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Biomedical subjects

A Locatelli

Publications and source records attributed to A Locatelli.

At least 73 records · Page 4Linked to original sources

Effect of long-term cocaine administration to pregnant ewes on fetal hemodynamics, oxygenation, and growth.

OBJECTIVE: To assess uterine and fetal blood flows by Doppler velocimetry and fetal growth and oxygenation in pregnant ewes treated daily with cocaine and to determine whether cocaine impairs fetal cardiac and cerebral reactivity. METHODS: The study groups received 70 mg (n = 7) or 140 mg (n = 7) of cocaine and the control group (n = 7) received placebo injected intramuscularly daily on days 60-134. Hemodynamic data were measured at rest and during two acute hypoxic tests at cesarean delivery performed on day 134. RESULTS: The fetal heart rate (FHR) and umbilical and uterine resistance indices (RIs) were higher in the cocaine groups than in the control group (FHR: 187 +/- 8 and 166 +/- 8 beats per minute at 83 and 123 days, respectively, in controls and 9-11% higher in cocaine groups; umbilical RI: 0.79 +/- 0.06, 0.60 +/- 0.04, and 0.52 +/- 0.06, at 83, 105, and 123 days, respectively, in controls and 11-17% higher in the cocaine groups [P < .01]; and uterine RI: 0.40 +/- 0.05, 0.40 +/- 0.04, and 0.37 +/- 0.04, at 83, 105, and 123 days, respectively, in controls and 13-35% higher in cocaine groups [P < .05]). At delivery on day 134, the following characteristics were found to be different in the cocaine groups: fetal weight (4.03 +/- 0.2 kg in controls and 15-21% lower in the cocaine groups [P < .02]), partial pressure of oxygen (26.5 +/- 1.4 mmHg in controls and 15-16% lower in cocaine groups [P < .05]), umbilical RI (0.40 +/- 0.03 in controls and 11-17% higher in cocaine groups [P < .01]), cerebral RI (0.61 +/- 0.03 in controls and 9-15% lower in cocaine groups [P < .01]), and cerebral-umbilical ratio (1.52 +/- 0.04 in controls and 22-23% lower in cocaine groups [P < .001]). During the hypoxic tests, the cerebral RI (P < .05) and the cerebral-umbilical ratio (P < .05) decreased significantly less in the two cocaine groups. The FHR response was reduced significantly in the two cocaine groups (P < .05). CONCLUSION: Long-term exposure to cocaine induces uterine and fetal blood flow disorders, fetal growth restriction, and hypoxia. It reduces the capability of the cerebral vessels to vasodilate and the heart rate to increase during acute hypoxia.

Animals↗

Amnioinfusion for prevention of pulmonary hypoplasia in second-trimester rupture of membranes.

We conducted a study to evaluate the feasibility and benefits of transabdominal amnioinfusion in preterm premature rupture of membranes with persistent oligohydramnios for the prevention of pulmonary hypoplasia. To this purpose, we designed a cohort study in which the pregnancy outcome of women with rupture of membranes at < or = 25 weeks and persistent (> or = 4 days) oligohydramnios managed with serial amnioinfusions (n = 18) was compared with that of a historic cohort group (controls) with similar characteristics but managed expectantly (n = 16). Pulmonary hypoplasia was diagnosed at birth in the presence of strict radiological and pathological criteria. No amnioinfusion-related complications occurred. The prevalence of pulmonary hypoplasia was significantly lower among the amnioinfused cases compared with the controls (46% [6 of 13] vs 86% [12 of 14], odds ratio [OR] = 0.4, 95% confidence interval [CI] 0.2-0.9), despite a lower gestational age at rupture of membranes in the treated group. Within the group undergoing amnioinfusions, those in which the infused solution was rapidly lost had a higher rate of pulmonary hypoplasia compared with those in which amnioinfusion alleviated oligohydramnios for > 48 hours (considered successful) (0 of 4 vs. 6 of 9, OR = 2.3, 95% CI 1-5.5). Cases of successful amnioinfusion had a longer interval between membrane rupture and appearance of oligohydramnios than those in which the procedure failed to correct oligohydramnios, even though both groups had similar gestational age at appearance of oligohydramnios. This suggests that the rate of loss of amniotic fluid after membrane rupture may predict the rate of loss of the infused solution, and therefore identify a subset of patients who may benefit from the procedure.

