Serotonergic mechanisms on breathing modulation in the rat locus coeruleus

The locus coeruleus (LC) is a noradrenergic nucleus that plays an important role in the ventilatory response to hypercapnia. This nucleus is densely innervated by serotonergic fibers and contains high density of serotonin (5-HT) receptors, including 5-HT(1A) and 5-HT(2). We assessed the possible modulation of respiratory response to hypercapnia by 5-HT, through 5-HT(1A) and 5-HT(2) receptors, in the LC. To this end, we determined the concentrations of 5-HT and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) in the LC after hypercapnic exposure. Pulmonary ventilation (V(E), plethysmograph) was measured before and after unilateral microinjection (100 nL) of WAY-100635 (5-HT(1A) antagonist, 5.6 and 56 mM), 8-OHDPAT (5-HT(1A/7) agonist, 7 and 15 mM), Ketanserin (5-HT(2A) antagonist, 3.7 and 37 mM), or (+/-)-2,5-dimethoxy-4-iodoamphetaminehydrochloride (DOI; 5-HT(2A) agonist, 6.7 and 67 mM) into the LC, followed by a 60-min period of 7% CO(2) exposure. Hypercapnia increased 5-HTIAA levels and 5-HIAA/5-HT ratio within the LC. WAY-100635 and 8-OHDPAT intra-LC decreased the hypercapnic ventilatory response due to a lower tidal volume. Ketanserin increased CO(2) drive to breathing and DOI caused the opposite response, both acting on tidal volume. The current results provide evidence of increased 5-HT release during hypercapnia in the LC and that 5-HT presents an inhibitory modulation of the stimulatory role of LC on hypercapnic ventilatory response, acting through postsynaptic 5-HT(2A) receptors in this nucleus. In addition, hypercapnic responses seem to be also regulated by presynaptic 5-HT(1A) receptors in the LC.

Brain monoaminergic neurons and ventilatory control in vertebrates

Monoamines (noradrenaline (NA), adrenaline (AD), dopamine (DA) and serotonin (5-HT) are key neurotransmitters that are implicated in multiple physiological and pathological brain mechanisms, including control of respiration. The monoaminergic system is known to be widely distributed in the animal kingdom, which indicates a considerable degree of phylogenetic conservation of this system amongst vertebrates. Substantial progress has been made in uncovering the participation of the brain monoamines in the breathing regulation of mammals, since they are involved in the maturation of the respiratory network as well as in the modulation of its intrinsic and synaptic properties. On the other hand, for the non-mammalian vertebrates, most of the knowledge of central monoaminergic modulation in respiratory control, which is actually very little, has emerged from studies using anuran amphibians. This article reviews the available data on the role of brain monoaminergic systems in the control of ventilation in terrestrial vertebrates. Emphasis is given to the comparative aspects of the brain noradrenergic, adrenergic, dopaminergic and serotonergic neuronal groups in breathing regulation, after first briefly considering the distribution of monoaminergic neurons in the vertebrate brain. (C) 2008 Elsevier B.V. All rights reserved.

5-HT1A, but not 5-HT2 and 5-HT7, receptors in the nucleus raphe magnus modulate hypoxia-induced hyperpnoea

Aim: In the present study, we assessed the role of 5-hydroxytryptamine (5-HT) receptors (5-HT1A, 5-HT2 and 5-HT7) in the nucleus raphe magnus (NRM) on the ventilatory and thermoregulatory responses to hypoxia. Methods: To this end, pulmonary ventilation (V-E) and body temperature (T-b) of male Wistar rats were measured in conscious rats, before and after a 0.1 mu L microinjection of WAY-100635 (5-HT1A receptor antagonist, 3 mu g 0.1 mu L-1, 56 mM), ketanserin (5-HT2 receptor antagonist, 2 mu g 0.1 mu L-1, 36 mM) and SB269970 (5-HT7 receptor antagonist, 4 mu g 0.1 mu L-1, 103 mM) into the NRM, followed by 60 min of severe hypoxia exposure (7% O-2). Results: Intra-NMR microinjection of vehicle (control rats) or 5-HT antagonists did not affect V-E or T-b during normoxic conditions. Exposure of rats to 7% O-2 evoked a typical hypoxia-induced anapyrexia after vehicle microinjections, which was not affected by microinjection of WAY-100635, SB269970 or ketanserin. The hypoxia-induced hyperpnoea was not affected by SB269970 and ketanserin intra-NMR. However, the treatment with WAY-100635 intra-NRM attenuated the hypoxia-induced hyperpnoea. Conclusion: These data suggest that 5-HT acting on 5-HT1A receptors in the NRM increases the hypoxic ventilatory response.

