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PubMed2000

Analysis of breathing in the crawl as a function of skill and stroke characteristics.

The purpose of this study was to measure and compare the durations of exhalation (DE), inhalation (DI), and inhalatory apnea (DAI) expressed as percentage of stroke-cycle duration using two groups (more expert and less expert) of 6 front crawl swimmers each at near 100-m speed (high speed) and 800-m speed (low speed). Two breathing conditions were considered, breathing to the preferred side with and without a nose-clip. The relationships between stroking characteristics (swimming speed, stroke rate, and stroke length) and the three durations of breathing were examined as a function of skill and swimming speed. The data show that use of a nose-clip does not significantly change those measures. At high speed, the more expert group had a lower inhalation and a higher exhalation than the less expert group. The stroke rate correlated with speed .92 (p<.01) and was mainly associated with inhalation (r=-.78, p<.01). Inclusion of exhalation as a second variable improved significantly (p<.01) the accuracy of the regression up to .97. At low speed, the less expert had lower inhalatory apnea than the more expert. Stroke length correlated with speed .86 (p<.01) and was mainly associated with inhalatory apnea (r=.70, p<.05). At high speed, the more expert had a lower inhalation than at low speed, while durations of exhalation and inhalatory apnea did not vary significantly. On the contrary, the less expert had a lower exhalation and a higher inhalatory apnea, while duration of inhalation remained relatively unchanged. The present study shows that these durations and their relations to stroking characteristics could be considered significant indicators of skill in swimming.

Aerobiosis↗
PubMed2000

Alcoholic drinkers and road safety in the Republic of Slovenia.

In this study we were therefore interested in the percentage of road traffic offenses (RTO) and road traffic accidents (RTA) involving inebriated drivers one year before and one year after the passing of the new Law on Road Traffic Safety (LRTS) as well as measures (referrals, punishments and final decisions on the revoking of driver's licenses due to drunk driving). One year before the passing of the new LRTS, there were 40,702 RTA-s in the Republic of Slovenia (12.2% caused by drunk drivers). The average alcohol concentration in exhaled air for those analysed was 1.19 g/kg. One year after the passing of this law there were 36,479 RTA-s (8.6% caused by drunk drivers). The average alcohol concentration in exhaled air for those analysed was 1.32 g/kg (the differences were statistically significant). In 13.8% cases the reason for performing a measurement of the alcohol concentration in exhaled aier was an RTA with an average alcohol concentration in exhaled air of 1.22 g/kg and in 86.2% of cases an RTO with an average alcohol concentration in exhaled air of 1.25 g/kg (the differences were statistically significant). We found it interesting that the number of events minvolving lower concentrations decreased, but the percentage involving higher alcohol concentrations even increased. The results of this study indicate without a doubt that the law was not successful enough with its repressive and preventative measures in the field of drunk drivers. Experts on alcohol believe that punishment cannot make alcoholics and other drivers abandon their behavioural patterns and stop driving under the influence of alcohol. This can be achieved only by treatment, and the present practice (police--misdenveanour counts--repeat general medical check-up) has been ineffective as prevention among alcoholic drivers. We therefore believe that supplements to the LRTS should be adopted urgently, that would contribute, through better medical selection, to a reduction in the number of drunk drivers behind the wheel, both those who are alcohol dependent (and should be referred to treatment).

Accidents, Traffic↗
PubMed1984

Radioisomers of scoparone (6,7-dimethoxycoumarin) as a tool for in vivo differentiation of various hepatic monooxygenase inducers in mice using the breath test technique.

