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Biomedical subjects

K Beharry

Publications and source records attributed to K Beharry.

34 records · Page 2Linked to original sources
PubMed1991

Ibuprofen enhances retinal and choroidal blood flow autoregulation in newborn piglets.

The role of prostanoids in setting the range of autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) in the newborn was assessed. The RBF, ChBF, and arterial and cerebral sinus concentrations of PGE, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 were measured over a wide range of mean systemic blood pressure (blood pressure (BP): 17-117 mm Hg) in newborn piglets treated with ibuprofen (30 mg/kg iv) or its vehicle (n = 8, in each group). Hypertension and hypotension were induced 80 min apart on each animal, by inflating balloon-tipped catheters placed at the aortic isthmus and root, respectively. Blood flow and prostanoid concentrations were measured 20 min before (basal) and during the induced changes in BP. In vehicle-treated piglets, RBF did not change with BP between 50 and 90 mm Hg (r = 0.33, P = 0.27), but changed as a function of BP beyond this range (tau = 0.52, P less than 0.01); ChBF increased with BP throughout the range studied (17-117 mm Hg; tau = 0.89, P less than 0.001). The relationship between O2 delivery to the retina and choroid and BP (tau greater than 0.43, P less than 0.01) was similar to that seen between RBF and ChBF with BP. The concentration of all prostanoids increased when BP was reduced to less than 50 mm Hg. When BP was raised to more than 90 mm Hg, prostaglandin concentrations increased, and those of TXB2 did not change. Ibuprofen treatment reduced the basal concentrations of all prostanoids to nearly undetectable levels and prevented their changes during hypotension and hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of adenosine on total and regional cerebral blood flow of the newborn piglet.

The effect of adenosine on total and regional CBF, measured by radiolabeled microspheres, was assessed in 16 anesthetized and ventilated newborn (1-3 days old) piglets. They received a ventriculocisternal perfusion containing either CSF alone (controls, n = 5) or CSF mixed with two different concentrations of adenosine (15 min each) randomly assigned using the following doses: 0.1 microM, 10 microM, 100 microM, 1 mM (n = 4), or 10 mM (n = 6). Mean CSF adenosine concentration (by HPLC) before perfusion was 0.6 +/- 0.4 microM. Total and regional CBF were not altered by the perfusion of CSF alone. All adenosine concentrations, except at low doses, increased total and regional CBF, without altering the cerebral metabolic rate for oxygen. Brainstem blood flow was increased by a mean of 110, 145, 306, and 378% with 10 microM, 100 microM, 1 mM, and 10 mM concentrations, respectively. Except for the highest concentration, CBF response was dose dependent in each region of the brain with the following order of potency: brainstem greater than periventricular area greater than telencephalon, midbrain, total brain, and cerebellum. These data indicate that, in the newborn, adenosine is a potent vasodilator of cerebral vessels. If the newborn brain can synthesize appropriate concentrations of adenosine, this nucleoside may play a major role in regional CBF regulation during the neonatal period.

Adenosine↗
PubMed1990

Influence of adenosine on cerebral blood flow during hypoxic hypoxia in the newborn piglet.

This study investigated the role of adenosine in the regulation of neonatal cerebral blood flow (CBF) during moderate (arterial PO2 = 47 +/- 9 Torr) and severe (arterial PO2 = 25 +/- 4 Torr) hypoxia. Twenty-eight anesthetized and ventilated newborn piglets were assigned to four groups: 8 were injected intravenously with the vehicle (controls, group 1); 13 received an intravenous injection of 8-phenyltheophylline (8-PT), a potent adenosine receptor blocker, either 4 mg/kg (group 2, n = 6, mean cerebrospinal fluid (CSF) levels less than 1 mg/l) or 8 mg/kg (group 3, n = 7, mean CSF levels less than 3.5 mg/l); and 7 received an intracerebroventricular injection of 10 micrograms 8-PT (group 4). During normoxia, CBF was not altered by vehicle or 8-PT injections. In group 1, 10 min of moderate and severe hypoxia increased total CBF by 112 +/- 36 and 176 +/- 28% (SE), respectively. Compared with controls, the cerebral hyperemia during moderate hypoxia was not altered in group 2, attenuated in group 3 (to 53 +/- 13%, P = NS), and completely blocked in group 4 (P less than 0.01). CBF increase secondary to severe hypoxia was attenuated only in group 4 (74 +/- 29%, P less than 0.05). CSF concentrations of adenosine and adenosine metabolites measured by high-performance liquid chromatography increased during hypoxia. Arterial O2 content was inversely correlated (P less than 0.005) to maximal CSF levels of adenosine (r = 0.73), inosine (r = 0.87), and hypoxanthine (r = 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1990

Changes in cerebrovascular prostaglandins and thromboxane as a function of systemic blood pressure. Cerebral blood flow autoregulation of the newborn.

