Improvement in Ventilation-Perfusion Matching by Almitrine in COPD

Mélot, Christian; Naeije, Robert; Rothschild, Thomas; Mertens, P.; Mols, Pierre; Hallemans, Roger

doi:10.1378/chest.83.3.528

Cited by 101 publications

(32 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the con trary, Préfaut [11], Sergysels et al [14], Simonneau et al [5] did not observe any significant ventilatory modifications in hypercapnic COPD patients. Rigaud et al [4], Castaing et al [3] and Melot et al [6] observed a redistribution of lung perfu sion with ABM which was not observed by Nunn et al [2], Several factors can explain these discrepancies. In order to assess the role of ABM plasma level we examined different doses of ABM in normocapnie COPD patients.…”

Section: Discussionmentioning

confidence: 99%

“…Some authors [1,2] have reported ventilatory effects which they have linked mainly to modifications of alveolar ventilation. More often, others [3][4][5][6][7] have related the observed modifica tions of the VA/Q ratios to an effect on pulmonary perfusion. ABM may have a double action on ventilation and perfu sion and the different authors' findings may be the result of different methods: '1 15 58 61 172 30 100 62 C O PD +E M P 16 75 88 175 50 80 48 COPD 17 75 76 165 60 73 40 COPD 18 77 41 162 35 80 25 COPD 19 63 78 173 40 112 32 C O PD +E M P 20 79 57 168 30 105 1 21 66 61 156 40 72 60 COPD 22 78 66 166 40 119 42 COPD + Asthma 23 61 50 150 15 139 30 COPD 24 48 77 170 30 100 46 COPD 25 63 52 153 40 114 59 COPD 26 75 61 163 50 84 ABM pla sm a levels, ng/ml pulmonary diseases of variable degree (normocapnic and/or hypercapnic pa tients) different follow-up durations, dif ferent doses without control of blood ABM level.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Is the Mode of Action of Almitrine Bismesylate Dose Dependent?

Merre¹,

Ansquer

Clark

et al. 1989

Respiration

View full text Add to dashboard Cite

In order to assess whether different doses and/or plasma levels of almitrine bismesylate (ABM) could induce preferential effects on ventilation or on lung perfusion, we performed a single-blind placebo-controlled study of ABM treatment with different dosages (0.75, 1.5 and 2.25 mg • kg^-1 single oral dose) in 26 patients suffering from chronic obstructive pulmonary disease (COPD). All measurements were performed according to the same time table. At control and at three 1.5-hour intervals, we measured alveolar-arterial (A-a) differences, alveolar dead space, total ventilation and ABM plasma levels. The effect on ventilation was estimated using changes in ventilatory parameters and (A-a)O₂ differences. The effect on perfusion was indirectly estimated by analysis of arterial-end-tidal (a-ET)CO₂ difference and alveolar dead space. The response to treatment was significant for the 1.5- and the 2.25-mg • kg^-1 ABM groups, but not for the 0.75 mg • kg^-1 ABM and the placebo group. A ventilatory response was often present in both 1.5- and 2.25-mg kg^-1 ABM groups, but a nonventilatory effect was present only at the highest dose according to the Severinghaus and Stupfel concept. Only the parameters reflecting an effect of the distribution of perfusion (a-ET)CO₂ difference and alveolar dead space were significantly correlated with ABM plasma levels. The results suggest that a dose-dependent effect of ABM on lung perfusion may explain the controversial data in the literature about the mode of action of ABM.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Is the Mode of Action of Almitrine Bismesylate Dose Dependent?

Merre¹,

Ansquer

Clark

et al. 1989

Respiration

View full text Add to dashboard Cite

show abstract

“…The intensity of HPV varies between individuals and can diminish with disease or medication (Table 1). [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] For example, calcium channel blockers, Suppression of HPV is a common adaptation to life at high altitude. The yak (Bos grunniens), native to the Himalayan region of Central Asia (altitudes > 3,500 m) has blunted HPV and thus maintains low PAP.…”

Section: Clinical Relevance Of Hpvmentioning

confidence: 99%

Hypoxic Pulmonary Vasoconstriction

Dunham‐Snary

Sykes

et al. 2017

Chest

336

144

View full text Add to dashboard Cite

Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation/perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in pulmonary artery smooth muscle cells (PASMC). This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction. Sustained hypoxia activates rho kinase, reinforcing vasoconstriction, and hypoxia-inducible factor (HIF)-1a, leading to adverse pulmonary vascular remodeling and pulmonary hypertension (PH). In the nonventilated fetal lung, HPV diverts blood to the systemic vasculature. After birth, HPV commonly occurs as a localized homeostatic response to focal pneumonia or atelectasis, which optimizes systemic PO 2 without altering pulmonary artery pressure (PAP). In single-lung anesthesia, HPV reduces blood flow to the

show abstract

“…In these circumstances, constricting the shunting vascular bed whilst simultaneously vasodilating well-ventilated areas would be therapeutically attractive [86][87][88]. Almitrine, a peripheral chemoreceptor agonist, improves V9/Q9 matching in patients with chronic obstructive pulmonary disease, presumably through an enhancement of HPV [89]. Recently, almitrine has been shown to improve gas exchange in patients with ARDS without decreasing cardiac output, despite increasing [91].…”

Section: Almitrene Bismesylatementioning

confidence: 99%

Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome

Moloney

Evans²

2003

Eur Respir J

112

View full text Add to dashboard Cite

Pulmonary hypertension (PH) is a characteristic feature of the acute respiratory distress syndrome (ARDS). The magnitude of PH has been shown to correlate with the severity of lung injury in patients with ARDS independently of the severity of associated hypoxaemia and has an adverse prognostic significance.Early in the histopathological evolution of ARDS, pulmonary vasoconstriction, thromboembolism and interstitial oedema contribute to the development of PH, although pulmonary vascular remodelling probably occurs eventually. Intravenous vasodilator agents lead to an increase in intrapulmonary shunting and systemic hypotension, which can limit their therapeutic use, and have not been shown to improve survival. By contrast, rapidly metabolised vasodilators administered by inhalation induce selective pulmonary vasodilatation and decrease shunting, but again do not appear to confer a survival benefit.Research aimed at further understanding the mechanisms that underlie pulmonary hypertension, a characteristic feature of the acute respiratory distress syndrome, are expected to provide improvements in pharmacological interventions for the treatment of pulmonary hypertension in the acute respiratory distress syndrome.

show abstract

Improvement in Ventilation-Perfusion Matching by Almitrine in COPD

Cited by 101 publications

References 17 publications

Is the Mode of Action of Almitrine Bismesylate Dose Dependent?

Is the Mode of Action of Almitrine Bismesylate Dose Dependent?

Hypoxic Pulmonary Vasoconstriction

Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome

Contact Info

Product

Resources

About