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Biomedical subjects

F Coceani

Publications and source records attributed to F Coceani.

144 records · Page 8Linked to original sources

Lamb ductus arteriosus: effect of prostaglandin synthesis inhibitors on the muscle tone and the response to prostaglandin E2.

The prostaglandin synthesis inhibitors, indomethacin and eicosa-5,8,11, 14-tetraynoic acid (ETA), have been tested on the isolated lamb ductus arteriosus at low and high PO2 levels. Both compounds produced a gradual contraction of the hypoxic vessel, and at equal doses the effect of indomethacin was stronger. The maximal tension output of the hypoxic tissue under indomethacin was equal to that of the oxygen-contracted control. ETA- and indomethacin-treated preparations contracted further upon transfer from a low to a high oxygen environment, and the response under indomethacin exceeded a significantly control values. Control preparations were relaxed markedly by PGE2 in low oxygen but showed little or no response in high oxygen. In contrast, preparations pretreated with the inhibitors retained their sensitivity to PGE2 during exposure to high oxygen. The data are consistent with the idea that E-type prostaglandins play a role in the regulation of the intrinsic tone of the ductus arteriosus during foetal life. It is also suggested that the sensitivity of ductal muscle to E-type prostaglandins is controlled by the rate of endogenous prostaglandin formation.

Animals↗

Responses of spinal neurons to iontophoretically applied prostaglandin E1 in the frog.

Prostaglandin E1 (PGE1) has been tested by microiontophoresis on interneurons and motoneurons in the isolated spinal cord of the frog. PGE1 action was almost exclusively excitatory, regardless of the cell type and the test condition used. In general, the excitatory response had rapid onset and termination, and was susceptible to tachyphylaxis. Responsive interneurons were scattered throughout the tissue, and the incidence of responses showed no obvious relation to the mono- vs. polysynaptic connection of cells to primary afferents and descending fibers of the lateral funiculus. PGE1-sensitive interneurons were encountered more often in preparations from summer than from winter animals. These findings, coupled with the demonstration of prostaglandin biosynthesis and catabolism in the tissue, suggest that PGE1 plays a role in the normal function of spinal neurons. The intimate mechanism of PGE1 action remains to be elucidated.

Animals↗

Cardiopulmonary bypass in ewe's fetus: advances and setbacks in our learning curve.

Fetal cardiac surgery represents a surgical challenge and several centers are attempting to establish a suitable methodology in animals. We present our experience with extra-corporeal bypass procedures in preterm and term sheep fetuses. Twenty-two fetuses (103-139 days gestation, mean 115 days gestation) underwent a 1-hour period of right heart-to-pulmonary artery extracorporeal circulation followed by 1 hour of observation. Animals were divided into group 1 and group 2, according to gestational age (above and below 0.85). Three pumps were used: centrifugal without (group 1) reservoir, centrifugal with (group 2) reservoir, and roller with reservoir (group 2). Experiments were completed in 75% of fetuses in group 1 and in 37% of fetuses in group 2. Bleeding was the main cause of failure, especially for group 2. A slow deterioration of blood gas status was noted in group 1, while this trend could be partially reversed in group 2 with corrective measures. Complete heart bypass could not be achieved in either group, and residual fluctuations in arterial pressure were observed. During bypass, body temperature decreased more in group 2 than in group 1. We conclude that cardiac bypass is feasible over a short period in near-term fetuses. A successful outcome may also be obtained in younger fetuses, but better measures need to be implemented for the prevention of surgical bleeding.

Animals↗

Prostaglandin E2 and fever: a continuing debate.

Prostaglandin (PG) E2 is a potent hyperthermic agent and has been assigned an intermediary function in the response of thermoregulatory neurons to pyrogens. Though attractive, this idea has been challenged on several grounds. The present study confirms that brain PGE2 synthesis increases during fever, the time course of the elevation according with a causative role of the compound. Our experimental data also argue against the involvement of a second cyclooxygenase product, specifically thromboxane (TX) A2, in the action of pyrogens. The sequence of events leading to PGE2 production and fever differs depending on the pyrogen, bacterial vs. leucocytic, and its route of administration. Blood-borne interleukin-1 (IL-1) acts on a discrete site in the central nervous system (CNS) which is tentatively identified with the organum vasculosum laminae terminalis (OVLT). The same site may also be the target for blood-borne endotoxin. In addition, endotoxin may promote PGE2 synthesis in the cerebral microvasculature. Both pyrogens, on the other hand, act diffusely throughout the CNS when given intrathecally. We conclude that PGE2 is well suited for an intermediary role in the genesis of fever and ascribe the reported inconsistencies to methodological factors.

Animals↗

ATP-gated potassium channel activity of pulmonary resistance vessels in the lamb.

There are conflicting reports on the role of ATP-gated potassium channels (KATP) in the perinatal pulmonary circulation. To investigate this issue, we have used isolated pulmonary resistance vessels from near-term fetal lambs and have tested levcromakalim and glybenclamide, respectively a KATP opener and blocker, on muscle tone at fetal and neonatal PO2, and under hypoxia. Levcromakalim (from 1 microM upwards) relaxed arteries and veins precontracted with a thromboxane A2 (TXA2) analogue (ONO-11113) at neonatal PO2. This effect was nearly completely inhibited by glybenclamide (10 microM) and NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). Conversely, levcromakalim relaxed little arteries precontracted with activating solution (5 mM Ca2+ in K(+)-Krebs) or hypoxia. Equally modest was the response of endothelium-denuded, ONO-11113-contracted arteries. Glybenclamide (10 microM) by itself did not raise the basal tone of vessels, regardless of PO2. We conclude that fetal pulmonary resistance vessels have KATP channels. In the arteries, these channels are located in the endothelium, and their opening causes relaxation by promoting nitric oxide formation. However, this relaxing mechanism does not become active when PO2 is raised from fetal to neonatal levels, nor does its inhibition contribute to hypoxic vasoconstriction.

Adenosine Triphosphate↗