Development of the pulmonary surfactant system in the green sea turtle, Chelonia mydas

This study describes the developmental changes in pulmonary surfactant (PS) lipids throughout incubation in the sea turtle, Chelonia mydas. Total phospholipid (PL), disaturated phospholipid (DSP) and cholesterol (Chol) harvested from lung washings increased with advancing incubation, where secretion was maximal at pipping, coincident with the onset of pulmonary ventilation. The DSP/PL ratio increased, whereas the Chol/PL and the Chol/DSP ratio declined throughout development. The phospholipids, therefore, are independently regulated from Chol and their development matches that of mammals. To explore whether hypoxia could elicit an effect on the development of the PS system, embryos were exposed to a chronic dose of 17% O-2 for the final similar to 40% of incubation. Hypoxia did not affect incubation time, absolute, nor relative abundance of the surfactant lipids, demonstrating that the development of the system is robust and that embryonic development continues unabated under mild hypoxia. Hypoxia-incubated hatchlings had lighter wet lung weights than those from normoxia, inferring that mild hypoxia facilitates lung clearance in this species. (C) 2001 Elsevier Science B.V. All rights reserved.

Natural abundance of stable carbon and nitrogen isotopes in Cannabis sativa reflects growth conditions

Stable carbon and nitrogen isotope signatures (delta C-13 and delta N-15) of Cannabis sativa were assessed for their usefulness to trace seized Cannabis leaves to the country of origin and to source crops by determining how isotope signatures relate to plant growth conditions. The isotopic composition of Cannabis examined here covered nearly the entire range of values reported for terrestrial C-3 plants. The delta C-13 values of Cannabis from Australia, Papua New Guinea and Thailand ranged from -36 to -25 parts per thousand, and delta N-15 values ranged from -1.0 to 15.8 parts per thousand. The stable isotope content did not allow differentiation between Cannabis originating from the three countries, but delta C-13 values of plantation-grown Cannabis differed between well-watered plants (average delta C-13 of -30.0 parts per thousand) and plants that had received little irrigation (average delta C-13 of -26.4 parts per thousand). Cannabis grown under controlled conditions had delta C-13 values of -32.6 and -30.6 parts per thousand with high and low water supply, respectively. These results indicate that water availability determines leaf C-13 in plants grown under similar conditions of light, temperature and air humidity. The delta C-13 values also distinguished between indoor- and outdoor-grown Cannabis; indoor- grown plants had overall more negative delta C-13 values (average -31.8 parts per thousand) than outdoor-grown plants (average -27.9 parts per thousand). Contributing to the strong C-13-depletion of indoor- grown plants may be high relative humidity, poor ventilation and recycling of C-13-depleted respired CO2. Mineral fertilizers had mostly lower delta N-15 values (-0.2 to 2.2 parts per thousand) than manure-based fertilizers (7.6 to 22.7 parts per thousand). It was possible to link delta N-15 values of fertilizers associated with a crop site to soil and plant delta N-15 values. The strong relationship between soil, fertilizer, and plant delta N-15 suggests that Cannabis delta N-15 is determined by the isotopic composition of the nitrogen source. The distinct delta N-15 values measured in Cannabis crops make delta N-15 an excellent tool for matching seized Cannabis with a source crop. A case study is presented that demonstrates how delta C-13 and delta N-15 values can be used as a forensic tool.

