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Biomedical subjects

M E Pedersen

Publications and source records attributed to M E Pedersen.

At least 19 recordsLinked to original sources
PubMed2000

Peripheral chemoreflex function in hyperoxia following ventilatory acclimatization to altitude.

After a period of ventilatory acclimatization to high altitude (VAH), a degree of hyperventilation persists after relief of the hypoxic stimulus. This is likely, in part, to reflect the altered acid-base status, but it may also arise, in part, from the development during VAH of a component of carotid body (CB) activity that cannot be entirely suppressed by hyperoxia. To test this hypothesis, eight volunteers undergoing a simulated ascent of Mount Everest in a hypobaric chamber were acutely exposed to 30 min of hyperoxia at various stages of acclimatization. For the second 10 min of this exposure, the subjects were given an infusion of the CB inhibitor, dopamine (3 microg. kg(-1). min(-1)). Although there was both a significant rise in ventilation (P < 0.001) and a fall in end-tidal PCO(2) (P < 0.001) with VAH, there was no progressive effect of dopamine infusion on these variables with VAH. These results do not support a role for CB in generating the persistent hyperventilation that remains in hyperoxia after VAH.

Acclimatization↗
PubMed1999

Identification of fast and slow ventilatory responses to carbon dioxide under hypoxic and hyperoxic conditions in humans.

1. Under conditions of both euoxia and hypoxia, it is generally accepted that the ventilatory response to CO2 has both rapid (peripheral chemoreflex) and slow (central chemoreflex) components. However, under conditions of hyperoxia, it is unclear in humans whether the fast component is completely abolished or merely attenuated in magnitude. 2. The present study develops a technique to determine whether or not a two-compartment model fits the ventilatory response to CO2 significantly better than a one-compartment model. Data were collected under both hypoxic (end-tidal PO2 = 50 Torr) conditions, when two components would be expected, and under hyperoxic (end-tidal PO2 = 200 Torr) conditions, when the presence of the fast compartment is under question. 3. Ten subjects were recruited, of whom nine completed the study. The end-tidal PCO2 of each subject was varied according to a multi-frequency binary sequence that involved 13 steps into and 13 steps out of hypercapnia lasting altogether 1408 s. 4. In four out of nine subjects in hypoxia, and six out of nine subjects in hyperoxia, the two-compartment model fitted the data significantly better than the one-compartment model (F ratio test on residuals). This improvement in fit was significant for the pooled data in both hypoxia (P < 0.05) and hyperoxia (P < 0.005). Mean ventilatory sensitivities for the central chemoreflex were (mean +/- s.e.m.) 1. 69 +/- 0.39 l min-1 Torr-1 in hypoxia and 2.00 +/- 0.32 l min-1 Torr-1 in hyperoxia. Mean ventilatory sensitivities for the peripheral chemoreflex were 2.42 +/- 0.36 l min-1 Torr-1 in hypoxia and 0.75 +/- 0.16 l min-1 Torr-1 in hyperoxia. 5. It is concluded that the rapid and slow components of the ventilatory response to CO2 can be separately identified, and that a rapid component persists under conditions of hyperoxia.

Adult↗
PubMed1999

Effects of somatostatin on the control of breathing in humans.

1. Somatostatin depresses the ventilatory response to hypoxia (AHVR). This study sought to determine whether somatostatin also reduced the peripheral chemoreflex sensitivity to hypercapnia, and if so, whether this was related to the reduction in AHVR. 2. Nine subjects completed the study. AHVR and the ventilatory responses to hypercapnia under both hyperoxic and hypoxic conditions were assessed both without and with an infusion of somatostatin (0.5 BsBs5mgBs5 h-1). Peripheral (fast) and central (slow) responses to hypercapnia were distingushed by use of a multi-frequency binary sequence input in end-tidal PCO2 (PET,CO2) that included 13 steps into and out of hypercapnia. 3. The acute ventilatory response to a reduction in end-tidal PO2 (PET,O2) from 100 to 50 Torr (at a PET, CO2 of +1.5-2.0 Torr above normal) was reduced from (mean +/- s.e.m. ) 16.4 +/- 3.3 to 9.5 +/- 3.2 l min-1 (P < 0.005, Student's t test) by somatostatin. The magnitude of the ensuing hypoxic ventilatory decline was unaltered (8.8 +/- 2.7 l min-1 in control vs. 8.0 +/- 2. 9 l min-1 with somatostatin). 4. The peripheral chemoreflex sensitivity to CO2 in hypoxia was reduced from 2.42 +/- 0.36 to 1.18 +/- 0.20 l min-1 Torr-1 (P < 0.005) with somatostatin. The reduction under hyperoxic conditions from 0.75 +/- 0.34 to 0.49 +/- 0.09 l min-1 Torr-1 did not reach significance. Central chemoreflex sensitivity to CO2 was unchanged. Changes in peripheral chemoreflex sensitivity to CO2 in hypoxia correlated with changes in AHVR. 5. We conclude that peripheral chemoreflex sensitivity to CO2 is reduced by somatostatin, probably via the same mechanism as that by which somatostatin exerts its effects on AHVR.

