Biomedical subjects

Dino A Giussani

Publications and source records attributed to Dino A Giussani.

At least 19 recordsLinked to original sources

PubMed2006

Differential effects of maternal dexamethasone treatment on circulating thyroid hormone concentrations and tissue deiodinase activity in the pregnant ewe and fetus.

Clinically, treatment of pregnant women at risk of preterm delivery with synthetic glucocorticoids accelerates fetal maturation. This study investigated the effect of maternal dexamethasone treatment, in clinically relevant doses, on plasma thyroid hormone concentrations and tissue deiodinase activities (D1, D2, and D3) in ewes and their fetuses. From 125 d of gestation (term 145 +/- 2 d), pregnant ewes were injected twice im with either saline (2 ml of 0.9% NaCl, n = 11) or dexamethasone (2 x 12 mg in 2 ml of saline, n = 10) at 24-h intervals. Maternal dexamethasone treatment increased plasma T(3) and reverse T(3) (rT(3)), but not T(4), concentrations in the fetuses. In the dexamethasone-exposed fetuses, hepatic D1 activity was higher, and renal and placental D3 activities were lower, than in the saline-exposed fetuses. In the ewes, plasma concentrations of T(3) and T(4) were reduced, and rT(3) increased, by dexamethasone treatment without any change in tissue deiodinase activity. Therefore, maternal dexamethasone treatment has different effects on the thyroid hormone axis of the pregnant ewe and fetus. In the fetus, the dexamethasone-induced rise in circulating T(3) may be due to both increased hepatic production of T(3) from T(4), and reduced clearance of T(3) by the kidney and placenta. Changes in T(3) bioavailability may mediate some of the maturational effects of antenatal glucocorticoid treatment in the preterm fetus.

Animals↗

PubMed2006

Development of the ovine fetal cardiovascular defense to hypoxemia towards full term.

We tested the hypothesis that fetal cardiovascular responses to hypoxemia change close to full term in relation to the prepartum increase in fetal basal cortisol and investigated, in vivo, the neural and endocrine mechanisms underlying these changes. Fetal heart rate and peripheral hemodynamic responses to 1 h of hypoxemia were studied in 25 chronically instrumented sheep within three narrow gestational age ranges: 125-130 (n = 13), 135-140 (n = 6), and >140 (n = 6) days (full term approximately 145 days). Chemoreflex function and plasma concentrations of vasoconstrictor hormones were measured. Reductions in fetal arterial Po(2) during hypoxemia were similar at all ages. At 125-130 days, hypoxemia elicited transient bradycardia, femoral vasoconstriction, and increases in plasma concentrations of catecholamines, neuropeptide Y (NPY), AVP, ACTH, and cortisol. Close to full term, in association with the prepartum increase in fetal basal cortisol, there was a developmental increase in the magnitude and persistence of fetal bradycardia and in the magnitude of the femoral constrictor response to hypoxemia. The mechanisms mediating these changes close to full term included increases in the gain of chemoreflex function and in the magnitudes of the fetal NPY and AVP responses to hypoxemia. Data combined irrespective of gestational age revealed significant correlations between fetal basal cortisol and fetal bradycardia, femoral resistance, chemoreflex function, and plasma AVP concentrations. The data show that the fetal cardiovascular defense to hypoxemia changes in pattern and magnitude just before full term because of alterations in the gain of the neural and endocrine mechanisms mediating them, in parallel with the prepartum increase in fetal basal cortisol.

Acid-Base Equilibrium↗

PubMed2006

Development of baroreflex function and hind limb vascular reactivity in the horse fetus.