The oxidative removal of two different methyl groups from scoparone by a cytochrome P-450-mediated reaction proceeds with greater velocity for the 6-methyl group than for the 7-methyl group. In vivo experiments in mice were carried out with the two respective radioisomers [6-methyl-14C]scoparone and [7-methyl-14C]scoparone. The consecutive administration of the scoparone to the same animal is followed by collecting the 14CO2 exhaled (breath test). The maximal exhalation rate, measured 4 min after i.p. administration of the substrates, is four times greater for [6-methyl-14C]scoparone than for the [7-methyl-14C]scoparone. The total recovery of radioactivity in the whole animal (except skin) including the exhaled 14CO2 is 86% for [7-methyl-14C]scoparone and 84% for [6-methyl-14C]scoparone. Further analysis shows that the proportion of radioactivity found in various excretory routes is different; however, in the case of the poorly exhaled [7-methyl-14C]scoparone, almost twice as much radioactivity is found in bile and urine than for the more rapidly exhaled [6-methyl-14C]scoparone, whereas liver and other organs show little changes. Pretreatment of animals with various inducers, such as phenobarbital, 3-methylcholanthrene, warfarin and cobaltous chloride, characteristically affects the ratio of the two demethylations of scoparone. In the case of warfarin pretreatment, the ratio of the 6- to 7-demethylation is elevated to nearly 6, after cobaltous chloride the ratio is lowered to 2.8, whereas phenobarbital and 3-methylcholanthrene have no effect. These results may provide possibilities of noninvasive in vivo recognition of the inductive state of a pretreated animal.

Animals↗
PubMedDate not supplied

[The use of dobutamine during the intraoperative period to prevent organ hypoperfusion in non-heart surgery. Administration modality and monitoring].

Dobutamine is strongly recommended in the treatment of critical intensive care patients in order to improve cardiac performance and peripheral perfusion. In non-cardiac surgery there are frequent cases of organ hypoperfusion that could be treated with dobutamine; the drug, however, is not advocated since it is difficult to control without invasive hemodynamic monitoring. This study analyzed the possibilities of using and controlling dobutamine in non-cardiac surgery. The study covered 186 patients ranging from 40 to 80 years of age who were divided into two groups according to ASA class and the type of surgery they were to undergo (Group I ASA 1-2 major surgery, group 2 ASA 3-4 standard and major surgery). Of these, 93 patients were treated with dobutamine infusion, 3 mu/kg/min, started before anesthesia and modulated for the duration of the operation on the basis of the patient's monitoring values. The remaining 93 patients were the controls who underwent the same anesthesiological procedure without receiving the drug. During anesthesia we monitored: mean blood pressure, pulsioxiometry, fraction of exhaled CO2 and heart rate. Analyses were done using a personal computer network connected to the patient monitoring system. For each parameter we calculated the number of times per hour of anesthesia that different readings were taken (higher or lower) with respect to the value recorded immediately after premedication. The following variations were considered significant. 5 mmHg for blood pressure, 10 b/min for heart rate, 4% higher or lower for exhaled CO2; plus or minus 95% for pulsioximetry. The data were evaluated using the chi 2 test. The treated patients showed significantly higher blood pressure, exhaled CO2 and heart rate values, demonstrating that dobutamine infusion can be piloted on the basis of these monitoring parameters. The treated patients had 4% higher exhaled CO2 levels showing the close correlation between exhaled CO2 and the use of the inotrope. The overall results show that dobutamine is easy to use and readily piloted during anesthesia for non-cardiac surgery.

Adult↗
PubMed1996

Airborne nitric oxide: inflammatory marker and aerocrine messenger in man.

