Recovery pattern of motor reflex after a single bout of neuromuscular electrical stimulation session.

We aimed at determining the recovery pattern of neural properties of soleus muscle after a single bout of neuromuscular electrical stimulation (NMES) session. Thirteen subjects performed an NMES exercise (75 Hz, 40 contractions, 6.25 s per contraction). Maximal voluntary contraction (MVC), H-reflex at rest and during voluntary contraction fixed at 60% of MVC (respectively, H(max) and H(sup) ) and volitional (V) wave were measured before and during the recovery period following this exercise [i.e., immediately after, 2 h (H2), 2 days (D2) and 7 days (D7)]. MVC exhibited an immediate and a delayed declines at 2 days (respectively, -29.8±4.6%, P<0.001; -13.0±3.4%, P<0.05). Likewise, V/M(sup) was decreased immediately and 2 days after NMES session (respectively, -43.3±11.6%, P<0.05; 35.3±6.6%, P<0.05). The delayed decrements in MVC and V-wave occurred concomitantly with muscle soreness peak (P<0.001). It could be concluded that motor command alterations after an NMES resistance session contributed to the immediate and also to the delayed decreases in MVC without affecting resting and active H-reflex excitability. These results suggested that spinal circuitry function of larger motoneurons was inhibited by NMES (as indicated by the depressed V-wave responses) contrary to the smaller one (indicated by the unchanged H-reflex responses).

[Pulmonary function testing of 156 children exposed to automobile pollution in the municipality of Cotonou]. / Evaluation Du DEM(25) Chez 156 Enfants Exposes A La Pollution Automobile Dans La Municipalite De Cotonou.

AIMS: To evaluate the risk of disruption of distal airways in children exposed to pollutants automobiles. MATERIAL AND METHODS: Study included 156 children selected assigned in groups "Most Exposed" and "Less Exposed" separated respectively 15 meters and 150 meters of road traffic. Children in both groups were subjected to lung function tests before and after an exercise test that was to perform a series of flexion / extension of the knees to the fatigue. FEV and MEF(25) were parameters selected. RESULTS: Change in FEV post exercise of each group is below 5%. The group "Less Exposed" presented a mean value of MEF(25) before exercise similar to that recorded after exercise. Within the group "Most Exposed", the mean value of MEF(25) post exercise is significantly lower than that observed at rest of 8.65%. CONCLUSION: The fact of living permanently near the traffic, poses serious risks of disruption of the distal airways.

Participants' sports characteristics related to heavy episodic drinking among French students.

BACKGROUND: The relationships between involvement in sports and alcohol consumption appear to be complex in the alcohol literature. In this study we aimed to examine this link among French students, taking into account their sports characteristics. We also examined variations in alcohol use among sport sciences students between 2002 and 2006, and the difference in alcohol use and heavy episodic drinking among sport sciences, law and pharmacy students. DESIGN: repeated survey; cross-sectional study; SETTING: self-questionnaire survey; PARTICIPANTS: French (south-east France) sport sciences (n=693), law (n=325) and pharmacy (n=338) students (females=58%). RESULTS: In 2002, 38% of the male sport sciences students reported repeated heavy episodic drinking, and this proportion has risen to 48% in 2006 (p<0.05). When compared to law and pharmacy students, female and male sport sciences students were less likely to report repeated heavy episodic drinking (p<0.05). Engaging in physical activity (whether or not it takes place within an institution) and practising martial art were negatively related to heavy episodic drinking (p<0.05). Other factors related to heavy episodic drinking were gender-specific: among males, practising sport in a formal context, team sports, and competitive participation at a departmental or regional level represented risk factors (p<0.05), while practising an individual sport was a protective factor among females (p<0.05). CONCLUSION: This study corroborated the importance to take into account the context of practice and the type of sport practised to examine the link between sport participation and alcohol consumption. The normative context of peer socialization among competitive and team sports participants seemed to play a role in alcohol use. Further studies are needed to confirm the role of this putative factor.

EMG threshold determination in eight lower limb muscles during cycling exercise: a pilot study.

The first aim of this study was to verify the occurrence of the EMG threshold (EMG (Th)) in each of eight lower limb muscles (vastus lateralis [VL], vatus medialis [VM], rectus femoris [RF], semimembranosus [SM], biceps femoris [BF], gastrocnemius lateralis [GL] and medialis [GM], and tibialis anterior [TA]) during incremental cycling exercise. The second aim was to investigate the test-retest reproducibility of the EMG (Th) occurrence. Six sedentary male subjects (27 +/- 1 years) performed the same incremental cycling test until exhausted, (workload increments of 25 W/min starting at 100 W) twice. During the tests, the EMG Root Mean Square (RMS) response was studied in the aforementioned muscles. The EMG (Th) was detected mathematically from the RMS vs. workload relationship. All the subjects showed an EMG (Th) in the VL muscle, and the response was reliable in both tests (246 +/- 33 W and 254 +/- 33 W for the first and second test, respectively; coefficient of variation: 9.6 %, standard error of measurement: 28.9). However, few of them showed an EMG (Th) in the other muscles, especially in RF, SM or GM. When present, the EMG (Th) occurred at 75 - 80 % of the peak power output obtained during the tests. Our results suggest that EMG (Th) determination can be used as a reliable method for studying neuromuscular adjustments in the VL of untrained individuals, but not in other lower limb muscles.