This study investigated, in vivo, the mechanisms underlying the development of cardiovascular function in the horse fetus, with particular relevance to baroreflex function and hind limb vascular arterial reactivity to constrictor agonists. Under general anaesthesia, vascular catheters were inserted and a Transonic flow probe was implanted around one of the metatarsal arteries of 13 horse fetuses, either at 0.6 of gestation (n= 6) or at 0.9 of gestation (n= 7, term approximately 335 days). At least 5 days after surgery, pressor, vasoconstrictor and cardiac chronotropic responses to exogenous bolus doses of phenylephrine, angiotensin II and arginine vasopressin were recorded. Fetal cardiac baroreflex slopes were obtained using the peak pressor and heart rate responses to increasing doses of phenylephrine. Fetal treatment with phenylephrine, angiotensin II and vasopressin produced significant changes in arterial blood pressure, hind limb vascular resistance and heart rate. Pressor and vasopressor responses to all agonists were greater at 0.9 than at 0.6 of gestation; however, fetal cardiac baroreflex sensitivity decreased with advancing gestational age. Correlation analysis revealed that fetal plasma cortisol rather than gestational age was a greater determinant of pressor and vasopressor reactivity. In contrast, gestational age rather than cortisol better determined heart rate and baroreflex responsiveness in the equine fetus. The data show that development of cardiovascular function in the equine fetus occurs via cortisol-dependent and -independent pathways.

Animals↗

PubMed2006

Intrauterine programming of physiological systems: causes and consequences.

The intrauterine conditions in which the mammalian fetus develops have an important role in regulating the function of its physiological systems later in life. Changes in the intrauterine availability of nutrients, oxygen, and hormones program tissue development and lead to abnormalities in adult cardiovascular and metabolic function in several species. The timing, duration, severity, and type of insult during development determines the specific physiological outcome. Intrauterine programming of physiological systems occurs at the gene, cell, tissue, organ, and system levels and causes permanent structural and functional changes, which can lead to overt disease, particularly with increasing age.

Aging↗

PubMed2005

Acute hypoxia increases S100beta protein in association with blood flow redistribution away from peripheral circulations in fetal sheep.

We investigated in fetal sheep during late gestation the effects of acute hypoxemia on fetal plasma S100beta protein concentrations and how these relate to fetal redistribution of blood flow and acid-base status. Under general anesthesia, five Welsh Mountain sheep fetuses were instrumented with vascular catheters, and transit-time flow transducers were implanted around a femoral artery and an umbilical artery. At least 5 d after surgery, fetuses were subjected to 1 h of normoxia, 0.5 h of hypoxemia, and 1 h of recovery. Hypoxemia induced significant falls in fetal pH(a), arterial oxygen pressure, acid-base excess, and [HCO(3)(-)], without alteration to arterial partial pressure of carbon dioxide. An increase in arterial blood pressure, a fall in heart rate, an increase in femoral vascular resistance, and a decrease in umbilical vascular resistance occurred in all fetuses. During hypoxemia, plasma S100beta increased significantly and remained elevated until the end of the protocol. Within individual fetuses, plasma S100beta correlated with femoral vascular resistance and pH. In contrast, no relationship was found between S100beta and umbilical vascular resistance. This study reports for the first time that a controlled period of fetal hypoxemia with associated acidemia leads to persistent elevations in plasma S100beta concentrations that strongly correlate with hemodynamic changes that are known to occur during fetal blood flow redistribution. These findings open up a new role for changes in fetal S100beta concentrations as a possible early marker of fetal hypoxia with associated acidemia in perinatal medicine.

Animals↗

PubMed2005

Vasodilator tone in the llama fetus: the role of nitric oxide during normoxemia and hypoxemia.

