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Biomedical subjects

J V Aranda

Publications and source records attributed to J V Aranda.

At least 55 records · Page 3Linked to original sources
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

Effects of adenosine and its analogues on isolated internal carotid arteries from newborn and adult pigs.

Vasorelaxant effects of adenosine and its analogues, 5'-N-(ethylcarboxamide) adenosine (NECA), N6-(l-phenylisopropyl)-adenosine (l-PIA) and N6-cyclohexyladenosine (CHA), on isolated internal carotid arteries from newborn (1-3 days) and adult (6 months) pigs were compared. The order of vasorelaxant potencies of adenosines was: NECA greater than l-PIA greater than adenosine greater than CHA for the adult arteries and NECA greater than l-PIA greater than adenosine = CHA for the newborn arteries. Sensitivities of vessels from the newborn and mature animals to CHA and l-PIA did not differ. However, carotid arteries from the newborn pigs were less sensitive to NECA and adenosine than the adult arteries (p less than 0.05). Theophylline caused an approximately 3-fold shift to the right of the relaxant concentration-response curves to all the four adenosines on arteries from pigs of both age groups. These data suggest that adenosine is not as effective a vasodilator in the newborn as it is in the adult.

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

Alternating sequential dosing with furosemide and ethacrynic acid in drug tolerance in the newborn.

Drug tolerance seems to develop rapidly after the administration of sequential doses of the same loop diuretic. We evaluated whether alternating different loop diuretics could achieve the same initial diuretic response in the newborn. In a randomized double crossover study, we examined the diuretic and saliuretic effects of alternating doses of furosemide and ethacrynic acid (1 mg/kg administered intravenously every 24 hours) in 10 newborns, who received the drugs in the following sequential order: (1) furosemide, (2) ethacrynic acid, and (3) furosemide (group 1, n = 5); and (1) ethacrynic acid (2) furosemide, and (3) ethacrynic acid (group 2, n = 5). Hourly urine specimens were collected for the determination of rates of urinary and fractional excretion of sodium, chloride, and potassium and of urinary flow, before and 6 hours after dosing. There were no differences between the groups at each dose for all parameters measured. A significant decrease in prediuretic and postdiuretic rates of urinary flow, in sodium and chloride excretion, and in the fractional excretion of these electrolytes was observed before and after dosing. The associated reduction in patients' weights suggested a depletion in plasma volume. In conclusion, consecutive alternation of furosemide and ethacrynic acid in the same newborn does not prevent the development of pharmacologic tolerance to loop diuretics, since diuresis, natriuresis, and chloriuresis decrease after successive sequential administration of these drugs.

Creatinine↗
PubMed1989

Pharmacology of diuretics in the newborn.

Diuretics are used in various conditions with fluid overload. Their efficacy in the management of congestive heart failure is well documented. In contrast, the indication of diuretics in chronic lung disease and central nervous system disorders of the newborn have not been clearly established. Substantial pharmacologic knowledge of diuretics in the young infant remains to be described. Most investigations on diuretics in the sick newborn infant have examined furosemide. In contrast, the pharmaco-dynamics, pharmacokinetics, clinical indications, and toxicity of other diuretics used in the newborn require considerable further evaluation. Future studies using a combination of diuretics, acting at different segments of the nephron, also may provide newer therapeutic modalities to overcome or prevent the development of frequently observed tolerance to diuretics, as well as to treat refractory edema.

Acute Kidney Injury↗
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↗
PubMed1989

Use of caffeine in the treatment of apnea associated with the Arnold-Chiari malformation.

The occurrence of significant apnea has been reported in infants with Arnold-Chiari malformation (ACM). We report 1 infant with ACM and severe apnea treated with caffeine therapy. There was a marked decrease in apnea frequency, less variability in breathing patterns, and a shift to the left of the CO2 response curve with caffeine. Our findings in 1 infant suggest that caffeine may be an effective adjunct in the treatment of apnea associated with ACM.

Arnold-Chiari Malformation↗
PubMed1988

Need for endotracheal intubation and suction in meconium-stained neonates.

