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Biomedical subjects

O Werner

Publications and source records attributed to O Werner.

At least 55 records · Page 3Linked to original sources
PubMed1996

The contribution of the sarcoplasmic reticulum Ca2+-transport ATPase to caffeine-induced Ca2+ transients of murine skinned skeletal muscle fibres.

The present study was carried out to investigate the contribution of the Ca2+-transport ATPase of the sarcoplasmic reticulum (SR) to caffeine-induced Ca2+ release in skinned skeletal muscle fibres. Chemically skinned fibres of balb-C-mouse EDL (extensor digitorum longus) were exposed for 1 min to a free Ca2+ concentration of 0.36 microM to load the SR with Ca2+. Release of Ca2+ from the SR was induced by 30 mM caffeine and recorded as an isometric force transient. For every preparation a pCa/force relationship was constructed, where pCa = -log10 [Ca2+]. In a new experimental approach, we used the pCa/force relationship to transform each force transient directly into a Ca2+ transient. The calculated Ca2+ transients were fitted by a double exponential function: Y0 + A1 . (-t/t1) + A2 . exp(t/t2), with A1 < 0 < A2, t1 < t2 and Y0, A1, A2 in micromolar. Ca2+ transients in the presence of the SR Ca2+-ATPase inhibitor cyclopiazonic acid (CPA) were compared to those obtained in the absence of the drug. We found that inhibition of the SR Ca2+-ATPase during caffeine-induced Ca2+ release causes an increase in the peak Ca2+ concentration in comparison to the control transients. Increasing CPA concentrations prolonged the time-to-peak in a dose-dependent manner, following a Hill curve with a half-maximal value of 6.5 +/- 3 microM CPA and a Hill slope of 1.1 +/- 0.2, saturating at 100 microM. The effects of CPA could be simulated by an extended three-compartment model representing the SR, the myofilament space and the external bathing solution. In terms of this model, the SR Ca2+-ATPase influences the Ca2+ gradient across the SR membrane in particular during the early stages of the Ca2+ transient, whereas the subsequent relaxation is governed by diffusional loss of Ca2+ into the bathing solution.

Animals↗
PubMed1996

Circulatory effects of hypoxia, acute normovolemic hemodilution, and their combination in anesthetized pigs.

BACKGROUND: Because hemodilution decreases the oxygen-carrying capacity of blood, it was hypothesized that severe hemodilution would decrease the tolerance to alveolar hypoxia. METHODS: Hemodynamics, oxygen transport, and blood lactate concentrations were compared in ten pigs with normal hematocrit (33 +/- 4%), and ten hemodiluted pigs (hematocrit 11 +/- 1%; mean +/- SD) anesthetized with ketamine-fentanyl-pancuronium during stepwise decreases in inspired oxygen fraction (FIO2; 1.0, 0.35, 0.21, 0.15, 0.10, 0.05). RESULTS: Median systemic oxygen delivery (DO2SY) became critical (the DO2SY value when arterial lactate exceeded 2.0 mmol.l-1) at 10.4 ml.kg-1.min-1 (range 6.9-16.1) in hemodiluted animals and at 11.8 ml.kg-1.min-1 (5.9-32.2) in animals with normal hematocrits (NS). The relationship between mixed venous oxygen saturation and arterial lactate values was less consistent and median critical mixed venous oxygen saturation was higher (P < 0.05) in the hemodiluted group (35%, range 21-64), than in animals with normal hematocrits (21%, 7-68%). In animals with normal hematocrit, decreasing FIO2 from 1.0 to 0.10 resulted in a decrease in DO2SY from 26.3 +/- 9.1 to 9.3 +/- 3.9 ml.kg-1.min-1 (P < 0.01). Cardiac output did not change, systemic oxygen extraction ratio increased from 0.23 +/- 0.08 to 0.68 +/- 0.13 (P < 0.01), and arterial lactate from 0.9 +/- 0.2 to 3.4 +/- 3.0 mmol.l-1 (P < 0.05). Cardiac venous blood flow, as measured by retrograde thermodilution, increased from 5.7 +/- 2.9 to 12.6 +/- 5.7 ml.kg-1.min-1 (P < 0.01). When FIO2 was reduced to 0.05, three animals became hypotensive and died. In the second group, hemodilution increased cardiac output and systemic oxygen extraction ratio (P < 0.01). Cardiac venous blood flow increased from 4.1 +/- 1.7 to 9.8 +/- 5.1 ml.kg-1.min-1 (P < 0.01), and cardiac venous oxygen saturation from 22 +/- 5 to 41 +/- 10% (P < 0.01). During the subsequent hypoxia, cardiac output and DO2SY were maintained until FIO2 = 0.15 (DO2SY = 10.1 +/- 3.3 ml.kg-1.min-1). Cardiac venous blood flow was then 18.5 +/- 10.7 ml.kg-1.min-1 (P < 0.01), but in spite of this, myocardial lactate production occurred. At FIO2 = 0.10 (DO2SY = 7.7 +/- 3.0 ml.kg-1.min-1), arterial lactate concentration increased to 8.5 +/- 2.3 mmol.l-1 (P < 0.01), and most animals became hypotensive. All hemodiluted animals died when FIO2 was decreased to 0.05 (P < 0.01 when compared to animals with normal hematocrit). CONCLUSIONS: Systemic and myocardial lactate production occurred at similar systemic oxygen delivery rates in hemodiluted and nonhemodiluted animals. Mixed venous oxygen saturation may be a less reliable indicator of inadequate oxygen delivery during hemodilution.