The fetal llama responds to hypoxemia, with a marked peripheral vasoconstriction but, unlike the sheep, with little or no increase in cerebral blood flow. We tested the hypothesis that the role of nitric oxide (NO) may be increased during hypoxemia in this species, to counterbalance a strong vasoconstrictor effect. Ten fetal llamas were operated under general anesthesia. Mean arterial pressure (MAP), heart rate, cardiac output, total vascular resistance, blood flows, and vascular resistances in cerebral, carotid and femoral vascular beds were determined. Two groups were studied, one with nitric oxide synthase (NOS) blocker N(G)-nitro-L-arginine methyl ester (L-NAME), and the other with 0.9% NaCl (control group), during normoxemia, hypoxemia, and recovery. During normoxemia, L-NAME produced an increase in fetal MAP and a rapid bradycardia. Cerebral, carotid, and femoral vascular resistance increased and blood flow decreased to carotid and femoral beds, while cerebral blood flow did not change significantly. However, during hypoxemia cerebral and carotid vascular resistance fell by 44% from its value in normoxemia after L-NAME, although femoral vascular resistance progressively increased and remained high during recovery. We conclude that in the llama fetus: 1) NO has an important role in maintaining a vasodilator tone during both normoxemia and hypoxemia in cerebral and femoral vascular beds and 2) during hypoxemia, NOS blockade unmasked the action of other vasodilator agents that contribute, with nitric oxide, to preserving blood flow and oxygen delivery to the tissues.

Animals↗

PubMed2005

Development of cardiovascular function in the horse fetus.

In mammals, the mechanisms regulating an increase in fetal arterial blood pressure with advancing gestational age remain unidentified. In all species studied to date, the prepartum increase in fetal plasma cortisol has an important role in the maturation of physiological systems essential for neonatal survival. In the horse, the prepartum elevation in fetal cortisol and arterial blood pressure are delayed relative to other species. Hence, the mechanisms governing the ontogenic increase in arterial blood pressure in the horse fetus may mature much closer to term than in other fetal animals. In the chronically instrumented pony mare and fetus, this study investigated how changes in fetal peripheral vascular resistance, in plasma concentrations of noradrenaline, adrenaline and vasopressin, and in the maternal-to-fetal plasma concentration gradient of oxygen and glucose relate to the ontogenic changes in fetal arterial blood pressure and fetal plasma cortisol concentration as term approaches. The data show that, towards term in the horse fetus, the increase in arterial blood pressure occurs together with reductions in metatarsal vascular resistance, elevations in plasma concentrations of cortisol, vasopressin, adrenaline and noradrenaline, and falls in the fetal : maternal ratio of blood P(a,O(2)) and glucose concentration. Correlation analysis revealed that arterial blood pressure was positively related with plasma concentrations of vasopressin and noradrenaline, but not adrenaline in the fetus, and inversely related to the fetal : maternal ratio of blood P(a,O(2)), but not glucose, concentration. This suggests that increasing vasopressinergic and noradrenergic influences as well as changes in oxygen availability to the fetus and uteroplacental tissues may contribute to the ontogenic increase in fetal arterial blood pressure towards term in the horse.

Animals↗

PubMed2005

Endocrine and metabolic programming during intrauterine development.

In humans, low birth weight is associated with an increased risk of metabolic dysfunction in adult life. Many of these metabolic disorders have an endocrine origin and are accompanied by abnormal hormone concentrations. This has led to the hypothesis that adult metabolic disease arises in utero as a result of programming of key endocrine systems during suboptimal intrauterine conditions associated with fetal growth retardation. This review examines the experimental evidence for prenatal endocrine programming with particular emphasis on endocrine axes involved in growth and metabolism, namely, the hypothalamic-pituitary-adrenal axis, the endocrine pancreas and the somatotrophic axis. It also considers how changes in these endocrine systems contribute to the programming of metabolism in later life.

Endocrine System↗

PubMed2005

Carotid endarterectomy impairs blood pressure homeostasis by reducing the physiologic baroreflex reserve.

