Impact of four different recumbencies on the distribution of ventilation in conscious or anaesthetized spontaneously breathing beagle dogs: An electrical impedance tomography study.

The aim was to examine the effects of recumbency and anaesthesia on distribution of ventilation in beagle dogs using Electrical Impedance Tomography (EIT). Nine healthy beagle dogs, aging 3.7±1.7 (mean±SD) years and weighing 16.3±1.6 kg, received a series of treatments in a fixed order on a single occasion. Conscious dogs were positioned in right lateral recumbency (RLR) and equipped with 32 EIT electrodes around the thorax. Following five minutes of equilibration, two minutes of EIT recordings were made in each recumbency in the following order: RLR, dorsal (DR), left (LLR) and sternal (SR). The dogs were then positioned in RLR, premedicated (medetomidine 0.01, midazolam 0.1, butorphanol 0.1 mg kg-1 iv) and pre-oxygenated. Fifteen minutes later anaesthesia was induced with 1 mg kg-1 propofol iv and maintained with propofol infusion (0.1-0.2 mg kg-1 minute-1 iv). After induction, the animals were intubated and allowed to breathe spontaneously (FIO2 = 1). Recordings of EIT were performed again in four recumbencies similarly to conscious state. Centre of ventilation (COV) and global inhomogeneity (GI) index were calculated from the functional EIT images. Repeated-measures ANOVA and Bonferroni tests were used for statistical analysis (p < 0.05). None of the variables changed in the conscious state. During anaesthesia left-to-right COV increased from 46.8±2.8% in DR to 49.8±2.9% in SR indicating a right shift, and ventral-to-dorsal COV increased from 49.8±1.7% in DR to 51.8±1.1% in LLR indicating a dorsal shift in distribution of ventilation. Recumbency affected distribution of ventilation in anaesthetized but not in conscious dogs. This can be related to loss of respiratory muscle tone (e.g. diaphragm) and changes in thoracic shape. Changing position of thoraco-abdominal organs under the EIT belt should be considered as alternative explanation of these findings.

Effect of ticagrelor on pulmonary function in healthy elderly volunteers and asthma or chronic obstructive pulmonary disease patients.

BACKGROUND: Ticagrelor is a direct-acting, reversibly binding, oral P2Y12 platelet inhibitor that reduces thrombotic cardiovascular events in patients with acute coronary syndrome. Dyspnea is one of the most commonly reported adverse events associated with ticagrelor. OBJECTIVE: To determine the effect of ticagrelor on pulmonary function in healthy elderly volunteers and asthma or chronic obstructive pulmonary disease (COPD) patients. METHODS: Two randomized, double-blind, placebo-controlled, two-way crossover, single-center studies were conducted: 1) healthy elderly volunteers (55-75 years; n = 12); 2) patients with mild asthma (n = 11) or mild-to-moderate COPD (n = 7). Subjects were randomized to receive ticagrelor (a single 450 mg dose, 180 mg 12 hours later, twice daily for 2 days, and once on day 4) or placebo, with a 7 day washout. Pulmonary function at rest and during exercise was monitored using similar schedules and assessments across the two studies. RESULTS: Resting pulmonary function parameters, including respiratory rate, minute ventilation, or tidal volume, were similar between ticagrelor and placebo in any cohort. Furthermore, bronchospasm (as determined by spirometry and pulse oximetry), was not observed with either ticagrelor or placebo in any cohort. Perception of breathing was generally similar following ticagrelor or placebo. Exercise performance was not affected, and no clinically relevant differences were seen in pulmonary parameters during exercise for ticagrelor or placebo. There was no apparent relationship between plasma concentrations of ticagrelor and its main metabolite and pulmonary function. Ticagrelor was well tolerated in all cohorts. Study limitations include the use of relatively few subjects without documented coronary artery disease. CONCLUSIONS: Short-term administration of high doses of ticagrelor did not appear to alter pulmonary function at rest and during exercise in subjects at risk of (healthy elderly) or with respiratory impairment (mild asthma or mild-to-moderate COPD).

