Influence of alveolar hypoxia on pulmonary vasomotor responses to almitrine in the dog.
Almitrine bismesylate (5-10 micrograms/kg) was given as an intravenous bolus to anaesthetized, paralysed dogs with closed-chest (n = 5) and with open-chest (n = 7) in whom the retrocardiac lobe was separately ventilated. Pulmonary, lobar and systemic haemodynamics were measured under hypoxic, normoxic and hyperoxic conditions. Total pulmonary blood flow was measured by thermodilution and lobar flow by electromagnetic flow meter. In the closed-chest preparations, almitrine caused an increase in pulmonary vascular resistance (PVR) at all levels of inspired oxygen, the increments being 82% (30% O2), 91% (air) and 9% (13% O2). The control PVR varied inversely with arterial PO2 but there was no significant interaction between the almitrine and hypoxia induced vasoconstriction with multiple linear regression analysis. In the open-chest preparations, PVR and lobar vascular resistance (LVR) increased after almitrine by 48% and 41% respectively when both lung and lobe inspired 30% O2. When the lobe was switched to 12.5% O2 or nitrogen (lung inspiring 30%) PVR again increased (+52%) after almitrine but LVR decreased in five of seven lobes (lobar flow increasing despite constant cardiac output), the overall change being -4%. Analysis of covariance showed that the lobar response to almitrine was significantly different under hypoxic conditions compared with hyperoxic (P less than 0.05). With ventilation maintained constant, there was no significant change in arterial PO2 after almitrine in any experimental condition. In conclusion, almitrine is generally a pulmonary vasoconstrictor but can dilate vessels when they are constricted by local hypoxia. Almitrine does not enhance local hypoxic vasoconstriction in the dog.
J M
JM
Hughes
D J
DJ
Allison
A
A
Goatcher
A
A
Tripathi
D015765:Almitrine; D000818:Animals; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000503:physiopathology; D011659:Pulmonary Gas Exchange; D014655:Vascular Resistance; D014666:Vasomotor System / Q000187:drug effects* / Q000503:physiopathology
D010879:Piperazines; D015765:Almitrine