Pulmonary chemoreflexes elicited by intravenous injection of lactic acid in anesthetized rats

Experiments were carried out to characterize the cardiorespiratory reflex responses to intravenous injection of lactic acid and to determine the involvement of vagal bronchopulmonary C-fiber afferents in eliciting these responses in anesthetized rats. Bolus injection of lactic acid (0.2 mmol/kg i.v.) immediately elicited apnea, bradycardia, and hypotension, which were then followed by a sustained hyperpnea. The immediate apneic and bradycardiac responses to lactic acid were completely abolished by bilateral vagotomy and were absent when the same dose of lactic acid was injected into the left ventricle. The subsequent hyperpneic response was substantially attenuated by denervation of carotid body chemoreceptors. After a perineural capsaicin treatment of both vagus nerves to block the conduction of C fibers, lactic acid no longer evoked the immediate apnea and bradycardia, whereas the hyperpneic response became more pronounced and sustained, presumably because of the removal of the inhibitory effect on breathing mediated by pulmonary C-fiber activation. Single-unit electrophysiological recording showed that intravenous injection of lactic acid consistently evoked an abrupt and intense burst of discharge from the vagal C-fiber afferent endings in the lungs. In conclusion, the cardiorespiratory depressor responses induced by lactic acid are predominantly elicited by activation of vagal pulmonary C fibers.     

Tracheal vascular dilatation elicited by vagal nerve stimulation in rats

We investigated the effects of the electrical stimulation of a unilateral cervical vagal nerve on the blood flow in the trachea using laser Doppler flowmetry in urethane anesthetized Wistar King rats. Stimulation for 30 s at 1, 2, 5, 10, 20 or 50 Hz with 10 V intensity caused an increase in tracheal blood flow (TBF) in a frequency-dependent manner; the effects were most dominant with the 10-Hz stimulation among the six frequencies used. The increased responses of TBF with the muscarinic receptor antagonist atropine (1.0 mg/kg, i.v.) were significantly reduced when compared with those without atropine at 5 Hz stimulation (123.3 +/- 11.9% vs. 180.1 +/- 24.5%). This shows the existence of vasodilation due to a cholinergic mechanism. The increased responses of TBF after the ganglion blocking agent hexamethonium (20 mg/kg) i.v. administration were significantly reduced when compared with those without hexamethonium at 1, 2 Hz stimulation (1 Hz: 18.9 +/- 2.7% vs. 35.4 +/- 4.7%, 2 Hz: 40.5 +/- 8.9% vs. 58.8 +/- 6.7%); this shows the existence of vasodilation due to a non-cholinergic parasympathetic efferent mechanism which itself appears to be due to the release of neuropeptides such as VIP and PHI. The increased responses after hexamethonium administration were augmented probably because of the enhanced release of other neuropeptides like SP and CGRP especially at 10 Hz and 20 Hz stimulation. These findings suggest that the mechanism of vasodilation by the activity in the vagal fibers in the trachea of the rat has cholinergic and non-cholinergic efferent components and a non-cholinergic afferent component. In rats, the afferent component may play an important role in controlling tracheal vascular changes.     

Mechanism of the acute pressor effect and bradycardia elicited by diaspirin crosslinked hemoglobin in anesthetized rats

Although intracellular pH (pHi), is a regulator of numerous biological processes, it has received relatively little attention with regard to the physiology of the mammalian preimplantation embryo. Interestingly, there is some controversy as to whether the early embryo can recover from an acid load. The significance of this is that two constituents of mouse embryo culture media are pyruvate and lactate. These carboxylic acids are utilised by the early mouse embryo for energy production. However, as weak acids, pyruvate and lactate may induce perturbations in the pHi and thus alter the physiology of the embryo. The aims of this study were therefore to measure the pHi of the mouse preimplantation embryo and to determine the effect of lactate on pHi at different developmental stages. The pHi was measured using the ratio-metric fluorophore carboxy-seminaphthorhodafluor-1-acetoxymethylester (SNARF-1) in conjunction with confocal microscopy. The pHi increased significantly with development from the zygote to the morula stage. Furthermore, at concentrations greater than 5 mM, lactate caused the pHi of the zygote to become significantly more acidic. It was demonstrated that facilitative transport in association with a smaller passive component was responsible for the movement of lactate into the zygote. Metabolic studies revealed that, through their acidifying effect, weak acids caused a reduction in glycolytic activity in the early embryo. In contrast, the pHi of the compacted embryo remained unchanged by the presence of lactate in the external media. Furthermore, incubation with weak acids did not affect the rate of glycolysis in the morula. These data suggest that, by the generation of a transporting epithelium at compaction, the embryo develops the ability to regulate pHi against an acid load.     