Adult↗
PubMed1999

Sulfated glycosaminoglycans and collagen in two bovine muscles (M. Semitendinosus and M. Psoas major) differing in texture.

M. semitendinosus (ST) and M. psoas major (PM) were used as models for tough and tender meat to study a possible role of sulfated glycosaminoglycans (GAGs) for muscle tenderness. The difference in texture was confirmed by Warner Bratzler shear force measurements. No significant difference in total amount of GAGs in the muscles was found. In contrast, a significant difference in the ratio of GAG/collagen was found between the two muscles. After separation of the GAGs by density gradient ultracentrifugation and ion-exchange chromatography, dermatan sulfate (DS), keratan sulfate (KS), chondroitin sulfate (CS), and heparan sulfate (HS) were identified by cellulose acetate electrophoresis after use of specific enzymes and chemical methods. The content of DS was higher in the tougher muscle (ST) than in PM, and the difference in DS content was statistically significant. Furthermore, a significant difference in the GAG composition pattern of the two muscles was found. The yield of GAGs extracted from the muscles was 77% for ST and 87% for PM. The residue after extraction was further analyzed and found to contain mainly HS. Immunohistochemical studies using antibodies against CS/DS showed a staining pattern of the perimysium of ST different from that of PM.

Animals↗
PubMed1999

Effects of dopamine and domperidone on ventilatory sensitivity to hypoxia after 8 h of isocapnic hypoxia.

Acclimatization to altitude involves an increase in the acute hypoxic ventilatory response (AHVR). Because low-dose dopamine decreases AHVR and domperidone increases AHVR, the increase in AHVR at altitude may be generated by a decrease in peripheral dopaminergic activity. The AHVR of nine subjects was determined with and without a prior period of 8 h of isocapnic hypoxia under each of three pharmacological conditions: 1) control, with no drug administered; 2) dopamine (3 microg. min-1. kg-1); and 3) domperidone (Motilin, 40 mg). AHVR increased after hypoxia (P </= 0. 001). Dopamine decreased (P </= 0.01), and domperidone increased (P </= 0.005) AHVR. The effect of both drugs on AHVR appeared larger after hypoxia, an observation supported by a significant interaction between prior hypoxia and drug in the analysis of variance (P </= 0. 05). Although the increased effect of domperidone after hypoxia of 0. 40 l. min-1. %saturation-1 [95% confidence interval (CI) -0.11 to 0. 92 l. min-1. %-1] did not reach significance, the lower limit for this confidence interval suggests that little of the increase in AHVR after sustained hypoxia was brought about by a decrease in peripheral dopaminergic inhibition.

Acclimatization↗
PubMed1998

Human ventilatory response to 8 h of euoxic hypercapnia.

Ventilation (VE) rises throughout 40 min of constant elevated end-tidal PCO2 without reaching steady state (S. Khamnei and P. A. Robbins. Respir. Physiol. 81: 117-134, 1990). The present study investigates 8 h of euoxic hypercapnia to determine whether VE reaches steady state within this time. Two protocols were employed: 1) 8-h euoxic hypercapnia (end-tidal PCO2 = 6.5 Torr above prestudy value, end-tidal PO2 = 100 Torr) followed by 8-h poikilocapnic euoxia; and 2) control, where the inspired gas was air. VE was measured over a 5-min period before the experiment and then hourly over a 16-h period. In the hypercapnia protocol, VE had not reached a steady state by the first hour (P < 0.001, analysis of variance), but there were no further significant differences in VE over hours 2-8 (analysis of variance). VE fell promptly on return to eucapnic conditions. We conclude that, whereas there is a component of the VE response to hypercapnia that is slow, there is no progressive rise in VE throughout the 8-h period.