Adult↗

Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer.

PURPOSE: We performed a pharmacologic investigation of paclitaxel (PTX) infused over 3 hours and bolus doxorubicin (DOX) to assess the role of sequence, interval between drugs, and duration of doxorubicin infusion on paclitaxel and anthracycline plasma disposition. We also explored possible mechanisms of pharmacokinetic interference involving the physiologic role of the multidrug resistance phenotype in anthracycline and taxane biliary excretion. PATIENTS AND METHODS: Pharmacokinetics was performed in 80 cycles and 36 women with previously untreated metastatic breast cancer. PTX, DOX, and their metabolites 6 alpha-hydroxyl-PTX (6 alpha OH-PTX) and doxorubicinol (DOL) were measured by high-pressure liquid chromatography (HPLC). Human breast cancer MCF-7 wild-type (WT) and resistant (TH) cell lines were cultured in whole human plasma to study anthracycline retention after treatment with different combinations of PTX, Cremophor EL (CEL) (PEG35 castor oil; BASF, Parsippany, NJ), and DOX. RESULTS: Pharmacokinetic interference between PTX and DOX was responsible for nonlinearity of DOX plasma disposition and increased concentrations of DOX and DOL. These effects were PTX dose-dependent, DOX concentration-dependent, and likely a result of interference at the level of liver elimination. In view of the physiologic role of P-glycoproteins (P-gp) in xenobiotic biliary excretion, retention of DOX was assessed in MCF-7 WT and MCF-7 TH cells. Intracellular was significantly higher in MCF-7 WT than MCF-7 TH (P < .05). However, concomitant exposure to DOX, PTX, and CEL caused similar DOX retention in both MCF-7 WT and TH cells. CONCLUSION: PTX, as clinically formulated in CEL, is responsible for a nonlinear disposition of DOX and DOL. Nonlinearity is PTX- and DOX-dependent, and possibly caused by competition for biliary excretion of taxanes and anthracyclines mediated by P-gp. Nonlinearity indicates that even minor modifications of dose and infusion duration of DOX and PTX may lead to unpredictable pharmacodynamic consequences. The postulated role of P-gp suggests that CEL is clinically active, and advises caution in designing combinations of PTX with other drugs that are substrate for P-gp.

Adult↗

Potential antitumor agents. 24. Synthesis and pharmacological behavior of imidazo[2,1-b]thiazole guanylhydrazones bearing at least one chlorine.

In connection with a previous research dealing with the antitumor activity of imidazo[2,1-b]-thiazole guanylhydrazones, this paper reports the synthesis of new derivatives which were tested for antitumor and positive inotropic activity. In most cases the cytotoxic data from the in vitro experiments (HeLa) were in agreement with the antitumor data in vivo (Ehrlich). The active compounds bear a phenyl ring at the 6 position. On the other hand, the most active cardiotonic agents were devoid of the phenyl ring.

Animals↗

Transabdominal amnioinfusion in oligohydramnios at term before induction of labor with intact membranes: a randomized clinical trial.