Effects of Fastac 50 EC on bumble bee Bombus terrestris L. respiration: DGE disappearance does not lead to increasing water loss.

Sublethal effects of pesticides in insects can be observed through physiological changes, which are commonly estimated by metabolic rate and respiratory patterns, more precisely by the patterns of discontinuous gas-exchange (DGE) cycles. The aim of the present research was to study the effect of some low concentrations of Fastac 50 EC on the cycles of CO(2) release and respiratory water loss rates (WLR) in bumble bee Bombus terrestris L. foragers. Bumble bees were dipped into 0.004% and 0.002% Fastac 50 EC solution. Flow-through respirometry was used to record the respiration and WLR 3h before and after the treatment. The respirometry was combined with infrared actography to enable simultaneous recording of abdominal movements. Our results show that Fastac 50 EC has an after-effect on bumble bee respiratory rhythms and muscle activity but does not affect WLR. Treatment with 0.004% Fastac 50 EC solution resulted in disappearance of the respiration cycles; also the lifespan of treated bumble bees was significantly shorter. Treatment with 0.002% Fastac 50 EC solution had no significant effect on respiration patterns or longevity. We found no evidence for the DGE cycles functioning as a water saving mechanism.

Impacts of ocean acidification on respiratory gas exchange and acid-base balance in a marine teleost, Opsanus beta.

The oceanic carbonate system is changing rapidly due to rising atmospheric CO(2), with current levels expected to rise to between 750 and 1,000 µatm by 2100, and over 1,900 µatm by year 2300. The effects of elevated CO(2) on marine calcifying organisms have been extensively studied; however, effects of imminent CO(2) levels on teleost acid-base and respiratory physiology have yet to be examined. Examination of these physiological processes, using a paired experimental design, showed that 24 h exposure to 1,000 and 1,900 µatm CO(2) resulted in a characteristic compensated respiratory acidosis response in the gulf toadfish (Opsanus beta). Time course experiments showed the onset of acidosis occurred after 15 min of exposure to 1,900 and 1,000 µatm CO(2), with full compensation by 2 and 4 h, respectively. 1,900-µatm exposure also resulted in significantly increased intracellular white muscle pH after 24 h. No effect of 1,900 µatm was observed on branchial acid flux; however, exposure to hypercapnia and HCO(3)(-) free seawater compromised compensation. This suggests branchial HCO(3)(-) uptake rather than acid extrusion is part of the compensatory response to low-level hypercapnia. Exposure to 1,900 µatm resulted in downregulation in branchial carbonic anhydrase and slc4a2 expression, as well as decreased Na(+)/K(+) ATPase activity after 24 h of exposure. Infusion of bovine carbonic anhydrase had no effect on blood acid-base status during 1,900 µatm exposures, but eliminated the respiratory impacts of 1,000 µatm CO(2). The results of the current study clearly show that predicted near-future CO(2) levels impact respiratory gas transport and acid-base balance. While the full physiological impacts of increased blood HCO(3)(-) are not known, it seems likely that chronically elevated blood HCO(3)(-) levels could compromise several physiological systems and furthermore may explain recent reports of increased otolith growth during exposure to elevated CO(2).

Pretreatment with hemoglobin-based oxygen carriers protect isolated rat heart from myocardial infarction.

This study was designed to investigate whether polymerized human placenta hemoglobin (PolyPHb) pretreatment provided protection to the heart after ischemia/reperfusion (I/R) injury. After 10-min basal perfusion, isolated Sprague-Dawley rat hearts were pretreated with 0.1 gHb/dL PolyPHb and subjected to I/R injury. PolyPHb pretreatment greatly reduced the decreases in left ventricular developed pressure (LVDP), maximum LVDP increase and decrease rate (+/-dp/dt), and the increase in left ventricular end-diastolic pressure (LVEDP) as compared to the control group. Moreover, the myocardial infarction and troponin-I release were significantly reduced in the pre-HBOCs group. Therefore, PolyPHb pretreatment was protective to the isolated I/R heart.

Respiratory responses to microinjections of leptin into the solitary tract nucleus.

