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Five conscious rabbits each received a single injection of almitrine bismesylate via a marginal ear vein. Measurements were made of ventilation and breathing pattern using a barometric method, and blood gases, pH and lactate concentration ([Lac]) were measured from arterial blood samples throughout the hour following the injection. Almitrine caused an immediate increase in ventilation through an increase in tidal volume (VT), frequency ( showing a small decline. After 15 min f increased to above control level and VT declined. Slower, deeper breathing was reinstated by 40 min post-injection. Large changes in blood gases occurred in the first 15 min, with PO2 raised by 30 Torr and PCO2, lowered by 20 Torr. These recovered to be within 10 and 7.5 Torr of control at the end of 1 h. [Lac] increased steeply at first, then declined towards control levels. The acid-base situation was mixed, comprising a respiratory alkalosis, resulting from CO2 washout, and a metabolic acidosis from high [Lac]. These results are discussed in the context of assessing the primary and secondary effects of almitrine and recognition of the possibility that the drug may act more than one site to alter respiration. [ABSTRACT FROM AUTHOR]

Background: General practice in the United Kingdom is experiencing a workforce crisis. Greater multidisciplinary working, including more general practice pharmacists, is seen as part of the solution. However, it is unknown what impact and cost-consequences that pharmacists may have in freeing general practitioner (GP) capacity., Objective: To evaluate the cost-consequences of additional pharmacists in releasing GP capacity., Methods: This cost-consequences evaluation of a prospective observational cohort study in 15 urban practices involving 69 GPs in 1 locality serving a population of 82,000 people. GPs recorded the time they spent addressing key targeted prescribing activities during 5 distinct 2-week audit periods. Pharmacists performed these key prescribing activities to release GP capacity. An additional 225 h of pharmacists' time per week was committed to the locality. Standardized staff costings were used to estimate the financial impact. Prescribing indicator performance was assessed against the other 7 localities within the health board., Results: When compared with employing extra nonsalaried GPs this required an estimated additional investment of £16.73 (range £5.97-20.87) per h to free GP capacity. This achieved a sustainable 47% (73 h per week, F(4,56) = 16.05, P < 0.001) reduction in GP time spent on key prescribing activities; equating to 4.9 h (95% confidence interval 3.1-6.7) per practice per week. No significant step changes in locality safety and quality prescribing measures, and no negative effects on locality-level prescribing cost-efficiency work were observed., Conclusion: Appropriately resourced general practice pharmacy teams delivered prescribing cost-efficiencies as well as sustainably freeing GP capacity by performing key prescribing activities., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety climatological model and the Automated Radiation Measurements for Aerospace Safety (ARMAS) statistical database are presented as polynomial fit equations. Using equations based on altitude, L shell, and geomagnetic conditions an effective dose rate for any location from a galactic cosmic ray (GCR) environment can be calculated. A subset of the ARMAS database is represented by a second polynomial fit equation for the GCR plus probable relativistic energetic particle (REP; Van Allen belt REP) effective dose rates within a narrow band of L shells with altitudinal and geomagnetic dependency. Solar energetic particle events are not considered in this study since our databases do not contain these events. This work supports a suggestion that there may be a REP contribution having an effect at aviation altitudes. The ARMAS database is rich in Western Hemisphere observations for L shells between 1.5 and 5; there have been many cases of enhanced radiation events possibly related to effects from radiation belt particles. Our work identifies that the combined effects of an enhanced radiation environment in this L shell range are typically 15% higher than the GCR background. We also identify applications for the equations representing the Nowcast of Atmospheric Ionizing Radiation for Aviation Safety and ARMAS databases. They include (i) effective dose rate climatology in comparison with measured weather variability and (ii) climatological and statistical weather nowcasting and forecasting. These databases may especially help predict the radiation environment for regional air traffic management, for airport overflight operations, and for air carrier route operations of individual aircraft.