Anesthesia↗
PubMed1996

Use of the polymerase chain reaction for the detection of reticuloendotheliosis virus in Marek's disease vaccines and chicken tissues.

Reticuloendotheliosis virus (REV) proviral DNA appears to be a frequent contaminant in Marek's disease (MD) vaccines. A polymerase chain reaction (PCR) was established and evaluated for its ability to detect REV proviral DNA in infected cell cultures and chicken tissues. Deoxynucleotide primers were selected from the highly conserved gag region of the REV genome. The amplification products were identified by electrophoresis, nested PCR and by hybridization with a digoxigenine-labelled oligonucleotide. The PCR results correlated well with the diagnosis obtained by conventional procedures, i.e. virus isolation or indirect immuno-fluorescence test (IIFT).

Animals↗
PubMed1996

Changes in lung volume and static expiratory pressure-volume diagram after surfactant rescue treatment of neonates with established respiratory distress syndrome.

The effect of natural surfactant on respiratory system mechanics in infants with respiratory distress syndrome (RDS) is incompletely understood, possibly because the analysis has usually been confined to the tidal breath. We studied 11 paralyzed neonates weighing 540 to 1,850 g before and approximately 30 min after surfactant, which was instilled at 4 to 41 h of age. Diagrams relating airway pressure to expired volume were obtained by having the infant exhale passively through a flowmeter, starting at 30 and ending at 0 cm H20 of pressure. An interrupter intermittently stopped the flow so that pressure could be recorded under static conditions. FRC was measured by sulfur hexafluoride washout, and TLC was calculated from FRC and the pressure-volume (P-V) curve. Ventilation homogeneity was assessed from the washout curve as pulmonary clearance delay (PCD). TLC increased by 10% or more in five infants, but it remained unchanged in the others. Median TLC was 19 ml/kg before and 21.5 ml/kg after surfactant (p = 0.39). The P-V curve became markedly steeper at low pressures after surfactant in most infants, the slope of the steepest segment, i.e., maximal compliance, increasing from 0.65 to 1.22 ml/cm H20/kg (medians, p = 0.008). Dynamic compliance (Cdyn) was unchanged at 0.28 ml/cm H20/kg, whereas specific dynamic compliance (Cdyn/FRC) decreased (p = 0.04). There was no significant immediate change in PCD. The findings imply that during the first 30 min surfactant acted mainly by stabilizing already ventilated air spaces.

Biological Products↗
PubMed1996

Lung volumes and pressure-volume relations of the respiratory system in small ventilated neonates with severe respiratory distress syndrome.