The regulatory peptide leptin has a respiratory stimulating effect along with its well known hypothalamic effects. The present study, performed on anesthetized rats, addressed respiratory responses to microinjections of 10(-10)-10(-4) M leptin into the solitary tract nucleus, which contains a high concentration of leptin receptors. Injections of 10(-8)-10(-4) M leptin led to stimulation of respiration, inducing a dose-dependent increase in the level of pulmonary ventilation and an increase in respiratory volume, accompanied by an increase in bioelectrical activity in the inspiratory muscles; 10(-6) M leptin also induced a transient increase in respiratory rate due to shortening of inhalation and exhalation. A characteristic feature of the response was the appearance of "sighs" - deep, prolonged inhalations accompanied by increased volley activity on the electromyograms of the inspiratory muscles and lengthening of the subsequent intervolley interval. These leptin effects, along with data on the high concentrations of specific leptin receptors (ObRb) in the solitary tract nucleus, suggested that endogenous leptin has a role in controlling respiration at the level of the dorsal segment of the respiratory center.

Beyond anemia: the clinical impact of the physiologic effects of erythropoietin.

Although we have known that oxygen tension affects erythrocyte production since the 19th century, we have only recently begun to understand many subtleties of erythropoietin (EPO) physiology. EPO administration has allowed hundreds of thousands of patients to avoid transfusions. With the beneficial effects so apparent a detailed understanding of the full clinical physiology of this plasma factor seemed less important. However, the unanticipated increase in mortality found in recent randomized studies is prompting a reassessment of this view. We will review what is known about the physiology of this plasma factor that, it is now clear, is more than just an erythrocyte production factor.

[Respiratory responses to microinjections of leptin into the solitary tract nucleus].

Regulatory polypeptide leptin, apart from its well-known hypothalamic effects, stimulates ventilation. The present study on anaesthetised rats was undertaken to elucidate the respiratory effects of 10(-10)-10(-4) M leptin microinjected into the solitary tract nucleus, containing a high concentration of leptin receptors. Injections of 10(-8)-10(-4) M leptin induced dose-dependent increase in ventilation, tidal volume and electric activity of inspiratory muscles; 10(-6) M leptin additionally induced a short-term increase in respiratory frequency and a shortening of both inspiratory and expiratory duration. The respiratory responses to leptin is also characterised by appearance of sighs: deep and prolonged inspirations associated with an augmented burst in the activity of the inspiratory muscles and prolonged post-sigh inter-burst interval. The results taken together with evidence of high concentration of specific leptin ObRb-receptor in the solitary tract nucleus suggest involvement of endogenous leptin in the control of breathing via dorsal structures of the respiratory center.

Effect of aerial O2 partial pressure on bimodal gas exchange and air-breathing behaviour in Trichogaster leeri.

The effects of experimental alterations of aerial O2 partial pressure (PO2,air) on bimodal gas exchange and air-breathing behaviour were investigated in the aquatic air-breathing fish Trichogaster leeri in normoxic water. Fish responded to increasing PO2,air by decreasing air-breathing frequency, increasing aerial O2 consumption rate (VO2), increasing mean O2 uptake per breath (VO2/breath) and decreasing aquatic VO2 to maintain a constant total VO2. The rate of oxygen uptake from the air-breathing organ (ABO) during apnoea (VO2,ap) was derived on a breath-by-breath basis from VO2/breath and apnoea duration. VO2,ap and estimates of ABO volume were used to calculate the PO2 in the ABO at the end of apnoea. This increased with increasing PO2,air, suggesting that ABO-PO2 is not regulated at a constant level by internal chemoreceptors. Furthermore, mean VO2,ap increased with increasing PO2,air, indicating that the observed increase in VO2/breath with increasing PO2,air was facilitated not only by an increase in apnoea duration but also by an increase in the air-blood PO2 gradient.

[Effect of nebivolol on the blood oxygen transport].