Background: General practice in the UK is experiencing a workforce crisis. However, it is unknown what impact prescribing support teams may have on freeing up GP capacity and time for clinical activities., Aim: To release GP time by providing additional prescribing resources to support general practices between April 2016 and March 2017., Design and Setting: Prospective observational cohort study in 16 urban general practices that comprise Inverclyde Health and Social Care Partnership in Scotland., Method: GPs recorded the time they spent dealing with special requests, immediate discharges, outpatient requests, and other prescribing issues for 2 weeks prior to the study and for two equivalent periods during the study. Specialist clinical pharmacists performed these key prescribing activities to release GP time and Read coded their activities. GP and practice staff were surveyed to assess their expectations at baseline and their experiences during the final data-collection period. Prescribing support staff were also surveyed during the study period., Results: GP time spent on key prescribing activities significantly reduced by 51% (79 hours, P <0.001) per week, equating to 4.9 hours (95% confidence interval = 3.4 to 6.4) per week per practice. The additional clinical pharmacist resource was well received and appreciated by GPs and practices. As well as freeing up GP capacity, practices and practitioners also identified improvements in patient safety, positive effects on staff morale, and reductions in stress. Prescribing support staff also indicated that the initiative had a positive impact on job satisfaction and was considered sustainable, although practice expectations and time constraints created new challenges., Conclusion: Specialist clinical pharmacists are safe and effective in supporting GPs and practices with key prescribing activities in order to directly free GP capacity. However, further work is required to assess the impact of such service developments on prescribing cost-efficiency and clinical pharmacist medication review work., (© British Journal of General Practice 2018.)

In mammals and birds, all oxygen used (VO2) must pass through the lungs; hence, some degree of coupling between VO2 and pulmonary ventilation (VE) is highly predictable. Nevertheless, VE is also involved with CO2 elimination, a task that is often in conflict with the convection of O2. In hot or cold conditions, the relationship between VE and VO2 includes the participation of the respiratory apparatus to the control of body temperature and water balance. Some compromise among these tasks is achieved through changes in breathing pattern, uncoupling changes in alveolar ventilation from VE. This article examines primarily the relationship between VE and VO2 under thermal stimuli. In the process, it considers how the relationship is influenced by hypoxia, hypercapnia or changes in metabolic level. The shuffling of tasks in emergency situations illustrates that the constraints on VE-VO2 for the protection of blood gases have ample room for flexibility. However, when other priorities do not interfere with the primary goal of gas exchange, VE follows metabolic rate quite closely. The fact that arterial CO2 remains stable when metabolism is changed by the most diverse circumstances (moderate exercise, cold, cold and exercise combined, variations in body size, caloric intake, age, time of the day, hormones, drugs, etc.) makes it unlikely that VE and metabolism are controlled in parallel by the condition responsible for the metabolic change. Rather, some observations support the view that the gaseous component of metabolic rate, probably CO2, may provide the link between the metabolic level and VE., (2011 American Physiological Society)

Arterial haemoglobin saturation during exercise in healthy young women [eight subjects mean (SEM) age 20.8 (1.8) years] was measured to confirm the theory that young women experience exercise-induced arterial hypoxaemia (EIAH) at a lower relative percentage of maximal oxygen uptake (VO(2max)) than has been documented in their male counterparts. To determine if flow limitation [the percentage of the tidal volume ( V(T)) that met or exceeded the boundary established by multiple maximal expiratory manoeuvres] and/or post-exercise lung diffusing capacity are linked to EIAH in women, and to investigate the influence of exercise intensity and duration on post-exercise carbon monoxide lung diffusing capacity ( D(L, CO)), these parameters were measured during and after three exercise tests (incremental test until exhaustion, 5 km run and 5 km run with sprint). All subjects experienced physiologically significant EIAH (a fall of more than 3% in oxygen saturation of arterial blood from levels at rest) and seven subjects experienced flow limitation during the VO(2max) protocol [mean (SD) 12.2 (8.8)% of V(T)]. Even though there was no significant relationship between aerobic capacity and the degree of flow limitation ( r=0.33, P>0.05), the flow limitation was related to absolute ventilation in the subjects studied ( r=0.82, P<0.05). There was no significant relationship between decrements in post exercise D(L, CO) and EIAH ( r=0.05, P>0.05), however there was a strong correlation between the extent of flow limitation (% of V(T)) and EIAH ( r=0.71). Significant decreases in D(L, CO) lasted for up to 16 h after each of the exercise tests ( P<0.05) and lasted for a further 8 h after the maximal test ( P<0.05). Exercise intensity was the main contributing factor to the observed decreases in post-exercise D(L, CO) with the percentage of VO(2max) attained during the various tests being significantly related to the fall in D(L, CO) for 1, 2, 3, 16 and 24 h after exercise ( P<0.05). As the appearance of flow limitation closely coincided with the appearance of EIAH, the results from the present study suggest that flow limitation is a contributing factor to EIAH in women although the exact mechanism remains unclear.