OBJECTIVE: Our purpose was to determine the effectiveness of transabdominal amnioinfusion before induction of labor in reducing the incidence of fetal distress in pregnancies with oligohydramnios at term. STUDY DESIGN: Between June 1991 and September 1994 primiparous women with ultrasonographic evidence of oligohydramnios at term, intact membranes, and unripe cervix (Bishop score < or = 6), candidates for induction of labor with cervical or vaginal prostaglandin E2 gel, were randomly selected to receive transabdominal amnioinfusion (amnioinfused group, n = 39) or to proceed with direct labor induction (control group, n = 40). Inclusion criteria were (1) singleton gestation, (2) vertex presentation, (3) ultrasonographic estimation of fetal weight > or = 2500 gm, and (4) reactive nonstress test. Fetoneonatal outcome variables were compared between the two groups. Statistical analysis used contingency tables, Student t test, or Wilcoxon rank-sum tests, where applicable. RESULTS: Amnioinfusion was successfully performed in 100% of the patients randomized for the procedure. The incidence of severely abnormal fetal heart rate tracings was significantly higher in the control than in the amnioinfused group (42% [17/33] vs 5% [2/37], relative risk 12.9, 95% confidence interval 2.4 to 56.4). The rate of cesarean sections performed for fetal distress was fivefold higher in the control group (25% [10/40] vs 5% [2/39], relative risk 4.9, 95% confidence interval 1.1 to 32.4). No bleeding complications or fetomaternal infectious morbidity were noticed. CONCLUSION: Transabdominal amnioinfusion is a safe, effective option for the prevention of fetal distress in pregnancies with oligohydramnios at term with intact membranes and unripe cervix.

Abdomen↗

Pineal microdialysis of the melatonin in conscious sheep: methodology, application to a diurnal rhythm and effect of isoproterenol.

This paper describes the development of a new technique to measure melatonin contents in the pineal gland of moving sheep: the microdialysis. A dialysis probe was used to collect extracellular fluid in the sheep pineal gland, but also to inject directly into it different drugs such as isoproterenol at a very low concentration. The probe was implanted the day before the beginning of the experiment in order to obtain low levels of melatonin. This technique makes it possible to measure melatonin in the dialysate and plasma of rams submitted to 8L:16D. No melatonin either in the dialysate or in the plasma was found during the light phase. Shortly after lighting off, the melatonin concentration increased in the dialysate and plasma and remained stable during the dark phase. Melatonin concentrations began to decrease before lighting on and no detectable levels were found during the following light phase. The secretion of melatonin is, at least, under adrenergic regulation. Local infusion of isoproterenol (90 microliters at 10(-6) M), an agonist of beta adrenergic receptor, through the probe, increased melatonin levels during 2 h, even when infusions were repeated 3 times. This demonstrates the presence of beta adrenergic receptors. The technique presented in this paper could be of considerable interest for studying sheep pineal gland and its main secretion, melatonin, for example during diurnal rhythms or for studying its regulation.

Animals↗

Clinical significance of fetal intracranial hemorrhage.

OBJECTIVE: We reviewed our experience with six consecutive cases of fetal intracranial hemorrhage and the cases published in the English literature in an attempt to devise an original prognostic scoring system for antenatal intracranial hemorrhage. STUDY DESIGN: The series included the cases of fetal intracranial hemorrhage detected at our institution between 1992 and 1994 by transabdominal ultrasonography. In addition, we performed an English literature search (Medline computer search, National Library of Medicine) of all reported cases of a prenatal diagnosis of intracranial hemorrhage. The prenatal ultrasonographic findings were correlated with the clinical outcome, which was divided into (1) normal outcome or mild neurologic sequelae and (2) poor outcome (severe neurologic impairment and fetal or neonatal death). RESULTS: Six cases of intracranial hemorrhage were detected in a population of 6641 pregnancies (0.9/1000) at our institution. Parenchymal involvement was present in three cases. Review of the English literature revealed 35 additional cases with prenatal ultrasonographic findings and postnatal follow-up. The total cases (n = 41) were divided into three groups: (1) isolated intraventricular hemorrhage (n = 20), (2) parenchymal hemorrhage (n = 13), and (3) subdural or subarachnoid hemorrhage (n = 8). Overall, poor outcome was present in 68% of cases, including 45% (9/20) of intraventricular hemorrhage, 92% (12/13) of parenchymal hemorrhage, and 88% (7/8) of subdural or subarachnoid hemorrhage. The heterogeneity of the intraventricular hemorrhage group in both severity of antenatal findings and outcome prompted us to devise a prognostic scoring system based on prenatal ultrasonographic lesions, grouping cohorts with similar outcomes. Outcome was favorable in 100% (5/5) of grade 1 intraventricular hemorrhage cases, in 50% (6/12) of grade 2 cases, and in 0% (0/3) of grade 3 cases. CONCLUSIONS: Fetal intracranial hemorrhage can be classified on the basis of the anatomic location of the intracranial bleeding. The prognosis is poor in nearly 90% of parenchymal and subdural hemorrhages, whereas it is better in the subgroup with intraventricular hemorrhage. The prognostic scoring system we propose for intraventricular hemorrhage may assist the physician in providing patients with prognostic information.