The effect of nebivolol (30.0, 60.0, or 90.0 microM) on the blood oxygen transport was studied by incubation with blood samples for 120 min. Nebivolol increased the values of p50 (pO2 at 50% hemoglobin saturation with oxygen) under real pH and pCO2 (by 4.3 +/- 0.8 mm Hg at the lowest concentration (p < 0.01). The further (2- or 3- fold) growth in the concentration of nebivolol increased these values by 7.5 +/- 1.1 and 10.6 +/- 0.7 mm Hg, respectively (for both p < 0.01), thereby indicating the dose dependence of the drug effect. Greater drug concentration resulted in higher methemoglobin level and nitrate/nitrite content. The data can be explained by a change in the hemoglobin-oxygen affinity as a result of the influence of nebivolol through an autonomous intraerythrocyte system that regulates the blood oxygen-binding properties. In this case, NO acts as an important modifier of the hemoglobin function.

Clarification of cyanide's effect on oxygen transport characteristics in a canine model.

OBJECTIVE: To clarify the cardiovascular mechanisms of cyanide poisoning by evaluating oxygen transport characteristics using a canine model. METHODS: A prospective controlled experiment was performed at a hospital-based animal laboratory. Five male beagle (17 (2) kg) dogs were anesthetised with alpha-chloralose, paralysed with pancuronium bromide and mechanically ventilated. Potassium cyanide was infused at 0.045 mg/kg/min for 110 min. Heart rate, blood pressure, cardiac output, oxygen delivery (DO2), oxygen consumption (VO2) and oxygen extraction ratio (OER) were measured every 10 min for 140 min. DO2 was measured by an indirect calorimeter. RESULTS: Cyanide and lactate levels peaked at 1.52 (0.25) mg/l and 9.1 (1.5) mmol/l, respectively. Systolic blood pressure remained relatively constant whereas diastolic blood pressure decreased by 19%. Cardiac output, heart rate and DO2 increased to a maximum of 6%, 10% and 10%, respectively, at 40 min, after which they declined to a low of 32%, 28% and 30% below baseline, respectively. Stroke volume remained constant. Oxygen consumption initially increased by 5%, then decreased to 24% below baseline. The OER initially declined to 35% below baseline, then increased throughout the rest of the study. CONCLUSION: Cyanide poisoning in the canine model showed two phases of injury. The first (compensated) phase had a mechanism consistent with a traditional global oxygen consumption defect. The second (decompensated) phase had a mechanism consistent with heart failure. This heart failure was due to bradycardia. These data suggest chronotropy as an avenue of further study in the temporary treatment of cyanide poisoning.

Adverse effects of dopamine on systemic hemodynamic status and oxygen transport in neonates after the Norwood procedure.

OBJECTIVES: The purpose of this study was to evaluate the effects of dopamine on hemodynamic status and oxygen transport in neonates after the Norwood procedure. BACKGROUND: Dopamine is widely used to augment cardiac performance and increase oxygen delivery (DO2) in patients after cardiopulmonary bypass (CPB). This might be at the expense of increased myocardial and systemic oxygen consumption (VO2), thus offsetting the improved DO2. This balance is particularly fragile in critically ill neonates. METHODS: Systemic oxygen consumption was continuously measured with respiratory mass spectrometry in 13 sedated, paralyzed, and mechanically ventilated neonates for 72 h after the Norwood procedure. Arterial, superior vena caval, and pulmonary venous blood gases were measured to calculate pulmonary blood flow (Q(p)) and systemic blood flow (Q(s)), DO2, and oxygen extraction ratio (ERO2). Rate-pressure product was calculated. Dopamine at a dose of 5 microg/kg/min was routinely administered at cessation of CPB and terminated within the first 48 h. Hemodynamic and oxygen transport measures were obtained before and at 100 min after the termination of dopamine. RESULTS: Terminating dopamine was not associated with significant changes in arterial pressure, Q(p), Q(s), or DO2 but was associated with a significant decrease in heart rate (p = 0.003), rate-pressure product (p = 0.03), and VO2 (-20 +/- 11%, p < 0.0001), resulting in a significant decrease in ERO2 (p = 0.01). CONCLUSIONS: Dopamine induces a significant increase in VO2 in neonates after the Norwood procedure, and termination is associated with an improved balance of VO2-DO2. These data further emphasize the importance of understanding changes in VO2 as well as DO2 in infants after cardiac surgery.