Total lung capacity (TLC), inspiratory capacity (IC), functional residual capacity (FRC), and deflation pressure-volume (P-V) curves were studied in 16 intubated neonates (540-3300 g), 10 with severe respiratory distress syndrome (RDS) and 6 air-ventilated with normal chest radiograms. FRC was measured using washout of a tracer gas (sulfur hexafluoride), and TLC and IC were calculated after inflating the lungs to 30 cm H2O. P-V curves were obtained during expiration from TLC using an interrupter technique, and the steepest slope of the curve, i.e. the maximum compliance (Crs-max), was calculated. In addition, an index of ventilation inhomogeneity (pulmonary clearance delay, PCD) was computed from the shape of the SF6 washout curve. TLC/body weight was less in the RDS group than in the air-ventilated group (median 19 and range 16-43 mL/kg versus 48 and 43-52 mL/kg, respectively; p < 0.01), mainly because of a marked reduction in IC (median 11 and range 8-24 mL/kg versus 29 and 28-40 mL/kg; p < 0.01). The flatter P-V curve in the RDS group was reflected also in a lower Crs-max (median 0.7 and range 0.4-1.7 cm H2O-1 kg-1) than in the air-ventilated group (2.3 and 2.0-3.1 mL cm H2O-1 kg-1, respectively; p < 0.01). Thus, there was no overlap in IC or Crs-max between the groups, suggesting that reductions in these measures may be main characteristics of RDS. On the other hand, no difference in PCD was found, indicating that, in infants with RDS, the tidal volume is distributed fairly homogeneously to the ventilated parts of the lungs.

Functional Residual Capacity↗
PubMed1995

Transcriptional activation by Myc is under negative control by the transcription factor AP-2.

The Myc protein binds to and transactivates the expression of genes via E-box elements containing a central CAC(G/A)TG sequence. The transcriptional activation function of Myc is required for its ability to induce cell cycle progression, cellular transformation and apoptosis. Here we show that transactivation by Myc is under negative control by the transcription factor AP-2. AP-2 inhibits transactivation by Myc via two distinct mechanisms. First, high affinity binding sites for AP-2 overlap Myc-response elements in two bona fide target genes of Myc, prothymosin-alpha and ornithine decarboxylase. On these sites, AP-2 competes for binding of either Myc/Max heterodimers or Max/Max homodimers. The second mechanism involves a specific interaction between C-terminal domains of AP-2 and the BR/HLH/LZ domain of Myc, but not Max or Mad. Binding of AP-2 to Myc does not preclude association of Myc with Max, but impairs DNA binding of the Myc/Max complex and inhibits transactivation by Myc even in the absence of an overlapping AP-2 binding site. Taken together, our data suggest that AP-2 acts as a negative regulator of transactivation by Myc.

Animals↗
PubMed1995

Faster recovery after anesthesia in infants after intravenous induction with methohexital instead of thiopental.

BACKGROUND: To determine possible delays in recovery after intravenous anesthesia induction with thiopental, the drug was compared with methohexital in infants 1-12 months of age who were scheduled for hernia repair or circumcision. METHODS: The infants were given equipotent doses of methohexital (3.0 mg/kg, n = 21) or thiopental (7.3 mg/kg, n = 20), in random and blind fashion. After tracheal intubation, anesthesia was maintained with isoflurane in nitrous oxide/oxygen. All children received 0.75 ml/kg caudal bupivacaine (2.5 mg/ml). Isoflurane was discontinued at the beginning of skin closure, and nitrous oxide was terminated immediately after the last suture (end of surgery). RESULTS: There were no differences between the two groups with respect to age, weight, or duration of surgery, which lasted 19 min (14-23 min) in the methohexital group and 16 min (15-19 min) in the thiopental group (median and inner quartile range). Time from termination of nitrous oxide to extubation did not differ significantly between the groups. Time to spontaneous eye opening after end of surgery was 23 min (5-44 min) after methohexital induction and 55 min (25-74 min) after thiopental induction (P < 0.05). Recovery, assessed as postanesthetic recovery scores by a blinded observer, was significantly more rapid in the methohexital group at arrival in the recovery room and 5, 15, and 45 min after arrival. After 120 min, almost all infants of both groups were awake. CONCLUSIONS: Recovery after short surgical procedures in infants is faster after intravenous induction with methohexital than with thiopental.