Chronic electrostimulation after nerve repair by self-anastomosis: effects on the size, the mechanical, histochemical and biochemical muscle properties.

This study tests the effects of chronic electrostimulation on denervated/reinnervated skeletal muscle in producing an optimal restoration of size and mechanical and histochemical properties. We compared tibialis anterior muscles in four groups of rats: in unoperated control (C) and 10 weeks following nerve lesion with suture (LS) in the absence of electrostimulation and in the presence of muscle stimulation with either a monophasic rectangular current (LSEm) or a biphasic modulated current (LSEb). The main results were (1) muscle atrophy was reduced in LSEm (-26%) while it was absent in LSEb groups (-8%); (2) the peak twitch amplitude decreased in LS and LSEm but not in LSEb groups, whereas the contraction time was shorter; (3) muscle reinnervation was associated with the emergence of type IIC fibers and proportions of types I, IIA and IIB fibers recovered in the superficial portion of LSEb muscles; (4) the ratio of oxidative to glycolytic activities decreased in the three groups with nerve injury and repair; however, this decrease was more accentuated in LSEm groups. We conclude that muscle electrostimulation following denervation and reinnervation tends to restore size and functional and histochemical properties during reinnervation better than is seen in unstimulated muscle.

[Metabolic stability and physiological adaptation of muscle under conditions of exercise]. / Métabosensibilité musculaire et adaptations physiologiques au cours de l'exercice.

The first role played by group III (thin myelinated) and group IV (unmyelinated) afferent fibres from skeletal muscle is to transmit nociceptive information from muscle to the central nervous system. The second role of these free endings located in the interstitium of the muscle is to induce cardiovascular and respiratory adjustments during muscular exercise. These respiratory and circulatory responses during muscular exercise may be reflexly induced via muscular afferents. Indeed, static contraction of hindlimb muscles in anaesthetised mammals has been shown to reflexly increase the ventilatory function, the myocardial contractility and heart rate. The mechanical muscle deformation and the accumulation of metabolites in its intersitium are the cause of raised activity in small nerve fibres which in turn induces the physiological responses. It is also admitted that the central locomotor areas on the medullary and spinal neuronal pools control ventilatory and cardiovascular function during exercise. This mechanism is called "central command". Furthermore, adjustments of the locomotor activity during exercise is mediated by the thinly myelinated and unmyelinated fibres with endings in the working muscle. These fibres, also called "metaboreceptor" may be responsible of the coupling between the ventilation and the locomotion. Thickly myelinated muscle afferents (i.e. group I and II) appear to play little role in causing the reflex autonomic responses to contraction.

Occurrence of electromyographic and ventilatory thresholds in professional road cyclists.

The temporal relationship between the electromyographic (EMG) and ventilatory thresholds was investigated during incremental exercise performed by eight professional road cyclists. The exercise, performed on a cycloergometer, started at 100 W with successive increments of 26 Wx min(-1) until exhaustion. Gas exchange and the root mean square value of EMG (RMS) from eight lower limb muscles were examined throughout the exercise period. Professional cyclists achieved a maximal oxygen consumption, i.e. VO(2max), of 5.4 (0.5) l x min(-1) [74.6 (2.5) ml x min(-1) x kg(-1), range: 67.8-82.4 ml x min(-1) x kg(-1)] and a maximum power ( W(max)) of 475 (30) W (range: 438-516 W). Our results showed at least the occurrence of a first EMG threshold (EMG(Th1)) in 50% (gastrocnemius lateralis) of the subjects and a second EMG threshold (EMG(Th2)) in 63% (gastrocnemius medialis). EMG(Th1) occurred significantly before the first ventilatory threshold (VT(1)), i.e. at 52 (2)% and 62 (9)% of W(max), respectively. Inversely, no significant difference was observed between the occurrence of EMG(Th2) and the second ventilatory threshold (VT(2)), i.e. at 86 (1)% and 89 (7)% of W(max), respectively. These results suggest that the use of EMG may be a useful non-invasive method for detecting the second ventilatory threshold in most of the muscles involved in cycling exercise.

A dynamic pattern analysis of coordination between breathing and rhythmic arm movements in humans.

