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Biomedical subjects

C E Hunt

Publications and source records attributed to C E Hunt.

At least 73 records · Page 4Linked to original sources
PubMed1987

A study of atherosclerotic lesion development in the injured pulmonary arteries of dogs with induced hyperlipemia.

Studies of experimental atherosclerosis in the dog demonstrate that many months at plasma cholesterol concentrations greater than 750 mg/dl are required to produce lipid containing atherosclerotic lesions. Since it has been recognized for many years that vascular injury in combination with hyperlipemia will result in rapid formation of atherosclerotic lesions, we attempted to combine vascular injury with hyperlipemia as a means of accelerating this process in the dog. Injury was produced in pulmonary arteries with experimental Dirofilaria immitis (DI or heartworm) infection. This filarial parasite produces characteristic lipid-free lesions containing smooth muscle cells and occasional monocytes and collagen. Plasma cholesterol was increased by feeding 10 dogs an essential fatty acid-deficient diet (EFAD) for 90 days. Five of the EFAD dogs were infected with 30 to 31 adult DI worms to produce pulmonary artery injury. The remaining 5 EFAD dogs were not subjected to any form of vascular injury. An additional 5 control dogs were not subjected to vascular injury nor to the EFAD diet. The arteries of dogs infected with DI developed myointimal proliferative lesions which contained smooth muscle cells and macrophages. In addition, the EFAD diet produced significant elevations in LDL but not VLDL plasma cholesterol in all 10 dogs fed the diet. However, the plasma cholesterol was less than 750 mg/dl in all EFAD-fed dogs. Although smooth muscle cells and macrophages in the pulmonary arteries of DI-infected dogs were focal points for lipid accumulation, cholesterol content of these injured arteries was not increased compared to noninjured EFAD dogs. The results suggest that even severe vascular injury does not reduce the threshold of 750 mg/dl required to produce significant lipid accumulation in canine arteries.

Animals↗
PubMed1986

The early involvement of pulmonary prostaglandins in hyperoxic lung injury.

To further study the role of arachidonic acid metabolites in the development of hyperoxic lung injury and the function of PMNs and/or alveolar macrophages in facilitating this role, we exposed adult rabbits to greater than 95% O2 or air for 24, 40, 48, or 65 hours. At the end of each study, bronchoalveolar lavage [BAL] of the left lung was performed, and the right lung was inflated and fixed for light and electron microscopy. PGE2, 6-keto-PGF1 alpha and thromboxane B2 were measured by RIA in arterial and venous plasma at the beginning and end of each study and in BAL fluid obtained at sacrifice. Production of these three PGs by BAL cells placed in cell culture was also measured. Significant hyperoxic lung injury did not develop until 65 hours, as evidenced by significant increase in BAL total protein and percent PMNs, and by morphologic findings. At 40 hours, however, BAL fluid PGE2 and 6-keto-PGF1 alpha increased and BAL cell production of all 3 PGs was significantly increased (p less than .05). In summary, the early PG increases observed in these studies may directly contribute to the development of hyperoxic lung injury or, rather, may be representative of a generalized increase in all arachidonic acid metabolites, including the lipoxygenase pathway. The increase in BAL cell PG production and increased PG concentrations in BAL fluid prior to any increase in BAL PMNs suggest that the AM may be the source of the early arachidonic acid metabolite increase in response to hyperoxia.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effects of birth weight and ethnicity on incidence of sudden infant death syndrome.