Adolescent↗
PubMed1997

Effects of 8h of eucapnic and poikilocapnic hypoxia on middle cerebral artery velocity and heart rate in humans.

This study examines the effects of prolonged hypoxia, with and without control of end-tidal CO2 partial pressure (PET,CO2), on the intensity-weighted mean velocity of blood flow in the middle cerebral artery (VIWM) and on heart rate (HR). Specifically, the time course of the responses, their reversibility with brief periods of hyperoxia and the recovery phase following prolonged hypoxia were all investigated. Twelve subjects were studied, of whom nine provided satisfactory data. A purpose-built chamber was used for the prolonged control of the end-tidal gases, and an end-tidal forcing system was used for generating the brief variations in end-tidal gases. Three 16 h protocols were employed: (1) 8 h eucapnic (average PET,CO2 = 39 mmHg) hypoxia (end-tidal O2 partial pressure, PET,O2 = 55 mmHg) followed by 8 h eucapnic euoxia (PET,O2 = 100 mmHg); (2) 8 h poikilocapnic (average PET,CO2 4 mmHg below eucapnia) hypoxia (PET,O2 = 55 mmHg) followed by 8 h poikilocapnic euoxia (PET,O2 = 100 mmHg); and (3) control (air inspired throughout). VIWM (using Doppler ultrasound) and HR were measured during brief exposures to hypoxic/euoxic and hyperoxic conditions with PET,CO2 held 1-2 mmHg above eucapnia, at 0, 20, 240 and 480 min in the first 8 h, and at the same times in the second 8 h. There were no significant trends in VIWM under hypoxic conditions for either hypoxic protocol (ANOVA) and no significant differences between the three protocols for VIWM in hyperoxia (ANOVA). In contrast to VIWM, there was a significant increase in HR over time during both hypoxic exposures (P < 0.01, ANOVA). HR increased to a similar extent for the two types of hypoxia, and there was some suggestion that HR remained elevated after the relief of hypoxia. The results suggest that, with the level of hypoxia employed, progressive changes in HR occur, but that this level and duration of hypoxia has little sustained effect on VIWM.

Blood Flow Velocity↗
PubMed1997

Human ventilatory response to acute hyperoxia during and after 8 h of both isocapnic and poikilocapnic hypoxia.

During 8 h of either isocapnic or poikilocapnic hypoxia, there may be a rise in ventilation (VE) that cannot be rapidly reversed with a return to higher PO2 (L. S. G. E. Howard and P. A. Robbins. J. Appl. Physiol. 78:1098-1107, 1995). To investigate this further, three protocols were compared: 1) 8-h isocapnic hypoxia [end-tidal PCO2 (PETCO2) held at prestudy value, end-tidal PO2 (PETO2) = 55 Torr], followed by 8-h isocapnic euoxia (PETO2 = 100 Torr); 2) 8-h poikilocapnic hypoxia followed by 8-h poikilocapnic euoxia; and 3) 16-h air-breathing control. Before and at intervals throughout each protocol, the VE response to eucapnic hyperoxia (PETCO2 held 1-2 Torr above prestudy value, PETO2 = 300 Torr) was determined. There was a significant rise in hyperoxic VE over 8 h during both forms of hypoxia (P < 0.05, analysis of variance) that persisted during the subsequent 8-h euoxic period (P < 0.05, analysis of variance). These results support the notion that an 8-h period of hypoxia increases subsequent hyperoxic VE, even if acid-base changes have been minimized through maintenance of isocapnia during the hypoxic period.

Adolescent↗
PubMed1997

Effects of haloperidol on ventilation during isocapnic hypoxia in humans.

Exposure to isocapnic hypoxia produces an abrupt increase in ventilation [acute hypoxic ventilatory response (AHVR)], which is followed by a subsequent decline [hypoxic ventilatory depression or decline (HVD)]. In cats, both anesthetized and awake, haloperidol has been reported to increase AHVR and almost entirely abolish HVD. To investigate whether this occurs in humans, the ventilatory responses of 15 healthy young volunteers to 20 min of isocapnic hypoxia (end-tidal PO2 = 50 Torr) were assessed at 1, 2, and 4.5 h after placebo (control) and after oral haloperidol (Seranace, 0.05 mg/kg) on different days. Three subjects were unable to complete the study because of akathisia. AHVR was significantly greater with haloperidol compared with control (P < 0.01, analysis of variance). However, no significant change in HVD was found [control HVD = 9.3 +/- 1.6 (SD) l/min, haloperidol HVD = 9.9 +/- 2.1 l/min; P = not significant, analysis of variance]. We conclude that combined central and peripheral dopamine-receptor antagonism in humans with haloperidol produces a similar pattern of change to that reported previously with the peripheral antagonist domperidone. We have been unable to show in humans a decrease in HVD by the centrally acting drug as observed in cats.