Short-term effects of glipizide (an adenosine triphosphate-sensitive potassium channel inhibitor) on cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep.

In severe sepsis and septic shock, hemodynamic support is often complicated by a tachyphylaxis against exogenous catecholamines. Because activation of adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels plays a pivotal role in the pathogenesis of hyperdynamic vasodilatory shock, we hypothesized that it may be beneficial to administer a specific K(ATP) channel inhibitor to prevent, or at least attenuate, hemodynamic dysfunction in sepsis. The present study was designed as a prospective and controlled laboratory experiment to elucidate the short-term effects of glipizide, a specific K(ATP) channel inhibitor, on cardiopulmonary hemodynamics and global oxygen transport in healthy sheep and sheep with endotoxemia. Ten adult ewes were anesthetized and operatively instrumented with a pulmonary artery, a femoral artery, and a foley catheter. After 24 h of recovery, healthy sheep received glipizide as a bolus infusion (4 mg/kg over 15 min). After 24 h of recovery, a continuous infusion of endotoxin (Salmonella typhosa, 10 ng.kg.(-1)min) was started in the same sheep and administered for the next 17 h. After 16 h of endotoxemia, glipizide was given as described above. Administration of glipizide was followed by a transient, but significant, increase in mean arterial pressure in both healthy controls (95 +/- 3 mmHg vs. 101 +/- 2 mmHg, P < 0.05) and sheep with endotoxemia (86 +/- 3 mmHg vs. 93 +/- 3 mmHg, P < 0.05). However, the increase in mean arterial pressure was longer lasting in ewes with endotoxemia. Cardiac index, oxygen delivery index, arterial lactate concentrations, and arterial pH were not significantly affected by glipizide. Therefore, administration of glipizide may represent a beneficial therapeutic option to treat arterial hypotension resulting from sepsis and systemic inflammatory response syndrome. Additional studies are required to determine the effects of continuous infusion of glipizide in the presence of systemic inflammation.

[Experimental basis for using hypoxic training in the correction of oxygen transport system damage in aplastic anemia].

There was created a model of aplastic anemia (AA) of toxic radiatig genesis (rats; benzene with subsequent gamma-irradiation). On this model the possibility of correction of oxygen transport system damages was studied with the help of the standard experimental therapy (ET) and hypoxic training (HT) in three ranges of tests: I range--preventive application HT, before the establishment of AA; II--the application HT during modeling AA; Ill--HT during implementing ET. Final results show positive effects of preventive application HT and HT during ET on the restoration of oxygen transport system in AA.

Oxygen transport dynamics after resuscitation with a conjugated hemoglobin solution.

HYPOTHESIS: Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), a hemoglobin-based oxygen carrier, is effective in restoring hemodynamic balance and oxygen delivery after moderate hemorrhage but may be less effective in off-loading oxygen at the tissue level. DESIGN: Before-after trial. SETTING: Animal research laboratory of an academic institution. PARTICIPANTS: Ten female Yorkshire swine. INTERVENTIONS: Anesthetized swine underwent a 25% controlled hemorrhage followed by resuscitation with crystalloid plus either shed blood or PHP. Hemodynamic parameters, including heart rate, mean arterial pressure, mean pulmonary arterial pressure, and cardiac index were continuously monitored. Arterial and mixed venous blood samples were collected at baseline, after hemorrhage, after resuscitation, and every 15 minutes for 90 minutes after resuscitation. Oxygen delivery and consumption, oxygen extraction ratios, and percentage of contribution to oxygen delivery and consumption were determined in whole blood, red blood cells, and plasma by using a compartmentalized approach. MAIN OUTCOME MEASURES: Intergroup and intragroup comparisons were performed for hemodynamic parameters and oxygen transport dynamics. RESULTS: Heart rate returned closer to baseline levels in the PHP group (P<.05) and mean pulmonary arterial pressure was transiently elevated after infusion of PHP (P =.028), but otherwise no significant differences in hemodynamic balance were observed. The extraction ratio from the red blood cells in the PHP group more than doubled, whereas the extraction ratio from plasma remained constant. The percentage of contribution of plasma, including PHP, to oxygen delivery exceeded 20% (P <.05), but the relative contribution to oxygen consumption did not markedly change from baseline. CONCLUSIONS: Pyridoxalated hemoglobin polyoxyethylene conjugate is at least as effective as shed blood in restoring hemodynamic balance and oxygen delivery after moderate hemorrhage. There is a disproportionately low contribution from plasma to oxygen consumption, which suggests that PHP may act as an oxygen sink in moderate anemia.