Cerebral Hemorrhage↗

Unorthodox antibiotic combinations including ciprofloxacin against high-level gentamicin resistant enterococci.

Development of high-level gentamicin resistance among enterococci represents a serious therapeutic problem as it precludes synergy between aminoglycosides and cell-wall active agents. As part of a search for active antibiotic combinations against enterococci with high-level gentamicin resistance, we tested by the time kill curve method the efficacy of ciprofloxacin combined with ampicillin, trimethoprim-sulphamethoxazole, vancomycin or teicoplanin against ten isolates of Enterococcus faecium, three of Enterococcus casseliflavus and 13 of Enterococcus faecalis that exhibited a MIC of gentamicin > or = 2000 mg/L. Most of the E. faecium were also resistant to ampicillin and to ciprofloxacin. The combination of ciprofloxacin with ampicillin was bactericidal against five of seven E. faecium strains that exhibited a ciprofloxacin MIC < or = 4 mg/L, but was inactive against the three E. faecium that were highly resistant to ciprofloxacin. This combination was also bactericidal against the E. casseliflavus and all the E. faecalis strains. The combination of ciprofloxacin with trimethoprim-sulphamethoxazole was bactericidal against five of the seven E. faecium and seven of the nine E. faecalis strains with a ciprofloxacin MIC < or = 4 mg/L. No bactericidal activity of this combination was seen against the enterococci that were highly resistant to either ciprofloxacin or to trimethoprim-sulphamethoxazole. The combination of ciprofloxacin with glycopeptides was inactive against E. faecium and E. casseliflavus and against E. faecalis, it was either ineffective or antagonistic; in only one case it was bactericidal. Five strains of E. faecium were resistant to all antibiotic combinations tested.

Ampicillin↗

Expression of messenger ribonucleic acids of insulin-like growth factor binding protein-2, -4, and -5 in the ovine ovary: localization and changes during growth and atresia of antral follicles.