Cerebrovascular concentrations of prostaglandin E (PGE), prostaglandin F2 alpha (PGF2 alpha), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2) were determined over a blood pressure range of 17-117 mm Hg (induced by inflation of balloon-tipped catheters placed in the thoracic descending aorta and at the aortic root) in eight newborn piglets to access the role of prostanoids in cerebral blood flow (CBF; measured using radioactive microspheres) autoregulation. Basal systemic blood pressure, heart rate, blood gases, total CBF, and prostanoid concentrations were stable. CBF was constant between 50 and 90 mm Hg, but beyond this range CBF varied directly with blood pressure (tau = 0.48; p less than 0.05). Sagittal sinus concentrations of PGE, PGF2 alpha, and 6-keto-PGF1 alpha varied with blood pressure according to a quadratic function (R2 = 0.92 to 0.96; p less than 0.0001), exhibiting lowest values between mean blood pressures of 60 and 90 mm Hg. During hypotension (17-49 mm Hg), there was a greater relative increase in sagittal sinus concentrations of TXB2 than of PGE, PGF2 alpha, and 6-keto-PGF1 alpha; at the lowest blood pressures, TXB2 increased by 658 +/- 44%, and prostaglandins increased on the average by 331 +/- 49% (p less than 0.01) from their values during normotension (50-90 mm Hg). During hypertension (91-117 mm Hg), cerebrovascular production and concentrations of prostaglandins increased by 142 +/- 31% and 45 +/- 10%, respectively, but did not change for TXB2.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Prostanoids determine the range of cerebral blood flow autoregulation of newborn piglets.

To assess whether prostanoids have a role in setting the blood pressure limits of cerebral blood flow autoregulation in newborn animals, we measured cerebral blood flow and prostanoid concentrations in blood from the sagittal sinus over a wide range of mean systemic blood pressures (17-117 mm Hg) in eight newborn piglets treated with 30 mg/kg i.v. ibuprofen and in eight vehicle-treated piglets. Blood pressure was adjusted by inflating balloon-tipped catheters placed at the aortic isthmus and root to induce hypertension and hypotension, respectively, 80 minutes apart in each piglet. Cerebral blood flow and concentrations of prostaglandins E and F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 in blood from the sagittal sinus and left subclavian artery were measured 20 minutes before (baseline) and during each blood pressure adjustment. In vehicle-treated piglets, cerebral blood flow was constant at blood pressures between 50 and 90 mm Hg (r = 0.06, p = 0.85). When blood pressure was reduced to less than 50 mm Hg, thromboxane B2 concentration in the sagittal sinus increased by 597 +/- 42% and concentrations of the prostaglandins increased by an average of 308 +/- 45% (p less than 0.05). When blood pressure was raised to greater than 90 mm Hg, concentrations of the prostaglandins increased by an average of 46 +/- 11%, with no change in the concentration of thromboxane B2. Treatment with ibuprofen reduced the baseline concentrations of all prostanoids and prevented their changing during hypotension and hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Pharmacodynamic effects and pharmacokinetic profiles of keto-doxapram and doxapram in newborn lambs.

