Ventral medulla pHi measured in vivo by 31P NMR is not regulated during hypercapnia in anesthetized rat

Chemoreceptors in the ventral medulla contribute to the respiratory response to hypercapnia. Do they ‘sense’ intracellular pH (pH_i)? We measured pH_i in the ventral medulla or cortex (control) using ³¹P-NMR obtained via a novel 3×5 mm² surface coil in anesthetized rats breathing air or 7% CO₂. During air breathing over 240 min, pH_i decreased slightly from 7.13±0.02 to 7.05±0.02 (SEM; n=5; 2 cortex, 3 ventral medulla). During 180 min of hypercapnia, cortical pH_i (n=4) decreased from 7.17±0.02 to 6.87±0.01 by 90 min and recovered by 150 min. Ventral medulla pH_i showed no such regulation. It decreased from 7.11±0.02 to 6.88±0.02 at 90 min and recovered only after cessation of hypercapnia (n=5), results consistent with pH_i being the chemoreceptor stimulus. However, non-chemoreceptor neurons that contribute to our medullary NMR signal also do not appear to regulate pH_i in vitro. Regional differences in pH_i regulation between cortex and ventral medulla may be due to both chemosensitive and non-chemosensitive neurons.     

The effects of blood osmolality changes on cat carotid body chemoreceptors in vivo

The possibility that carotid chemoreceptors respond to changes in plasma osmolality was investigated in the cat, perfusing the carotid artery with blood made hyper- or hypo-osmotic and recording chemoreceptor activity from carotid nerve fibers. Blood made hyperosmotic with sucrose or NaCl reduced the chemoreceptor discharge, while hypoosmotic blood increased chemoreceptor activity. The minimal osmolality variation necessary to obtain a detectable frequency change was 3–8% of the control. Frequency changes of 30% of the control were obtained with a 20% variation in osmolality. The frequency variations produced by the osmotic changes lasted as long as the infusion was maintained (up to 15 min). In some instances a rebound was observed when iso-osmotic saline was perfused again. A transient change in frequency and a clear rebound were obtained when blood made hyperosmotic with glycerol was perfused. These effects probably reflect a rapid change in intracellular osmolality due to the free passage of glycerol across cellular membranes.The modifications in chemoreceptor activity consecutive to osmolality variations are the opposite of those observed in isolated and superfused carotid bodies. As it is known that osmolality values affect the smooth muscle of the blood vessels, we conclude that our results are mainly produced by changes in carotid body blood flow due to a direct effect of hyper- and hypo-osmotic solutions on vascular muscle tone. Chemoreceptor excitation during a decrease in blood osmolality may contribute reflexly to the increased vascular resistance observed during acute osmolality reductions in man.     

Ventilatory response to oscillating and non-oscillatingPa CO 2 in the anesthetized cat

Summary In 11 adult cats, lightly anesthetized with chloralose-urethane, blood from both common carotid arteries was led into a plastic chamber of 15–20 ml and returned to the carotids at a point 1.5 cm more cranial. By doing so arterial blood was assumed to pool within the chamber and lose itsP _{CO 2} oscillations which are normally known to exist as a result of the respiratory cycle. In control periods blood bypassed the chamber, thus maintaining respiratoryP _{CO 2} oscillations. Spontaneous ventilation was measured spirometrically. The animals were breathing pure O₂.Results. 1. When the sinus (carotid) nerves were intact or sectioned there was no significant difference in ventilation before or after switching from non-oscillating to oscillatingPa _{CO 2}. 2. When the vertebral arteries were ligated a drop in ventilation occurred after turning to oscillatingPa _{CO 2} which was followed by a slight rise above control values after 30–50 sec. This phenomenon was independent of sinus nerve integrity. Thus in hyperoxie condition the smallPa _{CO 2} oscillations known to occur in phase with respiration do not seem to provide a respiratory stimulus to resting ventilation above that generated by the mean level ofPa _{CO 2}. The ventilatory depression after vertebral artery ligation must at this time remain unexplained.     

家兔一侧颈总动脉缺失探讨

目的 探讨家兔不同条件下一侧颈总动脉缺失对动脉血压的影响,为研究影响动脉血压的作用机制提供数据支持.方法 将24只家兔随机分为实验组和对照组两组,分别进行不同预处理条件下,如正常、麻醉、破坏等四部分夹闭一侧动脉实验,观察另一侧动脉血压的变化.将所得各组数据进行统计学分析,比较动脉血压变化的差异.结果 实验发现,在一侧动脉正常、麻醉、破坏等条件下进一步夹闭该侧颈总动脉,家兔另一侧颈动脉血压明显变化,与操作前比较,差异有统计学意义（P〈0.05或P〈0.01）;实验组动脉血压变化较对照组更为明显（P〈0.05）.但当破坏两侧颈总动脉时,无论是实验前后比较还是组间比较,动脉血压差异均无统计学意义（P〉0.05）.结论 在家兔一侧颈动脉正常、麻醉、破坏等多种条件下,若该侧颈总动脉缺失时,另一侧颈总动脉血压会受到明显的影响,且变化比未缺失时要大.     

