Biomedical subjects

G M Verleden

Publications and source records attributed to G M Verleden.

44 records · Page 3Linked to original sources

PubMed1994

5-HT modulates noncholinergic contraction in guinea pig airways in vitro by prejunctional 5-HT1-like receptor.

5-Hydroxytryptamine (5-HT) has been demonstrated to cause both constriction and relaxation of guinea pig airways, partly through direct action on airway smooth muscle and partly through postganglionic facilitation of cholinergic neurotransmission. We performed an in vitro study to investigate whether 5-HT can modulate the noncholinergic contraction in guinea pig airways due to release of neuropeptides from airway sensory nerves. In the presence of atropine (1 microM), ketanserin (10 microM), and indomethacin (10 microM), 5-HT (0.1-100 microM) produced concentration-dependent inhibition of electrical field stimulation-induced noncholinergic contraction with maximal inhibition of approximately 72 +/- 4%. Tropisetron (ICS-205-930, 1 microM), a 5-HT3 and 5-HT4 receptor antagonist, was unable to prevent the inhibition produced by 5-HT. Methiothepin (1-100 nM), a 5-HT1 and 5-HT2 receptor antagonist, produced a concentration-dependent inhibition of the effect of 5-HT (1 microM) with a 50% inhibition concentration value of 66 nM. 5-HT (100 microM) had no effect on the cumulative concentration-response relationship to exogenous substance P (10 nM-10 microM). The concentration of agonist causing 35% inhibition of the noncholinergic contraction (EC35) was calculated, and a rank order of potency was established: 5-carboxamidotryptamine (EC35 = 0.24 microM) > 5-HT (EC35 = 0.77 microM) > 8-hydroxy-2-(dipropylamino)tetralin (EC35 = 8.1 microM) > sumatriptan (EC35 = 18 microM). We conclude that 5-HT concentration dependently modulates noncholinergic contraction in guinea pig airways in vitro by a prejunctional mechanism. This effect is probably mediated through a 5-HT1-like receptor; however, the exact subtype remains to be elucidated.

Animals↗

PubMed1994

Furosemide and bumetanide, but not nedocromil sodium, modulate nonadrenergic relaxation in guinea pig trachea in vitro.

Furosemide has recently been shown to be effective in inhibiting various indirect challenges in asthmatic patients, but its mode of action is not yet clear. There is some evidence that furosemide has an inhibitory effect on sensory and cholinergic nerves in the airways. We have investigated the effects of furosemide, bumetanide, and nedocromil sodium on inhibitory nonadrenergic, noncholinergic (iNANC) responses in guinea pig trachea in vitro using electrical field stimulation (50 V, 0.5 ms, 2 to 32 Hz for 30 s) and exogenously applied vasoactive intestinal peptide (VIP) or nitroprusside. In the presence of atropine (1 microM), indomethacin (10 microM), and propranolol (1 microM), both furosemide and bumetanide but not nedocromil sodium produced a concentration-dependent inhibition of the iNANC response (maximum inhibition, 31.2 +/- 5.6% with 100 microM furosemide at 16 Hz and 44.2 +/- 4.1% with 10 microM bumetanide at 4 Hz). Furthermore, after pretreatment of the tissues with L-NG-monomethyl arginine (90 microM), alpha-chymotrypsin (2 U/ml), or both, furosemide and bumetanide produced a further inhibition of the iNANC relaxation. Neither loop diuretic had any effect on the concentration-response curves to exogenous VIP (10(-9) to 10(-7) M) or nitroprusside (10(-8) to 10(-6) M). These results indicate that loop diuretics may inhibit nonadrenergic relaxation in guinea pig trachea in vitro by a prejunctional mechanism, probably through inhibition of nerve activation, the exact mechanism of which is still undefined.

Animals↗

PubMed1993

Beta 2-adrenoceptor agonists inhibit NANC neural bronchoconstrictor responses in vitro.

