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Biomedical subjects

B J Buckley

Publications and source records attributed to B J Buckley.

33 records · Page 2Linked to original sources

Glutathione redox status of control and cadmium oxide-exposed rat lungs during oxidant stress.

Activities of enzymes responsible for the maintenance of reduced glutathione (GSH) levels have been shown in a previous study to be increased in rat lungs following a 3-h exposure to cadmium oxide aerosols at 5.0 mg/m3. In this study, the ability of the lung to maintain levels of GSH during challenge with tert-butyl hydroperoxide (tBuOOH) was evaluated in isolated perfused lungs from control and cadmium oxide-exposed rats. Changes in glutathione redox status were indicated by measurements of nonprotein sulfhydryls (NPSH), total glutathione (1/2 GSH + GSSG), and glutathione disulfide (GSSG) in liquid nitrogen freeze-clamped lungs after 3-min infusions with 0-0.6 mM tBuOOH. In control and cadmium oxide-exposed lungs, levels of 1/2 GSH + GSSG remained constant over the range of 0-0.6 mM tBuOOH, indicating that no loss of glutathione from the system had occurred. In experiments with control lungs, levels of NPSH fell from 8.04 +/- 0.22 to 3.09 +/- 0.40 mumol/g dry weight when tBuOOH concentrations were increased from 0 to 0.6 mM (n = 20-23). In cadmium oxide-exposed lungs, NPSH levels also decreased proportionally to increases in GSSG. However, at concentrations of 0.075 and 0.15 mM tBuOOH, significantly smaller decreases in NPSH levels were observed in cadmium oxide-exposed lungs compared with controls. This protection against the GSH-depleting effects of tBuOOH might be explained by increased tissue levels of GSH-related enzymes.

Aerosols↗

Liposome-mediated augmentation of catalase in alveolar type II cells protects against H2O2 injury.

Oxidant injury to the alveolar epithelium can be mediated by exposure to oxidant gases such as O2 at high concentrations and O3, inflammatory cell-derived reactive O2 species, and the intracellular metabolism of xenobiotics such as paraquat. An in vitro model of alveolar epithelial oxidant injury was developed based on exposure of cultured rat type II pneumocytes to superoxide and hydrogen peroxide (H2O2) enzymatically generated in the culture medium. Cytotoxicity was assessed by the release of lactate dehydrogenase (LDH) into the culture medium, which was a more reliable indicator of damage than release of 51Cr by prelabeled cells. Incubation of cells for 6-8 h with xanthine plus xanthine oxidase and glucose plus glucose oxidase induced the release of greater than 50% of total intracellular LDH. Oxidant exposure also resulted in significant detachment of cells from culture dishes. Modulation of oxidant damage was accomplished using liposomes as vectors for the delivery of catalase. Treatment of cells with catalase liposomes for 2 h resulted in augmentation of cellular catalase specific activities up to 631% of controls. Catalase was partitioned into intracellular and surface-associated compartments in catalase liposome-treated cells. Partial and complete protection against oxidant injury, induced by xanthine plus xanthine oxidase and glucose plus glucose oxidase, respectively, was achieved by pretreatment of cells with catalase liposomes. LDH release during oxidant exposure was inversely related to augmentation of cellular catalase activities. Catalase liposome-treated cells also exhibited an enhanced ability to scavenge enzymatically generated H2O2 from the culture medium. These observations suggest a useful approach to modulation of alveolar injury induced by reactive O2 species.

Animals↗

Chest pain, dyspnea on exertion, and exercise induced asthma in children and adolescents.

UNLABELLED: The contribution of maximal exercise tests to the evaluation of 180 patients with chest pain associated with exercise (n = 147) or dyspnea on exertion (DOE, n = 33) was examined. The ages ranged from 5 to 22 (mean 13.2) years, and 68 patients were females. All patients had a normal cardiovascular examination, electrocardiogram, chest x-ray, and 2D-echocardiogram. Maximal exercise tests were performed on a treadmill or bicycle ergometer, and flow volume loops were performed before and after exercise (n = 65). Exercise tests did not reveal any cardiovascular abnormalities, but 14 patients with chest pain (9.5%) and seven patients with DOE (21.2%) developed exercise-induced asthma. Postexercise decrease in peak expiratory flow rate was 26.2 +/- 3.7 percent in patients with chest pain and 39.4 +/- 8.9 percent in those with DOE. Only five patients had a personal history and four others had a family history of asthma. Seven patients had a personal or family history of allergies. IMPLICATIONS: exercise-induced asthma should be considered in pediatric patients with symptoms of chest pain or dyspnea on exertion; when exercise tests are performed, flow volume loops should be included before and after exercise; maximal exercise tests are unlikely to unmask any cardiovascular abnormalities in such patients.

