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Biomedical subjects

J V Aranda

Publications and source records attributed to J V Aranda.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of group B streptococcal meningitis on retinal and choroidal blood flow in newborn pigs.

PURPOSE: To assess the effect of group B streptococcal (GBS) meningitis on retinal blood flow (RetBF) and choroidal blood flow (ChBF) autoregulation in sedated newborn piglets (1 to 5 days of age). METHODS: Fourteen study animals injected with 0.5 ml heat-killed GBS (10(9)) were compared to 10 control animals injected with 0.5 ml saline. The site of injection for both groups was the cerebral lateral ventricles. RetBF and ChBF were measured by radioactive microspheres (141Ce, 51Cr, 113Sn, 85Sr, 95Nb, 46Sc) over a mean arterial blood pressure (MABP) range of 20 to 150 mm Hg. Hypertension and hypotension were induced 2 hours apart in random sequence on each animal by inflating balloon-tipped catheters placed at the descending aorta and the aortic root, respectively. RetBF and ChBF were measured 15 minutes before and after injection of GBS or saline (baseline) and during hypotension or hypertension. RESULTS: Fifth-order polynomial regression analyses of RetBF and ChBF (ml/100 g per minute) versus MABP showed that in control animals, blood flows were constant at MABP of 60 to 110 mm Hg for RetBF and was pressure passive above and below these ranges. However, no autoregulation was observed for ChBF throughout the MABP range. In contrast, RetBF of GBS-treated animals increased with increasing blood pressure throughout range of MABP studied, and absence of autoregulation was maintained in the choroid. Vascular resistance (mm Hg/ml per minute/100 g) increased as MABP was raised to maintain constant flow and was correlated linearly with MABP at 60 to 110 mm Hg (r = 0.6682, P = 0.0003) in RetBF of control animals but not in GBS-treated animals (r = -0.291, P = NS). Vascular resistance did not change with MABP for ChBF of control animals (r = -0.264, P = NS) but decreased as MABP was raised in GBS-treated animals (r = -0.548, P < 0.0001). GBS did not alter oxygen delivery, which varied directly with MABP in control animals (RetBF: r = 0.74, P < 0.001; ChBF: r = 0.68, P < 0.001) and in GBS-treated animals (RetBF: r = 0.55, P < 0.001; ChBF: r = 0.68, P < 0.001). CONCLUSION: Group B streptococcal meningitis significantly impairs eye blood flow autoregulation and may contribute to increased risk of retinal damage in infants with meningitis.

Animals↗
PubMed1994

Role of adenosine in the hypoxic ventilatory response of the newborn piglet.

The role of intracerebral adenosine levels in the control of ventilatory response to hypoxia was explored in 15 spontaneously breathing intubated piglets, 1-5 days old, sedated with chloral hydrate. Respiration was recorded via by a pneumotachograph. In all animals exposed to hypoxia (12% O2) for 10 minutes. There was an initial increase in ventilation followed by a late decrease (the biphasic ventilatory response). Both intravenous caffeine citrate (20 mg/kg) and an FiCO2 of 0.05 separately abolished or attenuated the late ventilatory depression associated with hypoxia. In the same piglets, the administration of 10 micrograms dipyridamole, a competitive inhibitor of adenosine receptors, directly into the cerebral ventricles abolished the hyperventilatory response to hypoxia. Conversely, the use of 20 micrograms intraventricular 8-phenyltheophylline abolished the late ventilatory depression associated with hypoxia. Neither drug had a direct effect on ventilation at the time of injection. These results suggest that adenosine is a part of the diphasic ventilatory response to hypoxia.

Adenosine↗
PubMed1994

Effect of caffeine on the ventilatory response to inhaled carbon dioxide.

We investigated the effect of caffeine on the hypercapnic ventilatory response (HCVR) using steady state (SS) and rebreathing (RB) methods in 6 subjects. They received caffeine (5 mg/kg) or saline intravenously in a randomized, double-blind, crossover manner, with measurement of serum caffeine levels. PETCO2 and (VE), normalized for vital capacity (VC), were measured continually during RB and during the last 5 min of SS runs. The slope of the VE-PETCO2 response increased from 0.21 +/- 0.14 to 0.38 +/- 0.14 and from 0.23 +/- 0.12 to 0.59 +/- 0.45 VC.min-1.mmHg-1, measured by RB and SS respectively (P < 0.05). Plotting VT vs PETCO2 revealed a parallel shift (additive effect) in the response measured by RB after caffeine; but an increased slope (multiplicative effect) in the VT-PETCO2 relation measured in SS. We conclude that caffeine acts as a respiratory stimulant and increases the HCVR, but that assessment of the caffeine-CO2 interaction is dependent on the methodology employed.