Nonadrenergic noncholinergic (NANC) contractile responses in guinea pig bronchi are due to the release of tachykinins from airway sensory nerves. The purpose of this study was to determine whether beta 2-receptor agonists modulate NANC contractions in guinea pig bronchi in vitro. Bronchial rings were suspended in organ baths for isometric measurement of tension, and comparable contractions were induced by electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) or by exogenous substance P (3 microM). Aformoterol and salbutamol produced concentration-dependent inhibition of the NANC contraction, with aformoterol being ninefold more potent than salbutamol; approximate 50% inhibitory concentrations for aformoterol and salbutamol were 1.03 nM (n = 6) and 9.3 nM (n = 6), respectively. Aformoterol also inhibited the contraction induced by exogenous substance P but to a far lesser extent than its inhibition of EFS-induced responses. The inhibitory effects of formoterol (10 nM) on responses to EFS at 8 Hz were significantly prevented by propranolol (1 microM) and ICI 118551 (a beta 2-antagonist, 0.1 microM) but not by atenolol (a beta 1-antagonist, 1 microM) or phentolamine (10 microM). These experiments demonstrate that beta 2-agonists may modulate the release of tachykinins from airway sensory nerves by prejunctional receptors.

Adrenergic beta-Agonists↗

PubMed1992

Inhibition of cholinergic neurotransmission in human airways by opioids.

Opioids reduce the cholinergic responses to electrical field stimulation (EFS) in guinea pig and canine airways by a prejunctional effect. We determined whether a similar effect operates in human airways in vitro. [D-Ala2-NMePhe4-Gly-ol5]enkephalin (DAMGO) (10(-8)-10(-6) M), a selective mu-opioid receptor agonist, inhibited the response to EFS in a dose- and frequency-dependent manner. DAMGO (10(-6) M) produced 86% inhibition at 0.5 Hz and 38% inhibition at 4 Hz, but at 32 Hz there was no significant inhibition. Another selective mu-opioid receptor agonist H-Tyr-D-Arg-Gly-Phe(4-NO2)-Pro-NH2 diacetate (BW 443C) also inhibited responses to EFS, producing 57.7% inhibition at 4 Hz at a concentration of 10(-6) M. The inhibitory effect on EFS was blocked by the opioid receptor antagonist naloxone (10(-5) M), indicating that opioid receptors are involved. DAMGO (10(-6) M) had no effect on the contractile response to exogenous acetylcholine, indicating a prejunctional effect. We conclude that mu-opioid agonists inhibit cholinergic neurotransmission in human airways in vitro, and this could have therapeutic potential in the treatment of airway disease.

Adolescent↗

PubMed1992

Inhibitory NANC nerves in human tracheal smooth muscle: a quest for the neurotransmitter.

Inhibitory nonadrenergic noncholinergic (i-NANC) nerves are the only neural bronchodilator pathway in human airways. Possible candidates for the neurotransmitter include vasoactive intestinal peptide (VIP) and nitric oxide (NO) and purines such as ATP. We have investigated the potential role of these neurotransmitters. Phosphoramidon (10(-5) M) significantly potentiated relaxations to low doses of VIP with no effect on i-NANC responses. Relaxations induced by VIp were abolished with alpha-chymotrypsin (2 U/ml), but i-NANC responses were unaffected. Reactive blue 2 had no effect on i-NANC neural responses, indicating that endogenous ATP was not involved. The NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 10(-4) M) produced a concentration-dependent inhibition of the i-NANC response, producing almost complete inhibition at every frequency studied (0.5-40 Hz), whereas L-NG-monomethyl arginine was effective only at low stimulation frequencies. The inhibitory effect of L-NAME was partially reversed by L- but not D-arginine, and D-NAME was without effect. These results suggest that in human tracheal segments the neural bronchodilator response is mediated by NO, and there is no functional evidence for implicating VIP in this response.

Adenosine Triphosphate↗

PubMed1991

Nedocromil sodium modulates nonadrenergic, noncholinergic bronchoconstrictor nerves in guinea pig airways in vitro.

Nonadrenergic, noncholinergic (NANC) neural bronchoconstrictor responses in guinea pig airways are due to the release of tachykinins from sensory nerves. We have performed an in vitro study using electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) in guinea pig bronchi to investigate the effect of nedocromil sodium (NS) on NANC bronchoconstrictor responses. NS inhibited NANC bronchoconstriction in bronchi in a concentration-dependent manner, with a maximum inhibition of 40 +/- 4% (p less than 0.001, n = 6) at 100 microM. Cromolyn sodium, however, produced only 9 +/- 8% inhibition at the same molar concentration (p less than 0.05). NS did not affect the contractile response to substance P, nor did it modulate the cholinergic bronchoconstrictor response to EFS in tracheal smooth muscle. These results indicate that NS may modulate the release of tachykinins from airway sensory nerves.

Animals↗

PubMedDate not supplied

Modification of the arterial anastomotic technique improves survival in porcine single lung transplant model.