Adolescent↗

Age-related responses to stimulation of cardiopulmonary receptors in swine.

Cardiovascular responses to stimulation of cardiopulmonary receptors were evaluated in standard breed developing swine (1-2 days, 1-2 wk, and 2 mo of age) and sexually mature miniswine anesthetized with 0.25-0.50% halothane in O2. Cryptenamine, a mixture of veratrum viride alkaloids (VVA), was administered as right atrial or left ventricular bolus injections in doses of 5-20 micrograms/kg. In developing swine, mean aortic pressure (AoP) decreased after 10-20 micrograms/kg VVA in 1- to 2-wk olds and after 5-20 micrograms/kg VVA in 2-mo olds. Bradycardia was always elicited. Renal (Ren) and femoral (Fem) vasodilation occurred in the 1- to 2-wk-old and 2-mo-old groups after 5-20 micrograms/kg VVA. Mesenteric (Mes) vasodilation was elicited with 10-20 micrograms/kg VVA in the 1- to 2-wk-old group and with 5-20 micrograms/kg VVA in 2-mo olds. In the 1- to 2-day-old group, VVA did not significantly alter Ren, Fem, and Mes vascular resistance. In mature miniswine, 20 micrograms/kg VVA elicited decreases in AoP and heart rate that were similar in magnitude to responses obtained with only 5 micrograms/kg VVA in dogs. Cardiovascular responses to VVA were abolished after bilateral vagotomy but were not altered after denervation of the carotid sinuses. The results indicate postnatal maturation of the Bezold-Jarisch reflex in swine.

Aging↗

Age-dependent cardiovascular effects of verapamil in newborn swine.

Since there are limited studies concerning the hemodynamic effects of verapamil in pediatric patients, cardiovascular effects of clinical doses (100 or 300 micrograms/kg) of verapamil, given as a 2-min intravenous infusion, were examined in sodium pentobarbital anesthetized swine, aged 1 day (n = 15) and 2 wk (n = 18). Aortic and left ventricular pressures, index of left ventricular contractility, heart rate, and phasic superior mesenteric, renal, and femoral arterial flows were recorded; mean aortic pressure and vascular resistances were calculated. Maximum changes in cardiovascular function (mean % delta +/- SEM) occurred at the end of the infusion. Mean aortic pressure and index of left ventricular contractility decreased in all animals; responses were larger in magnitude with the higher dose. By 30 min after infusion of 300 micrograms/kg verapamil had ended, mean aortic pressure in both 1 day and 2 wk olds and index of left ventricular contractility and femoral flow in 1 day olds were still decreased. During infusion of verapamil, heart rate decreased (-11.6 +/- 2.9) to the high dose in 1 day olds but increased (+6.4 +/- 2.7) to 100 and 300 micrograms/kg verapamil in 2 wk olds. After infusion of 300 micrograms/kg verapamil ended, heart rate decreased and reached the nadir (-10.0 +/- 2.9) by 10 min in 2 wk olds. Decreases in renal resistance (-7.6 +/- 1.7) were not dose dependent while superior mesenteric resistance decreased (-12.9 +/- 2.7) only to low dose verapamil in 2 wk olds. In 1 day olds decreases in renal and superior mesenteric resistance were not sustained throughout the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Cardiovascular responses to arterial and venous hemorrhage in neonatal swine.

The cardiovascular effects of graded arterial or venous hemorrhage were evaluated in developing swine (less than or equal to 1 day, 2-5 days, 1 wk, and 2 wk of age) anesthetized with halothane in 50% N2O-50% O2. Serial 5-ml/kg aliquots of arterial or venous blood were removed at 3- to 4-min intervals to a cumulative total of 20 ml/kg. Tachycardia occurred in most animals. Decreases in aortic pressure to arterial, but not to venous, hemorrhage were age dependent. Renal, femoral, and carotid arterial flows decreased with hemorrhage in all animals; the decreases in blood flow did not differ among the three circulations and were not age dependent. Increases in femoral resistance were obtained to both arterial and venous hemorrhage only in the 2-wk-old group. As the degree of hemorrhage was increased, aortic pressure, regional blood flow, and femoral resistance (2 wk olds) responses were larger in magnitude. Aortic pressure in piglets 1-5 days of age could not be restored to within 20% of the prehemorrhage level at a smaller bleeding volume with arterial than with venous hemorrhage. Pressor responses to norepinephrine (0.5 micrograms/kg) and to bilateral common carotid occlusion were still present after 20-ml/kg hemorrhage. These responses indicate the presence of a progressive maturation-related compensation to the stress of arterial but not venous hemorrhage.