Administration, Inhalation↗
PubMed1993

Topical anesthesia during circumcision in newborn infants.

OBJECTIVE: To determine the efficacy of topical anesthetic cream, eutectic mixture of local anesthetics (EMLA), in alleviating pain from neonatal circumcision. DESIGN: Randomized, controlled trial. SETTING: Normal newborn nursery in a university teaching hospital. PATIENTS: Twenty-seven newborn, full-term male neonates, aged 1 to 3 days. OUTCOME MEASURES: Heart rate, transcutaneous oxygen saturation, facial activity, and crying. RESULTS: Compared with baseline, all newborns experienced pain as evidenced by increased heart rate of an average of 40 beats per minute (F [8, 25] = 14.12; P < .0001), decreased oxygen saturation of 3% (F [8, 25] = 15.02; P < .0001), and more facial actions indicative of pain (F [8, 25] = 5.25; P < .002) during all phases of the procedure. Compared with placebo, EMLA significantly attenuated the pain response as shown by lower heart rate of an average of 25 beats per minute (F [1, 25] = 14.92; P < .001), higher oxygen saturation of 5%, particularly during the clamping and lysis phases (F [1, 25] = 19.83; P < .0001), 20% less facial activity (F [1, 25] = 12.01; P < .002), and 15% less crying during the clamping, Gomco clamp application, and incision of the foreskin. There were no differences between groups in the spectral crying parameters. CONCLUSIONS: Circumcision procedure produces pain responses that EMLA diminishes. Thus, EMLA may be a useful agent for pain management in neonatal circumcision.

Administration, Topical↗
PubMed1992

Enhanced cerebral blood flow autoregulation in the newborn piglet by d-tubocurarine and pancuronium but not by vecuronium.

Neuromuscular blockers may affect cerebral blood flow (CBF) regulation in the newborn. We studied the effects of d-tubocurarine (0.1 mg.kg-1, n = 8), pancuronium (0.1 and 0.4 mg.kg-1, n = 6 and 7), and vecuronium (0.1 and 0.4 mg.kg-1, n = 6 and 7) on CBF measured over the same range of mean systemic blood pressure ([BP] 15-122 mmHg) in each group of newborn pigs; controls received normal saline (n = 7). The levels of BP during hypotension and hypertension were scaled at intervals of 5 +/- 1.6 mmHg and adjusted by inflating balloon-tipped catheters placed in the aorta. After saline, the low dose of pancuronium (0.1 mg.kg-1), and the two doses of vecuronium, CBF was constant over the BP range of 50-90 mmHg (r = -0.07-0.35, P greater than 0.20) but varied directly with BP beyond this range (tau = 0.38 - 0.60, P less than 0.05). In contrast, in pigs treated with d-tubocurarine and high-dose pancuronium, CBF remained constant from 35 to 122 mmHg of BP (r = 0.14 - 0.37, P greater than 0.10) and changed minimally (4-12%) with BP greater than 105 mmHg compared to the other groups (41-59%, P less than 0.01). When BP was reduced below 30 mmHg, CBF also decreased less (20-38%) in animals treated with d-tubocurarine and high dose-pancuronium than after the other treatments (58-67%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Interactive ventilatory effects of two respiratory stimulants, caffeine and doxapram, in newborn lambs.

Caffeine and doxapram are two respiratory stimulants used in the treatment of apnea in newborns. When used concurrently, these drugs may produce interactive effects on the control of breathing in the newborn. The ventilatory effects of these drugs, given alone or together, were measured during 150 min of drug infusion in two groups of awake lambs 2-5 days old. The first group (n = 5) received a caffeine loading dose of 10 mg/kg followed by a maintenance dose of 0.1 mg/kg/h and incremental doses of doxapram: 0.25, 0.5, 1.25 and 2.5 mg/kg/30 min. The second group (n = 5) received a doxapram loading dose of 5.5 mg/kg followed by a maintenance dose of 1 mg/kg/h and incremental doses of caffeine: 2.5, 5.0, 7.5 and 10.0 mg/kg/30 min. In the first group, ventilation increased after the caffeine loading dose from 566 +/- 55 to 680 +/- 74 ml/kg/min (plasma caffeine = 14.7 +/- 1.6 mg/l) and progressively increased with the addition of incremental doses of doxapram up to 1,000 +/- 108 ml/kg/min at 2.5 mg/kg of doxapram (p less than 0.001 compared to baseline and caffeine loading dose). In contrast, in the second group, the doxapram loading dose markedly increased ventilation from 582 +/- 50 to 936 +/- 75 (p less than 0.002 and p less than 0.04 compared to caffeine loading dose) at plasma doxapram of 5.3 +/- 0.8 mg/l, but incremental doses of caffeine had no effects. We conclude that doxapram exerts a brisk and powerful respiratory stimulant effect and produces an additional dose-dependent ventilatory response when added to caffeine.

