Stomach Region Stimulated Determines Effects on Duodenal Motility in Rats

Gastric electrical stimulation (GES) is used clinically to promote proximal GI emptying and motility. In acute experiments, we measured duodenal motor responses elicited by GES applied at 141 randomly chosen electrode sites on the stomach serosal surface. Overnight-fasted (H2O available) anesthetized male rats (n = 81) received intermittent biphasic GES for 5 min (20s-on/40s-off cycles; I = 0.3mA; pw = 0.2ms; 10 Hz). A strain gauge on the serosal surface of the proximal duodenum of each animal was used to evaluate baseline motor activity and the effect of GES. Using ratios of time blocks compared to a 15-min pre-stimulation baseline, we evaluated the effects of the 5-min stimulation on concurrent activity; on the 10-min immediately after the stimulation, and on the 15-min period beginning with the onset of stimulation. We mapped the magnitude of the duodenal response (3 different motility indices) elicited from the 141 stomach sites. Post hoc electrode site maps associated with duodenal responses suggested three zones similar to the classic regions of forestomach, corpus and antrum. Maximal excitatory duodenal motor responses were elicited from forestomach sites, whereas inhibitory responses occurred with stimulation of the corpus. Moderate excitatory duodenal responses occurred with stimulation of the antrum. Complex, weak inhibitory/excitatory responses were produced by stimulation at boundaries between stomach regions. Patterns of GES efficacies coincided with distributions of previously mapped vagal afferents, suggesting that excitation of the duodenum is strongest when GES electrodes are situated over stomach concentrations of vagal intramuscular arrays, putative stretch receptors in the muscle wall.

Subcortical structures: The cerebellum, basal ganglia, and thalamus

Less is known of the function of the cerebellum, thalamus, and basal ganglia than of other structures in the brain, but there is an increasing appreciation of their complex role in motor and non-motor functions of the entire nervous system. These structures exercise functions that far exceed their previously assumed supporting parts as simple ‘relay stations’ between cortex and spinal cord. The subcortical structures receive massive different inputs from the cerebral cortex and peripheral sense organs and stretch receptors. Through recurrent feedback loops this information is integrated and shaped to provide output which contributes to scaling, sequencing, and timing of movement, as well as learning and automatization of motor and non-motor behaviours.

The Antitussive Benzonatate Is Not Tumorigenic in Rodent Carcinogenicity Studies

Benzonatate is a peripheral oral antitussive that dampens the activity of cough stretch receptors. Rodent carcinogenicity studies were performed in Tg.rasH2 mice and Wistar Han rats. Mice were orally gavaged benzonatate at 10, 30, 75, and 100 mg/kg/day for males and 5, 15, and 50 mg/kg/day for females. Rats were gavaged at 10, 30, and 90 mg/kg/day for males and 5, 15, and 50 mg/kg/day for females. Higher doses in males were due to differences in maximum tolerated doses in dose-ranging studies. In both species, benzonatate was not detected in plasma because of rapid ester hydrolysis producing 4-(butylamino) benzoic acid (BBA) and methylated polyethylene glycol polymer. This metabolism was similar in human plasma; therefore, plasma BBA was used to show systemic exposure. Both species had no evidence of a benzonatate-related increase in any neoplasm. A slight increase in nasal cavity exudative inflammation was present in benzonatate-dosed male mice. Retinal atrophy was observed in male rats at ≥30 mg/kg/day, but the incidence was within historical control data range and not related to benzonatate. In conclusion, benzonatate and its 2 major metabolites were not carcinogenic in rodent carcinogenicity studies at BBA exposures of ≥32 and 70 times a 200 mg human benzonatate dose, respectively.

Respiratory

This chapter describes the pathophysiology of the respiratory system as it applies to Emergency Medicine, and in particular the Primary FRCEM examination. The chapter outlines the key details of the control of ventilation, reflexes, pressure, chemical, and irritant receptors, J receptors, pulmonary stretch receptors, Golgi tendon organs, muscle spindles, lung volumes, pulmonary mechanics, oxygen and carbon dioxide transport, DO2/VO2 relationships, carbon monoxide, pulse oximetry, effects of altitude, and dysbarism. This chapter is laid out exactly following the RCEM syllabus, to allow easy reference and consolidation of learning.

Bronchodilatory effect of deep inspiration in freshly isolated sheep lungs

Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect. Neural reflex initiated by stretch receptors in the lung are known to inhibit the broncho-motor tone and enhance vasodilatation; the former directly reduces airway resistance, and the latter facilitates removal of contractile agonists through the bronchial circulation. If the DI effect is solely mediated by factors extrinsic to the lung, the DI effect would be absent in isolated, nonperfused lungs. Here we examined the DI effect in freshly isolated, nonperfused sheep lungs. We found that imposition of DI on isolated lungs resulted in significant bronchodilation, that this DI effect was present only after the lungs were challenged with a contractile agonist (acetylcholine or histamine), and that the effect was independent of the difference in lung volume observed pre- and post-DI. We conclude that a significant portion of the bronchodilatory DI effect stems from factors internal to the lung related to the activation of ASM.

Proprioceptive feedback modulates coordinating information in a system of segmentally distributed microcircuits

The system of modular neural circuits that controls crustacean swimmerets drives a metachronal sequence of power-stroke (PS, retraction) and return-stroke (RS, protraction) movements that propels the animal forward efficiently. These neural modules are synchronized by an intersegmental coordinating circuit that imposes characteristic phase differences between these modules. Using a semi-intact preparation that left one swimmeret attached to an otherwise isolated central nervous system (CNS) of the crayfish, Pacifastacus leniusculus, we investigated how the rhythmic activity of this system responded to imposed movements. We recorded extracellularly from the PS and RS nerves that innervated the attached limb and from coordinating axons that encode efference copies of the periodic bursts in PS and RS axons. Simultaneously, we recorded from homologous nerves in more anterior and posterior segments. Maintained retractions did not affect cycle period but promptly weakened PS bursts, strengthened RS bursts, and caused corresponding changes in the strength and timing of efference copies in the module's coordinating axons. Changes in these efference copies then caused changes in the phase and duration, but not the strength, of PS bursts in modules controlling neighboring swimmerets. These changes were promptly reversed when the limb was released. Each swimmeret is innervated by two nonspiking stretch receptors (NSSRs) that depolarize when the limb is retracted. Voltage clamp of an NSSR changed the durations and strengths of bursts in PS and RS axons innervating the same limb and caused corresponding changes in the efference copies of this motor output.

Sensory structures of lungs and airways

The оptimum realization to respiratory function depends on varied sensory feedbacks from ensemble of the sources of the body. Pulmonary sensory receptors are the initiating sites for lung reflexes. The information arriving from lungs and airways information is one of the most important feedbacks that provide the adaptation of the respiratory centre for producing of the pattern optimal in terms of work and force of breathing. In article the review of currently existing data about morphology and functional characteristics of sensitive pulmonary structures is presented: slowly adapting stretch receptors, rapidly adapting receptors, C-fiber receptors and neuroepithelial bodies.