Sudden infant death syndrome occurs with increased frequency in low birth weight infants and in black infants. The degree to which the higher LBW rate among blacks might explain this higher SIDS rate is unknown. To address this question, we analyzed the 1233 SIDS deaths that occurred among 252,376 neonatal survivors in Cook County from 1975 to 1980, using computer-coded matched infant birth and death records. Birth weight and ethnic group were identified. The overall SIDS rates in blacks, Hispanics, and whites were 5.1, 1.2, and 1.3/1000 neonatal survivors, respectively. Within each ethnic group, the SIDS rates increased progressively with decreasing birth weight. Within the less than or equal to 1500 gm birth weight groups, the SIDS rates were 16.4, 3.9, and 5.5/1000 neonatal survivors in blacks, Hispanics, and whites. Using direct standardization, we found that 27% of the SIDS rate disparity between blacks and whites could be explained by the higher LBW rate in blacks (14% vs 6% in whites). The good outcomes in both LBW and SIDS rates for the Hispanic population were unexpected because, like blacks, Hispanics are socioeconomically disadvantaged. Findings for this group suggest that the remaining 73% of the increased SIDS rate in blacks cannot be attributed in a straightforward manner to differences in income or educational attainment.

Black or African American↗
PubMed1986

Effects of almitrine on genioglossal and diaphragmatic electromyograms.

We previously demonstrated dose-dependent increases in both hypoglossal and phrenic electroneurograms after almitrine in anesthetized, paralyzed, and vagotomized cats. We have now investigated the effect of this peripheral chemoreceptor stimulant on diaphragmatic and genioglossal (GG, an upper airway-maintaining muscle) electromyograms in five unanesthetized, chronically instrumented, spontaneously breathing adult cats during slow-wave sleep. In 12 studies almitrine doses of 1.0-6.0 mg/kg increased inspired minute ventilation (VI), frequency (f), and tidal volume (VT) and decreased expiratory time (TE). However, almitrine doses as high as 6.0 mg/kg failed to augment phasic inspiratory GG activity. To determine why almitrine induced phasic inspiratory upper airway activity in anesthetized, vagotomized cats but not in sleeping cats, additional studies were performed. In four dose-response studies in three pentobarbital-anesthetized cats, almitrine, 1.0-6.0 mg/kg, did not produce phasic inspiratory GG activity. Almitrine did induce phasic inspiratory GG activity in two of three studies in three vagotomized, tracheostomized, alpha-chloralose-urethan-anesthetized cats. These results suggest that almitrine would not be useful in obstructive sleep apnea, yet because almitrine markedly increased VI, f, and VT and decreased TE in unanesthetized sleeping cats the drug may be effective in patients who lack normal central neural respiratory drive, such as the preterm infant.

Almitrine↗
PubMed1986

Respiratory dysrhythmia. A new cause of central alveolar hypoventilation.

An infant developed chronic respiratory failure after aseptic meningoencephalitis at 5 months of age. Neurologic evaluations at 16 and 17 months were normal except for an abnormal pharyngeal stage of swallowing, lower extremity hypotonia, and a mild left hemiparesis. Spontaneous breathing during sleep at 16 months was characterized by alveolar hypoventilation, athetoid truncal movements, and disorganized respiratory muscle activity. At 27 months of age, improvement in sleep-related breathing was accompanied by a change in respiratory pattern characterized by alternating inspiratory and expiratory muscular activation. The findings indicate that disorganized as well as diminished output from the central respiratory pattern generator may result in central alveolar hypoventilation.

Chronic Disease↗
PubMed1986

Ventilatory effects of almitrine bismesylate in congenital central hypoventilation syndrome.

Patients with congenital central hypoventilation syndrome (CCHS) lack hypercapnic and hypoxic stimulation of ventilation but have demonstrated carotid body function in response to hyperoxia and to pharmacological stimulation with doxapram. This study investigated the ventilatory effects of almitrine bismesylate, a carotid body stimulant, in 12 patients with CCHS. Measurements of minute ventilation, tidal volume (VT), respiratory rate (RR) and transcutaneous PO2 (TCPO2) were taken before and after administration of 4.5 mg/kg and 6 mg/kg of almitrine. Twenty-four hour pharmacokinetic studies were performed in 7 patients who received 4.5 mg/kg and in 6 patients who received 6 mg/kg almitrine. There was no significant improvement in ventilatory and gas exchange parameters at either dose of almitrine despite appropriate peak serum concentration of the drug at the time of the studies. These results suggest that almitrine is not a useful ventilatory stimulant in children with CCHS.