Keto-doxapram (keto-dox), an oxidative metabolite of doxapram, is a possible ventilatory stimulating agent. Our study characterizes its ventilatory properties, pharmacodynamic effects, and pharmacokinetic profile, and those of its parent compound, doxapram. Two groups of five awake, unsedated, newborn lambs (2- to 6-d old) received, respectively, i.v. infusions of keto-dox or doxapram (2.5 mg/kg) over a period of 1 min. Ventilatory parameters were continuously recorded before and for 1 h after the drug infusion. The pharmacokinetic profiles of both drugs were determined from blood samples collected serially before and after drug injection. Both drugs stimulated ventilation. Keto-dox increased baseline minute ventilation by 46 +/- 6.1% and 27.8 +/- 8.1% (p less than 0.002) at 1 and 5 min, respectively, an effect that decreased after 5 min of infusion. Doxapram increased minute ventilation by 57 +/- 9% (p less than 0.002) at 1 min, and by 48 +/- 7% at 5 min, but its effect lasted for 20 min after injection. Compared with the effects of keto-dox, this doxapram increase was significantly higher (p less than 0.02). Also, doxapram, but not keto-dox, caused an increase in systolic blood pressure (from 110 +/- 3.5 to 118 +/- 3.4 mm Hg at 10 min, p less than 0.01), as well as a change in neuro-behavior. Both drugs exhibited a biexponential decay curve, characterized by a short alpha and a longer beta t1/2, but keto-dox has a faster elimination rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of prostaglandins and indomethacin on cerebral blood flow and cerebral oxygen consumption of conscious newborn piglets.

The effects of the prostaglandins (PG) PGE1, PGE2, PGF2 alpha and PGI2, and of indomethacin on cerebral blood flow (CBF) and cerebral metabolic rate for O2 (CMRO2) were studied in 60 1- to 3-day-old conscious piglets. Effects of PGs in indomethacin-treated animals were also measured. CBF was measured by radiolabelled microspheres prior to and 45 s after intracarotid bolus injections of 0.1-10 micrograms/kg PGE1 and 0.01-1 micrograms/kg PGE2, PGF2 alpha and PGI2. PGE1 decreased CBF by 30% at the dose of 0.1 micrograms/kg and increased it by 39.5% (n = 6) at the higher dose of 10 micrograms/kg. PGE2 (n = 6) increased CBF at all doses administered. PGF2 alpha (0.01 micrograms/kg, n = 8), which is a potent cerebral vasoconstrictor in adults, and PGI2 (0.1 micrograms/kg, n = 6) significantly increased CBF in newborn piglets (p less than 0.05). CMRO2 correlated with CBF in all groups of animals, except for those injected with PGI2. Indomethacin (3 mg/kg i.v.) decreased CBF by 39% (p less than 0.01, n = 6). This effect was partially reversed by PGI2, but not by PGE1 and PGF2 alpha. Sagittal venous blood and arterial-sagittal venous blood differences in concentrations of PGF2 alpha, but not of PGE and 6-keto-PGF1 alpha, correlated weakly but positively (r = 0.4, p less than 0.05) with CBF in indomethacin-treated piglets. These data indicate that PGs exert significant effects on cerebral circulation in the newborn. Primary PGs are principally cerebral vasodilators and are devoid of vasoconstrictive effects in the newborn, except for PGE1 which produces vasoconstriction at low dose (0.1 micrograms/kg). Thus, we speculate that a relative deficiency in cerebral vasoconstrictor effect of PGs may contribute to the reduced upper limit of the CBF autoregulatory range of the newborn.

Animals↗
PubMed1989

Ontogeny of adenosine production and degradation and its implications in neonatal cerebral blood flow regulation.

Adenosine is a neuromodulator and potent vasoactive metabolite involved in various CNS regulatory mechanisms. We have recently shown that the newborn has maturationally related deficiency in adenosine production. The brains of Sprague-Dawley rats studied at ages 1, 7, 21 and 60 days (n = 6-12/group) showed that adenosine and its metabolites (measured by high-pressure liquid chromatography) is deficient in the newborn. Adenosine brain concentration was 0.99 nmol/g brain in newborn rats (day 0-1) and progressively increased postnatally to an adult value of 14.4 nmol/g brain. Inosine, a degradative product of adenosine by deaminase is significantly increased in newborns (mean +/- SEM = 48.3 +/- 14.3 nmol/g brain) relative to the 7-day-old rat (7.4 +/- 1.1 nmol/g brain) and to the adult (17.8 +/- 3.6 nmol/g brain). Thus, newborns have deficient adenosine brain concentration and this is due in part to increased deamination of adenosine. However, adenosine brain production may be augmented by ischemic-hypoxic insult. This was tested in 2 age groups of rats: 7 days old (n = 35) and adults (n = 35). Under nembutal anesthesia, bilateral carotid arteries were exposed and loosely tied, then both carotids were ligated and 5 animals from each group were decapitated and heads immediately frozen in liquid N2 at 5, 15, 30, 60, 120 and 300 s after ligation. Similar animals with carotids exposed but not ligated served as control (time zero). Brains were removed and assayed for adenosine and metabolites using high-pressure liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1987

Caffeine enzyme immunoassay in neonatal and pediatric drug monitoring.