Effects of titrated arginine vasopressin on hemodynamic variables and oxygen transport in healthy and endotoxemic sheep.

OBJECTIVE: To determine the effects of titrated arginine vasopressin (AVP) alone or in combination with norepinephrine (NE) on hemodynamics and oxygen transport in healthy and endotoxemic sheep. DESIGN: Prospective controlled trial. SETTING: University research laboratory. SUBJECTS: Six adult ewes. INTERVENTIONS: Healthy sheep received AVP as a titrated infusion, initiated with 0.6 units/hr and increased by 0.6 units/hr every 15 mins, either until mean arterial pressure was increased by 20 mm Hg vs. baseline or a maximum of 3.6 units/hr was administered. After 90 mins, AVP infusion was continued with the investigated dosage, and NE (0.2 microg x kg(-1) x min(-1)) was also infused for 90 mins. After a 24-hr period of recovery, endotoxemia was induced and maintained (Salmonella typhosa endotoxin, 10 ng x kg(-1) x min(-1)) in the same sheep for the next 19 hrs. After 16 hrs of endotoxemia, AVP and NE were administered as described previously. MEASUREMENTS AND MAIN RESULTS: Hemodynamics were obtained at baseline, every 15 mins during the titration period, and 60 and 90 mins after additional NE infusion. Variables of oxygen transport were calculated before and after the titration period. In healthy and endotoxemic sheep, AVP reduced heart rate and cardiac index (p <.001) and compromised oxygen delivery (p <.001) and oxygen consumption (healthy sheep, p =.003; endotoxemic sheep, p <.001). Vasopressin infusion did not alter mean pulmonary arterial pressure but increased pulmonary vascular resistance index in both groups (p <.001). Additional infusion of NE further augmented mean arterial pressure and increased cardiac index during endotoxemia (p <.001). This was accompanied by an increase in oxygen delivery and consumption (p <.05 each). CONCLUSIONS: During ovine endotoxemia, AVP decreased cardiac index, compromised oxygen delivery, and increased pulmonary vascular resistance index. These side effects may limit its use as a sole vasopressor during sepsis. Potentially, a simultaneous infusion of AVP and NE could represent a useful therapeutic option.

Terlipressin dose response in healthy and endotoxemic sheep: impact on cardiopulmonary performance and global oxygen transport.

OBJECTIVE: To determine whether a goal-directed terlipressin infusion increases mean arterial pressure without causing a pulmonary vasopressive effect and whether this response impacts on key parameters of oxygen transport in healthy and endotoxemic sheep. DESIGN AND SETTING: Prospective controlled trial in a university research laboratory. ANIMALS AND INTERVENTIONS: Six conscious adult ewes instrumented for chronic study received terlipressin as titrated infusion started with 10 microg x kg(-1) x h(-1) and increased by 5 microg x kg(-1) x h(-1) every 15 min, either until mean arterial pressure was increased by 15 mmHg from baseline, or a maximum of 40 microg x kg(-1) x h(-1) was given. Following 24 h of recovery sepsis was induced and maintained in the same ewes by a continuous infusion of endotoxin ( Salmonella typhosa, 10 ng x kg(-1) min(-1)). After 16 h of endotoxemia the sheep were again treated with terlipressin. MEASUREMENTS AND RESULTS: Systemic oxygen delivery and consumption were calculated before and after the titration period; hemodynamic parameters were measured every 15 min. The increase in mean arterial pressure was greater during endotoxemia than in healthy controls. In both states terlipressin administration decreased cardiac index and diminished oxygen delivery and consumption. While mean pulmonary arterial pressure remained constant, terlipressin increased the pulmonary vascular resistance index in endotoxemic sheep. CONCLUSIONS: During ovine endotoxemia titrated terlipressin reversed hypotension but impaired the pulmonary circulation. The observed decrease in oxygen delivery may carry the risk of tissue hypoxia especially in sepsis, where oxygen demand is typically increased.