BACKGROUND: Lung transplantation is a valuable therapeutic option for selected patients with end-stage pulmonary disease. However, this treatment is complicated by ischaemia-reperfusion injury (IRI) of the lung in 10-20% of the recipients. We developed an unilateral porcine lung transplant model to study IRI and describe our experience with two different arterial anastomotic techniques. MATERIAL & METHODS: Twenty four domestic pigs [n = 6 x (donor + recipient)/group] were used in this study. Donor lungs were harvested using an antegrade flush with cold Perfadex and stored in the same solution for +/- 8 hours. Recipient animals underwent a left thoracotomy. After native pneumonectomy, the left donor lung was transplanted in the following order: 1. left atrial cuff; 2. bronchus; 3 pulmonary artery. 2 The outcome in recipients from historical groups differing in anastomotic technique was compared. An end-to-end anastomosis on the left pulmonary artery was performed in group I versus a patch anastomosis on the main pulmonary artery in group II. One hour after reperfusion, the right pulmonary artery and main bronchus were ligated forcing the recipient to survive on the transplanted lung only. The animals were further observed for 6 hours. RESULTS: Survival 6 hours after exclusion of the right lung was 33% (2/6) in group I versus 83% (5/6) in group II. Animals in group I died of right heart failure manifested by acute dilation of the right ventricle following ligation of the hilum of the right lung. CONCLUSION: Single lung transplantation with exclusion of the contralateral native lung is a critical model. Arterial end-to-end anastomosis resulted in an increased right ventricular afterload. The use of a patch technique improved the compliance of the arterial anastomosis and decreased early mortality. This transplant model is currently used in our laboratory to assess new methods for pulmonary preservation.

Anastomosis, Surgical↗

PubMedDate not supplied

Lung volume reduction surgery (LVRS) for emphysema: initial experience at the University Hospital Gasthuisberg. Leuven LVRS Group.

Emphysema is a disabling disease, for which there is no curative therapy available today. Lung transplantation offers a valuable option for a very selected number of patients, however, due to the enormous organ shortage, only few patients can be offered such a therapy. Recently there has been important resurgence of interest in lung volume reduction surgery and as a consequence, we have embarked in such a program since may 1997. We have now performed unilateral lung volume reduction surgery in 29 emphysema patients (25 on the right and 4 on the left side). Twenty-four patients were already discharged home. There has been no perioperative mortality. The mean hospital stay was 19.8 +/- 11.4 days (range, 8-47 d). Twenty patients of whom we already have follow-up data during 6 months (m) form the further basis of this report. Six weeks after the procedure the FEV1 increased from 0.82 +/- 0.28 L (28 +/- 8%) to 1.05 +/- 0.39 L, a mean increase of 28%. There was a further increase of the FEV1 to a maximum of 1.06 +/- 0.42 L at 6 m, a mean maximum increase of 29% (p = 0.0046, ANOVA). Similarly, the FVC increased from 2.80 +/- 1.10 L to 3.15 +/- 1.00 L, a mean increase of 12.5%. A further increase was also obtained at 6 m and was 19.6% (3.35 +/- 1.05 L, p = 0.014, ANOVA). The maximum decrease in RV was obtained at 3 m (from 5.91 +/- 1.37 L to 4.37 +/- 0.85 L (p = 0.0001, ANOVA), a mean decrease of 26%. The maximum TLC decrease was demonstrated at 3 m (from 8.71 +/- 1.71 L to 7.60 +/- 1.56 L (p = 0.002, ANOVA), a mean decrease of 12.8%. Afterwards there was again a gradual raise of the TLC. The six minute walking distance increased from 231 +/- 31 m to 272 +/- 34 m (p = NS) after pulmonary rehabilitation and to 416 +/- 77 m at 3 m and 415 +/- 18 m at 6 m (p = 0.0002, ANOVA) after the operation. The quality of life (measured with a standardized questionnaire, the Nottingham Health Profile) improved significantly in several domains (e.g. mobility, pain, energy, emotions and social) at 3 m postoperatively. There was one late death (at 6 m) due to an unknown cause. The actuarial survival rate was therefore 100% at 3 m and 95% at 12 m. In conclusion, unilateral thoracoscopic lung volume reduction surgery is a new and safe treatment modality for patients suffering from severe end-stage emphysema. The objective and subjective improvement is marked and the mortality is very low. Rigid selection criteria are, however, necessary to be able to guarantee an optimal result.

Actuarial Analysis↗