Animals↗

Cardiac effects of esophageal stimulation: possible relationship between gastroesophageal reflux (GER) and sudden infant death syndrome (SIDS).

Twenty-six artificially ventilated newborn pigs were subjected to simulated gastroesophageal reflux; saline (10 cc) of varying pH was flushed through the esophagus from below. At a given pH threshold, reflex bradycardia, which could be blocked by atropine, was elicited. Transecting of the superior laryngeal nerves, the recurrent laryngeal nerves, and the pharyngeal plexus nerves did not block the reflex bradycardia. However, bypassing the regions superior to the esophagus with a shunt prevented the bradycardia. These results indicate that bradycardia caused by gastroesophageal reflux is independent of changes in ventilation and may be an important cause of sudden infant death.

Animals↗

Maturation-related differences in regional circulatory effects of dopamine infusion in swine.

The cardiovascular effects of dopamine (DPA) infusions were evaluated in developing swine, less than or equal to 1 day, 2 weeks, and 2 months of age, anesthetized with halothane in 50% N2O and O2. DPA was given by intravenous infusion in randomized doses of 2, 5, 10 and 20 micrograms/kg/min for 10 min. Depressor responses and bradycardia were observed during 2 micrograms/kg/min in 2-week-olds and during 2, 5 and 10 micrograms/kg/min in 2-month-olds. During infusion of 20 micrograms/kg/min, DPA pressor responses were observed in animals less than or equal to 2 weeks of age; in addition, tachycardia occurred in 1-day-old swine. Renal resistance decreased during infusion of 2 micrograms/kg/min in all swine. It increased during 10 and 20 micrograms/kg/min in the 1-day and 2-week groups, but not in the 2-month group. Mesenteric resistance decreased during infusion of 2, 5 and 10 micrograms/kg/min in less than or equal to 2-week-olds and at all doses in 2-month-olds. Following combined alpha- and beta-adrenergic receptor blockade, infusion of 20 micrograms/kg/min DPA inhibited renal vasoconstriction in most animals and elicited mesenteric vasodilation in all. The results indicate that dopaminergic responses undergo a postnatal maturation which has a different time course for different regional circulations.

Aging↗

Maturation of central autonomic control of the circulation.

Postnatal maturation of central neural regulation of cardiovascular function is being examined in developing swine. Three major types of investigations have been undertaken: 1) alterations of inputs from visceral and somatic afferents, e.g., baroreceptor manipulation, stimulation of sciatic nerves; 2) stimulation of central vasoactive sites; 3) subjecting the animals to the stresses of hemorrhage, hypoxia, or hypercapnia. Our findings indicate that cardiovascular reflexes mature at different postnatal ages. For example, the J-receptor reflex had almost the adult pattern of response at birth, whereas the Bezold-Jarisch reflex had a markedly delayed postnatal maturation. Recordings of spontaneous discharge in a major efferent sympathetic supply, i.e., the greater splanchnic nerve, have indicated that neural innervation to the adrenal medulla and splanchnic vasculature is present at birth in piglets.

Animals↗

Age-related effects of single injections of dopamine on cardiovascular function in developing swine.

The cardiovascular effects of single intravenous injections of dopamine (DPA; 2, 5, 10 and 25 micrograms/kg) were evaluated in swine, less than or equal to 1 day to 2 months of age, anesthetized with halothane in 50% N2O-O2. Mean aortic pressure increased following all doses of DPA in swine less than or equal to 1 month of age. Renal vasoconstriction was obtained with 5-25 micrograms/kg in the younger animals and with 25 micrograms/kg in the oldest. After 2 micrograms/kg, renal vasodilation occurred in 2-month-old swine. Femoral and carotid vasoconstriction was elicited in day-old swine after 5-25 micrograms/kg DPA, but carotid vasodilation occurred in the oldest swine. Responses to 25 micrograms/kg DPA after combined alpha and beta adrenergic receptor blockade were generally vasodilator. Thus, dopaminergic receptors were unmasked and a postnatal maturation of these receptors was revealed.

Aging↗

Autonomic regulation of cardiovascular function in neonates.