Almitrine↗
PubMed1986

Fat emulsions and lung function.

IVFE infusion can impair lung function in healthy adults, premature infants, and adults with pre-existing lung injury, and in experimental animals with acute injury. Although all observed IVFE-related lung dysfunction was initially attributed to the temporally associated hyperlipemia, this explanation may in fact be correct only with fat overload syndrome. When serum triglyceride levels are in a more appropriate range, all subsequent studies have shown the same alterations in lung function unrelated to triglyceride increases and indomethacin-related blocking of lung function impairment, despite comparable serum triglyceride increases. Furthermore, our studies with Liposyn demonstrated the most significant increases in serum triglyceride levels, but the smallest PaCO2 and PaO2 changes. In general, the lung function abnormalities associated with IVFE infusion have thus been caused by increases in VA/Q inequalities. Although elucidation of the relationship between IVFE-related increased PG production and secondary VA/Q changes may be of significant physiologic import, the PaO2 and PaCO2 changes even with pre-existing lung injury have generally not been of sufficient magnitude to be of much clinical significance. The IVFE-related increases in plasma PG concentrations may, however, still have significant nonpulmonary clinical effects related to known or postulated consequences of increased plasma PG concentrations, including effects on ductus arteriosus patency, retinal and cerebral blood flow, and immune competence.

Adult↗
PubMed1986

Hyperoxic lung injury in mice: a possible protective role for prostacyclin.

Arachidonic acid metabolites have biologic properties that can mimic the pulmonary changes produced by hyperoxic exposure, but little information is available regarding their importance in this setting. The role of prostacyclin (PGI2) and thromboxane (Tx) A2 in oxygen-induced lung injury was evaluated by exposing mice to 100% oxygen for up to 4 days and measuring plasma and bronchoalveolar lavage (BAL) fluid concentrations of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of PGI2, and TxB2, a metabolite of TxA2. To determine whether a relationship exists between changes in these arachidonic acid metabolites and the severity of the lung injury, we also measured mortality, BAL protein concentration, BAL angiotensin-converting enzyme (ACE) activity, and plasma lactate dehydrogenase activity, and we examined lung sections by light and electron microscopy. After 3 days of exposure to 100% oxygen, microscopic and biochemical changes consistent with mild lung damage were found, but there was no increase in either plasma or BAL 6-keto-PGF1 alpha concentration. On day 4, severe lung damage was present. and BAL 6-keto-PGF 1 alpha level increased threefold (P less than 0.001). The level of TxB2 in BAL fluid did not change on any day. Twice-daily administration of either a high (5 mg/kg) or a low (1 mg/kg) dose of indomethacin reduced BAL concentrations of 6-keto-PGF1 alpha, and it resulted in increased mortality and higher BAL protein concentration and BAL ACE activity. These data suggest that TxA2 has little if any role in the pathogenesis of oxygen-induced lung injury, whereas prostacyclin may play a protective role.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Diet induced atherogenic hyperlipoproteinaemia and liver injury in cynomolgus macaques.

This study was conducted to determine the efficacy of an experimental anti-atherosclerosis drug in the adult male cynomolgus monkey. A semipurified diet containing 0.5% cholesterol and 25.5% butter was fed to groups of 20, each, drug and placebo-treated animals for 18 months. Similar liver and arterial changes were present in both groups. However, we report here tissue changes seen in animals given placebo only, with plasma lipid and lipoprotein values of placebo-treated animals compared to those in animals fed nonatherogenic commercial ration. Animals fed atherogenic diet had enlarged livers (mean 3.9% b.w.), and all had evidence of hepatocellular lipid accumulation which was often marked and diffuse. Cholangitis was common including mononuclear cell infiltration, bile ductule proliferation and portal tract fibrosis. Five animals had severe portal fibrosis with bands of connective tissue extending into and around lobules (bridging fibrosis). All animals fed atherogenic diet developed hypercholesterolemia (greater than 600 mg/dl) which was the result of a three-fold increase in five cholesterol and cholesterol ester. Oleic acid was increased and linoleic acid was reduced in plasma phospholipids and cholesterol esters. Plasma lipoprotein distribution was altered with a marked increase in low density lipoproteins, increased very low density lipoproteins and decreased high density lipoproteins. These changes were undoubtedly caused by diet, i.e., high in cholesterol and saturated fat and limiting in linoleic acid. It is probable that diet-induced liver injury would affect the pathogenesis of atherosclerosis in this model since the liver is central in the synthesis and metabolism of lipoproteins.

