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Biomedical subjects

F Coceani

Publications and source records attributed to F Coceani.

At least 127 records · Page 7Linked to original sources

Age-dependent changes in the response of the lamb ductus arteriosus to oxygen and ibuprofen.

Circular strips of ductus arteriosus from lambs of gestational age between 90 and 144 days (term 147 days) were studied in vitro at low (8--16 torr (1 torr = 133.322 Pa)) and high (426--622 torr) PO2. Potassium- and oxygen-induced contractions increased with the gestational age and attained a maximum at term. At low PO2, ibuprofen, a blocker of prostaglandin synthesis, produced a dose-dependent contraction of the ductus at all ages and enhanced the potassium-induced contraction of the immature ductus (90--124 days). Both effects were relatively greater in the 103- to 107-day gestational group. At that age, ibuprofen also potentiated the oxygen-induced contraction. These findings, while confirming that a prostaglandin is involved in ductus patency, indicate that the prostaglandin-relaxing mechanism becomes functional at an early stage of gestation and reaches maximal activity before term. The existence of an active, prostaglandin-mediated relaxation in the preterm ductus may account, in part, for the reduced responsiveness of the vessel to oxygen. It is confirmed that ibuprofen and other nonsteroidal antiinflammatory drugs are well suited for the management of the premature infant with patent ductus arteriosus.

Animals↗

Prostaglandin I2 is less relaxant than prostaglandin E2 on the lamb ductus arteriosus.

Prostaglandin (PG) I2 and its stable metabolite, 6-keto-PGF1alpha, were tested on the isolated ductus arteriosus from mature fetal lambs. PGI2 relaxed the ductus in high doses (threshold 10(-6)M) and its activity disappeared on standing at room temperature for 30 minutes. 6-keto-PGF1alpha was inactive at all doses. By contrast, PGE2 produced a dose-dependent relaxation over a range between 10(-10) and 10(-6)M. These findings confirm that PGE2 is the most potent ductal relaxant among the known derivatives of arachidonic acid. PGE2 probably maintains ductus patency in the fetus and, together with PGE1, remains the compound of choice in the management of newborns requiring a viable ductus for survival.

Animals↗

The prostaglandin challenge. Test to unmask obstructed total anomalous pulmonary venous connections in asplenia syndrome.

The patient with complex congenital heart disease, severe pulmonary outflow obstruction, and visceral heterotaxia, may have 'silent' obstruction of the pulmonary venous return. Severe reduction of pulmonary blood flow secondary to pulmonary stenosis or atresia in such patients may prevent the usual radiographic appearance of pulmonary oedema. If such obstructed anomalous pulmonary venous connections are not diagnosed before operation, construction of a systemic to pulmonary artery anastomosis will unmask the obstruction, usually resulting in pulmonary oedema and death. We have recently 'challenged' a neonate with dextrocardia, vesceral heterotaxia, presumed asplenia, and complex congenital heart disease including pulmonary atresia, with an infusion of prostaglandin E1 to increase pulmonary blood flow via his ductus arteriosus. This resulted in severe pulmonary oedema which partially resolved after the infusion was discontinued. This was interpreted as consistent with obstructed total anomalous pulmonary venous return. This was confirmed at necropsy. Thus, the infusion of prostaglandin E1 before operation in the patient with asplenia or similar cardiac disease may be of aid in unmasking 'silent' obstructions of the pulmonary veins, and is of obvious value in the preoperative assessment of such patients.

Heart Defects, Congenital↗

Action of prostaglandins, endoperoxides, and thromboxanes on the lamb ductus arteriosus.

Prostaglandin (PG) E2, the PG endoperoxides PGG2 and PGH2, and enzymatically generated PGI2 and thromboxane A2 (TXA2) were tested in vitro on circular strips of ductus arteriosus from mature fetal lambs. Both PGE2 and the PG endoperoxides produced a dose-dependent relaxation of the ductus at low PO2 (7-11 torr), and their action was reduced or abolished at high PO2 (410-660 torr). PGE2, however, was more potent than the endoperoxides. The reaction mixture containing PGI2 relaxed the hypoxic ductus, but this response was not due to PGI2 but to two, more stable and as yet unidentified, compounds, one of which is most certainly PGE2. TXA2 was inactive on the vessel at low and high PO2. These results confirm that PGE2 is the most effective PG acting on the ductus and provide further support to the hypothesis that this PG is responsible for patency of the vessel during fetal life. PGE2 action, however, may be complemented by that of another endoperoxide derivative formed in the PGI2 synthetic reaction which remains to be identified.

Animals↗

Prostaglandins and the control of muscle tone in the ductus arteriosus.