An enzyme immunoassay technique (EMIT) for microdeterminations of caffeine was compared with high performance liquid chromatography (HPLC) and evaluated in 113 neonates and young infants, and in 18 asthmatic and 15 epileptic children. The EMIT assay was found reliable in therapeutic drug monitoring. It offers advantages over HPLC in its rapidity and simplicity. It is not affected by hemolysis, hyperbilirubinemia, or lipemia. In the neonate, greater accuracy is obtained with blood samples containing no heparin.

Anticoagulants↗
PubMed1986

Interaction between chloramphenicol and acetaminophen.

Acetaminophen has been reported either to prolong or not to affect the clearance of chloramphenicol. To confirm one of these findings we studied the clearance of chloramphenicol and its metabolites using high pressure liquid chromatography in five patients (ages 2.5 to 5 years) before and during oral treatment with acetaminophen (50 mg/kg/day). Significant differences were observed in mean (SD) peak serum chloramphenicol concentration (-9.7 (3.2) mg/l), mean (SD) apparent volume of distribution (+225 (162) ml/kg), mean (SD) chloramphenicol half life (-1.9 (1.1) hours), mean (SD) chloramphenicol clearance (+236 (94) ml/kg/h), mean (SD) area under the curve (-83.5 (33.0) mg/l/h), and mean (SD) elimination constant (+0.34 (0.13) h-1) between samples obtained before and during treatment with acetaminophen. Acetaminophen, when given orally for several days, increased the clearance of chloramphenicol, perhaps by increased glucuronidation. This report re-emphasises the need for therapeutic drug monitoring whenever these two drugs are used together.

Acetaminophen↗
PubMed1986

Indomethacin metabolism in liver microsomes during postnatal development in the rat.

Indomethacin is now widely used during the neonatal period, but few data exist concerning its metabolism during this period. Thus, we studied the maturational changes in the metabolism of indomethacin into desmethylindomethacin by isolated liver microsomes from 1- to 60-day-old rats. From 8 days of age on, there was a progressive increase in enzymatic activity which was inversely correlated with the change in Michaelis-Menten constant. However, the maximal velocity was not significantly affected by the age. These findings suggest that the deficient metabolism of indomethacin in the newborn rat is due to decreased affinity between enzyme and substrate, or presence of competitive inhibitors. To determine the substrate specificity of the monooxygenase-catalyzing inducers, sodium phenobarbital and beta-naphthoflavone given during 3 days in neonatal rats were also studied. Although beta-naphthoflavone did not exhibit any significant effect, phenobarbital significantly increased the activity and maximal velocity of indomethacin O-demethylation.

Aging↗
PubMed1986

Effect of phenobarbital on cerebral blood flow in the newborn piglet under stress.

Heart rate, cardiac output, mean arterial blood pressure (MABP), and cerebral blood flow (CBF) were measured in 12 newborn piglets (6 controls and 6 pretreated with 20 mg/kg phenobarbital), under two different stresses: pain stimulation and intravenous injection of 2.5 mg/kg phenylephrine. Phenobarbital prevented pain-induced tachycardia (p less than 0.05 versus controls) but failed to prevent hemodynamic changes induced by phenylephrine. CBF remained relatively constant throughout the study. A better correlation between cerebral vascular resistance and MABP was noted in the phenobarbital group (r = 0.58, p less than 0.01) than in the controls (r = 0.15, p = NS), suggesting that phenobarbital potentiates the vasoconstrictor effect of catecholamines.

Animals↗
PubMedDate not supplied

The role of prostanoids in neonatal cerebral blood flow autoregulation.