OBJECTIVE: To assess the impact of carotid endarterectomy on blood pressure homeostasis and baroreflex function, with particular reference to the presence or absence of significant contralateral carotid artery disease, we conducted a prospective study in 80 patients with symptomatic extracranial carotid disease undergoing carotid endarterectomy in a regional teaching hospital over 2 years. METHODS: Patients were divided into two groups: the control group (n = 37) had no significant contralateral carotid disease; patients in the diseased group (n = 23) had either >70% stenosis or occlusion of the contralateral carotid artery. Seventeen patients with abnormal heart rhythms, poor quality recordings, or with intermediate degrees of contralateral carotid stenosis were excluded. Three patients who had previously undergone contralateral carotid endarterectomy were separately evaluated. Atheromatous plaque was removed from carotid lumen and the baroreflex mechanism received direct intraoperative stimulation before and after carotid endarterectomy. The main outcome measures were (1) the hemodynamic response to the carotid endarterectomy, baroreflex sensitivity, and operating set point (the resting blood pressure, which the baroreflex mechanism maintains) before and after removal of the atheromatous plaque, and (2) the responsiveness of the ipsilateral baroreceptor mechanism to direct stimulation. The impact of the presence of contralateral carotid stenosis on these variables was also evaluated. RESULTS: Patients in the two groups were comparable for preoperative demographic, medication, and hemodynamic variables. Carotid endarterectomy led to a rise in mean arterial pressure from 81.3 +/- 3.9 mm Hg to 103.5 +/- 4.6 mm Hg ( P < .00001) and from 87.6 +/- 4.3 mm Hg to 94.0 +/- 4.5 mm Hg ( P < .003) in the diseased and control groups, respectively. The magnitude of blood pressure response was significantly greater in the diseased group than in the control group ( P < .00001). This hypertensive shift was not accompanied by the expected fall in heart rate. Direct baroreflex stimulation prior to carotid endarterectomy caused a significantly greater response in the diseased group, suggesting sensitization of the ipsilateral carotid baroreceptor in the presence of contralateral carotid disease. Furthermore, the baroreflex response was obliterated after endarterectomy. There were significant reductions in baroreflex sensitivity and a hypertensive shift in the operating set point, the magnitude of which was significantly greater in patients with contralateral carotid disease. CONCLUSIONS: Carotid endarterectomy impairs blood pressure homeostasis through surgical destruction of the ipsilateral carotid baroreflex mechanism. Patients with contralateral carotid stenosis have a reduced baroreflex reserve and show greater baroreflex dysfunction and hemodynamic instability after endarterectomy. These patients are at greater risk of postendarterectomy complications and should be monitored closely.

Aged↗

PubMed2004

Effects of gestational age and cortisol treatment on ovine fetal heart function in a novel biventricular Langendorff preparation.

Structural and functional maturation of a number of fetal organs and physiological systems occurs in the immediate period prior to term, in association with the prepartum increase in fetal plasma cortisol concentration. At present, little is known about how myocardial sensitivity to adrenergic and muscarinic cholinergic stimulation changes as the fetus approaches term, nor the role of the prepartum increase in plasma cortisol concentration in mediating these changes. This study used a novel Langendorff, biventricular, ovine fetal heart preparation to investigate the effects of advancing gestation and cortisol treatment on myocardial sensitivity to adrenergic (isoprenaline) and muscarinic cholinergic (carbachol) stimulation. It was hypothesized that cortisol infusion would fully mimic developmental changes in myocardial responsiveness to adrenergic and cholinergic stimulation. Sixteen Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters. At 125 +/- 1 days gestational age (dGA; term, 145 dGA) fetuses were infused with saline vehicle (n= 7; Premature Control) or with cortisol (n= 4; 2-3 mg kg(-1) d(-1)i.v.; Premature Cortisol) for 5 days. The Term Control group (n= 5) comprised fetuses that were surgically prepared at 130 dGA and infused with vehicle for 5 days prior to delivery (n= 2), or that received no surgery (n= 3). Under terminal anaesthesia, Premature Control and Premature Cortisol fetuses were delivered at 130 dGA and Term Control fetuses between 135 and 143 dGA. Following exsanguination under anaesthesia, fetal hearts were mounted in the Langendorff preparation, allowing measurement of left ventricular (LV) developed pressure and right ventricular (RV) developed pressure, heart rate (HR), coronary perfusion pressure and perfusate distribution to the myocardium. Cortisol infusion elevated fetal plasma cortisol concentrations to values similar to those measured close to term (45.0 +/- 7.1 ng ml(-1)). Advancing gestational age, but not cortisol treatment, enhanced fetal LV developed pressure, RV developed pressure and HR responses to carbachol (P < 0.05). Advancing gestational age, but not cortisol treatment, suppressed fetal LV developed pressure, RV developed pressure and HR responses to isoprenaline (P < 0.05). Maximum doses of either carbachol or isoprenaline had no effect on coronary perfusate distribution. Changes in myocardial responsiveness to adrenergic and muscarinic cholinergic stimulation with advancing gestation provide mechanisms that contribute to the maturation of the cardiovascular system as the ovine fetus approaches term. These changes in myocardial responsiveness are not solely dependent on preparturient elevations in fetal plasma cortisol concentration.