The degree of participation of the vascular bed supplied by the superior mesenteric artery in autonomic regulation of cardiovascular function during postnatal maturation was evaluated in piglets, ranging in age from birth to two months. Animals were anaesthetized with 0.25-0.5% halothane in a 50% mixture of N2O and O2, paralysed with decamethonium bromide and artificially ventilated to maintain normal arterial blood gases and pH. Mesenteric arterial flow was recorded continuously with an electromagnetic flow transducer; simultaneously aortic pressure, heart rate, and femoral, renal and carotid flows were monitored. Resistance was calculated as the ratio of mean aortic pressure to mean flow. The central neural regulation of the cardiovascular system was altered: (1) by electrical stimulation of medullary vasoactive sites, (2) by changing the input from visceral or somatic afferents and (3) by subjecting the animals to stress, such as haemorrhage or hypoxia. Postnatal development of adrenergic mechanisms was studied with the aid of adrenergic agonist both in vivo and in vitro (helical strips cut from superior mesenteric artery were placed in an organ bath for isometric tension recordings). Recordings of spontaneous efferent splanchnic discharge permitted a more direct examination of autonomic regulation of the mesenteric vascular bed. The results indicate that the vascular bed supplied by the superior mesenteric artery and innervated by the efferent splanchnic nerve is actively involved in the cardiovascular responses to alterations in the cardiovascular regulatory system. Furthermore, this vascular bed may have an inappropriate response to both feeding and stress such that pathological changes in the gastrointestinal tract may result.

Aging↗

Integrated cardiovascular responses to combined somatic and visceral afferent stimulation in newborn piglets.

Mean aortic pressure, arterial flow and heart rate response to interactions of afferent stimulation of the sciatic nerve (SNS) and carotid sinus stimulation by infusion (CSI) or inhibition by bilateral common carotid occlusion (BCCO) were studied in 25 newborn piglets under halothane-N2O anesthesia. Combined stimulation of the somatic and visceral afferents produced no heart rate changes. Combinations of pressor stimuli (BCCO and high frequency SNS) showed facilitation; femoral and renal resistances increased. However, combinations of depressor stimuli (CSI and low frequency SNS) showed occlusion. In combinations of pressor with depressor stimuli, the pressor pattern of responses dominated. Thus, dissimilar types of excitatory afferent inputs are capable of evoking facilitation in the neonatal cardiovascular regulatory system.

Afferent Pathways↗

Integrated cardiovascular responses to combined somatic afferent stimulation in newborn piglets.

Heart rate, mean aortic pressure and arterial flow responses to interactions of afferent stimulation of the sciatic (SNS) and median nerve of the brachial plexus (BNS) were studied in 30 newborn piglets under halothane-N2O anesthesia. High frequency or intensity SNS or BNS stimulation resulted in pressor responses accompanied by significant increases in the femoral flow and carotid and renal resistance. Combined stimulation produced responses smaller than the estimated sum of the responses. Low frequency or intensity SNS or BNS resulted in depressor responses accompanied by significant decreases in mean femoral flow without change in heart rate; combined stimulation produced responses smaller than the estimated sum. When pressor and depressor patterns of stimulation were combined, pressor responses always dominated. The absence of facilitation to any combination of interactions implies that the cardiovascular regulatory system is not fully developed at birth and undergoes, therefore, postnatal maturation.

Afferent Pathways↗

Analgesic efficacy and safety of two oral controlled-release morphine preparations in orthopedic postoperative pain.

This single-dose, double-blind, randomized, parallel-group study compared the analgesic efficacy and safety of MS Contin (MSC) and Oramorph SR (OSR), two controlled-release preparations of oral morphine sulfate, in patients following orthopedic surgery. One hundred patients received MSC 30 mg, MSC 60 mg, or OSR 60 mg (two 30-mg tablets) when postoperative pain became moderate or severe. Patients self-rated pain intensity and relief on categorical (CAT) and visual analogue scales (VAS) hourly for up to 12 hours. MSC 60 mg produced the greatest peak analgesic effect and was more efficacious than OSR 60 mg through the sixth hour, with statistical significance achieved at 1, 2, and 3 hours postdosage. Compared with OSR 60 mg, both MSC dosages provided significantly more rapid times to peak effect by CAT and VAS ratings. The OSR group experienced almost twice as many adverse events as did the two MSC groups and also reported somnolence and dizziness more frequently. MSC 60 mg provided more rapid and greater peak analgesia with fewer adverse effects than did OSR 60 mg.

Administration, Oral↗