The regulatory role of prostanoids in acute cerebrovascular adaptations in newborns was determined using awake neonatal piglets (ages 0-5 days, n = 60). Cerebral blood flow (CBF) was measured by radiolabelled microspheres before and 45 s after intracarotid injections of PGE1 (0.1-10 micrograms/kg, n = 6), PGE2 (0.01-2 micrograms/kg, n = 6), PGF2 alpha (0.01 microgram/kg, n = 8) and PGI2 (0.1 microgram/kg, n = 6). CBF increased with PGE1 (10 micrograms/kg) by 39.5% and with all doses of PGE2 (p < 0.01) compared to zero dose. PGF2 alpha, a known adult vasoconstrictor increased total CBF from 97 +/- 8 to 130 +/- 14 ml/min per kg. PGI2 also increased CBF by 27% (p < 0.01). When CBF and prostanoid levels were measured with balloon catheters placed at the aortic root and the descending aorta and were inflated to adjust arterial blood pressure (BP) from 17 to 117 mmHg, sagittal sinus concentrations of prostanoids inversely correlated with total CBF (for PGs, tau = -0.52 to -0.66, p < 0.001; for TXB2, tau = -0.91 to 0.99, p < 0.0001). During hypotension (MABP < 50 mmHg) PGE, PGF2(2)alpha, 6-keto-PGF1 alpha and TXB2 increased by 311 +/- 56, 330 +/- 50, 301 +/- 44 and 658 +/- 44%, respectively. Net cerebrovascular production [total CBF x (sagittal sinus-arterial plasma prostanoid concentration)] of PGE, PGF2 alpha, and 6-keto-PGF1 alpha and TXB2 increased during hypotension compared to normotension (BP = 50-90 mmHg). At MABP = 91-117 mmHg, net production of prostanoids increased by 142-31%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Combined effects of antenatal corticosteroids and surfactant supplementation on the outcome of very low birth weight infants.

Antenatal corticosteroids in preterm pregnancy may result in the reduction of the incidence of respiratory distress syndrome (RDS) and neonatal mortality. It is well known that postnatal use of surfactant in very low birth weight (VLBW) infants with RDS results in decreased neonatal morbidity and mortality. To evaluate the additive beneficial effects of combined antenatal corticosteroids and postnatal use of rescue surfactant on the outcome of VLBW infants, we retrospectively reviewed 286 maternal/infant charts of preterm infants with gestational ages 23 to 32 weeks and birth weights 501 to 1500 gm who were born at our institution from 1991 through 1994. Of the 87 (30%) infants who were treated with corticosteroids before birth, 41 (47%) had RDS, and of the 199 (70%) infants who were not treated with corticosteroids before birth, 162 (81%) had RDS (p < 0.001). The infants who had RDS and who were treated with corticosteroids before birth had a decreased incidence of pulmonary air leaks and a decreased need for diuretic therapy. In addition, they had a significant reduction in O2 requirement and ventilator settings as reflected by FIO2, mean airway pressure, ventilator rate, O2 index, and A-aDO2 before they received the first dose of rescue surfactant (p < 0.05 to p < 0.01) in contrast to other VLBW infants who had RDS and who were not treated with corticosteroids before birth. We conclude that antenatal corticosteroid therapy in threatened premature labor combined with the use of postnatal rescue surfactant is associated with a decreased incidence of RDS and may be beneficial for reducing the severity of RDS and improving the eventual outcome of VLBW infants.

Betamethasone↗
PubMedDate not supplied

Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity.

OBJECTIVES: To determine the comparative efficacy of Exosurf Neonatal and Survanta surfactants on the early course of respiratory distress syndrome (RDS), arterial blood gases, ventilatory support, outcome morbidity rate, and complications of prematurity and RDS. STUDY DESIGN: Medical records from 203 premature newborn infants undergoing mechanical ventilation for respiratory distress syndrome, and who received up to four rescue doses of either Exosurf or Survanta, were retrospectively reviewed. RESULTS: All groups were comparable for birth weight and gestational age. Although the two randomized groups were similar in severity of RDS based on fraction of inspired oxygen (FIO2) and ventilatory support, a significantly greater improvement in respiratory function as evidenced by FIO2, mean airway pressure, alveolar-arterial partial pressure of oxygen difference, and oxygen index, was observed in the Survanta group from 12 hours (p < 0.05) through 48 hours (p < 0.01). Comparison of outcome morbidity rate by gestational age showed a higher occurrence of retinopathy of prematurity (p < 0.02) among the older infants (28 to 32 weeks) who were treated with Exosurf. CONCLUSION: Survanta exerted a significantly faster response in the early clinical course of RDS compared with Exosurf. However, no difference in the impact on eventual respiratory outcome was observed. We therefore conclude that both surfactants are effective for the treatment of RDS.

Biological Products↗