Adrenergic beta-Agonists↗

PubMed2004

Pituitary-adrenal responses to acute hypoxemia during and after maternal dexamethasone treatment in sheep.

The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal axis function were determined during basal and hypoxemic conditions in maternal and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117 d gestation (term = 145 d). Starting at 124 d, the ewes received i.m. injections of two doses of either dexamethasone (12 mg) or saline at 24-h intervals. All animals experienced one episode of hypoxemia when the dexamethasone was present in the maternal and fetal circulations [125 +/- 1 d (H1)] and a second episode of hypoxemia when the steroid was no longer detectable in either the maternal or fetal circulations [128 +/- 1 d (H2)]. The fall in partial pressure of oxygen in arterial blood in response to hypoxia was similar in the two episodes in both the fetal and the maternal blood. Maternal dexamethasone treatment diminished maternal and fetal basal plasma cortisol but not ACTH during the normoxic period of H1 but not H2. In control animals, hypoxemia induced increases in fetal but not maternal ACTH and cortisol concentrations. In dexamethasone-treated animals, maternal ACTH and cortisol concentrations also remained unchanged from baseline in both H1 and H2. In contrast, fetal plasma ACTH and cortisol responses to hypoxemia were significantly suppressed during H1 but not H2. Correlation of fetal plasma ACTH and cortisol concentrations suggested diminished cortisol output without a change in adrenocortical responsiveness in dexamethasone-treated fetuses during H1 but not H2. Maternal treatment with dexamethasone transiently suppressed maternal and fetal basal hypothalamic-pituitary-adrenal axis function and the fetal plasma ACTH and cortisol responses to acute hypoxemia in sheep.

Acute Disease↗

PubMed2004

Effects of dexamethasone on the uterine and umbilical vascular beds during basal and hypoxemic conditions in sheep.

OBJECTIVE: The purpose of the study was to test the hypotheses that maternal treatment with dexamethasone leads to a reduction in basal umbilical blood flow and diminishes the fetal umbilical hemodynamic response to acute hypoxemic stress in sheep. STUDY DESIGN: While under general anesthesia, 23 ewes and their fetuses were instrumented with vascular catheters and transonic blood flow probes around a uterine and umbilical artery at 117 days of gestation (term, approximately 145 days). At 124 days, the ewes were injected intramuscularly with 2 doses of either dexamethasone (12 mg) or saline solution at 24-hour intervals. All animals experienced 2 episodes of hypoxemia during treatment (125+/-1 days) and after treatment (128+/-1 days). RESULTS: Maternal dexamethasone treatment caused a sustained increase in fetal arterial blood pressure (from 41+/-3 mm Hg to 45+/-3 mm Hg) and a transient fall in umbilical vascular conductance (from 6.2+/-0.9 mL. min(-1). [mm Hg](-1) to 5.4+/-0.7 mL. min(-1). [mm Hg](-1)). During both episodes of hypoxemia, there was a significant increase in umbilical blood flow in the controls, but not in the dexamethasone-treated animals. CONCLUSION: Maternal dexamethasone treatment with doses used in human clinical practice significantly decreased basal umbilical vascular conductance and prevented the normal increase in umbilical blood flow that is induced by acute hypoxemia in fetal sheep.