Animals↗
PubMed1992

Effects of phenobarbital on cerebral blood flow in the newborn piglet.

To determine the neonatal cerebrovascular effect of a therapeutic dose and a high dose of phenobarbital (Pb), the effect of Pb on cerebral blood flow (CBF) and total brain oxygen consumption (CMRO2) was studied in three groups of awake newborn piglets (aged 1-3.5 days). Group I (control n = 9) received normal saline solution, group II (n = 9) received a therapeutic dose of Pb (15 mg/kg i.v.) and group III (n = 9) received a high Pb dose (45 mg/kg i.v.). Four CBF measurements per piglet using radioactive microspheres (141Ce, 85Cr, 95Nb, 46Sc), arterial blood gases, O2 content, hematocrit and plasma glucose were obtained at 0, 15, 30, 60 min after saline or Pb injections. In all groups, pH, PaO2, PaCO2, blood pressure, heart rate, temperature and plasma glucose remained unchanged except a 14% decrease (p < 0.01) in blood pressure and an increase (p < 0.05) in PaCO2, 60 min after drug injection in groups II and III. Total CBF in group II decreased by 14% (p < 0.05) 15 min after drug injection and was significantly lower (p < 0.05) than control (group I) but returned to baseline after 30 min. High Pb dose progressively lowered CBF by 11% 15 min after drug injection and produced a significant decrease by 20% (p < 0.01) 30 min after drug injection with return to baseline after 60 min. Similar effects were noted in different brain regions (cerebrum and thalamus). CMRO2 remained unchanged in the control group; however, it was decreased by 35% (< 0.01 p > 0.05) 15 min after drug injection and returned to baseline after 60 min. In group III, high Pb dose lowered CMRO2 by 31% 30 min (p = 0.02) after drug injection. Data indicate that Pb exerts a minimal but transient dose-dependent effect on CBF and CMRO2.

Animals↗
PubMed1992

Dissociation between prostaglandin levels and blood flow to the retina and choroid in the newborn pig after nonsteroidal antiinflammatory drugs.

To assess whether prostaglandins contribute to the control of basal retinal and choroidal hemodynamics, retinal (RBF) and choroidal blood flow (ChBF) were measured by a microsphere technique in 1- to 4-day-old pigs before and after (at 20 and 60 min) administration of indomethacin (0.3 mg/kg, n = 6 or 10 mg/kg, n = 5), ibuprofen (40 mg/kg, n = 7), naproxen (20 mg/kg, n = 5) or vehicle (n = 8). In 40 other animals, PGF2 alpha, PGE2, and 6-keto-PGF1 alpha were measured in the retina and choroid at times corresponding to blood flow measurements. Mean arterial blood pressure and blood gases and pH were not altered by any of the agents. Except for the lower dose of indomethacin (0.3 mg/kg), which did not change retinal and choroidal prostaglandin concentrations, the prostaglandin levels were decreased similarly (P < 0.01) by the three drugs. However, RBF and ChBF were not changed by ibuprofen and naproxen, but decreased to the same extent after low and high doses of indomethacin. The data suggest that the effects of indomethacin on RBF and ChBF cannot be simply attributed to prostaglandin synthesis inhibition, and that prostaglandins may not play a significant role in controlling basal blood flow to the retina and choroid.

Animals↗
PubMed1991

Ventilatory response to keto-doxapram in intact and carotid body denervated lambs.