Several lines of evidence implicate E-type PGs in the maintenance of patency of the foetal ductus arteriosus. The PGE mechanism is functional in man, sheep, rat and rabbit, but it is seemingly absent in guinea pig. The role of the PGs in the closure of the vessel at birth is uncertain. Work with different species suggests that as PO2 rises at birth the relaxant effect of PGEs on the ductal muscle decreases. This decreased sensitivity may facilitate the oxygen triggered contraction. The calf ductus is an exception and its closure may be mediated by PGF2alpha. An important fact emerging from this review is that species may differ with regard to the occurrence and possible function of the PGs in the ductus arteriosus. The significance of these differences to the function of the oxygen-sensing mechanism remains a major question for future research.

5,8,11,14-Eicosatetraynoic Acid↗

Neurological and electroencephalographic changes in newborns treated with prostaglandins E1 and E2.

Six newborns with obstructive right heart lesions were examined neurologically and electroencephalographically during treatment with prostaglandin (PG) E1 or E2 given to maintain patency of the ductus arteriosus and to increase pulmonary blood flow. PG was administered intravenously or intraarterially in the aortic isthmus proximal to the ductus arteriosus. Besides a rise in arterial oxygen saturation, all patients had some sign of central nervous system involvement. The electroencephalogram showed minor changes suggestive of sedation. In addition, three patients in whom PG was given intravenously presented various combinations of neurological abnormalities ("myoclonic jerks", apnoeic spells, hiccup) of subcortical origin. Side-effects subsided after stopping the treatment and posed no problem in the management of the patients. These findings confirm the usefulness and safety of the PG therapy and indicate that the intraaortic route of administration is preferable.

Apnea↗

Microiontophoresis of 5-hydroxytryptamine, epinephrine, and prostaglandin E1 on spinal neurons in the frog.

5-Hydroxytryptamine (5-HT) and epinephrine were applied by microiontophoresis to single neurons in the isolated spinal cord of the frog. 5-HT depressed all but two of the responsive cells, whereas the response to epinephrine consisted exclusively of depression. 5-HT action was more marked than that of epinephrine on most cells. With either compound, responseve units were diffusely distributed throughout the tissue. While it was proven that prostaglandin E1 (PGE1) exerts a direct excitatory action on spinal neurons, no evidence of an antagonism between PGE1 and the monoamines was obtained. These findings provide additional support to the hypothesis that 5-HT and epinephrine are transmitters in the frog spinal cord. The possibility that PGE1 may 'modulate' the responsiveness of spinal neurons to the monoamines was not confirmed.

Action Potentials↗

E-type prostaglandins: a new emergency therapy for certain cyanotic congenital heart malformations.

Prostaglandin E2 (PGE2) has been used to maintain patency of the ductus arteriosus in four neonates with cyanotic congenital heart disease due to obstructive right heart malformations. PGE2 was infused prior to surgery, and in three patients, during surgery until a satisfactory aorto-pulmonary shunt was established. PGE2 produced consistently an immediate and persistent rise in arterial oxygen saturation, which could be ascribed to dilation of the ductus arteriosus. No major side effects occurred, except for pyrexia in two infants. All patients recovered well from surgery. We propose this treatment as preparation for surgery in any infant with congenital heart defects and ductus-dependent pulmonary blood flow. The same treatment may be useful preoperatively in patients with aortic interruption who also depend on continued patency of the ductus for blood supply to the lower half of the body.

Dilatation↗

Prostaglandins: a possible regulator of muscle tone in the ductus arteriosus.

We have shown that E-type prostaglandins are potent relaxant of the lamb ductus arteriosus at low, but not high, oxygen tensions, and that their effect is possibly controlled by the rate of endogenous PG synthesis. These findings, together with the demonstration of the contractile effect of PG synthesis blockers on the hypoxic ductus in vitro and in vivo and of the relaxant effect of GSH in vitro, strongly suggest that E-type prostaglandins are responsible for maintaining ductus patency during fetal life. The endoperoxide intermediates may act in concert with PGEs. While our findings argue against the idea that PGF2alpha mediates the oxygen-induced constriction, they suggest that suppression of PGE activity in a high oxygen environment might be important to the initiation of ductus closure at birth. An extension of this concept is that continued patency of the ductus after birth results from either the excessive formation of PGEs or from the persistence of a "fetal-like" response of ductal muscle to endogenous or bloodborne PGEs, or both. The present scheme of PGE action is amenable to practical applications. Our work and that of Elliott et al. (15) prove that PGEs can be used to reopen a constricted ductus in children with cyanotic congenital heart disease, thus improving their change of survival during subsequent corrective surgery. Conversely, treatment with blockers of PG synthesis is envisaged as an alternative to surgery for closing a persistent ductus.

Animals↗