The Pulmonary Haemodynamic Effects of Almitrine Infusion in Men with Chronic Hypercapnia

Dull, William L.; Polu, J. M.; Sadoul, P

doi:10.1042/cs0640025

Cited by 21 publications

(5 citation statements)

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“…One small trial, however, did show rises 1131. Tests with almitrine given acutely led only to transient increases in Ppa [14]. In this connection, the dilator effect, observed by several groups as well as ourselves, must be born in mind [2-41; this might counteract any tendency to a rise in Ppa caused by its vasoconstrictor action.…”

Section: Discussionmentioning

confidence: 95%

Interactions between hypoxic and almitrine-induced vasoconstriction in the rat lung

et al. 1992

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1. To test whether almitrine might improve the arterial partial pressure of O2 in patients with chronic obstructive airways disease by improvement of ventilation-perfusion matching, we looked at the interaction between hypoxic and almitrine-induced vasoconstriction in isolated rat lungs perfused with blood at constant flow. Increases in pressure represented increases in resistance. 2. Almitrine, given in increasing doses between challenges with 2% O2, enhanced hypoxic vasoconstriction at low doses but attenuated it at high doses. 3. Stimulus-response curves to hypoxia of increasing severity gave a sigmoid curve. 4. Almitrine solvent caused small changes in pulmonary artery pressure and shifted the stimulus-response curve slightly in a parallel fashion. 5. Small doses of almitrine enhanced the action of mild to moderate hypoxia, medium doses attenuated moderately severe hypoxia, whereas high doses depressed vasoconstriction due to all degrees of hypoxia. 6. These effects of almitrine on hypoxic vasoconstriction were compared with the effect of solvent by analysis of variance; the results substantiated significant enhancement of hypoxia by small doses and attenuation by large doses. 7. In patients, if similar effects apply, small doses of almitrine would assist ventilation-perfusion matching, but large doses might worsen it. 8. Almitrine-induced vasoconstriction was attenuated by a fall in perfusate temperature in a similar manner to hypoxic vasoconstriction. It was also attenuated by three drugs, chlorpheniramine, propanolol and diethylcarbamazine, all of which also decrease hypoxic vasoconstriction. The similarity between hypoxic and almitrine-induced pulmonary vasoconstriction is further confirmed.

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Section: Discussionmentioning

confidence: 95%

Interactions between hypoxic and almitrine-induced vasoconstriction in the rat lung

et al. 1992

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“…An acute rise of PAP and pulmonary vascular resistance has been observed after intravenous infusion of almitrine [5][6][7] and was generally attributed to an enhancement of hypoxic vasoconstriction by the drug. When almitrine was given orally the short-term results were contradictory and varied from no increase in PAP [11] to a slight but significant increase [8] and to a marked increase [9).…”

Section: Discuss Loomentioning

confidence: 99%

“…However, there is still some uncertainty about the pulmonary haemodynamic effects of almitrine, since an acute increase of pulmonary artery mean pressure (PAP) has been observed in short-term studies after either intravenous infusion of almitrine [5][6][7] or oral intake of the drug [8,9), but these results were not confirmed by other studies [10,11). One to six month's treatment with oral almitrine has been shown to increase PAP (9) or was not associated with any change in pulmonary haemodynamics [12][13][14].…”

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confidence: 99%

One year treatment with almitrine improves hypoxaemia but does not increase pulmonary artery pressure in COPD patients

Weitzenblum¹,

Schrijen²,

Apprill³

et al. 1991

Eur Respir J

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Almitrine bismesylate, a chemoreceptor agonist, improves hypoxaemia in a high percentage of chronic obstructive pulmonary disease (COPD) patients and its long-term use may thus be of interest in these patients. The course of pulmonary haemodynamics during a one year treatment was investigated in severe COPD patients (forced expiratory volume in one second FEV1 = 1,040 +/- 80 SEM ml) with persistent hypoxaemia (initial arterial oxygen tension (PaO2) in the range 6.6-8.6 kPa (50-65 mmHg]. Patients were given either almitrine (A, n = 27), 100 mg.day-1, during two consecutive months per quarter followed by a one month wash-out period (intermittent "schedule"), or placebo (P, n = 18) with the same schedule. Eleven patients in group A and 8 in group P could not complete the one year study because of lack of compliance, worsening of respiratory insufficiency, or for other reasons. In the remaining patients, PaO2 significantly increased in group A (n = 16) from 7.6 +/- 0.1 to 8.3 +/- 0.2 kPa (56.9 +/- 1.0 to 62.7 +/- 1.7 mmHg) (p less than 0.001) but not in group P (n = 10) from 7.5 +/- 0.3 to 7.9 +/- 0.3 kPa (56.1 +/- 2.3 to 59.1 +/- 2.1 mmHg). PaCO2 did not significantly change in either group. Pulmonary artery mean pressure (PAP) was stable in both groups: from 26.8 +/- 2.1 to 25.4 +/- 1.9 mmHg in group A, and from 20.6 +/- 1.1 to 20.9 +/- 1.5 mmHg in group P.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…It would be difficult to detect, because tests cannot be made under the controlled conditions available in animals. Nevertheless the rise in PPA which it has caused in COAD is often ill-sustained despite continued intravenous infusion (Dull et al 1983).…”

Section: Action Of Almitrine On Lung Vessels In Hypoventilated Lungmentioning

confidence: 99%

Action of Almitrine Bismesylate on Ventilation‐perfusion Matching in Cats and Dogs With Part of the Lung Hypoventilated

Wach

Gill

Suggett

et al. 1986

Clin Exp Pharma Physio

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Ventilation to one lobe of lung was reduced in anaesthetized open-chest cats and dogs to simulate the ventilation/perfusion (V/Q) mismatching of chronic lung disease. Blood flow to this lobe fell less than ventilation; thus lobar V/Q diminished. In seven cats almitrine (0.5 mg/kg + 10 micrograms/kg per min, i.v.) caused a rise in pulmonary artery pressure (PPA), increased flow through the hypoventilated lobe in six out of seven cats and both increased or decreased lobar vascular resistance (PVR); the lobar V/Q ratio therefore fell. Arterial and lobar venous oxygen tension (PO2) fell. In five dogs almitrine caused a rise in PPA and PVR but lobar flow changes were variable. Arterial and lobar venous PO2 fell. With fixed ventilation, almitrine failed to improve V/Q matching; there was no improvement in gas exchange in the hypoventilated lobe. In eight dogs the hypoventilated lobe was perfused at constant flow with right atrial blood (i.e. while V/Q was held constant). Almitrine caused a rise in perfusion pressure, vasoconstriction, followed, in five out of eight dogs, by vasodilatation. In six similar cat preparations, vasoconstriction but not vasodilatation was clearly shown. In two cats dilatation after almitrine was demonstrated during ventilation with Nitrogen. In all experiments there was no significant effect of the solvent. Thus the dual action of almitrine seen in other species was seen in a proportion of cats and dogs. Results do not support the view that improved arterial gas tensions in patients after almitrine are attributable to diversion of blood flow away from hypoxic lung. Alternative mechanisms are discussed.

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The Pulmonary Haemodynamic Effects of Almitrine Infusion in Men with Chronic Hypercapnia

Cited by 21 publications

References 0 publications

Interactions between hypoxic and almitrine-induced vasoconstriction in the rat lung

Interactions between hypoxic and almitrine-induced vasoconstriction in the rat lung

One year treatment with almitrine improves hypoxaemia but does not increase pulmonary artery pressure in COPD patients

Action of Almitrine Bismesylate on Ventilation‐perfusion Matching in Cats and Dogs With Part of the Lung Hypoventilated

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