as in Ca2+-depleted solutions. The order of potency of the contractile agonists was LTD4 greater than ACh greater than 5-HT greater than Hist greater than BaCl2 greater than TEA greater than KCl. The efficacy of the physiological agonists ACh, Hist and LTD4 was moderately depressed in Ca2+-free solutions while the responses to non-specific agonists and 5-HT were markedly reduced. Diltiazem and verapamil reduced basal tone at concentrations greater than or equal to 10(-4) M. Diltiazem displaced all agonist concentration-effect curves to the right. The four Ca2+ antagonists studied had a marked effect on non-physiological agonists as compared to that on physiological agents. Increasing Ca2+ concentration only partially reversed the inhibitory effect of diltiazem.

Airway Resistance↗

Effect of the Ca2+ antagonist nifedipine on the release of platelet-activating factor (PAF-acether), slow-reacting substance and beta-glucuronidase from human neutrophils.

Ca2+ antagonists such as nifedipine (Nif) inhibit processes that depend on extracellular Ca2+ in many muscular and secretory cells. The effect of Nif on mediator release and Ca2+ uptake by human polymorphonuclear neutrophils (PMN) has been investigated. Nif caused a concentration-dependent inhibition of the Ca2+ ionophore-induced release of platelet-activating factor (PAF-acether), slow-reacting substance (SRS) and to a lesser degree beta-glucuronidase (beta-glu). Nif inhibited the synthesis of PAF-acether rather than its release. Increasing Ca2+ concentration in the bathing medium from 1.3 to 2.8 mM completely reversed the effect of Nif on PAF-acether secretion. Nif at 1 and 5 microM reduced PMN45Ca2+ uptake induced by the Ca2+ ionophore A 23187. These results indicate that the inhibition by Nif of mediator release depends probably on the Ca2+-antagonistic property of the drug. A preliminary ex vivo study suggests that this inhibitory effect on neutrophil functions exists during therapeutic use.

Autacoids↗

Sodium cromoglycate, verapamil and nicardipine antagonism to leukotriene D4 bronchoconstriction.

1--The effects of nicardipine, verapamil and sodium cromoglycate (SCG) on the increase in pulmonary airway resistance(RAw) and decrease in pulmonary dynamic compliance (CDyn) induced by leukotriene D4 (LTD4) 0.5 micrograms kg-1 and acetylcholine (ACh) 3 micrograms kg-1 were investigated in anaesthetized guinea-pigs. The effects of these three agents on the contractile effects of LTD4 and ACh were tested on isolated tracheal preparations of the guinea-pig. 2--Nicardipine and verapamil (0.3 and 1 mg kg-1), as well as SCG (3 and 10 mg kg-1), partially but significantly inhibited the effects of LTD4 on RAw. Partial inhibition of the effect of LTD4 on CDyn was only observed with verapamil (0.3 and 1 mg kg-1). Nicardipine and verapamil had no effect on ACh-induced bronchoconstriction in vivo. 3--In concentrations higher than 10(-5) M, nicardipine and verapamil inhibited the contractile effects of LTD4 and ACh on guinea-pig isolated trachea. SCG had no effect on this preparation. 4--These results suggest that nicardipine, verapamil and SCG partially reduce the component of bronchoconstriction associated with stimulation of irritant receptors by LTD4. However, the site and mechanism of action of Ca2+-entry antagonists remain uncertain.

Airway Resistance↗