We aimed to investigate the role of the carotid bodies in the ventilatory response to keto-doxapram, and whether this response was dose-dependent; we studied two group (n = 5 per group) of awake, intact and carotid-body denervated (CBD) lambs, aged 10-15 days. At 20 min intervals, they received 0.5, 1.0, 2.5 and 5.0 m g/kg mg/kg of keto-doxapram as an intravenous bolus infusion. Plasma keto-doxapram was measured (HPLC). Ventilation was recorded via a face mask and a pneumotachograph. In intact lambs, an immediate dose-dependent increase in minute ventilation (V1) was observed. At 2 min, VI increased from baseline by 125 +/- 28, 212 +/- 49, 378 +/- 41 and 637 +/- 92 mol.kg 1.min 1 (mean +/- SE, P less than 0.01) corresponding to the foregoing incremental doses. A significant correlation was observed between the peak VI and the corresponding plasma keto-doxapram concentrations (r = 0.73, P less than 0.0003). In CBD lambs, VI increased significantly less than in intact animals. In conclusion, early ventilatory response to keto-doxapram depends mainly on intact carotid bodies, and the effect is dose-dependent.

Animals↗
PubMed1991

Doxapram metabolism in human fetal hepatic organ culture.

The biotransformation of doxapram, a respiratory stimulant was studied with use of explants from human fetal livers (n = 15 fetuses) obtained from therapeutic abortions (gestational age, 10 to 20 weeks). Explants were cultured in Leibowitz medium and the media from cultured samples were collected before and at 3, 6, 12, and 24 hours after incubation with 2.5, 5.0, and 10 micrograms/ml doxapram. The concentrations of doxapram and its metabolites (AHR 0914, an analog of doxapram, AHR 5955 or ketodoxapram, and AHR 5904) were measured by high pressure liquid chromatography. Explant histopathology and alkaline phosphatase activity showed no direct toxic effects of the drug on liver tissue. The fastest rate of doxapram metabolism occurred during the first 3 hours of incubation (198 +/- 73.3, 438 +/- 63.3, and 538 +/- 62 ng/mg/hr liver protein at doxapram concentrations of 2.5, 5.0, and 10.0 micrograms/ml, respectively). At 3 hours of incubation, the amount of doxapram metabolized (nanogram per milligram of liver protein) was significantly higher (p less than 0.01) at doxapram concentrations of 10.0 (1616 +/- 186) and 5.0 microgram/ml (1315 +/- 190) than at 2.5 micrograms/ml (594 +/- 220). The oxidative pathway producing keto-doxapram, or AHR 5955 and AHR 5904, is more active than the de-ethylation producing the analog of doxapram AHR 0914. Data indicate substantial metabolism of doxapram by the human fetal lives.

Biotransformation↗
PubMed1991

The role of adenosine in the vascular adaptation of neonatal cerebral blood flow during hypotension.

This study investigated the potential role of adenosine in cerebral blood flow (CBF) regulation in the neonate during moderate and severe hypotension. Experiments were done in anesthetized, 1- to 3-day-old piglets. Regional CBF (determined by radiolabeled microsphere technique) and cerebral metabolic rate for O2 (CMRO2) were measured (a) during normotension and (b) during a 3-min period of moderate (58 +/- 9 mm Hg) or severe (36 +/- 7 mm Hg) hypotension produced by the inflation of a balloon catheter placed in the aortic root. Measurements of CBF and CMRO2 were performed successively after intracerebroventricular (i.c.v.) injections of vehicle (n = 17), the adenosine receptor blocker 8-phenyltheophylline (8-PT, 10 micrograms, n = 14), and the A2-receptor agonist 5'-N-(ethylcarboxamide)adenosine (NECA, 2 ng, n = 8). After i.c.v. administration of vehicle, none of the parameters studied was significantly altered by moderate hypotension, but severe hypotension decreased the total CBF (mean +/- SD) from 86 +/- 24 to 40 +/- 15 ml min-1 100 g-1 and CMRO2 from 3.2 +/- 0.8 to 1.8 +/- 1.0 ml min-1 100 g-1 (p less than 0.05). Administration of 8-PT did not alter these parameters during normotension, but significantly decreased CBF during moderate hypotension compared to postvehicle values (53 +/- 11 versus 81 +/- 12 ml min-1 100 g-1, p less than 0.05). This loss of autoregulation was completely reversed by NECA. During severe hypotension, 8-PT altered the CBF redistribution towards the brainstem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1991

Gastrointestinal absorption of doxapram in neonates.

