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.

Effect of oxygen tension on NMR spin-lattice relaxation rate of blood in vivo.

Spin-lattice relaxation rate (1/T1) was measured in the left (LV) and right (RV) ventricular cavities in four conscious normal humans and four anesthetized greyhound dogs breathing spontaneously. Inspired oxygen concentration (FIO2) was varied in five steps from 21 to 100%. In dogs, blood was sampled from indwelling catheters in the pulmonary artery and aorta for measurement of PO2. Saturation-recovery and inversion-recovery tomographic images of the ventricular cavities were obtained supine during quiet breathing using a whole-body NMR scanner operating at a static magnetic field strength of 0.15 Tesla. From FIO2 21 to 100%, 1/T1 of LV increased by 11.6% in humans and 9.6% in dogs. In dogs, 1/T1 increased by 2.8% per 100 mm Hg increase in aortic PO2 (r greater than 0.87). There was no correlation in dogs between 1/T1 in RV and pulmonary artery PO2. The LV/RV 1/T1 ratio in dogs increased by 4% per 100 mm Hg increase in the LV-RV PO2 difference, and by 8% in humans as FIO2 increased from 21 to 100%. A rise in dissolved oxygen concentration increases NMR spin-lattice relaxation rates of blood in vivo to a small but significant extent.

Action of almitrine bismesylate on pulmonary vasculature in the dog: preliminary report.

The effects of almitrine bismesylate on the pulmonary circulation have been investigated in anaesthetized dogs, paralysed and artificially ventilated. An i.v. bolus of almitrine bismesylate (10 micrograms X Kg-1) caused a 35% increase in specific pulmonary vascular resistance under normoxic or hyperoxic conditions but only a 2% increase when pulmonary vessels were constricted by hypoxia (13% inspired O2). With local hypoxia, confined to the retrocardiac lobe, almitrine bismesylate caused lobar vasodilation (specific vascular conductance increased by 10%) while at the same time conductance fell by 38% in the rest of the lung which was hyperoxic. The almitrine-induced vasoconstriction was not abolished by alpha- or beta blockade, indomethacin, vagotomy or bilateral clamping of both common carotids in the neck. With constant ventilation, no rise of arterial PO2 occurred following almitrine bismesylate . In the presence of local hypoxia, the drug by virtue of its inhibition of local hypoxic vasoconstriction caused PaO2 to fall slightly. In conclusion, almitrine bismesylate constricts pulmonary vessels in normoxia and dilates them when they are constricted by hypoxia. The mechanism is unknown but it is likely to be an intra-rather than an extrapulmonary site of action.