In the sheep as in many mammalian species, growth and atresia of antral follicles are characterized, respectively, by a decrease and a high increase in the intrafollicular levels of insulin-like growth factor binding proteins of less than 40 kDa (IGFBPs < 40 kDa), mainly IGFBP-2, -4, and -5. The objective of this study was to investigate whether such changes are associated with changes in follicular expression of the corresponding mRNA. For this purpose, ovaries were recovered from ewes slaughtered at the end of follicular phase (i.e., 30 h after progestagen sponge removal; control ewes) or at 24 h, 36 h or 72 h after hypophysectomy (hypox) performed 30 h after sponge removal. The expression of mRNA of IGFBPs of less than 40 kDa (IGFBPs < 40 kDa mRNA) was studied in ovine antral follicles from control and hypox ewes by in situ hybridization using [35S]-labeled human IGFBP-2, -4, and -5 cRNA as probes. In control ewes, IGFBP-2 mRNA was mainly expressed in granulosa as a gradient in healthy follicles, the expression being higher in granulosa cells close to the basal membrane than in granulosa cells bordering the antrum and within the cumulus. The level of IGFBP-2 mRNA was lower both in granulosa cells close to the basal membrane and in those bordering the antrum from small follicles than in the corresponding compartments of granulosa cells from large healthy follicles (p < 0.05). In healthy follicles, IGFBP-4 and -5 mRNA were mainly expressed in thecal cells. No change in level of IGFBP-4 mRNA was observed between small and large follicles, whereas the level of IGFBP-5 mRNA tended to be lower in thecal cells from large compared to small follicles (p = 0.055). In atretic follicles, expression of IGFBPs < 40 kDa mRNA strongly increased in granulosa (IGFBP-2 and -5, p < 0.01) and in thecal cells (IGFBP-2 and -4, p < 0.01). In hypox ewes, the chronology of changes in expression of follicular IGFBPs < 40 kDa mRNA and in intrafollicular levels of the corresponding proteins was studied during atresia of large antral follicles. Early atresia of large follicles was associated with a strong decrease in intrafollicular estradiol levels (p < 0.001); an increase in intrafollicular levels of IGFBP-2, -4, and -5 (p < 0.001) an increase in both IGFBP-2 (p < 0.001) and -5 (p < 0.01) mRNA expression in granulosa and thecal cells; but no changed in IGFBP-4 mRNA expression. Late atresia of large follicles was associated with a further decrease in intrafollicular estradiol levels (p < 0.01); a further increase in intrafollicular levels of IGFBP-2, -4, and -5 (p < 0.001); an increase in IGFBP-4 (p < 0.01) and -5 (p < 0.05) mRNA expression in theca and granulosa, respectively; a decrease in IGFBP-5 mRNA expression in theca (p < 0.05); but no further increase in IGFBP-2 mRNA expression. Overall, these data suggest that the decrease and the increase in expression of mRNA of follicular IGFBPs < 40 kDa during follicular growth and atresia, respectively, are involved in the decrease and the increase in intrafollicular levels of the corresponding proteins. Moreover, the increases in expression of follicular IGFBPs < 40 kDa during atresia of large follicles in hypophysectomized ewes followed a specific time course, the increase in IGFBP-2 and -5 mRNA expression being early than the increase in IGFBP-4 mRNA expression.

Animals↗

Sexually transmitted diseases and risk of HIV infection.

We have analyzed the association between sexually transmitted diseases (STD) and HIV infection, using data from a cross-sectional survey of subjects attending STD clinics in Northern Italy conducted since 1988. A total of 1,711 subjects (1,259 males, 452 females), who had referred themselves to three STD clinics in Northern Italy for suspected STD or STD treatment, were included for the study. Out of these, 145 subjects (113 males and 32 females) were HIV-positive. A total of 58 HIV-positive and 368 HIV-negative subjects reported a history of STD; the corresponding odds ratio (OR) was 2.3 (95% confidence interval (CI) 1.5-3.6) for subjects reporting a history of STD. Considering various STD in details, the estimated OR was 1.8 (95% CI 0.8-3.8) for a history of gonorrhoea and 1.5 (95% CI 0.8-2.7) of syphilis, and the OR was 1.8 (95% CI 1.0-3.2) and 2.2 (95% CI 1.3-3.8), respectively, for a positive TPHA and VDRL test. The results of the test for HbsAg were available in 50 HIV-positive and 1,028 HIV-negative subjects; the OR of HIV infection in subjects with HbSAg was 3.9 (95% CI 1.7-9.0). Presence of genital ulcers at clinical examination was not significantly associated with the risk of HIV infection (OR yes vs no genital ulcers 1.5, 95% CI 0.6-2.8).

Adolescent↗

Characterization of ovine SRY transcript and developmental expression of genes involved in sexual differentiation.