Anesthesia Recovery Period↗
PubMed1994

Clinical experience with minimal flow xenon anesthesia.

Xenon is a more potent anesthetic than nitrous oxide, and give more profound analgesia. This investigation was performed to assess the potential of xenon for becoming an anesthetic inspite of its high manufacturing cost. Seven ASA I-II patients undergoing cholecystectomy (n = 4), hernia repair (n = 2), or mammoplasty (n = 1) were studied. Denitrogenation by 15-20 min of oxygen breathing under propofol anesthesia was followed by fentanyl-supplemented xenon anesthesia administered via an automatic minimal flow system which held the oxygen concentration at 30%. Xenon anesthesia lasted 76-228 min and 8-14 l of xenon (ATPD) was used, of which 5.6-8.1 l was expended during the first 15 min. Anesthesia appeared to be satisfactory, and the patients woke up rapidly after xenon was discontinued. The automatic system made minimal flow xenon anesthesia easy to administer, but nitrogen accumulation is still a problem. Assuming a xenon price of 10 US$ per litre, the average cost for xenon was about 65 US$ for the first 15 min and then about 25 US$ for each subsequent hour of anesthesia.

Adult↗
PubMed1994

Pressure-volume relations of the respiratory system in healthy children.

Static pressure-volume (P-V) curves of the respiratory system were obtained in 48 healthy children (1 mo to 16 yr of age) during anesthesia and muscle paralysis. The lungs were inflated to a pressure of 25 to 40 cm H2O, and during the subsequent deflation an interrupter placed in the airway tubing opened and closed every 0.16 s. Airway flow was integrated to obtain the volume decrement between consecutive flow interruptions. Airway pressure was measured during interruptions, and a curve relating pressure to lung volume was plotted, assuming the lung volume at zero pressure to equal functional residual capacity (FRC). FRC was measured using tracer gas washout. The maximum slope of the P-V curve (maximum compliance = Crsmax, ml/cm H2O) was closely related to length (in centimeters) of the child: Crsmax = 7.7 x 10(-4) x length2.38; r = 0.97. The pressure coinciding with Crsmax was 6 +/- 1 cm H2O (mean +/- SD) in infants (1 to 6 mo of age) and 12 +/- 1 cm H2O in older children (> 1.5 yr of age). Total lung capacity (TLC) per kg body weight increased with age and was 52 +/- 13 ml/kg in infants and 87 +/- 11 mg/kg in older children. The FRC/TLC ratio was greater in infants (38 +/- 4%) than in older children (30 +/- 5%). The lung volume coinciding with Crsmax was nearly the same at all ages, when expressed as a percentage of TLC: 62 +/- 3%. Specific compliance of the respiratory system, that is, Crsmax/TLC, decreased with growth and was 0.044 +/- 0.006 cm H2O-1 in infants and 0.035 +/- 0.004 cm H2O-1 in older children. It is concluded that although the P-V relations of the respiratory system changed markedly with growth, especially during the first year of life, the lung volume (%TLC) at which maximum compliance occurred varied little.

Adolescent↗
PubMed1993

Exogenous surfactant therapy increases static lung compliance, and cannot be assessed by measurements of dynamic compliance alone.