Influence of fungal pathogens and environmental conditions on disease severity, flower fall and desiccation of harvested Geraldton waxflower - 2. Studies with commercial packages

Relationships were examined between environmental conditions mediated by packaging and handling and the deterioration of harvested Geraldton waxflower cv. 'Fortune Cookie'. Disease severity plus flower and leaf drop caused by inoculation with Botrytis cinerea were reduced by lowering handling temperatures to 0, 5 or 5/20 degreesC alternated daily, versus 20 degreesC. They were also reduced by inhibition of ethylene action with a silver thiosulfate pulse pretreatment. Additionally, treatments that enhanced water loss, such as packing dry, keeping forced air-cooling holes open and strategic placement of extra ventilation holes may also reduce disease severity and flower plus leaf fall. Inclusion of KMnO4-based Bloomfresh ethylene scrubbing sachets in packages did not reduce disease severity or lessen flower plus leaf fall. Thus, deterioration of waxflower packaged in commercial cartons can be minimised by keeping temperatures low, packing plant material dry, use of cartons with strategically placed ventilation holes and/or pretreatment with silver thiosulfate.

Controlled partial mine ventiliation recirculation trial at Mount Isa Mines

The ventilation and cooling of deep, hot mines present particular problems in Australia as a consequence of the surface climate, the size of the underground voids, the degree of mechanization and the cost of power in remote areas. A preliminary investigation of the effects of controlled partial recirculation of air was conducted in Mount Isa Mines' Deep Copper section. Gas and dust concentrations were measured in the exhaust air of the major working section to assess the potential for recirculating exhaust air to the intake airways to reduce the cost of providing an acceptable working environment in the deep parts of the mine. Studies were undertaken of airborne dust deposition in vertical airways and the efficiency of usage of the ventilation air in diluting contaminants. It was established that 45% of the respirable dust was deposited in a 130-m vertical raise and 60% of the air supplied to the section could be reused or recirculated. The first major field trial of a controlled partial recirculation system in Australia was undertaken in the light of these results and demonstrated excellent potential for significant reduction in ventilation costs. Gas and dust contaminant levels were well below the threshold limit values during the trial. It is concluded that controlled partial recirculation can be a practical, effective and safe aid to normal ventilation practice in Australian deep, hot mines.

Child-Pugh class, nutritional indicators and early liver transplant outcomes

Background/Aims: Patients with chronic liver disease undergoing liver transplantation have reduced body fat and muscle mass. The extent to which nutritional indicators and Child-Pugh class are predictive of postoperative outcome in adults is unclear. The aims of this study were to determine in adult patients undergoing transplant 1) the influence of preoperative Child-Pugh class and nutritional indicators on early transplant outcomes and one-year survival, 2) the relationship between nutritional indicators and Child-Pugh class and disease type. This study included 80 patients (1990-1994). Methodology: The nutritional indicators utilized were grip strength, triceps skinfold thickness and uncorrected mid-arm muscle area. Measured outcomes were ventilator time, intensive care stay, postoperative hospital stay and one-year survival. Results: Early morbidity was determined in survivors. Child-Pugh class C patients required longer ventilation and spent more time in the intensive care unit than Child-Pugh classes A and B. No significant relationships were found length of hospital stay. Relationships between the nutritional indicators (when controlled for Child-Pugh class) and early morbidity could not be determined due;to insufficient data. No relationship was established between one-year survival and Child-Pugh class or the nutritional indicators. Grip strength and mid-arm muscle area were lower in the patients in Child-Pugh:classes B and C. Parenchymal liver disease was associated with lower grip strength and mid-arm muscle area when compared to cholestatic disease. Conclusions: Child-Pugh class C is associated with greater early postoperative morbidity. Advanced Child-Pugh class is also associated with diminished muscle status and parenchymal disease.

Turning up the heat on subzero fish: thermal dependence of sustained swimming in an Antarctic notothenioid

We determined the maximum sustained swimming speed (U-crit), and resting and maximum ventilation rates of the Antarctic fish Pagothenia borchgrevinki at five temperatures between -1degreesC and 8degreesC. We also determined resting metabolic rate (VO2) at -1degreesC, 2degreesC, and 4degreesC. U-crit of P. borchgrevinki was highest at -1degreesC (2.7+/-0.1 BL s(-1)) and rapidly decreased with temperature, representing a thermal performance breadth of only 5degreesC. This narrow thermal performance supports our prediction that specialisation to the subzero Antarctic marine environment is associated with a physiological trade-off in performance at high temperatures. Resting oxygen consumption and ventilation rate increased by more than 200% across the temperature range, which most likely contribute to the decrease in aerobic swimming capabilities at higher temperatures. (C) 2002 Published by Elsevier Science Ltd.