In a prospective study, we determined whether routine immediate tracheal aspiration at birth is necessary in meconium-stained but otherwise normal infants delivered vaginally and having a 1-minute Apgar score greater than 8. A total of 572 newborn infants who met these criteria were randomly allocated to one of two groups. All infants underwent oropharyngeal suctioning with a DeLee catheter while the head was still on the perineum. In group I (n = 308) suctioning of the trachea under direct vision was performed instantly at birth; in group II (n = 264) this procedure was not done. There was no mortality among infants in the study, but morbidity, mainly pulmonary and laryngeal disorders, occurred in six of 308 group I infants and in none of the group II infants (P less than 0.025). Immediate tracheal suction is not a harmless intervention, and should be considered superfluous in a vigorous term neonate born with meconium-stained amniotic fluid.

Apgar Score↗
PubMed1988

Effect of indomethacin on cerebral blood flow velocity of premature newborns.

Using the Doppler technique, the effect of therapeutic doses of indomethacin on the cerebral blood flow velocity (CBFV) of anterior cerebral arteries was studied in 13 preterm infants with patent ductus arteriosus. The first intravenous injection of indomethacin (0.2 mg/kg, group 1, n = 10) induced a significant decrease in the area under the velocity curve at 15 min (-22%), which was sustained until 120 min (-28%, p less than 0.005). In contrast, no significant change in CBFV occurred after the third dose (group 2, n = 7). In both groups, capillary blood gases, mean arterial blood pressure, and heart rate remained stable throughout the study. In 5 mechanically ventilated infants, the increase in CBFV secondary to suctioning was significantly attenuated after the first dose of indomethacin (p less than 0.02) but not after the third (p = 0.56). Thus, an initial dose of indomethacin may attenuate CBFV increases secondary to clinical manipulations in the preterm newborn.

Apgar Score↗
PubMed1987

Cumulative increase in serum furosemide concentration following repeated doses in the newborn.

In order to test whether repeat doses of the diuretic furosemide result in plasma accumulation of this drug, eight newborns (mean birthweight, 1252 gm; mean gestational age, 27.5 weeks; mean postnatal age, 44.7 days; and normal renal function) were each given a 1-mg/kg iv bolus every 12 hr for four doses and maintained normally hydrated throughout the study period. Serum furosemide peak concentrations (1 hr after administration) were measured in eight newborns, and trough levels in four newborns, by HPLC. The mean 1-hr serum furosemide level increased with repeated doses of the drug, from 3.18 +/- 0.52 to 7.95 +/- 2.36 mg/liter (mean +/- SE) (p less than .05). In contrast, the mean serum trough concentration of furosemide remained at a plateau following the first dose (1.8 +/- 0.82 to 1.98 +/- 1.81 mg/liter), suggesting attainment of a steady state. This accumulation of furosemide following repeated doses of this diuretic, therefore, reflects the decreased plasma clearance of the drug, possibly due to contraction of its volume of distribution.

Chromatography, High Pressure Liquid↗
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↗
PubMed1987

Drug therapy in hypoxic-ischemic cerebral insults and intraventricular hemorrhage of the newborn.

Recent progress in understanding the pathophysiology of hypoxic-ischemic encephalopathies and intraventricular hemorrhages have enabled us to propose new therapeutic modalities in preventing the development and severity of these disorders in the newborn. Because neuronal damage may be reversible under certain conditions, appropriate evaluation of these drugs (single or in combination) is very important in the continuous attempt to ameliorate the neurodevelopmental outcome of these infants. An interventionist attitude should prove to be a better alternative than a supportive one.

Asphyxia Neonatorum↗
PubMed1986

Pharmacologic effects of theophylline in the newborn.

Theophylline is an effective respiratory stimulant for apnea of prematurity. In the newborn, theophylline stimulates the central nervous system, particularly the respiratory center, leading to decreased apnea frequency and increased ventilation. Neonates appear to be more sensitive to the cardiovascular effect of theophylline; tachycardia occurs at plasma concentrations of 13 mg/L. Minimal effects on renal and gastrointestinal function are observed at therapeutic doses. Augmentation in oxygen consumption and alteration in glucose homeostasis may occur, even at therapeutic doses. If used appropriately, the drug is safe and effective for the treatment of neonatal apnea.

Animals↗