Gastroduodenal resistance and neural mechanisms involved in saline flow decrease elicited by acute blood volume expansion in anesthetized rats

We have previously demonstrated that blood volume (BV) expansion decreases saline flow through the gastroduodenal (GD) segment in anesthetized rats (Xavier-Neto J, dos Santos AA & Rola FH (1990) Gut, 31: 1006-1010). The present study attempts to identify the site(s) of resistance and neural mechanisms involved in this phenomenon. Male Wistar rats (N = 97, 200-300 g) were surgically manipulated to create four gut circuits: GD, gastric, pyloric and duodenal. These circuits were perfused under barostatically controlled pressure (4 cmH2O). Steady-state changes in flow were taken to reflect modifications in circuit resistances during three periods of time: normovolemic control (20 min), expansion (10-15 min), and expanded (30 min). Perfusion flow rates did not change in normovolemic control animals over a period of 60 min. BV expansion (Ringer bicarbonate, 1 ml/min up to 5% body weight) significantly (P < 0.05) reduced perfusion flow in the GD (10.3 +/- 0.5 to 7.6 +/- 0.6 ml/min), pyloric (9.0 +/- 0.6 to 5.6 +/- 1.2 ml/min) and duodenal (10.8 +/- 0.4 to 9.0 +/- 0.6 ml/min) circuits, but not in the gastric circuit (11.9 +/- 0.4 to 10.4 +/- 0.6 ml/min). Prazosin (1 mg/kg) and yohimbine (3 mg/kg) prevented the expansion effect on the duodenal but not on the pyloric circuit. Bilateral cervical vagotomy prevented the expansion effect on the pylorus during the expansion but not during the expanded period and had no effect on the duodenum. Atropine (0.5 mg/kg), hexamethonium (10 mg/kg) and propranolol (2 mg/kg) were ineffective on both circuits. These results indicate that 1) BV expansion increases the GD resistance to liquid flow, 2) pylorus and duodenum are important sites of resistance, and, 3) yohimbine and prazosin prevented the increase in duodenal resistance and vagotomy prevented it partially in the pylorus.     

Transient respiratory augmentation elicited by acute head-down tilt in the anesthetized cat

Acute head-down tilt (AHDT, -30 degrees) in humans induces a transient ventilatory augmentation for 1-2 min accompanied by a high venous return. However, the mechanisms underlying this respiratory response remain obscure because of limitations of experiments carried out in human subjects. The present study was undertaken to determine whether AHDT-induced respiratory augmentation exists in the anesthetized, paralyzed, and ventilated cat and, if so, whether this response depends on 1) the cerebellum, 2) the carotid sinus (CS) and/or vagal afferents, and 3) elevation of central venous return. The integrated phrenic neurogram, arterial blood pressure, central venous pressure (CVP), and end-tidal PCO2 were recorded before, during, and after AHDT. The results showed that AHDT produced a transient ( approximately 2 min) enhancement of minute phrenic activity (approximately 30%) primarily via an increase in peak integrated phrenic neurogram amplitude associated with a remarkable elevation of CVP (approximately 3 min). Cerebellectomy, CS denervation, bilateral vagotomy, or clamping CVP did not affect the presence of the AHDT-induced minute phrenic activity response. These findings demonstrate that the anesthetized cat is a suitable model for investigating the mechanisms involved in AHDT-induced respiratory augmentation. Preliminary studies suggest that this response does not require the cerebellum, CS/vagal afferents, or an associated rise in central venous return.     