1. In healthy subjects, exhaled NO originates mainly from the upper airways with only a minor contribution from the lower airways and the lungs. A large NO production takes place in the epithelium of the paranasal sinuses and this NO contributes considerably to the levels of NO found in nasally exhaled air. Immunohistochemical and mRNA in situ hybridisation studies suggest that sinus NO synthase is identical or very closely related to the human iNOS. Furthermore, the NOS activity in sinus mucosa is mostly Ca(2+)-independent. However, the regulation of sinus NOS expression seems to differ fundamentally from what has earlier been described for iNOS. Thus, sinus NOS is constitutively expressed and seems resistant to steroids. The high local NO concentrations in the nasal airways and the sinuses may help to protect against airborne infectious agents. Thus, airborne NO may represent the very first line of defence in the airways, possibly acting on pathogens even before they reach the mucosa. 2. Nasal concentrations of NO are markedly reduced in children with Kartagener's syndrome and in patients with CF. A simple chemiluminescence test test could be of help in early non-invasive diagnosis of these chronic airway diseases. 3. Inhaled endogenous NO, derived from the upper airways, may be involved in regulation of pulmonary function in man. NO will reach the lower airways and the lungs with the inspired air and at levels that are especially high during nasal breathing. This NO may act by enhancing blood flow preferentially in well ventilated areas of the lung, thus optimizing ventilation/perfusion matching. The involvement of autogenous NO in regulation of pulmonary function may represent a novel physiological principle, namely that of an enzymatically produced airborne messenger. The term "aerocrine" may be appropriate for this action of NO in the airways. These findings may also help to explain one biological role of the enigmatic human paranasal sinuses, the major sources of NO in the upper airways. 4. A continuous production of NO takes place in the acidic stomach through chemical reduction of nitrite present in swallowed saliva. This is the first evidence of non-enzymatic NO production in humans. Stomach NO may be involved in local defence against swallowed pathogens and in regulation of superficial mucosal blood flow and mucus production. 5. Luminal concentrations of NO are increased in the lower airways of asthmatic children, in the colon of patients with inflammatory bowel disease, and in the urinary bladder of patients with cystitis. Local steroid treatment reduces orally exhaled NO levels in asthmatic children. Nasal NO levels did not differ between controls and asthmatic children with or without concomitant allergic rhinitis. In conclusion, nitric oxide found in exhaled air originates mainly in the upper airways. A large production of NO takes place in the paranasal sinuses from a constitutively-expressed, steroid-resistant "inducible-like" NO synthase in the epithelial cells. Sinus NO contributes substantially to levels of NO found in nasally exhaled air. Sinus NO may have a dual function. First, the very high concentrations in the sinuses may contribute to local host defence. Second, when diluted in the inhaled air, sinus-derived NO may act as an "aerocrine" messenger, with distal effects on pulmonary blood flow and oxygen uptake. Intubated patients are deprived of autogenous NO from the upper airways and might benefit from substitution. Measurements of local NO production in hollow organs may be done easily by analysing the concentrations of NO gas in luminal air. Such noninvasive methods may be useful not only to explore the role of NO in inflammation and host defence, but also in the diagnosis and monitoring of inflammatory mucosal diseases such as asthma, ulcerative colitis and cystitis. Thus, airborne NO may be looked upon as a marker of inflammation and as an aerocrine messenger in humans.

Adolescent↗
PubMed1998

Mechanics of lung ventilation in a larval salamander Ambystoma tigrinum.

The larval stage of the tiger salamander Ambystoma tigrinum is entirely aquatic, but the larvae rely on their lungs for a large proportion of their oxygen uptake. X-ray video and pressure measurements from the buccal and body cavities demonstrate that the larvae inspire using a two-stroke buccal pump and exhale actively by contracting the hypaxial musculature to increase body pressure. Larvae begin a breath by expanding the buccal cavity to draw in air through the mouth, while simultaneously exhaling air from the lungs to mix with the fresh air in the buccal cavity. The mouth then closes, and the buccal cavity compresses to pump a portion of the mixture into the lungs. The remaining air in the buccal cavity is then released as bubbles from the mouth and gill slits. Ventilatory volumes estimated from X-ray video records indicate that approximately 80 % of the air pumped into the lungs is fresh air and 20 % is previously expired air. Exhalation in larval tiger salamanders is active, powered by contraction of all four layers of lateral hypaxial musculature. Electromyography indicates that the transverse abdominis (TA) muscle is active for the longest duration and shows the highest-amplitude activity, but the external oblique superficialis, the external oblique profundus and the internal oblique also show consistent, low-level activity. The finding that the TA muscle is active during exhalation in larval tiger salamanders contributes to a growing body of evidence that the use of the TA for exhalation is a primitive character for tetrapods.