Genetically obese Zucker (Z) rats have been reported to display a body core temperature (Tb) that is consistently below that of their lean littermates. We asked the question whether the lower Tb was a result of deficits in thermoregulation or a downward resetting of the set point for Tb. For a period of 45 consecutive hours, lean and obese Z rats were free to move within a thermal gradient with an ambient temperature (T(a)) range of 15-35 degrees C, while subjected to a 12:12-h light-dark cycle. Tb was measured using a miniature radio transmitter implanted within the peritoneal cavity. Oxygen consumption (VO2) was measured using an open flow technique. Movements and most frequently occupied position in the gradient (preferred T(a)) were recorded using a series of infrared phototransmitters. Obese Z rats were compared with lean Z rats matched for either age (A) or body mass (M). Our results show that obese Z rats have a lower Tb [37.1 +/- 0.1 degrees C (SD) vs. 37.3 +/- 0.1 degrees C, P < 0.001] and a lower VO2 (25.3 +/- 1.9 ml x kg(-1) x h(-1)) than lean controls [33.1 +/- 3.7 (A) and 33.9 +/- 3.9 (M) ml x kg(-1) x h(-1), P < 0.001]. Also, the obese Z rats consistently chose to occupy a cooler T(a) [20.9 +/- 0.6 degrees C vs. 22.7 +/- 0.6 degrees C (A) and 22.5 +/- 0.7 degrees C (M), P < 0.001] in the thermal gradient. This suggests a lower set point for Tb in the obese Z rat, as they refused the option to select a warmer T(a) that might allow them to counteract any thermoregulatory deficiency that could lead to a low Tb. Although all rats followed a definite circadian rhythm for both Tb and VO2, there was no discernible circadian pattern for preferred T(a) in either obese or lean rats. Obese Z rats tended to show a far less definite light-dark activity cycle compared with lean rats.

We measured body temperature (Tb) and ventilatory and metabolic variables in lean (n = 8) and obese (n = 8) Zucker rats. Measurements were made while rats breathed air, 4% CO2, and 10% O2. Under control conditions, Tb in obese rats was always less than that of their lean counterparts. Obese rats adopted a more rapid, shallow breathing pattern than lean rats in air and had a lower ventilation rate in 4% CO2. Respiration in 10% O2 was similar for the two groups. Metabolic variables did not differ between lean and obese rats whatever the gas breathed. When lean rats were cooled to match Tb in control obese rats with an implanted abdominal heat exchanger, they increased ventilation and metabolism in air; there was no effect of cooling on responses to 4% CO2; and ventilation increased while metabolism decreased in 10% O2. When obese rats were warmed to match Tb in control lean rats, trends in ventilation and metabolism resulted in a tendency toward hyperventilation in air and 4% CO2, but not in 10% O2. Taken overall, matching Tb in lean and obese rats accentuated differences in respiratory and metabolic variables between the two groups. We conclude that differences in respiration between lean and obese Zucker rats are not due to the difference in Tb.

In many mammals the ventilatory response to hypoxia depends on ambient temperature (Ta), largely because of the hypometabolic effects of hypoxia below thermoneutrality. We questioned whether the ventilatory response to asphyxia also depends upon Ta, and the role played by metabolism and body temperature (Tb). Oxygen consumption (VO2) and pulmonary ventilation (VE) were measured in conscious rats at Ta = 27 degrees C (warm) and 11 degrees C (cold), breathing air or two levels of asphyxic gases, moderate (10% O2-4% CO2), or severe (10% O2-8% CO2), for approximately 30 min each. In the cold, the pattern of the VE response to moderate asphyxia was qualitatively similar to that seen in hypoxia alone, i.e the attained VE/VO2 was similar in warm and cold conditions, with, in the latter, a major drop in VO2 and little or no hyperpnea. During severe asphyxia, however, the VE/VO2 attained in the cold was less than in the warm, and it was accompanied by a large drop in Tb (approximately 6 degrees C). Blood gases confirmed the lower asphyxic hyperventilation in the cold. By maintaining Tb at 38 degrees C with an implanted abdominal heat exchanger, the VE/VO2 levels attained during asphyxia were the same between cold and warm conditions. We conclude that (a) the VE response to asphyxia is Ta-dependent, largely because of the hypometabolic effect of the hypoxic component in the cold, (b) during moderate asphyxia the hypercapnic component is qualitatively unimportant, and (c) with severe asphyxia the hypercapnia becomes an important contributor to the Ta-sensitivity by aggravating the decrease in Tb in the cold and lowering VE sensitivity.