Effects of a subconvulsant dose of kainic acid on afterdischarges elicited by cortical stimulation in rats

Trends in medical education include those occurring in medical practice, related with its contents, and in the educational sciences, related with methods and technics that could be employed. Trends in medical practice are related to epidemiologic, demographic and economic transitions, with the overwhelming influence of medical technology, specially molecular biology, the increasing social regulation, evidence based medicine and transdisciplinary contributions. In the field of pedagogy, trends include the acceptance of the strategic value of medical education, the importance of quality-and not only of covering, the attention to educational necessities, the recognition of the adulthood of most of the learners, the importance of its individual differences and the application of new educational technics.     

Comparison of behaviors elicited by electrical brain stimulation in dorsal brain stem and hypothalamus of rats.

Investigated 4 brain-stimulation phenomena elicited from both dorsal brain stem and hypothalamic sites, using a total of 20 male albino Holtzman Sprague-Dawley rats. Results show that (a) intracranial self-stimulation rate-intensity functions for dorsal brain stem and hypothalamic sites yielded very high (over 1,000 responses/15 min) to moderate (201-500 responses/15 min) response rates; (b) dextroamphetamine produced higher response rates than either levoamphetamine or saline at both dorsal brain stem and hypothalamic sites, indicating that noradrenergic dorsal brain stem fibers (or cell bodies) support intracranial self-stimulation; (c) dorsal brain stem and hypothalamic self-stimulation sites reliably produced escape behavior; (d) simultaneous stimulation of dorsal brain stem and hypothalamic sites at subthreshold intensities interacted to produce suprathreshold response rates. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posterior hypothalamic stimulation of anesthetized normothermic and hypothermic rats evokes shivering thermogenesis

Third-party insurers typically pay at least 50% more for cesarean sections than for vaginal deliveries, suggesting that a reduced national cesarean-section rate could save payers more than $1 billion annually. This paper discusses the payment implications of a cost-effectiveness study, based on the experience within one health maintenance organization, in which cesarean-section rates were unrelated either to direct costs or to perinatal outcomes. Given these results, insurers should consider paying a flat fee for obstetric services unless differing risk levels or risk-adjusted outcomes justify different amounts.     

Retention of cerebrovascular dilation after cortical spreading depression in anesthetized rabbits

BACKGROUND AND PURPOSE: We examined responses of rabbit pial arterioles to three different stimuli before and after induction of cortical spreading depression. METHODS: In urethane-anesthetized rabbits equipped with a closed cranial window, we measured pial arteriolar diameter during baseline conditions, topical application of calcitonin gene-related peptide (CGRP), topical application of acetylcholine, and inhalation of 10% CO2 in air (arterial hypercapnia) before cortical spreading depression and 30, 60, and 120 minutes after cortical spreading depression. Cortical spreading depression was induced by localized application of a 5% KCl solution anterior to the arteriole being measured. RESULTS: Average baseline diameter was approximately 90 microns. During cortical spreading depression, arteriolar diameter increased to a peak value that was 50 +/- 4% above baseline (n = 32). Before cortical spreading depression, arteriolar diameter changed 47 +/- 7% (n = 9) during hypercapnia, 17 +/- 3% (n = 4) during 10(-9) mol/L CGRP, 42 +/- 10% (n = 7) during 10(-7) mol/L CGRP, 29 +/- 6% (n = 4) during 10(-6) mol/L acetylcholine, and 61 +/- 13% (n = 6) during 10(-4) mol/L acetylcholine. Arteriolar responsiveness to any of these stimuli was not changed significantly by prior cortical spreading depression. CONCLUSIONS: Dilator capacity of pial arterioles is still intact in urethane-anesthetized rabbits after cortical spreading depression.     