Journal Article↗
PubMed1998

Mechanics of lung ventilation in a larval salamander Ambystoma tigrinum.

The larval stage of the tiger salamander Ambystoma tigrinum is entirely aquatic, but the larvae rely on their lungs for a large proportion of their oxygen uptake. X-ray video and pressure measurements from the buccal and body cavities demonstrate that the larvae inspire using a two-stroke buccal pump and exhale actively by contracting the hypaxial musculature to increase body pressure. Larvae begin a breath by expanding the buccal cavity to draw in air through the mouth, while simultaneously exhaling air from the lungs to mix with the fresh air in the buccal cavity. The mouth then closes, and the buccal cavity compresses to pump a portion of the mixture into the lungs. The remaining air in the buccal cavity is then released as bubbles from the mouth and gill slits. Ventilatory volumes estimated from X-ray video records indicate that approximately 80% of the air pumped into the lungs is fresh air and 20% is previously expired air. Exhalation in larval tiger salamanders is active, powered by contraction of all four layers of lateral hypaxial musculature. Electromyography indicates that the transverse abdominis (TA) muscle is active for the longest duration and shows the highest-amplitude activity, but the external oblique superficialis, the external oblique profundus and the internal oblique also show consistent, low-level activity. The finding that the TA muscle is active during exhalation in larval tiger salamanders contributes to a growing body of evidence that the use of the TA for exhalation is a primitive character for tetrapods.

Ambystoma↗
PubMed2003

Nasal nitric oxide measurements before and after repeated humming maneuvers.

BACKGROUND: It has been recently shown that humming greatly increases nasal nitric oxide (NO). This is most likely owing to a rapid washout of sinus NO caused by the oscillating sound waves. During repeated humming manoeuvres nasal NO gradually decreases, likely because NO accumulated in the sinuses is washed out. AIM: We studied whether humming before measurements would affect nasally exhaled NO. MATERIALS AND METHODS: NO output was measured by the chemiluminescence technique in orally and nasally exhaled air in 38 subjects: 18 healthy subjects (HS), 15 subjects with allergic rhinitis (AR) and five subjects with allergic nasal polyposis (AP). Each subject performed a NO measurement during quiet nasal exhalation either preceded by a period of silence/free speaking or immediately after five consecutive humming manoeuvres (posthumming). RESULTS: Mean nasal NO output (95% CI) after a period of silence/free speaking was 231 nL min-1 (178-284) in HS, 434 nL min-1 (347-522) in AR (P < 0.001) and 262 nL min-1 (163-361) in AP. Post-humming nasal NO output was 16% (5 to 50%) lower in HS and 14% (1 to 49%) lower in AR, while it remained unchanged in AP subjects. Intra-subject coefficient of variation of quiet nasal exhalation was 12% in HS, 13% in AR and 5% in AP. Post humming intraindividual coefficient of variation significantly decreased in both HS and AR, but it did not change in AP. CONCLUSIONS: Nasal NO levels measured immediately after repeated humming manoeuvres are consistently lower and more reproducible than nasal NO levels measured after a period of silence or free speaking. Repeated humming effectively empties the sinuses, thereby probably minimizing the normal contribution from the sinuses to nasal NO. This may be useful to better estimate NO output from the nasal cavity mucosa in health and disease.

Adolescent↗
PubMed2004

Humming-induced release of nasal nitric oxide for assessment of sinus obstruction in allergic rhinitis: pilot study.

