Journal of Applied Physiology, Vol 69, Issue 4 1330-1335, Copyright © 1990 by American Physiological Society
Almitrine mimics hypoxia in fetal sheep with lateral pontine lesions
B. M. Johnston, P. J. Moore, L. Bennet, M. A. Hanson and P. D. Gluckman
Department of Paediatrics, School of Medicine, University of Auckland, New Zealand.
Almitrine bimesylate is a potent and long-lasting respiratory stimulant in
adult species. It acts by stimulating the peripheral chemoreceptors, where
it has been shown to accumulate specifically, although its exact mechanism
of action is uncertain. In the fetal lamb, however, it produces a profound
inhibition of breathing even after denervation of the peripheral
chemoreceptors. In this respect its action is similar to hypoxia. To
investigate whether almitrine is hypoxia mimetic, we examined the effect of
almitrine in nine fetal lambs of 120-130 days gestation. Five had lesions
in the lateral pons that changed the fetal depressive response to hypoxia
to one of stimulation. In the remaining four fetuses, the lesions did not
bilaterally encompass the appropriate area of the pons; thus they still
showed the normal fetal depressive response to hypoxia and so acted as
controls. Almitrine (10 mg iv) caused a pronounced stimulation of breathing
that lasted 406 +/- 26 min in all five fetuses with lesions that caused a
stimulatory response to hypoxia. However, in the remaining four fetuses, in
which the response to hypoxia was inhibitory, almitrine caused an
inhibition of breathing that lasted 184 +/- 28 min. We conclude that the
action of almitrine is like that of hypoxia and that, because it acts
specifically on the chemoreceptors, it may prove to be a useful tool in the
study of possible central chemoreceptor mechanisms.