Impact of CPAP interface and mandibular advancement device on upper airway mechanical properties assessed with phrenic nerve stimulation in sleep apnea patients

Oronasal mask (ONM) can be used when mouth leaks impair nasal-CPAP effectiveness. However, ONM's constraint on the chin and straps' traction may alter upper airway (UA) mechanical properties. In contrast, mandibular advancement device associated with nasal-CPAP (NM+MAD) may reduce UA resistance. The aim of this exploratory study was to compare the effects of ONM, NM, and NM+MAD on UA mechanical properties. The three interface modalities were assessed in 11 OSAS patients at 6, 8, 10cmH(2)O CPAP using a phrenic nerve magnetic stimulation (PNMS) protocol. PNMS-twitches' related flow, pharyngeal pressures (nasopharynx, velopharynx, oropharynx) and UA resistances were determined. Regardless of CPAP level, twitch-induced maximum flow was higher with NM+MAD than with ONM. Velopharyngeal resistance was higher with ONM than with NM+MAD. Oropharyngeal resistance was higher with ONM than with NM. In conclusion, NM+MAD reduced velopharyngeal resistance compared to those measured with ONM and NM alone. We hypothesize that this strategy may help reducing the effective pressure level and thus further limit the risk for mouth leaks.     

Gastric satiation is volumetric, intestinal satiation is nutritive

Gerry Smith's thoughtful survey in his book Satiation (1998) outlined the established principles of gastric and intestinal satiation and delineated several questions still requiring clarification. Experiments since the time of the review have addressed some of these questions. A synthesis of the principles outlined in the Gerry Smith survey and the subsequent experimental results indicates that the direct controls, or neural feedback signals from the GI tract, that limit meal size consist of gastric volumetric signals and intestinal nutritive signals. The two types of negative feedback synergize in the control of feeding, and both are carried by vagal afferents.     

The effects of carbon monoxide on respiratory chemoreflexes in humans

As protection against low-oxygen and high-carbon-dioxide environments, the respiratory chemoreceptors reflexly increase breathing. Since CO is also frequently present in such environments, it is important to know whether CO affects the respiratory chemoreflexes responsiveness. Although the peripheral chemoreceptors fail to detect hypoxia produced by CO poisoning, whether CO affects the respiratory chemoreflex responsiveness to carbon dioxide is unknown. The responsiveness of 10 healthy male volunteers were assessed before and after inhalation of approximately 1200 ppm CO in air using two iso-oxic rebreathing tests; hypoxic, to emphasize the peripheral chemoreflex, and hyperoxic, to emphasize the central chemoreflex. Although mean (SEM) COHb values of 10.2 (0.2)% were achieved, no statistically significant effects of CO were observed. The average differences between pre- and post-CO values for ventilation response threshold and sensitivity were -0.5 (0.9) mmHg and 0.8 (0.3) L/min/mmHg, respectively, for hyperoxia, and 0.7 (1.1) mmHg and 1.2 (0.8) L/min/mmHg, respectively, for hypoxia. The 95% confidence intervals for the effect of CO were small. We conclude that environments with low levels of CO do not have a clinically significant effect acutely on either the central or the peripheral chemoreflex responsiveness to carbon dioxide.     

Acute ventilatory and circulatory reactions evoked by nicotine: are they excitatory or depressant?

Either excitatory or inhibitory cardio-respiratory responses induced by nicotine have been reported. We evaluated the joint and separate contributions of peripheral arterial chemoreceptors and pulmonary vagal afferences to nicotine-induced cardio-respiratory responses in 11 pentobarbitone-anaesthetized cats. Nicotine, given i.v. in doses of from 1 to 200 microg/kg, evoked dose-dependent transient increases in tidal volume (VT) and arterial blood pressure (BP), but the highest doses evoked brief apnoea, immediately followed by intense hyperventilation, as well as discrete early hypotension followed by late hypertension. Bilateral section of the aortic and carotid nerves abolished all hyperventilatory responses to nicotine, giving way to apnoea followed by few cycles of reduced VT and profound hypotension followed by slight hypertension in response to intermediate doses (50-100 microg/kg). Subsequent bilateral vagotomy (BV) suppressed apnoeic and hypotensive responses. In other cats initially subjected to BV, only increases in VT and BP were observed in response to nicotine, effects which were no longer observed after additional carotid and aortic deafferentation. These data suggest that excitatory effects of nicotine on respiration and BP are reflexes evoked by stimulation of peripheral arterial chemoreceptors, while inhibitory effects are also reflex responses but evoked from stimulation of pulmonary vagal afferences.     

Nociception and inflammatory hyperalgesia evaluated in rodents using infrared laser stimulation after Trpv1 gene knockout or resiniferatoxin lesion

TRPV1 is expressed in a subpopulation of myelinated Aδ and unmyelinated C-fibers. TRPV1⁺ fibers are essential for the transmission of nociceptive thermal stimuli and for the establishment and maintenance of inflammatory hyperalgesia. We have previously shown that high-power, short-duration pulses from an infrared diode laser are capable of predominantly activating cutaneous TRPV1⁺ Aδ-fibers. Here we show that stimulating either subtype of TRPV1⁺ fiber in the paw during carrageenan-induced inflammation or following hind-paw incision elicits pronounced hyperalgesic responses, including prolonged paw guarding. The ultrapotent TRPV1 agonist resiniferatoxin (RTX) dose-dependently deactivates TRPV1⁺ fibers and blocks thermal nociceptive responses in baseline or inflamed conditions. Injecting sufficient doses of RTX peripherally renders animals unresponsive to laser stimulation even at the point of acute thermal skin damage. In contrast, Trpv1−/− mice, which are generally unresponsive to noxious thermal stimuli at lower power settings, exhibit withdrawal responses and inflammation-induced sensitization using high-power, short duration Aδ stimuli. In rats, systemic morphine suppresses paw withdrawal, inflammatory guarding, and hyperalgesia in a dose-dependent fashion using the same Aδ stimuli. The qualitative intensity of Aδ responses, the leftward shift of the stimulus-response curve, the increased guarding behaviors during carrageenan inflammation or after incision, and the reduction of Aδ responses with morphine suggest multiple roles for TRPV1⁺ Aδ fibers in nociceptive processes and their modulation of pathological pain conditions.