Nonlinear analysis of visual evoked potentials elicited by color stimulation

The relationship between chromatically modulated stimuli and visual evoked potentials (VEPs) was considered. VEPs of normal subjects elicited by chromatically modulated stimuli were measured under several color adaptations, and their binary kernels were estimated. Up to the second-order, binary kernels obtained from VEPs were so characteristic that the VEP-chromatic modulation system showed second-order nonlinearity. First-order binary kernels depended on the color of the stimulus and adaptation, whereas second-order kernels showed almost no difference. This result indicates that the waveforms of first-order binary kernels reflect perceived color (hue). This supports the suggestion that kernels of VEPs include color responses, and could be used as a probe with which to examine the color visual system.     

Influence of the experimenter on pupillary dilation to sexually provocative pictures.

2 Es with markedly different personality characteristics and styles of interacting with Ss tested male undergraduates (Ns = 22 and 25) for pupillary dilation to pictures of nude and partially clothed women, as well as to pictures of men, and to control pictures. The Ss of E1, an aloof and businesslike graduate student, dilated equally to male and female pictures. The Ss of E2, a casual outgoing undergraduate, dilated more to pictures of women than to those of men. These results indicate that pupillary dilation to sexually provocative stimuli reflect S's relationship to the E and his view concerning permissible emotional responses to the stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of stimulation parameters on behavior elicited by stimulation of the hypothalamic defense area.

Elicited agonistic behavior by stimulating the ventromedial hypothalamus of 22 domestic cats. 12 different behavioral components were rated separately. Behavioral alerting, mydriasis, retraction of ears, piloerection, hissing, and protrusion of claws were the most characteristic components. The parameters of the stimulus were shown to be important determinants of the nature of the behavior. Results suggest that either discrete central neural circuits for the different components of agonistic behavior are diffusively organized within the ventromedial hypothalamus, or the components result from a general activation of neurons subserving discrete fixed-action patterns, the resultant behavior being determined by different factors, such as the intensity of the activation. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional and anatomical fiber analysis of the posterior commissure (PC) in the cat: evidence for PC fibers of which stimulation elicits non-oculosympathetic pupillary dilation

Pupillary responses were studied by electrical stimulation of the posterior commissure (PC) and the nuclei of origin and termination of PC fibers in the cat. Prior to stimulation experiments, cervical sympathectomy was carried out to study the pupillary responses not mediated by the ocular sympathetic nerve. Pupillary responses were recorded by using an infrared pupillo-analyzing system. The stimulus consisted of a 5 s train of cathodal square wave (0.5 ms duration, 50 Hz) pulses. Stimulation of the PC evoked a pupillary response complex (PRC), which began with a rapid pupillary constriction after the latency of 210-317 ms. The threshold of constriction was 10 or 20 microA. Constriction reached its peak shortly after the onset of the stimulus, then the pupil gradually re-dilated (pupillary escape, PE) even though the stimulus was still lasting. The pupil gradually returned, after stimulus termination, to the size before stimulation in the cases with the pupil area before stimulation larger than 20 mm2. On the other hand, in the cases with smaller pupil area before stimulation (< 20 mm2), rapid constriction and PE were followed, after stimulus termination, by a large dilation (after-dilation, AD). The thresholds of PE and AD were 20 or 40 microA. Pupillary constriction was evoked with a large range of stimulus frequency (1-100 Hz). To evoke PE and AD, stimulus frequencies of 10 and 50 Hz were required respectively, and lower frequencies were ineffective. The peak latency of AD increased in proportion to the increase in stimulus frequency and intensity. Following horseradish peroxidase (dissolved in 5% alkyl-phenol ethylene oxide) injection into the pretectal region where fibers from the PC fan out, retrogradely labeled neurons occurred in many subthalamic, pretectal and midbrain nuclei on the other side. They were classified into three groups in terms of the pupillary response evoked by electrical stimulation; the pupillo-constrictory nuclei (PCNs) of which stimulation evoked constriction with the threshold of 20 microA, the pupillo-dilatory nuclei (PDNs) of which stimulation evoked dilation with the threshold of 20 or 10 microA, and other nuclei with higher thresholds of constriction or dilation. The PDNs were further, classified into two groups (Type 1 and Type 2 PDNs) according to the relationship between stimulus intensity and the peak latency of dilation.(ABSTRACT TRUNCATED AT 400 WORDS)     

The change of vagal activity evoked by spinal cord thermal stimulation in anesthetized rabbits

Vagal activity decreased significantly during spinal cord warming and increased significantly during spinal cord cooling in anesthetized, immobilized rabbits. The results provide the first direct proff of changes in parsympathetic activity during spinal thermal stimulation.     