Physiological and symptomatic responses to cycling and walking in intermittent claudication

To shed light on the potential efficacy of cycling as a resting modality in the treatment of intermittent claudication (IC), this study compared physiological and symptomatic responses to graded walking and cycling tests in claudicants. Sixteen subjects with peripheral arterial disease (resting ankle:brachial index (ABI) < 0.9) and IC completed a maximal graded treadmill walking (T) and cycle (C) Lest after three familiarization tests on each mode. During cacti test, symptoms, oxygen uptake (VO2), minute ventilation (V-E), (respiratory exchange ratio) (RER) and heart rate (HR) were measured, and for 10 min after each Lest the brachial and ankle systolic pressures were recorded, All but One subject experienced calf pain as the primary limiting symptom during T whereas the symptoms were more varied during C and included thigh pain, calf pain and dyspnoea, Although maximal exercise time was significantly longer on C than T (690 +/- 67 vs, 495 +/- 57 s), peak VO2, peak, V-E and peak heart rate during C and T were not different; whereas peak RER was higher during C. These responses during C and T were also positively 1, (P < 0.05) with each other, with the exception of RER. The postexercise systolic pressures were also not different between C and T. However, the peak decline ill ankle pressures from resting values after C and T were not correlated with each other. Thew data demonstrate that cycling and walking induce a similar level of metabolic and cardiovascular strain, but that the primary limiting symptoms and haemodynamic response in an individual's extremity, measured after exercise, can differ substantially between these two modes.

Outcome of stroke patients admitted to intensive care: Experience from an Australian teaching hospital

The objective of this study was to determine the mortality rate and the functional outcomes of stroke patients admitted to the intensive care unit (ICU) and to identify predictors of poor outcome in this population. The records of all patients admitted to the ICU with the diagnosis of stroke between January 1994 and December 1999 were reviewed. Patients with subarachnoid haemorrhage were excluded. Data were collected on clinical and biological variables, risk factors for stroke and the presence of comorbidities. Mortality (ICU, in-hospital and three-month) and functional outcome were used as end-points. In the six-year-period, 61 patients were admitted to the ICU with either haemorrhagic or ischaemic stroke. Medical records were available for only 58 patients. There were 23 ischaemic and 35 haemorrhagic strokes. The ICU, in-hospital and three-month mortality rates were 36%, 47% and 52% respectively. There were no significant differences in the prevalence of premorbid risk factors between survivors and non-survivors. The mean Barthel score was significantly different between the independent and dependent survivors (94 +/- 6 vs 45 +/- 26, P < 0.001). A substantial number of patients with good functional outcomes had lower Rankin scores (92% vs 11%, P < 0.001). Only 46% of those who were alive at three months were functionally independent. Intensive care admission was associated with a high mortality rate and a high likelihood of dependent lifestyle after hospital discharge. Haemorrhagic stroke, fixed dilated pupil(s) and GCS < 10 during assessment were associated with increased mortality and poor functional outcome.

Balancing acts: Respiratory sensations, motor control and human posture

1. The present brief review covers some novel aspects of integration between respiration and movement of the body. 2. There are potent viscerosomatic reflexes in animals involving small-diameter pulmonary afferents that, when excited, would limit exercise. However, recent studies using lobeline injections to excite pulmonary afferents in awake humans suggest that there is no evoked reflex motoneuronal inhibition. Instead, the noxious respiratory sensations generated by the vagal afferents may be crucial in the decision to stop exercise. 3. While respiratory movements may affect limb movements, the control of the trunk and limbs can involve interaction (and even interference) with key respiratory muscles, such as the diaphragm. Recent studies have revealed that not only does the diaphragm receive feed-forward drive prior to some limb movements, but that it also contracts both phasically and tonically during repetitive limb movements. 4. Thus, challenges to posture can indirectly challenge ventilation, while coordinated diaphragm contraction may contribute to control of the trunk.