Doxapram was administered orally to six premature babies (3 males, 3 females) with refractory apnea at a mean gestational age of 29 +/- 2.3 weeks, mean birthweight of 1142 +/- 359 gm and a mean postnatal age of 24 days. They received 12, 24, and 36 mg/kg/6 hr on day 1, 2, and 3, respectively, assuming a bioavailability of 50%. Serial plasma doxapram concentrations, determined by high-performance liquid chromatography, increased with incremental doses. The drug underwent oxidative metabolism, producing ketodoxapram, the plasma concentration of which remained stable during treatment. The ratio of plasma concentrations to oral doses ranged from 0.10 to 0.12, suggesting that doxapram is poorly absorbed in the newborn. Oral doxapram may replace the intravenous infusion but doses may have to be increased to, but not exceeding, 24 mg/kg/6 hr to achieve therapeutic plasma concentrations. Interpatient variability, poor absorption and gastrointestinal adverse effects caution against the routine use of oral doxapram.

Administration, Oral↗
PubMed1991

Rapid effects of hypoxia on the cerebrospinal fluid levels of adenosine and related metabolites in newborn and one-month-old piglets.

The effect of hypoxia on the levels of adenosine, inosine and hypoxanthine in the cerebrospinal fluid (CSF) was determined by HPLC in newborn (1- to 3-day-old, n = 6) and 1-month-old (n = 5) piglets. Serial CSF samples (q 60 s) were obtained from the cisterna magna during normoxia and a 5-min hypoxia test (PaO2 = 26.5 +/- 2.9 Torr). In normoxia, newborns had a lower mean (+/- SEM) CSF concentration of adenosine (0.72 +/- 0.17 vs 2.60 +/- 0.44 microM) and a higher concentration of hypoxanthine (4.88 +/- 0.41 vs. 1.39 +/- 0.60 microM) than the mature piglets (p less than 0.05). In all animals, hypoxia induced an increase in CSF levels of adenosine and its metabolites between 2 and 4 min. However, peak adenosine concentrations were higher in mature (4.17 +/- 1.41 microM) than in newborn (1.55 +/- 0.29 microM) piglets (p less than 0.05). These data might explain deficient vasodilator adaptation required for neonatal CBF regulation.

Adenosine↗
PubMed1991

Differences in the effects in the newborn piglet of various nonsteroidal antiinflammatory drugs on cerebral blood flow but not on cerebrovascular prostaglandins.

To characterize the role of prostaglandins (PG) in the regulation of basal cerebral blood flow (CBF) in the newborn, we determined the effects of four nonsteroidal antiinflammatory drugs, indomethacin (3 mg/kg, n = 8 and 10 mg/kg, n = 5), aspirin (65 mg/kg, n = 6), ibuprofen (30 mg/kg, n = 8), and naproxen (15 mg/kg, n = 6), on CBF, cerebral metabolism, and cerebrovascular PG in conscious 1- to 3-d-old piglets. Drugs and vehicle (n = 8) were injected i.v., and measurements were made 5 min before and 20 and 60 min after injections. Neither the vehicle nor any of the nonsteroidal antiinflammatory drugs exerted significant effects on mean arterial blood pressure and on blood gases and pH. All four drugs, with the exception of indomethacin at the lower dose (3 mg/kg), decreased PG to nearly undetectable levels within 20 min; the low dose of indomethacin caused a small decrease (18-32%) in PG at 60 min. However, the effects of these agents on CBF were diverse. CBF increased after the administration of aspirin, decreased to almost the same extent after both low and high doses of indomethacin, and did not change after the administration of ibuprofen and naproxen. Cerebral metabolic rate for oxygen was increased by aspirin but was unaltered by the other drugs. The data suggest that PG may not play a critical role in the regulation of basal CBF in the newborn animal and that certain nonsteroidal antiinflammatory drugs may have additional actions unrelated to the inhibition of PG synthesis.

Animals↗
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

Drug therapy for bronchopulmonary dysplasia.

With improved survival of critically ill premature infants, BPD has become an important sequela of neonatal intensive care. A variety of medications are used in the management of BPD. In this article we have attempted to summarize clinical efficacy, pharmacokinetics, and side effects of many of these medications. Longer-term studies on the efficacy of drug therapy are needed and may be facilitated by the development of accurate and reproducible computerized techniques for the measurement of pulmonary mechanics in neonates. Ultimately, new pharmacologic agents or other strategies that will prevent lung injury from hyperoxia and mechanical ventilation or accelerate tissue repair once injury occurs will play a major role in the prevention and treatment of infants with BPD.

Bronchodilator Agents↗
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↗