Transfer of acipimox across the isolated perfused human placenta

The placental transfer of the new lipid-lowering agent, acipimox was investigated in the isolated perfused human placenta. Placentas obtained at caesarean section were perfused for 120 min, with both maternal and fetal circuits in closed recycling mode. Acipimox was added to either the maternal circuit alone (five experiments) or to both maternal and fetal circuits simultaneously (five experiments) to achieve initial concentrations of 5 micrograms/ml. Antipyrine (20 micrograms/ml) and l-(14C)-leucine (250 microM) were added in like fashion as reference compounds. Two hours after addition to the maternal circuit alone antipyrine was close to equilibrium across the placenta, but equilibration of acipimox was incomplete (fetal/maternal ratio = 0.58 +/- 0.11). Maternal to fetal placental clearance of acipimox (0.80 +/- 0.18 ml/min) was 25 per cent of antipyrine clearance. After simultaneous administration to both maternal and fetal circuits the l-(14C)-leucine fetal/maternal ratio was 1.44 +/- 0.13 at 120 min, whereas maternal and fetal concentrations of acipimox and antipyrine were at equilibrium for the duration of the experiment (fetal/maternal ratio of acipimox at 120 min = 1.10 +/- 0.06). This study shows that acipimox is transferred across the human placenta by diffusion at a slow rate. The low permeability of the placenta may afford some protection to the fetus from acipimox administered to the mother in vivo.     

Metabolic integrity of the isolated perfused lobule of human placenta

Tissue levels of lactate, pyruvate and the adenine nucleotides were measured in samples of human placenta obtained (1) immediately on delivery, (2) after perfusion on the maternal side for one hour, and (3) after a corresponding period of warm ischaemia. Metabolic activity in the isolated perfused placental lobule was assessed in terms of these tissue metabolites and by measuring protein synthetic rate by means of determining the incorporation of a labelled amino acid. Perfusion was found to lower significantly the lactate level whereas ATP was maintained at comparable levels with those in the placenta just after delivery. Perfused placental ATP levels are lower than in vivo levels seen in other tissues with high metabolic rates such as rat liver, kidney and also in guinea-pig placenta. Protein synthetic rate was found to be lower than that observed in other fetal tissues.     

Secretory function of isolated canine pancreas perfused with fluorocarbon emulsion

A canine gastroduodenopancreatic block was isolated and perfused ex vivo with fluorocarbon emulsion, oxygenated in vitro, and containing a simulated physiologic protein-free solution. Pancreatic and gastric secretions were collected. The pancreas was stimulated with secretin or cholecystokinin infused intra-arterially. The response of the pancreas to both hormones was essentially identical to that observed under in vivo conditions or during perfusion of the isolated pancreas with homologous blood. Secretin induced pancreatic secretion was rich in bicarbonate and poor in total protein. Cholecystokinin induced pancreatic secretion contained less bicarbonate and more protein than secretin induced secretion. Differences between secretory responses of the pancreas to these hormones were significant. Gastric secretion was alkaline and contained fluorocarbon emulsion. The results of this study demonstrated that, under the experimental conditions described, external secretory function of the isolated canine pancreas was preserved during perfusion of isolated organs with fluorocarbon emulsion.     

Nifedipine enhances the cardiac toxicity of magnesium sulfate in the isolated perfused Sprague-Dawley rat heart

Magnesium sulfate is commonly used in tocolytic regimens and as prophylaxis against seizures. Nifedipine may be used simultaneously in either situation. With the isolated perfused rat heart model (Sprague-Dawley rats), we investigated the effects of these agents on cardiac function. Whereas each agent alone depressed cardiac performance, the two drugs together had maximal depressive effects on the heart.     

The effects of the components of the renin-angiotensin system on the isolated perfused human placental cotyledon

Angiotensins I, II, and III, renin substrate, and des-Asp¹-angiotensin I were injected as a bolus into either the maternal or fetal circulation of human placental cotyledons perfused in vitro. All drugs tested produced dose-related increments in fetal perfusion pressure when injected into the fetal circulation, with the order of potency being angiotensin I ≈ angiotensin II ≈ angiotensin III ? des-Asp¹-angiotensin I ? renin substrate. The responses to all the drugs could be blocked by the competitive inhibitor of angiotensin II, (Sar¹, Ala⁸)-angiotensin II, but only the actions of angiotensin I, renin substrate, and des-Asp¹-angiotensin I could be blocked by angiotensin converting enzyme inhibitor. When the agents were injected into the maternal circulation, only angiotensins II and III caused dose-related increments in fetal perfusion pressure. Possibly, the placenta may be the main site of conversion of angiotensin I to angiotensin II in the fetoplacental unit, and angiotensin II produced by the placenta could act locally to control fetoplacental blood flow.     

Placental transfer of cefoperazone and sulbactam in the isolated in vitro perfused human placenta

The transfer of cefoperazone and sulbactam across the human placenta was studied qualitatively and quantitatively with the isolated in vitro bidirectionally perfused human placental lobule. Clearance indexes for both cefoperazone and sulbactam were derived. The absence of active transport and facilitated diffusion were documented, implying simple diffusion as the mechanism of placental transfer for both drugs. Placental tissue levels were also studied.