Animals↗
PubMed1986

Use of a rapid and highly sensitive fluorescamine-based procedure for the assay of plasma lipoproteins.

A rapid and sensitive method for determining protein concentrations using fluorescamine has been characterized for use in the analysis of intact lipoproteins. It was shown that there is no interference with the assay due to the presence of lipid-associated turbidity or primary amine content. The assay was shown to be sensitive to as little as 0.3 microgram of lipoprotein and to yield similar results when compared to the Lowry method.

Colorimetry↗
PubMed1985

Diaphragmatic pacing in infants: techniques and results.

Phrenic nerve pacing was employed in 8 infants with central hypoventilation syndrome. Their ages ranged from 2.5 to 8.5 months. Preoperative diagnosis was established by demonstrating inadequate ventilatory response to hypercapnia and hypoxia. Percutaneous measurements of phrenic nerve conduction time and diaphragmatic action potentials were performed prior to operation to assess the feasibility of diaphragmatic pacing. A single anterolateral thoracotomy incision was used for both electrode placement in the chest and receiver implantation in the flank. The stimulating electrode was inserted around a segment of intrathoracic phrenic nerve isolated with pleura and perineural blood supply. Follow-up is available on all patients six months to 8 years postoperatively. There were no complications or deaths related to the procedure. In all patients, bilateral phrenic nerve stimulation allowed either marked decrease in or discontinuation of positive-pressure ventilation. Phrenic nerve pacing can be performed safely in infants. It provides an effective alternative method for ventilatory support without the drawbacks of positive-pressure ventilation.

Action Potentials↗
PubMed1985

Respiratory insufficiency in newborns with abdominal wall defects.

Respiratory failure in newborns with abdominal wall defects has been attributed to increased intra-abdominal pressure and elevation of the diaphragm after closure. Despite surgical techniques designed to minimize intra-abdominal pressure, we have observed prolonged respiratory insufficiency in several such infants. We reviewed the charts of 108 infants from 1975 to 1982 who had abdominal wall defects: 53 with gastroschisis, 29 with small omphaloceles, 22 with liver-containing or giant omphaloceles (GO), and four with cloacal exstrophy. Nine infants with GO (41%) had prolonged respiratory insufficiency and five died. Infants with GO required longer periods of oxygenation and ventilation (P less than .001, ANOVA) than infants with other abdominal wall defects. Clinical observation suggested that infants with GO have a small, narrow thorax. We obtained detailed measurements from the chest radiographs of infants in all groups. After correction for birth weight, babies with GO had smaller chest widths (P less than .001) and lung areas (P less than .05) than infants with other abdominal wall defects. At autopsy, one newborn with GO was found to have severe pulmonary hypoplasia. Prolonged respiratory insufficiency in infants with GO may be explained by pulmonary hypoplasia and/or by a narrow chest deformity which limits lung expansion.

Abdominal Muscles↗
PubMed1985

Home pneumograms in normal infants.