OBJECTIVE: To study the immediate effects of exogenous surfactant therapy on blood gases, lung volumes, and lung mechanics in adult rabbits with experimentally induced respiratory distress syndrome. DESIGN: Prospective randomized, controlled study. SETTING: Laboratory and animal facility of a large university. SUBJECTS: Twelve adult New Zealand white rabbits. INTERVENTIONS: Respiratory failure was induced by repeated bilateral whole-lung lavage with saline (30 mL/kg body weight). After the last lavage, the animals were randomly assigned to two groups. Group 1 received surfactant (120 mg/kg body weight) that was suspended in a 0.6% sodium chloride solution. Group 2 received comparable volumes of the same hypotonic solution and served as controls. MEASUREMENTS AND MAIN RESULTS: Before and after endotracheal surfactant instillation, blood gases and functional residual capacity were measured, and lung mechanics from tidal volumes and pressure-volume curves were calculated. Functional residual capacity was measured by a computerized, multiple-breath, washin-washout method using sulfur hexafluoride (SF6) as tracer gas. The pressure-volume curves were obtained by an occlusion technique originally described for measuring static breath-by-breath compliance. The technique was modified for present use and fully computerized. Within 60 mins after surfactant instillation, there were marked improvements in Pao2 (61 +/- 7 torr [8.2 +/- 0.9 kPa] to 470 +/- 47 torr [62.6 +/- 6.2 kPa]) and in functional residual capacity (7.6 +/- 1.4 to 17.7 +/- 1.6 mL/kg body weight) at unchanged ventilatory settings. The pressure-volume curves became steeper over time and the pressure-volume curves for total lung volume were restored to an almost normal state. Maximum compliance calculated from the pressure-volume curves increased by 92% but there was no significant change in dynamic compliance. In the control group, no improvements in any measured or calculated lung parameters were seen. CONCLUSIONS: The findings indicate that during mechanical ventilation, the effects of surfactant therapy on lung mechanics are best characterized by changes in functional residual capacity and maximum compliance obtained from static pressure-volume curves and not by dynamic compliance.

Animals↗
PubMed1993

Left ventricular performance and cerebral haemodynamics during xenon anaesthesia. A transoesophageal echocardiography and transcranial Doppler sonography study.

The effects of xenon anaesthesia on myocardial function and cerebral blood flow velocities were investigated with transoesophageal echocardiography and transcranial Doppler sonography. Seventeen ASA 1 patients undergoing open cholecystectomy (n = 16) or abdominal hysterectomy (n = 1) were studied. Anaesthesia with 65% xenon in oxygen was induced by ventilating the lungs through a circle system with minimal fresh gas flow. The echocardiographically obtained mean (SD) fractional area change in a short axis view of the left ventricle at the level of the papillary muscles was 65 (10)% (n = 14) before xenon. There was no significant change after 5, 10 and 15 min of xenon anaesthesia. Cerebral blood flow velocities were unchanged during the first 5 min of xenon anaesthesia, but were significantly increased in the left and right middle, and the right anterior, cerebral arteries after 15 and 30 min (n = 16) (p < 0.05). In conclusion, xenon anaesthesia had no adverse effect on myocardial function, but probably increased cerebral flood flow.

Adult↗
PubMed1992

Dissolving methohexital in a lipid emulsion reduces pain associated with intravenous injection.

Pain often accompanies intravenous injection of 1% methohexital. The aim of the present study was to test whether pain on injection could be reduced by dissolving methohexital in a lipid emulsion (study A) and whether this would affect anesthetic potency (study B). In study A, 24 healthy volunteers, 36 +/- 1 yr (mean +/- SE), were given 1 ml 1% methohexital in saline, 1 ml 1% methohexital in lipid emulsion, and 5 ml 0.1% methohexital in saline in random order. The injections were given in a small vein in the forearm at 5-min intervals. One minute after each injection, the subject was asked to assess the injection pain on a visual analog scale (0-100 mm). The pain score (median [range]) was 44.5 (0-77) after 1% methohexital in saline, 0.5 (0-26) after 1% methohexital in a lipid emulsion, and 1.0 (0-26) after 0.1% methohexital in saline. The pain score for 1% methohexital in saline was significantly greater than those for the other two solutions (P less than 0.001 for each comparison). In study B, 42 patients, 41 +/- 3 yr, were given 1% methohexital in lipid emulsion (n = 22) or 1% methohexital in saline (n = 20). A bolus of either solution was administered over 10 s, and the patient was considered asleep if there was no gross movement or response to verbal command 40-70 s after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates.