Cardiovascular responses to gastric hypo-osmolar stimulation in anesthetized dogs

We compared the cardiovascular response to the gastric infusion of distilled water (DI) with that to the gastric infusion of 0.9% saline (SI) and gastric ballooning with 37 degrees C water (BA) through a gastric fistula in splenectomized mongrel dogs (n = 7). DI, and SI amounting to 5% of body wt and the same volume of water were infused in approximately 20 s through the tube and responses in mean arterial pressure (MAP), CVP, heart rate (HR), and intra-esophageal pressure (EP) were monitored continuously. After DI, SI, and BA, the measured variables showed significant increases and attained maximal increases at about 2 min after the treatments. After DI, the maximum elevation in MAP was 21.3 +/- 1.9 mmHg and 2 times higher than in SI and BA. The corresponding value in CVP was 5.0 +/- 0.3 mmHg and 2-3 times higher than with SI and BA, and HR increased by 26.1 +/- 3.0 beats/min showing 3 to 6 times larger increases compared with SI and BA. These gastro-cardiovascular reflexes were abolished after subdiaphragmatic truncal vagotomy. These findings suggest that both the mechanical and osmotic stimuli to the stomach induce cardiovascular reflexes and that the vagus is involved in the reflex.     

Cerebral extracellular lactate concentration and blood flow during chemical stimulation of the nucleus tractus solitarii in anesthetized rats

The extracellular lactate concentration and blood flow in the cerebral cortex of urethane-anesthetized, paralyzed and artificially ventilated rats were monitored continuously and simultaneously using an enzyme electrode and a laser Doppler flowmeter (LDF), respectively, during chemical stimulation of the nucleus tractus solitarii (NTS) by microinjection of L-glutamate (1.7 nmol 50 nl). Chemical stimulation of the NTS significantly decreased the arterial blood pressure (ABP) from 85 +/- 17 to 68 +/- 14 mmHg, heart rate from 418 +/- 13 to 402 +/- 19 beats x min(-1) and cerebral blood flow (CBF) by 17.9 +/- 6.2% (P < 0.001). However, chemical stimulation of the NTS significantly increased the lactate concentration by 58.9 +/- 17.3 microM (P < 0.001). Barostat maneuver, which held systemic ABP constant during chemical stimulation of the NTS attenuated the responses in CBF and lactate concentration by 30 and 27%, respectively. The onset of the increase in lactate concentration was delayed about 19 s after that of the CBF decrease. Circulatory lactate produced no significant change in the cerebral extracellular lactate concentration. These results indicate that chemical stimulation of the NTS induces an increase in extracellular lactate concentration in the cerebral cortex through a decrease in CBF via cerebral vasoconstriction.     

Electroclinical manifestations elicited by intracerebral electric stimulation "shocks" in temporal lobe epilepsy

In patients with severe drug-resistant partial epilepsy, undergoing Stereo-EEG investigations, spatial definition of the "epileptogenic area" is mainly based on spontaneous seizures recordings, but also on seizures induced by intracerebral electrical stimulation (ES). Only "trains" ES (TES, 50 pps) are currently used with this aim; "shocks" ES (SES, 1 pps) are principally applied to localize motor pathways. We have shown, during a prospective study concerning 10 temporal lobe epileptic patients, that SES could frequently induce seizures, especially when stimulation is applied in the anterior part of the Ammon's horn. Even if its efficacy seems lower than by TES, this kind of stimulation, in the majority of the cases, does reproduce isolated ictal subjective symptomatology, allowing the visualization of the progressive organisation of ictal electrical discharges, and avoids "unexpected" ("false positive"?) clinical responses.