In mammals, the presence of SRY, the sex-determining gene located on the Y chromosome is required to induce the gonadal anlage to differentiate as a testis, whereas its absence leads to the development of an ovary. We report here the characterization by 5' and 3' RACE analysis of several SRY transcripts which are expressed in the ovine male developing gonads. These transcripts were not detected in any other fetal tissues and were expressed only in the genital portion of the urogenital ridge. The temporal profile of SRY expression analyzed by RT-PCR suggests that in the sheep fetus the role of SRY is not limited to initiating Sertoli cell differentiation as in mice. Indeed, SRY transcripts persist after the full differentiation of the testis. In addition to SRY, other genes are known to be involved in mammalian sex determination: Wilms' tumor gene WT-1, steroidogenic factor gene Ftz-F1 (SF-1) and anti-Müllerian hormone (AMH). We investigated the expression patterns of these genes by RT-PCR during fetal development in sheep gonads. Concerning WT-1 and SF-1, our results are consistent with those described in mice where the earliest expression was detected before the sexual differentiation in both sexes. In male, the ontogenesis of AMH transcription corresponds to the seminiferous cords formation (30 dpc). In female, we have observed the presence of SF-1 transcripts from the undifferentiated stage until birth. In addition, P450 aromatase expression is detected from 30 dpc and is correlated with the presence of 17-beta estradiol in sheep ovary. These data reveal significant differences between rodent and ruminant models concerning the sex-determining pathway.

Aging↗

Different susceptibility of coagulase-positive and coagulase-negative staphylococci to ciprofloxacin.

Ciprofloxacin susceptibility was evaluated in 573 clinical staphylococcal isolates (Staphylococcus aureus 230, methicillin-resistant (MR) 36%; coagulase-negative strains 343, MR 66%) collected from 1989 to 1995. Resistance to ciprofloxacin for MR Staphylococcus aureus was 25% until 1991 when ciprofloxacin was introduced into the hospital formulary, and rose progressively to 90% in 1994-1995. MR Staphylococcus haemolyticus showed a ciprofloxacin resistance of 46% until 1991 and of 73% from 1992 to 1995. In contrast MR Staphylococcus epidermidis and other coagulase-negative strains showed a constant susceptibility to this agent (80%). Ciprofloxacin has limited usefulness against MR Staphylococcus aureus but can be still used to treat Staphylococcus epidermidis infections.

Ciprofloxacin↗

Thienylimidazo[2,1-b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase.

The synthesis of 6-substituted 5-(thienylvinyl)imidazo[2,1-b]thiazoles and 6-thienylimidazo[2,1-b]thiazoles is reported. These compounds were tested as specific inhibitors of the NADH: ubiquinone (UBQ) reductase activity of NADH dehydrogenase in mitochondrial membranes. The 6-thienylimidazo[2,1-b]thiazoles were more potent in mammalian than in nematode mitochondria and had an average titer of 0.11 mM for 2-methyl-6-(2-thienyl)imidazo[2,1-b]thiazole (10). This compound is noncompetitive with the ubiquinone substrate and interacts with a site which is mutually exclusive with that of rotenone but nonexclusive with that of piericidin and several other inhibitors of NADH dehydrogenase. In the series of 5-(thienylvinyl)imidazothiazoles, the hydrobromide of (E)-6-chloro-5-(2-thienylvinyl)imidazo[2,1-b]thiazole (E-5.HBr) was found to be more potent as an inhibitor of the NADH:UBQ activity (IC50 = 15-17 microM) than the 6-thienylimidazoles such as 10. The inhibitory action of E-5.HBr and its analogs is different from that of compound 10 as indicated by the mutual exclusivity with other inhibitors and the relative inhibition of the activity with various electron acceptors.

Animals↗

Involvement of the main but not the accessory olfactory system in maternal behavior of primiparous and multiparous ewes.

The respective roles of the main and accessory olfactory systems in the development of maternal behavior and selective suckling were investigated in parturient primiparous and multiparous ewes. Vomeronasal nerve section before parturition did not disturb either maternal behavior or maternal selectivity at suckling. By contrast, anosmia induced by zinc sulphate infusion had significant effects on the onset of maternal behavior in primiparous ewes. The onset of licking and of suckling were delayed and licking times and maternal bleats were reduced. Such disturbances were not observed in multiparous anosmic ewes, indicating that experience can compensate for the loss of olfactory information. On the other hand, anosmia prevented selective care regardless of maternal experience. Our results underline the importance of the main olfactory system for the development of adequate maternal behavior in sheep.