A modification of a computerized tracer gas (SF6) washout method was designed for serial measurements of functional residual capacity (FRC) and ventilation homogeneity in mechanically ventilated very-low-birth-weight infants with tidal volumes down to 4 ml. The method, which can be used regardless of the inspired O2 concentration, gave accurate and reproducible results in a lung model and good agreement compared with He dilution in rabbits. FRC was measured during 2-4 cmH2O of positive end-expiratory pressure (PEEP) in 15 neonates (700-1,950 g), most of them with mild-to-moderate respiratory distress syndrome. FRC increased with body weight and decreased (P less than 0.05) with increasing O2 requirement. Change to zero end-expiratory pressure caused an immediate decrease in FRC by 29% (P less than 0.01) and gave FRC (ml) = -1.4 + 17 x weight (kg) (r = 0.83). Five minutes after PEEP was discontinued (n = 12), FRC had decreased by a further 16% (P less than 0.01). The washout curves indicated a near-normal ventilation homogeneity not related to changes in PEEP. This was interpreted as evidence against the presence of large volumes of trapped alveolar gas.

Body Weight↗
PubMed1992

Lung mechanics (FRC and static pressure-volume diagram) after endotracheal surfactant instillation: preliminary observations.

Preliminary measurements of functional residual capacity (FRC) with the sulphurhexafluoride technique and static pressure volume diagrams were performed in newborn infants with respiratory distress syndrome receiving endotracheal instillation of natural porcine surfactant (Curosurf, 100 or 200 mg/kg). Within the first hour after surfactant treatment there was an increase in FRC and distensibility of the lungs persisting for 24-48 h.

Biological Products↗
PubMed1992

Natural surfactant instilled in premature lambs increases lung volume and improves ventilation homogeneity within five minutes.

The immediate effects on lung volume, ventilation homogeneity, and lung mechanics of tracheal instillation of surfactant were studied in premature lambs, gestational age 120-122 d, with respiratory distress syndrome. Six lambs received surfactant by tracheal instillation 25 min after delivery by cesarean section; five received only vehicle and served as controls. The lambs were studied for 60 min thereafter. Functional residual capacity was measured with a computerized tracer gas washin-washout technique using sulfur hexafluoride as tracer gas. A measure of ventilation inhomogeneity (pulmonary clearance delay) was also calculated from the washout curves. Pressure-volume curves were studied with an interrupter technique during deflation of the lungs from an airway pressure of 30 cm H2O. In the surfactant group, arterial oxygenation and ventilation homogeneity improved within 5 min of giving surfactant; major increases in functional residual capacity, vital capacity, and compliance occurred within 5 to 20 min and were followed by gradual further improvements. The pressure-volume curve thus increased in amplitude and became steeper, but the lung volumes at various inflation pressures, and compliance, remained constant when expressed as fractions of total lung capacity volume. It is concluded that an improvement in lung volume, respiratory mechanics, and ventilation homogeneity occurs very soon after surfactant instillation and that there is a phase of successive further improvement over the next hour. Although the amplitude of the pressure-volume curve varied considerably, its basic shape varied little. This suggests that opening of new distal airways by surfactant predominated over changes in the mechanics of already aerated lung regions.

Animals↗
PubMed1991

A minimal-flow system for xenon anesthesia.

We described a minimal-flow system for xenon anesthesia during controlled ventilation. A computer maintained oxygen concentration in the anesthesia circle within +/- 2% of the value set by the anesthesiologist. The ventilator and the circle were connected via a large dead space, through which oxygen from the ventilator entered the circle but which prevented xenon from escaping. This arrangement simplified the computer program. The system was tested on a lung model and in six pigs (37-39 kg). The xenon expenditure and the amount of xenon washed out from the pigs after the anesthetic were measured. Additional experiments with nitrous oxide were made in three pigs. The xenon expenditure during 2 h of xenon anesthesia was 7.6 +/- 0.8 l (mean +/- 1 standard deviation). The corresponding expenditure of nitrous oxide was 16.5 +/- 2.7 l. About 75% of the xenon expenditure was in the 1st h of anesthesia; thereafter 20-40 ml.min-1 was needed to maintain oxygen concentration at 30%. Nitrogen concentration in the circle increased to 12-16% during the xenon anesthetic, although it was preceded by a 20 min denitrogenation period. During the washout phase after the xenon anesthesia, mean expired xenon concentration decreased to below 2% within 4 min. Subsequently, washout was slower and the expired concentration remained above 0.1% for more than 90 min. The estimated total amount of xenon washed out from the lungs and body tissues during 4 h of oxygen breathing was about 4 l. We conclude that xenon anesthesia via a fully automated minimal-flow system is feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