1. This paper reviews current knowledge regarding interactions between body temperature and the respiratory responses to hypoxia and/or hypercapnia, with special emphasis on how these interactions might predispose towards sudden infant death syndrome (SIDS). 2. Use has been made of an adult rat model in which body core temperature is fixed by means of an intra-abdominal heat exchanger. Initial studies indicated that hyperthermia (Tb approximately 41 degrees C) enhanced the ventilatory response to hypercapnia, whereas hypothermia (Tb approximately 35 degrees C) interacted with hypoxia to depress respiration. 3. Studies involving hypothalamic lesions in urethane-anaesthetized rats have implicated the posterior hypothalamic area in the hypoxia/hypothermia interaction. Further studies are directed towards examining the role played by more caudal areas, including the raphe nuclei. 4. It has been shown that not only does the hypoxia/hypothermia interaction depress breathing but it also reduces, or sometimes eliminates, the ventilatory response to hypercapnia, which under normal circumstances provides one of the most powerful excitatory inputs to the respiratory centres. This implies that an expected reversal of the respiratory depression by build up of CO2 levels may not occur, which in turn has important implications for SIDS. 5. The literature dealing with the effects of hyperthermia on hypoxic and hypercapnic responses is also reviewed. It is concluded that environmental heat stress may only become a significant problem when it accompanies a febrile infection, under which circumstances it may seriously compromise thermoregulatory ability and alter breathing responses to chemical stimuli.

In resting euthermic mammals, hypoxia elicits a hyperventilation that results from a combination of hyperpnea and hypometabolism. Often accompanying the hypoxia-induced hypometabolism is a drop in body temperature. To separate the synergic effects of hypothermia per se from the direct effects of hypoxia on metabolic rate, ventilation (VE), and O2 consumption (VO2) were measured in anesthetized rats fitted with abdominal heat exchangers and maintained at either normothermic (37.5 degrees C) or hypothermic (35 degrees C) body temperatures while exposed to either normoxia or hypoxia (7% O2). Hypothermia induced parallel decreases in VE and VO2, thereby maintaining VE/VO2. Hypoxia resulted in a hyperventilation achieved with the same relative decrease in VO2 and increase in VE in both normothermic and hypothermic rats. The results suggest that 1) the changes in metabolic rate and VE during hypothermia reflect a direct effect of cold and, 2) because of similar levels of hypoxic hyperventilation in the hypothermic and normothermic rats, relative to metabolic rate, respiratory gain has not been depressed in hypothermic rats.

Male Hooded Wistar rats were exposed to three five-minute periods of hypoxia in which they breathed a gas mixture comprising 7% O2 and 93% N2. Before the second and third hypoxic exposures rats were injected (i.m.) with aminophylline (an adenosine antagonist) at a dose of 15 mg.kg-1. In control animals, hypoxia caused an increase in ventilation which was greater during the first than during the fifth minute of hypoxia. Each injection of aminophylline significantly increased ventilation in air-breathing rats. However, the first dose of the drug did not significantly alter the hypoxic ventilatory response. The second dose of aminophylline had two effects on ventilation during hypoxia. It reduced the ventilatory response during the first minute of hypoxia, and also prevented the fall in ventilation between the first and fifth minute of exposure. Ethylenediamine injections had no effect on ventilation or the responses to hypoxia. The results suggest that adenosine has a dual role in respiratory control during hypoxia, one excitatory and the other inhibitory. Although previous studies have already identified such roles for adenosine, the present study may represent the first time in which these have been demonstrated in a single animal model.

Urethane-anaesthetised rats were exposed to hypoxia (7% O2 in N2) for 5 min periods while body core temperature (Tbc) was maintained within the normal range (37-38 degrees C) using an abdominal heat exchanger. Animals were exposed to hypoxia and after placement of electrolytic lesions in either the anterior (n = 6) or posterior hypothalamus (n = 6). Neither lesion altered respiration while rats breathed air at either Tbc. At normal Tbc, rats responded to hypoxia with increased ventilation throughout the exposure period. This response was unchanged by lesions in either location. At reduced Tbc rats responded to hypoxia with an initial increase in ventilation followed by depression to below air-breathing levels. This depressive response was unchanged after anterior hypothalamic lesions but eliminated after posterior hypothalamic lesions. It is concluded that neurons either originating in the posterior hypothalamus, or passing through it, play a role in the interaction between cold and hypoxia which leads to inhibition of respiration.