Acid-Base Equilibrium↗

PubMed2003

Antenatal glucocorticoids reset the level of baseline and hypoxemia-induced pituitary-adrenal activity in the sheep fetus during late gestation.

This study examined the effects of dexamethasone treatment on basal hypothalamo-pituitary-adrenal (HPA) axis function and HPA responses to subsequent acute hypoxemia in the ovine fetus during late gestation. Between 117 and 120 days (term: approximately 145 days), 12 fetal sheep and their mothers were catheterized under halothane anesthesia. From 124 days, 6 fetuses were continuously infused intravenously with dexamethasone (1.80 +/- 0.15 microg.kg(-1).h(-1) in 0.9% saline at 0.5 ml/h) for 48 h, while the remaining 6 fetuses received saline at the same rate. Two days after infusion, when dexamethasone had cleared from the fetal circulation, acute hypoxemia was induced in both groups for 1 h by reducing the maternal fraction of inspired O2. Fetal dexamethasone treatment transiently lowered fetal basal plasma cortisol, but not ACTH, concentrations. However, 2 days after treatment, fetal basal plasma cortisol concentration was elevated without changes in basal ACTH concentration. Despite elevated basal plasma cortisol concentration, the ACTH response to acute hypoxemia was enhanced, and the increment in plasma cortisol levels was maintained, in dexamethasone-treated fetuses. Correlation of fetal plasma ACTH and cortisol concentrations indicated enhanced cortisol output without a change in adrenocortical sensitivity. The enhancements in basal cortisol concentration and the HPA axis responses to acute hypoxemia after dexamethasone treatment were associated with reductions in pituitary and adrenal glucocorticoid receptor mRNA contents, which persisted at 3-4 days after the end of treatment. These data show that prenatal glucocorticoids alter the basal set point of the HPA axis and enhance HPA axis responses to acute stress in the ovine fetus during late gestation.

Acid-Base Equilibrium↗

PubMed2003

Enhanced umbilical blood flow during acute hypoxemia after chronic umbilical cord compression: a role for nitric oxide.

BACKGROUND: The continuing incidence of intrapartum morbidity may be partly due to antenatal compromise, which influences the fetal defense to labor and delivery. We have shown that antenatal exposure of the ovine fetus to partial compression of the umbilical cord suppresses femoral vasoconstriction during subsequent acute hypoxemia through elevated nitric oxide (NO) activity. This study investigated whether elevated NO activity in cord-compressed fetuses enhanced the vasodilator response to hypoxemia in circulations in which blood flow is known to increase during acute hypoxemia, such as the umbilical vascular bed. METHODS AND RESULTS: Fifteen fetal sheep were chronically instrumented between 117 and 120 days of gestation with vascular catheters and an umbilical flow probe. In 8 of these fetuses, umbilical blood flow was reduced by 30% for 3 days between 125 and 128 days. The remaining 7 fetuses acted as sham-operated controls. Between 2 and 7 days after umbilical cord/sham compression, fetuses were exposed to 2 episodes of acute hypoxemia, on separate days, during infusion with either saline or treatment with a combination of NG-nitro-l-arginine methyl ester and sodium nitroprusside. The data show that umbilical cord compression significantly enhances the umbilical hyperemia through NO-dependent mechanisms during a subsequent episode of acute hypoxemia. CONCLUSIONS: Increased fetal NO activity after chronic cord compression has opposing effects in circulations that either constrict or dilate during subsequent acute hypoxemia. The data imply that antenatal compromise switches the fetal strategy to withstand episodes of subsequent acute hypoxemia of the type that may occur during labor and delivery from a reliance on vasoconstrictor mechanisms to those promoting NO-dependent vasodilation.

Acute Disease↗

PubMed2003

Cardiovascular and endocrine responses to acute hypoxaemia during and following dexamethasone infusion in the ovine fetus.