Animals↗

Vascular resistance quantification in high flow resistance areas using the Doppler method.

The objective of the present study is to define and validate on an animal model (ewe) a new Doppler parameter for the assessment and monitoring of the vascular resistances in high resistance to flow areas (lower limbs, placenta with vascular disease). The high resistance index (HRI) was derived from the transmission line theory and defined as: HRI = D/S with S the amplitude of the systolic peak and D that of the diastolic reverse flow. Validation of the HRI was performed on adult ewes. Distal lower limb vascular resistances were evaluated from the Doppler femoral waveform (HRI) and compared with the classic vascular resistances (Rv), calculated from pressure and flow (mmHg/mL/min). The femoral flow variations were measured by duplex (echo-Doppler) method and the mean pressure through an arterial catheter inserted into the abdominal aorta. Two tests were used in this study: (1) A calibrated venous compression of the lower limbs extremity: The femoral flow dropped by 29%, the pressure and heart rate did not change, the HRI increased by 37% (p < 0.01), and the vascular resistance (Rv) by 46% (p < 0.01). (2) The intravenous injection of 1 mg adrenaline: The arterial pressure increased by 70% (p < 0.001), the heart rate and femoral flow dropped by 50% (p < 0.001), and 35% (p < 0.001), the HRI increased by 70% (p < 0.01) and the vascular resistances (Rv) by 140% (p < 0.01). During the two tests, the HRI changed in proportion with the "classic" vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Assessment of the fetal PO2 changes by cerebral and umbilical Doppler on lamb fetuses during acute hypoxia.

The objective of the present study was to validate one or a combination of fetal Doppler parameters in order to assess acute fetal hypoxia in an ovine model. Acute hypoxia was induced by reducing umbilical, or maternal aortic flow (approx. 70%). A CW Doppler probe was fixed on the fetal cervical skin, facing the internal carotid artery and the fetal abdominal skin adjacent to the umbilical arteries. (The angle between Doppler beam and flow vector remained constant.) A "Doptek 3000" spectrum analyser was used to measure the maximal and mean Doppler frequencies. Heart rate (HR), umbilical blood flow (UBF), carotid blood flow (CBF), umbilical RI (URI), cerebral RI (CRI) and cerebroplacental ratio (CPR = CRI/URI) were calculated in real time. A catheter was inserted into the fetal femoral artery, for blood gas (PO2, PCO2 pH) and blood pressure (BP) measurements. After 1 min of aorta compression (70% aortic flow reduction), the URI increased by 10% (P < 0.05), and the UBF decreased by 10% (P < 0.05), but the CRI decreased by 20% (P < 0.02), and the CBF did not change significantly. Fetal PO2 and CPR fell down after 1 min (59% and 38%, respectively; P < 0.001), although strong fetal heart rate decelerations were observed. The blood pressure, PCO2 and pH did not change significantly during this test. Throughout the 12 min of cord compression (70% umbilical flow reduction) the URI increased (70% to 80% P < 0.001), and the UBF decreased (approx. 60%; P < 0.001), but the CRI decreased (approx. 25%; P < 0.01), and the CBF remained constant (+/- 5%; ns). Fetal PO2 and CPR all decreased during the compression (30% to 44% and 40% to 60%, respectively; P < 0.001). HR, pH and PCO2 did not change significantly. During cord compression the blood pressure did not change significantly. In both cases, the CPR decreased significantly (P < 0.001) with the PO2 in the same direction and with a comparable amplitude (-30% to -50%). Nevertheless, the drop in CPR was greater during cord compression than during aorta compression, probably because the compression of the cord induced a central hypovolemia in addition to the hypoxia. The CPR was found to be the hemodynamic parameter that followed most closely the PO2 acute changes. The amplitude of the variations of this parameter (-30% to -50%) were quite similar to those of the PO2 during the period of acute hypoxia.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