Adult↗
PubMed1992

Developmental regulation of lipoprotein lipase in rats.

To evaluate changes in lipoprotein lipase (LPL) expression during development, levels of LPL mRNA, protein, and enzyme activity were measured in heart, epididymal fat, kidney, and brain of rats, from late gestation through 24 mo. LPL mRNA, protein, and enzyme activity were low in fetal and neonatal hearts. LPL mRNA increased 11-fold by 60 days and remained at this level thereafter; LPL protein and enzyme activity increased 10-fold by weaning, before declining to low values by 3 mo. LPL mRNA levels, protein, and enzyme activity did not change in epididymal fat from 3 wk to 21 mo. In the kidney, LPL mRNA levels were high at the end of gestation but fluctuated during the first month. LPL protein and activity were low at day 1 and rose eightfold to peak values by day 7 before decreasing to low levels by weaning. LPL mRNA levels were relatively high in fetal brains and then fell 60% during the neonatal period. LPL protein peaked at day 7 before falling 95% by weaning. Thus LPL is under complex tissue-specific regulation involving transcriptional and posttranscriptional mechanisms.

Adipose Tissue↗
PubMed1992

Regulation of lipoprotein lipase in the diabetic rat.

Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity and development of hypertriglyceridemia. In the current experiments the mechanisms involved in the regulation of LPL have been examined in control rats, streptozocin-induced diabetic rats, and diabetic rats treated chronically or with a single injection of insulin. Diabetes decreased adipose tissue LPL activity partially by decreasing immunoreactive LPL protein and the steady-state levels of LPL mRNA, but primarily by reducing the catalytic activity of LPL. Both chronic and acute insulin increased adipose tissue LPL activity by correcting the defect in the catalytic activity of LPL and increasing immunoreactive LPL protein; however, only chronic insulin restored LPL mRNA levels to normal. In the heart, LPL activity tended to be elevated with diabetes in parallel to an increase in immunoreactive LPL protein even though levels of LPL mRNA declined. Both chronic and acute insulin normalized LPL activity and immunoreactive LPL protein, while only chronic insulin corrected the levels of LPL mRNA. No changes in the catalytic activity of LPL in heart were detected among the groups. Thus, diabetes and insulin treatment regulate LPL expression pretranslationally, translationally, and post-translationally, with tissue-specific differences apparent in the mechanisms involved.

Adipose Tissue↗
PubMed1988

Regulation of lipoprotein lipase immunoreactive mass in isolated human adipocytes.

Previous studies of human adipose tissue lipoprotein lipase (LPL) have focused on enzyme catalytic activity, and have not measured the LPL protein directly. To study the regulation of the LPL protein, an antibody against purified bovine LPL was used. To demonstrate the specificity of the antiserum, adipose homogenates were Western blotted, and adipocytes were radiolabeled and the cell homogenates immunoprecipitated, yielding a single specific band at 53 kD. Breakdown products of LPL were demonstrated at 35 and 20 kD by Western blotting. An ELISA for human adipose LPL was established, in which LPL was sandwiched between affinity-purified antibody and biotinylated affinity-purified antibody. The standard curves for bovine LPL and human adipose LPL were parallel, and LPL activity correlated strongly with LPL immunoreactive mass. Thus, the bovine LPL standard curve was used to estimate LPL immunoreactive mass from human adipose tissue. The regulation of LPL activity and immunoreactive mass were compared in cultured adipocytes in the presence an absence of insulinlike growth factor-I/somatomedin C (IGF-I), insulin, and fetal bovine serum. IGF-I and a high insulin concentration (70 nM) stimulated only the heparin-releasable (HR) component of LPL activity and immunoreactive mass, and neither IGF-I nor insulin affected LPL specific activity. In contrast, 10% fetal bovine serum stimulated HR activity, HR mass, and cellular extractable (EXT) immunoreactive mass, with no effect on EXT activity. This resulted in a decrease in EXT specific activity in response to serum. The effects of the locally produced nucleosides adenosine and inosine were studied in a similar manner. As with serum, adenosine stimulated HR activity, HR mass, and EXT immunoreactive mass, resulting in a decrease in EXT specific activity. Inosine stimulated an increase in HR activity and HR mass, but had no effect on EXT, and thus did not change LPL specific activity. Thus, a sensitive ELISA for adipose tissue LPL has been developed using a specific, well-characterized antibody. Regulation of human LPL immunoreactive mass was demonstrated in vitro by IGF-I, serum, high concentrations of insulin, adenosine, and inosine. This method will permit further investigations into the regulation of the LPL protein.