To obtain age-specific normative data, we performed home cardiorespiratory recordings (pneumograms) in 56 normal infants at 1 month of age. A repeat pneumogram was performed at 3 months in 39 infants. Total sleep time was determined and all sleep intervals were summed and analyzed for five respiratory pattern variables: frequency of all apneic episodes greater than or equal to 6 seconds in duration (A6/D%), periodic breathing, longest apneic episode, and number of episodes greater than 11 and greater than 15 seconds. The normal infants at 1 and at 3 months were compared with 66 patients with apnea of infancy. Median A6/D% was 0.1 in the normal infants at 1 and 3 months, compared with 0.64 in those with apnea of infancy (P less than 0.001). Median periodic breathing was 0.4 and 0.2 episodes per 100 minutes in the normal infants at 1 and 3 months, respectively, compared with 1.25 in infants with apnea of infancy (P less than 0.001). Median longest apneic episode was 8.0 seconds in the normal infants at 1 and 3 months, compared with 11 seconds in those with apnea of infancy (P less than 0.001). No normal infant had an apneic episode greater than 15 seconds in duration, whereas the group with apnea of infancy had 0.4 +/- 1.0 episodes of apnea of greater than 15 seconds (P less than 0.01). Despite these significant group differences, use of these respiratory patterns either alone or in combination permitted only about 80% correct classification of normal infants and those with apnea of infancy.

Age Factors↗
PubMed1985

Effects of almitrine on hypoglossal and phrenic electroneurograms.

Almitrine increases breathing by stimulating peripheral chemoreceptors. Previous studies suggest clinical usefulness in the adult with chronic obstructive pulmonary disease, but little data are available to decide whether almitrine would be helpful in diseases involving pharyngeal airway obstruction, such as apnea of prematurity or obstructive sleep apnea. We investigated the effect of intravenous almitrine on hypoglossal (HG), an upper airway nerve, and phrenic (PHR) neural activity in eight alpha-chloralose-urethan anesthetized, paralyzed, vagotomized, and artificially ventilated cats. Recordings were made of raw and integrated HG and PHR electroneurograms (ENGs), alveolar PCO2, arterial PO2, arterial blood pressure, and rectal temperature. A dose-response study of cumulative almitrine doses ranging from 0.1 to 4.0 mg/kg was performed in three cats. The interactive effects of almitrine and hypoxic stimulation were investigated in four cats. The interactive effects of almitrine and hypercapnic stimulation were investigated in five cats. The interactive effects of almitrine and ventilatory timing were investigated in six cats. We found that 1) almitrine doses as low as 0.1 mg/kg iv increased both HG and PHR ENG activity, with a maximum effect at approximately 1.0 mg/kg; 2) almitrine markedly increased HG and PHR ENG activity at all arterial PO2 values from 35-175 Torr; 3) almitrine increased HG and PHR ENG activity at all arterial PCO2 values from 30-70 Torr; and 4) almitrine increased the ratio of tidal volume to inspiratory time and decreased the inspiratory muscle duty cycle at normoxia and eucapnia.

Airway Obstruction↗
PubMed1985

Day-to-day pneumogram variability.

To determine day-to-day variability in respiratory pattern, we obtained 188 comparisons of pneumograms performed during two successive 24-h intervals. The respiratory pattern values calculated were total duration of brief apnea (apnea density), periodic breathing episodes, longest apnea, number of apneas greater than 11 s, and number of apneas greater than 15 s. For day 1 values for apnea density, periodic breathing, and longest apnea which were within the 90th percentile for normal infants at age 1 month, day 2 values fell outside that range in 4.3, 3.5, and 18% of comparisons, respectively. There was a systematic tendency for the day 2 values to be less than the day 1 values. For each parameter, the day 2 range was lower, the slope of the day 2 versus day 1 regression line was significantly less than 1 (p less than 0.01) and the y-intercept was significantly greater than zero (p less than 0.01). Knowledge of day-to-day pneumogram variability should be helpful in interpreting individual pneumogram results and in assessing the clinical usefulness of pneumogram recordings.

Apnea↗
PubMed1985

Hyperlipoproteinaemia and atherosclerosis in rabbits fed low-level cholesterol and lecithin.

Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model, dietary lecithin promotes a return to normal of the LP distribution profile and removal of lipid from established atherosclerotic plaque.

Animals↗