BACKGROUND: Humming greatly increases nasal nitric oxide (NO) in healthy people by causing a rapid washout of NO from the sinuses. This increase is abolished in patients with complete sinus ostial obstruction. OBJECTIVE: Allergic rhinitis is a risk factor for development of sinusitis and we wanted to study whether nasal NO measurement during humming could be used to detect sinus abnormalities in this disorder. METHODS: Fifty-nine consecutive subjects with mild to moderate allergic rhinitis were studied. Their present nasal symptoms were recorded. Then NO levels were measured by chemiluminescence during quiet single-breath nasal exhalations and humming exhalations at a fixed exhalation flow of 0.2 L s(-1). Based on the NO results the patients were divided into two groups: those with a great increase in nasal NO during humming (humming responders, n = 46) and those without a significant increase (humming nonresponders, n = 13). In 11 of the nonresponders and in 22 of the responders the passage to the osteomeatal complex area was assessed and scored by nasal endoscopy. This was carried out by an oto-rhino-laryngologist unaware of the NO results. RESULTS: Among the nonresponders nine of 11 patients (80%) had endoscopic signs of bilateral sinus obstruction, compared with one of the 22 (< 5%) humming responders. Baseline nasal symptom score and NO levels during quiet exhalation were not significantly different between the groups CONCLUSION: Absence of a nasal NO peak during humming is associated with endoscopic findings suggestive of sinus ostial obstruction in subjects with allergic rhinitis. Measurement of nasal NO during humming may be a simple method to detect sinus abnormalities in these patients.

Acoustic Stimulation↗
PubMed2006

Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury.

Cyclical recruitment of atelectasis with each breath is thought to contribute to ventilator-associated lung injury. Extrinsic positive end-expiratory pressure (PEEPe) can maintain alveolar recruitment at end exhalation, but PEEPe depresses cardiac output and increases overdistension. Short exhalation times can also maintain end-expiratory recruitment, but if the mechanism of this recruitment is generation of intrinsic PEEP (PEEPi), there would be little advantage compared with PEEPe. In seven New Zealand White rabbits, we compared recruitment from increased respiratory rate (RR) to recruitment from increased PEEPe after saline lavage. Rabbits were ventilated in pressure control mode with a fraction of inspired O(2) (Fi(O(2))) of 1.0, inspiratory-to-expiratory ratio of 2:1, and plateau pressure of 28 cmH(2)O, and either 1) high RR (24) and low PEEPe (3.5) or 2) low RR (7) and high PEEPe (14). We assessed cyclical lung recruitment with a fast arterial Po(2) probe, and we assessed average recruitment with blood gas data. We measured PEEPi, cardiac output, and mixed venous saturation at each ventilator setting. Recruitment achieved by increased RR and short exhalation time was nearly equivalent to recruitment achieved by increased PEEPe. The short exhalation time at increased RR, however, did not generate PEEPi. Cardiac output was increased on average 13% in the high RR group compared with the high PEEPe group (P < 0.001), and mixed venous saturation was consistently greater in the high RR group (P < 0.001). Prevention of end-expiratory derecruitment without increased end-expiratory pressure suggests that another mechanism, distinct from intrinsic PEEP, plays a role in the dynamic behavior of atelectasis.

Animals↗
PubMed1999

Design and test of a new tracheostoma valve based on inhalation.

BACKGROUND: Tracheostoma valves are used to make hand-free speaking possible for persons who have undergone a laryngectomy. OBJECTIVE: To design and test a new tracheostoma valve to improve existing tracheostoma valves. METHODS: The tracheostoma valve closes by means of strong inhalation so that all the air that is exhaled is available for phonation. The device automatically stays in the"speaking position" until the patient deliberately changes the device to the "breathing position" by a fast expiration. If all the air that has been exhaled has been consumed during phonation, the patient can inhale again, without changing the device, because a small valve automatically opens, thus allowing phonation without time limits. An experimental setup with a computer-based acquisition program was used to measure the pressure at which the valve opened and the flow at which the valve closed. The pressure and flow needed to open and close the magnetic adjustable valve were measured for different positions and contained in the computer through a data acquisition program. Also, the airflow resistance coefficients for inhaling and exhaling were measured. RESULTS: The airflow necessary to close the tracheostoma valve ranges from 1.6 to 3.8 L/s. The opening pressure of the valve ranges from 1 to 7 kPa. The airflow resistance coefficient is 290 Pa x s2 x L(-2) for inhalation and 430 Pa x s(2) x L(-2) for exhalation. CONCLUSIONS: The device appears to function well in physiological ranges and is optimally adjustable. The airflow resistance coefficient lies in the range of the entire airway resistance (120-470 Pa x s(2) x L(-2)) in quiet breathing.