Adenosine↗
PubMed1987

An enzyme-linked immunoassay for lipoprotein lipase.

Polyclonal antibodies against bovine milk lipoprotein lipase (LPL) were used to generate an enzyme-linked immunosorbent assay (ELISA) for rat LPL. The antibodies to LPL were affinity purified on bovine LPL columns and were shown to be specific for LPL by immunoprecipitation and enzyme inhibition. The solid-phase ELISA was sensitive from 1.0 to 20 ng/ml of LPL and paralleled enzyme activity. Denatured rat LPL showed the same LPL mass as undenatured samples, allowing LPL mass to be quantitated effectively in a variety of rat tissue extracts.

Adipose Tissue↗
PubMed1986

Homology of lipoprotein lipase to pancreatic lipase.

Bovine milk lipoprotein lipase was subjected to amino acid sequence analysis. The first 19 amino-terminal residues were Asp-Arg-Ile-Thr-Gly-Gly-Lys-Asp-Phe-Arg-Asp-Ile-Glu-Ser-Lys-Phe-Ala-Leu- Arg. In addition, reversed-phase high-performance liquid chromatography of a tryptic digest of reduced and alkylated lipase resolved a number of peptides, five of which contained cysteine. Sequence analysis of the tryptic peptides revealed in most instances a close homology to porcine pancreatic lipase. Based on this homology, the relative alignment of the sequenced lipoprotein lipase peptides can be made. In addition, a potential binding site for the triacylglycerol substrate and a carbohydrate-binding domain for lipoprotein lipase are postulated.

Amino Acid Sequence↗
PubMed1983

Immunocytochemical localization of the functional fraction of lipoprotein lipase in the perfused heart.

The functional (heparin-releasable) fraction of myocardial lipoprotein lipase (LPL) has been located at the lumen surface of capillary endothelium by means of an indirect immunocytochemical perfusion method for electron microscopy. The primary step immunoreactant was an IgG fraction of goat antiserum directed against LPL from rat heart. The second step antibody, conjugated with horseradish peroxidase, was rabbit IgG directed against goat IgG. Peroxidase reaction product, when present, appeared at the surface an in invaginations of the lumenal plasma membrane of capillary endothelium and also on chylomicrons adherent to that membrane. The highest coverage by such product occurred when the highest heparin-releasable heart LPL activity was attained after fat-feeding of rats. Coverage was low when a low level of heparin-releasable heart LPL activity was induced by carbohydrate-feeding. Coverage was very low in the perfused hearts after heparin-release of functional LPL activity. The positive association between these immunocytochemical results and actual levels of functional LPL activities indicates that functional LPL in the isolated rat heart is at the lumen surface of capillary endothelium.

Animals↗
PubMed1981

Hormonal mediation of rat heart lipoprotein lipase activity after fat feeding.

The effect of acute fat feeding on the response of two fractions of lipoprotein lipase in heart was explored. In rats, previously fasted, lipoprotein lipase activity released into the perfusate by heparin increased approximately 50% 4 h after fat feeding. The lipase activity remaining in the heart tissue after heparin perfusion showed no significant difference. When rats maintained ad libitum were intubated with glucose 2 h before the fat dose, a relatively larger increase (5-10-fold) in the heparin-releasable lipase activity was observed. The capacity of these hearts to hydrolyze 14C-labeled chylomicrons was also increased 4-5-fold over the controls. Fat ingestion has been reported to elevated plasma corticosteroid levels in rats. When adrenalectomized rats were fed fat, no significant changes in the heparin-releasable lipase activity were observed Hydrocortisone and corticotropin treatment increased the heparin-releasable lipase activity to the same degree as observed with fat feeding. These data suggest that the increase in heart lipoprotein lipase activity following fat feeding is mediated via corticosteroids.

Adrenocorticotropic Hormone↗