Effects of Quillaja saponins on growth, metabolism, egg production and muscle cholesterol in individually reared Nile tilapia (Oreochromis niloticus).

The effects of supplementation of a Quillaja saponin (QS) mixture in the diets of tilapia have been studied using a respirometer system that allowed feeding and continuous measurement of oxygen consumption of individual fish. Five fish each were given control diet (C group) and control diet supplemented with 150 mg kg(-1) (S150 group) or 300 mg kg(-1) (S300 group) QS. At the end of 14 weeks the weight gain of the S300 group was significantly higher than control (P<0.05) whereas that of the S150 group had an intermediate value. The S150 group had a higher growth rate (P=0.05) after the first 3 weeks of feeding with the experimental diets, compared to the other two groups. At the end of the experiment the S300 group had significantly higher (P<0.05) average values for energy retention, apparent lipid conversion, carcass fat, energy and significantly lower (P<0.05) average values for apparently unutilised energy and carcass ash content compared to the C group. The corresponding values of the S150 group were intermediate between the C and S300 groups. One out of two female fish in the S150 group and both female fish in the S300 group never produced eggs during the entire 14-week experimental period. Contrarily, all three female fish in the control group and one out of the two female fish in the S150 group regularly produced eggs, at a rate of approximately once in every 14 days. The muscle cholesterol level in the S300 group was significantly higher than that of the C group. Possible mechanisms of action of the dietary saponins are discussed.

Stimulation of airway mucociliary transport and epithelial ciliary motility by the triazolopyridazin derivative TAK-225.

To elucidate whether a newly developed antiallergic drug, the triazolopyridazin derivative TAK-225, alters airway mucociliary clearance and, if so, what the mechanism of action is, we measured mucociliary transport in the rabbit tracheal mucosa ex vivo and ciliary motility of the tracheal epithelium in vitro. Mucociliary transport function was determined by the transport rate of Evans blue dye that had been placed on the mucosal surface above the carina. Oral administration of TAK-225 (0.3-30 mg/kg) increased Evans blue transport toward the larynx in a dose-dependent manner. Addition of TAK-225 caused a rapid and sustained increase in the ciliary beat frequency of tracheal epithelium, as assessed by photoelectric method; the maximal increase from the base-line value was 25.1 +/- 4.6% (P < .01), and the concentration required to produce a half-maximal effect (EC50) was 3.1 +/- 0.8 x 10(-7) M. This effect was greatly attenuated by pretreatment with the cAMP antagonist adenosine 3',5'-cyclic monophosphorothioate, but not by Ca++-free medium containing ethylene glycol-bis [3-aminoethyl ether] N,N,N',N'-tetraacetic acid and [1,2-bis(2)aminophenoxy]ethane N,N,N',N'-tetraacetic acid-acetomethoxy ester. Incubation of tracheal epithelium with TAK-225 increased intracellular cAMP contents in a concentration-dependent manner. These results suggest that TAK-225 enhances airway mucociliary clearance probably through cAMP-mediated stimulation of ciliary motility of airway epithelium.

Three-dimensional fluid particle trajectories in the human larynx and trachea.

A computational fluid dynamics software package (FIDAP) has been employed to obtain three-dimensional flow data, which are used herein to calculate the trajectories of fluid particles. Our computations have demonstrated that the flow fields inside the larynx are very complex including eddies in the lumen and reverse motion along the surface. The effects of such flow fields will be to increase the residence times of entrained drug particles. Our computations have also demonstrated that the larynx has pronounced effects on the motion of air in the trachea.