Air↗
PubMed1999

Impairment of cardiac performance by laparoscopy in patients receiving positive end-expiratory pressure.

BACKGROUND: The cardiopulmonary effects of the combination of abdominal and thoracic pressures in humans have not been well delineated. OBJECTIVE: To study the cardiopulmonary effects of 15 mm Hg of intra-abdominal pressure in the presence and absence of 10 cm H20 of positive end-expiratory pressure (PEEP). DESIGN: Prospective. SETTING: University hospital. METHODS: Nine patients undergoing laparoscopic cholecystectomy had pulmonary compliance, cardiac output, exhaled carbon dioxide, and preload (left ventricular end-diastolic volume) determined at 4 points while undergoing ventilation with (1) no PEEP before pneumoperitoneum; (2) 10 cm H20 of PEEP and no pneumoperitoneum; (3) no PEEP and 15 mm Hg of pneumoperitoneum; and (4) 10 cm H20 of PEEP and 15 mm Hg of pneumoperitoneum. Preload and cardiac output were determined by means of transesophageal echocardiography. Pulmonary compliance and exhaled carbon dioxide were determined by an attachment to the end of the endotracheal tube. MAIN OUTCOME MEASURES: Preload, cardiac output, exhaled carbon dioxide, and pulmonary compliance. RESULTS: There was no significant change from baseline in preload, cardiac output, or pulmonary compliance when either PEEP or pneumoperitoneum was applied separately. However, there was a significant decrease in preload (P<.01), cardiac output (P = .01), and exhaled carbon dioxide (P =.04) when PEEP and pneumoperitoneum were applied together. Pulmonary compliance was not significantly affected at any of these points. CONCLUSIONS: There was a significant reduction in preload and cardiac output when there was intra-abdominal pressure of 15 mm Hg in the presence of 10 cm H20 of PEEP. This combination of pressures may pose a contraindication to laparoscopic surgery.

Cholecystectomy, Laparoscopic↗
PubMed2001

e-NO peak versus e-NO plateau values in evaluating e-NO production in steroid-naive and in steroid-treated asthmatic children and in detecting response to inhaled steroid treatment.

SUMMARY. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 +/- 0.7 years) were receiving inhaled steroids (flunisolide, 0.8-1 mg daily) or beclomethasone (0.2-0.4 mg daily), while the remaining 63 (mean age, 12.0 +/- 0.4 yrs) were-steroid naive and treated only with inhaled beta(2)-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8-1 mg daily, or beclomethasone, 0.2-0.4 mg daily). Regardless of the type of data analysis (peak, plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P < 0.01, each comparison). Similarly, in the subgroup of steroid-naive patients, the three methods were able to detect a decrease in e-NO levels by inhaled steroid therapy (P < 0.001, each comparison). Plotting the difference between e-NO peak and e-NO plateau values against their average, the peak e-NO concentrations were higher than e-NO plateau values. This difference was independent of the absolute e-NO concentration. The results of the two types of data analysis seems to agree more closely in steroid-naive patients than in steroid treated patients, or in the subgroup of steroid-naive patients who received a short course treatment with inhaled steroids. In steroid-treated subjects, the differences were up to five times higher for peak than plateau e-NO values. These data suggest that both e-NO plateau and e-NO peak values are useful in detecting airway NO production in atopic asthmatic children, but they cannot be used interchangeably. Because of possible nasal contamination in e-NO peak measurement, we prefer e-NO plateau levels for evaluating lower airway e-NO production.