This study investigated the effects of fetal treatment with dexamethasone on ovine fetal cardiovascular defence responses to acute hypoxaemia, occurring either during or 48 h following the period of glucocorticoid exposure. To address the mechanisms underlying these responses, chemoreflex function and plasma concentrations of catecholamines, neuropeptide Y (NPY) and vasopressin were measured. Under general halothane anaesthesia, 26 Welsh Mountain sheep fetuses were surgically prepared for long-term recording at between 117 and 120 days of gestation (dGA; term is approximately 145 days) with vascular catheters and a Transonic flow probe around a femoral artery. Following at least 5 days of recovery, fetuses were randomly assigned to one of two experimental groups. After 48 h of baseline recording, at 125 +/- 1 dGA, half of the fetuses (n = 13) were continuously infused I.V. with dexamethasone for 48 h at a rate of 2.06 +/- 0.13 microg kg-1 h-1. The remaining 13 fetuses were infused with heparinized saline at the same rate (controls). At 127 +/- 1 dGA, 2 days from the onset of infusions, seven fetuses from each group were subjected to 1 h of acute hypoxaemia. At 129 +/- 1 dGA, 2 days after the end of infusions, six fetuses from each group were subjected to 1 h of acute hypoxaemia. Similar reductions in fetal partial pressure of arterial oxygen occurred in control and dexamethasone-treated fetuses during the acute hypoxaemia protocols. In control fetuses, acute hypoxaemia led to transient bradycardia, femoral vasoconstriction and significant increases in plasma concentrations of catecholamines, vasopressin and NPY. In fetuses subjected to acute hypoxaemia during dexamethasone treatment, the increase in plasma NPY was enhanced, the bradycardic response was prolonged, and the plasma catecholamine and vasopressin responses were diminished. In fetuses subjected to acute hypoxaemia 48 h following dexamethasone treatment, femoral vasoconstriction and plasma catecholamine and vasopressin responses were enhanced, whilst the prolonged bradycardia and augmented plasma NPY responses persisted. These data show that fetal treatment with dexamethasone modifies the pattern and magnitude of fetal cardiovascular responses to acute oxygen deprivation. Modifications to different mechanisms mediating the fetal defence responses to acute hypoxaemia that occur during dexamethasone treatment may reverse, persist or even become enhanced by 48 h following the treatment period.

Acid-Base Equilibrium↗

PubMed2003

The role of neuropeptide Y in the ovine fetal cardiovascular response to reduced oxygenation.

This study investigated the role of neuropeptide Y (NPY) in mediating cardiovascular responses to reduced oxygenation in the late gestation ovine fetus by: (1) comparing the effects on the cardiovascular system of an exogenous infusion of NPY with those elicited by moderate or severe reductions in fetal oxygenation; and (2) determining the effect of fetal I.V. treatment with a selective NPY-Y(1) receptor antagonist on the fetal cardiovascular responses to acute moderate hypoxaemia. Under general anaesthesia, 14 sheep fetuses (0.8-0.9 of gestation) were surgically prepared with vascular and amniotic catheters. In 5 of these fetuses, a Transonic flow probe was also implanted around a femoral artery. Following at least 5 days of recovery, one group of fetuses (n = 9) was subjected to a 30 min treatment period with exogenous NPY (17 microg kg(-1) bolus plus 0.85 microg kg(-1) min(-1) infusion). In this group, fetal blood pressure and heart rate were monitored continuously and the distribution of the fetal combined ventricular output was assessed via injection of radiolabelled microspheres before and during treatment. The second group of fetuses instrumented with the femoral flow probe (n = 5) were subjected to a 3 h experiment consisting of 1 h of normoxia, 1 h of hypoxaemia, and 1 h of recovery during a slow I.V. infusion of vehicle. One or two days later, the acute hypoxaemia protocol was repeated during fetal I.V. treatment with a selective NPY-Y(1) receptor antagonist (50 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion). In these fetuses, fetal arterial blood pressure, heart rate and femoral vascular resistance were recorded continuously. The results show that fetal treatment with exogenous NPY mimics the fetal cardiovascular responses to asphyxia, and that treatment of the sheep fetus with a selective NPY-Y(1) receptor antagonist does not affect the fetal cardiovascular response to acute moderate hypoxaemia. These results support a greater role for NPY in mediating the fetal cardiovascular responses to acute asphyxia than to acute moderate hypoxaemia.