Ventilatory effects of neurophysiological facilitation and passive movement in patients with neurological injury

Thirteen intubated, high dependency patients with neurological injuries were studied in order to investigate the short term respiratory effects of neurophysiological facilitation and passive movement on tidal volume (V-T), minute ventilation (V-E), respiratory rate (V-R) and oxygen saturation (SpO(2)). The subjects were studied under four conditions: no intervention (control) and during periods of neurophysiological facilitation, passive movement and sensory stimulation. All periods were standardised to three minutes duration and all parameters were recorded before and after each intervention. Neurophysiological facilitation produced significant increases (p < 0.01) in V-E and SpO(2) (p < 0.05) when compared with control values, with an overall mean increase in V-E of 14.6%. Similarly, passive movement increased V-E (p < 0.01) by an average of 9.8% and also increased SpO(2) (p < 0.01). In contrast, sensory stimulation produced significant increases (p < 0.01) in SpO(2) with control levels, with no significant change in V-T or V-E. There was no significant difference in V-R with all treatments. This study provides preliminary evidence of improved short term ventilatory function following neurophysiological facilitation, independent of generalised sensory stimulation, which has not been previously examined in the literature, supporting its use in the management of high dependency neurological patients.

Dual mode cooling house in the warm humid tropics

Passive techniques as an alternative to artificial cooling can bring important energy, environmental, financial, operational and qualitative benefits. However, regions such as the wet tropics can reach high levels of thermal stress in which passive means alone are unable to provide appropriate thermal comfort standards for some parts of the year. Despite a great accumulation of empirical information on the passive performance of houses for either free-running or conditioned modes, very little work has been done on the thermal performance of buildings that can operate with a mixed-running strategy in warm-humid climates. Buildings with such design features are able to balance the needs for comfort, privacy, and energy efficiency during different periods of the year. As free-running and conditioned modes are believed by many to be 'opposite' approaches, and have been presented as separate strategies, this paper demonstrates that not all parameters are directly opposite and a possible dual-mode integrated operation can be used for warm-humid locations for maximum comfort and minimum energy requirements. For this purpose, simulation runs using ESP-R (University of Strathclyde, ESRU, UK) were based on the climate data of Darwin (Australia) and on the ventilation styles of the house: free running and conditioned. Design features applicable to both, i.e. for a dual mode operation could be identified and the differences between conditioned and free running were demonstrated and proved not to be totally conflicting and therefore suitable for a dual mode operation. Different daily usage profiles (five use patterns were defined), and zoning of sleeping and living areas are presented. The dual mode use patterns compared to the base case house, for all the user possibilities, had improved performances of 17-52%, when compared to the free-running mode and 66-98% when compared to the conditioned mode. Simulation runs using other warm-humid climates (Miami, USA; Sao Luis, Brazil; Kuala Lumpur, Malaysia) were also conducted and compared to the results found for Darwin. (C) 2002 Elsevier Science Ltd. All rights reserved.

Effect of manual hyperinflation on hemodynamics, gas exchange, and respiratory mechanics in ventilated patients

The authors investigated the effect of manual hyperinflation (MHI) with set parameters applied to patients on mechanical ventilation on hemodynamics, respiratory mechanics, and gas exchange. Sixteen critically ill patients post-septic shock, with acute lung injury, were studied. Heart rate, arterial pressure, and mean pulmonary artery pressure were recorded every minute. pulmonary artery occlusion pressure, cardiac output, arterial blood gases, and dynamic compliance (C-dyn) were recorded pre- and post-MHI. From this, systemic vascular resistance index (SVRI), cardiac index, oxygen delivery, and partial pressure of oxygen:fraction of inspired oxygen (PaO2:FiO(2)) ratio were calculated. There were significant increases in SVRI (P < 0.05) post-MHI and diastolic arterial pressure (P < 0.01)during MHI. C-dyn increased post-MHI (P < 0.01) and was sustained at 20 minutes post-MHI (P < 0.01). Subjects with an intrapulmonary cause of lung disease had a significant decrease (P = 0.02) in PaO2:FiO(2), and those with extrapulmonary causes of lung disease had a significant increase (P < 0.001) in PaO2:FiO(2) post-MHI. In critically ill patients, MHI resulted in an improvement in lung mechanics and an improvement in gas exchange in patients with lung disease due to extrapulmonary events and did not result in impairment of the cardiovascular system.