Administration, Inhalation↗
PubMedDate not supplied

The effect of glutathione depletion on 14CO2 evolution from [14C]methyl-labeled aminopyrine in intact rats.

The effect of hepatic glutathione depletion on 14CO2 evolution from [14C]methyl-labeled aminopyrine was assessed in fed male Sprague-Dawley rats. Within 30 min of i.p. administration of either diethylmaleate or phorone, hepatic glutathione fell approximately 75 to 80% and remained depressed for the ensuing 120 min. [14C]Aminopyrine was i.p. administered 30 min after the glutathione-lowering agents (zero time) and exhaled 14CO2 was collected at 15-min intervals for the next 120 min. Parameters of 14CO2 exhalation including peak exhalation rate, cumulative exhalation from 0 to 120 min and the elimination rate constant were all impaired in glutathione-depleted rats. Metabolism of the [14C]methyl groups involves N-demethylation with formation of formaldehyde, oxidation to formate and conversion to 14CO2. Glutathione depletion did not affect CO2 evolution from i.p. administered formate or bicarbonate. The glutathione-dependent step presumably involves either or both generation of formaldehyde or its subsequent oxidation to formate.

Aminopyrine↗
PubMed1993

Decreased mitochondrial oxidation of fatty acids in pregnant mice: possible relevance to development of acute fatty liver of pregnancy.

Severe impairment of the beta-oxidation of fatty acids, as a consequence of a single factor or a combination of different causes, leads to microvesicular steatosis of the liver. In an effort to understand the mechanism(s) leading to the development of acute fatty liver of pregnancy in some women, we determined the effects of pregnancy on the mitochondrial oxidation of fatty acids in mice. In vivo, the rate of oxidation of the whole fatty-acid chain length was determined by measuring the rate of exhalation of [14C]CO2 after intragastric administration of a tracer dose of [U-14C]palmitic acid. [14C]CO2 exhalation was not significantly decreased at 14 days of gestation, but it had declined by 40% at 18 days of gestation (i.e., 24 to 48 hr before delivery). The rate of first beta-oxidation cycle was assessed by measuring the rate of [14C]CO2 exhalation after administration of [1-14C]octanoic acid, [1-14C]butyric acid or [1-14C]palmitic acid. [14C]CO2 exhalation had declined by 60%, 46%, and 24% after administration of [1-14C]octanoic acid, [1-14C]butyric acid and [1-14C]palmitic acid, respectively, in 18-day-pregnant mice. Total hepatic lipids and triglycerides, expressed per gram of liver, remained unchanged in 18-day-pregnant mice. In vitro, the rate of mitochondrial beta-oxidation (expressed per milligram of protein) had decreased by 47% at 18 days' gestation with [U-14C]palmitic acid as substrate and by 33% with [1-14C]octanoic acid but remained unchanged with [1-14C]palmitic acid. The activity of the tricarboxylic acid cycle, assessed by the formation of [14C]CO2 from [1-14C]acetic acid, had decreased by 24%. We conclude that the mitochondrial oxidation of fatty acids decreased during late-term pregnancy in mice as a consequence of both decreased mitochondrial beta-oxidation of medium-chain fatty acids, and decreased activity of the tricarboxylic acid cycle. We suggest that this effect, in combination with other factors, may contribute to the development of fatty liver of pregnancy in some pregnant women.

Acyl-CoA Dehydrogenase↗
PubMed1987

In vivo ethane production in vitamin E-deficient rats with DMH-induced colon cancer.