Animals↗

PubMed2003

Enhanced nitric oxide activity offsets peripheral vasoconstriction during acute hypoxaemia via chemoreflex and adrenomedullary actions in the sheep fetus.

We tested the hypothesis that enhanced nitric oxide (NO) opposes fetal peripheral vasoconstrictor responses to acute hypoxaemia via actions involving the carotid chemoreflex and the adrenal medulla. The hypothesis was tested in the late gestation ovine fetus using a novel NO clamp technique, which involves fetal combined treatment with the NO synthase inhibitor, L-NAME, and the NO donor, sodium nitroprusside. In contrast to treatment with L-NAME alone, combined fetal treatment with L-NAME and nitroprusside prevents generalized vasoconstriction and pronounced hypertension, not only maintaining basal cardiovascular function, but also permitting blockade of the de novo synthesis of NO during hypoxaemia while compensating for the tonic production of the gas. Under general anaesthesia, seven sheep fetuses were surgically prepared with catheters and a femoral Transonic flow probe. Five days after surgery, fetuses were subjected to a 3 h protocol: 1 h normoxia, 1 h hypoxaemia and 1 h recovery. Fetal hypoxaemia was induced during either fetal infusion with saline or treatment with the NO clamp. During saline infusion, fetuses responded to hypoxaemia with transient bradycardia, femoral vasoconstriction and increases in plasma noradrenaline and adrenaline. During fetal treatment with the NO clamp, bradycardia persisted and there were greater peripheral vasoconstrictor and catecholaminergic responses to hypoxaemia. Further analysis showed that NO clamp treatment enhanced the chemoreflex component of the fetal cardiovascular defence to acute hypoxaemia. These data support the hypothesis that enhanced NO synthesis during acute hypoxaemia offsets fetal peripheral vasoconstrictor responses to hypoxaemia via chemoreflex and adrenomedullary actions.

Acute Disease↗

PubMed2003

Effect of dexamethasone on pulmonary and renal angiotensin-converting enzyme concentration in fetal sheep during late gestation.

OBJECTIVES: The effect of dexamethasone on tissue angiotensin-converting enzyme (ACE) was investigated in fetal sheep. STUDY DESIGN: Pulmonary and renal ACE concentrations were measured in 16 sheep fetuses at between 127 and 131 days of gestation (term 145+/-2 days): 6 were untreated, whereas 10 were chronically catheterized and infused intravenously with either saline solution (0.9%, n=4) or dexamethasone (45-60 microg. kg(-1). d(-1), n=6) for the previous 2 days. The dexamethasone dose increased plasma dexamethasone to around one fifth of that measured in newborn human infants delivered after maternal dexamethasone treatment. RESULTS: Over the period of infusion, arterial blood pressure increased significantly in the dexamethasone (+6.8+/-1.5 mm Hg, P<.05) but not saline-treated fetuses (+1.6+/-0.6 mm Hg). At delivery, pulmonary ACE in the dexamethasone-infused fetuses (1.24+/-0.26 nmoles hippurate. min(-1). mg protein(-1)) was significantly greater than in the control fetuses (0.50+/-0.07 nmoles. min(-1). mg protein(-1), P<.005); renal ACE was unchanged by dexamethasone treatment. Overall, pulmonary ACE and blood pressure were correlated on the last day of infusion (r=0.70, P<.05). CONCLUSION: The rise in pulmonary ACE seen in dexamethasone-treated sheep fetuses may contribute, in part, to the glucocorticoid-induced increase in blood pressure.

Animals↗