The effect of both a vitamin E-deficient and a high polyunsaturated fat (PUFA) diet was tested on rats injected with the colon carcinogen 1,2-dimethylhydrazine (DMH). In vivo lipid peroxidation was monitored by measuring exhaled ethane from the animals. Higher mean weights were found in animals fed high PUFA and vitamin E-sufficient diets. There was no difference in ethane exhalation between DMH-treated and control animals regardless of diet. Mean ethane exhalation was highest in animals fed either vitamin E-deficient or high PUFA diets. There was no difference in tumor formation between the vitamin E-deficient and the vitamin E-sufficient groups. The high PUFA groups had more tumors than the low PUFA groups. Diet was shown to be the major factor affecting ethane exhalation. There was no evidence that vitamin E-deficiency promoted DMH-induced tumors or that DMH caused increased lipid peroxidation.

1,2-Dimethylhydrazine↗
PubMed1997

The effect of systemic nitric oxide-synthase inhibition on ocular fundus pulsations in man.

There is experimental evidence that endothelium derived nitric oxide is involved in the regulation of ocular vascular tone. The purpose of this study was to investigate the effects of NO-synthase inhibition by N-monomethyl-L-arginine (L-NMMA) on ocular fundus pulsations in young healthy volunteers. Three milligrams per kilograms L-NMMA were administered i.v. over 5 minutes. Protocol 1: Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO-exhalation, and cardiac output were performed at baseline and 10, 30, 60, 90, 150, and 300 minutes after L-NMMA infusion (n = 8). Fundus pulsation amplitude, which has been shown to estimate the pulsatile component of the choroidal blood flow, was recorded with a recently developed laser interferometer. Protocol 2: Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO-exhalation, and blood flow velocity in the ophthalmic artery were performed in a randomized, placebo controlled cross over study (n = 10). Ten minutes after L-NMMA administration fundus pulsation amplitude decreased by 23 +/- 2% (protocol 1) and 19 +/- 1% (protocol 2, P < 0.01 each), cardiac output by 12 +/- 2% (P < 0.01), and exhaled NO by 55 +/- 6% (protocol 1) and 41 +/- 6% (protocol 2, P < 0.01 each). All parameters returned to baseline values within the 300 minutes observation period, with a faster recovery of fundus pulsation amplitude than of cardiac output and exhaled NO. Blood pressure, pulse rate, and ophthalmic artery blood flow velocity showed only minor changes during and after administration of L-NMMA. Our results suggest that systemic NO-synthase inhibition reduces pulsatile choroidal and most likely total choroidal blood flow in humans. The recovery of vascular tone in choroidal vessels seems to be different from the cardiovascular response. Our findings indicate that reduced fundus pulsations after L-NMMA are caused by systemic factors as well as by local reactions of the choroidal vasculature.

Adult↗
PubMed1994

Disposition and pharmacokinetics of isopropanol in F-344 rats and B6C3F1 mice.

The absorption, metabolism, disposition, and excretion of isopropanol (IPA) were studied in male and female rats and mice. Animals were exposed by i.v. (300 mg/kg) and inhalation (500 and 5000 ppm for 6 hr) routes; additionally, IPA was given by gavage to rats only in single and multiple 300 and 3000 mg/kg doses. In the rat approximately 81-89% of the administered dose was exhaled (as acetone, CO2, and unmetabolized IPA); approximately 76% of the dose in mice was exhaled after i.v. bolus but 92% was exhaled following inhalation. Approximately 3-8% of the administered dose was excreted in urine as IPA, acetone, and a metabolite tentatively identified as isopropyl glucuronic acid. Small amounts of radiolabel were found in feces and in the carcass. There were no major differences in the rates or routes of excretion observed either between sexes or between routes of administration. Additionally, repeated exposure had no effect on excretion. However, both the route of administration and the exposure or dose level influenced the form in which material was exhaled. Following exposure to 5000 ppm, a greater percentage of unmetabolized IPA was recovered in the expired air than following exposure to 500 ppm, implying saturation of metabolism.

1-Propanol↗