We investigated the behavioral dynamics of human breathing-wrist movement coordination in a 1:1 frequency locking task. A pronation-supination wrist movement and a short trial duration were chosen to limit both mechanical and metabolic constraints on the respiratory system. Subjects voluntarily controlled their breathing rhythm to follow the metronome. We found that pronation-expiration and pronation-inspiration patterns coexisted as the (sole) stable fixed-point attractors of the coordination system. The pronation-expiration pattern was more stable than the pronation-inspiration pattern. Depending on the oscillation frequency, this differential stability gave rise to both absolute and relative coordination. These results show that simple behavioral laws of coordination encapsulate neural coupling dynamics evidenced from experimental research in human beings and animals. They challenge the classical view that such a coupling is not present for all imposed movement frequencies. Rather, relative coordination emerges as a result of the modification of coupling strength with frequency. These results can be accommodated by the asymmetric version of the HKB model of coordination dynamics. Thus, our data suggest that the principles and models of coordination dynamics may be taken as a reference to study the coupling of the motor and physiological subsystems involved in breathing-movement coordination.

The COX inhibitors indomethacin and meloxicam exhibit anti-emetic activity against cisplatin-induced emesis in piglets.

We analysed the effects of four cyclooxygenases (COX) inhibitors on cisplatin-induced emesis in piglets. Ninety-five animals receiving cisplatin (5.5 mg kg(-1), i.v.) were observed for 60 h. One hour prior to cisplatin, controls (n=29) were dosed with a saline solution while experimental animals received an i.v. or i.p. injection of one of the COX inhibitors. Additional injections of COX inhibitor were given at 15 and 39 h after cisplatin administration (or every 6h in one group receiving diclofenac). The latencies to the first emetic episode (EE) compared to controls (2.1+/-0.4 h) increased in groups receiving naproxen (4.66+/-0.94 h, n=9, 30 mg kg(-1)) and indomethacin (6.19+/-1.13 h, n=7, 10 mg kg(-1)) i.v. Indomethacin significantly decreased the incidence of both the acute (by 40%) and delayed (by 66%) phases of emesis. The total number of EE during the 60 h compared to controls (28.3+/-1.9 EE) was significantly reduced in piglets receiving indomethacin (14.9+/-3.2 EE, n=7) and meloxicam (17.6+/-3.6 EE, n=11, 0.3 mg kg(-1)). Four piglets receiving meloxicam (0.3 mg kg(-1), i.v.) did not vomit during the delayed phase. The anti-emetic activity of two COX inhibitors suggests that prostaglandins contribute to the activation of the emetic reflex in response to cisplatin.

Effects of chronic hypoxemia on the afferent nerve activities from skeletal muscle.

An acute reduction of the oxygen supply to contracting muscles not only affects their metabolism but also modifies their sensorimotor control through changes in afferent discharge of the group I and group III-IV nerve fibers, the latter playing a pivotal role in the protective mechanisms against muscle fatigue. The effects of chronic hypoxemia on the muscle sensitivity are totally unknown. In the present study, group I fibers (mechanosensory afferents) and group III-IV fibers (mechanosensory and chemosensory afferents) from the anterior tibial muscle were recorded in normoxemic and chronic hypoxemic rats. Hypoxemic rats breathed for 45 d a gas mixture containing 9.5 to 10% O(2) in N(2). The data were compared with those obtained in normoxemic animals of the same age. To activate the different muscle afferents, we used different test agents, including electrically induced fatigue (EIF), KCl, lactic acid injections, as well as tendon vibrations. The conduction velocity of all nerve fibers was significantly (p < 0.01) higher in hypoxemic rats than in the normoxemic group. Chronic hypoxemia significantly depressed the response of the group III-IV muscle afferents to KCl injections and even abolished their response to lactic acid and EIF. However, the response to tendon vibrations of the group I afferents was similar in hypoxemic and normoxemic rats. These results suggest that chronic hypoxemia markedly alters the chemosensitivity of the group III-IV muscle afferents, which may explain the higher fatigability of hypoxemic subjects.

A nonpeptide vasopressin V(1a) receptor antagonist, SR 49059, does not prevent cisplatin-induced emesis in piglets.

We determined the pharmacological and the antiemetic properties of SR 49059, a selective nonpeptide V(1a) receptor antagonist, on cisplatin-induced emesis in the piglet. Firstly, we clearly demonstrate that SR 49059 is a potent V(1a) receptor antagonist in vitro and in vivo in the piglet. In binding studies, [3H]-SR 49059 exhibited high affinity for V(1a) receptors in piglet liver membranes (K(d) of 0.76 +/- 0.12 nM and B(max) of 138 +/- 22 fmol/mg prot.). In vivo, in decerebrate piglets, SR 49059 (1 mg/kg iv) antagonized AVP (500 ng/kg iv)-induced hypertension for at least 150 min and also blocked, for at least 270 min at 3 mg/kg iv, the pressor responses to exogenous LVP. After single and repeated iv or icv administration, we studied the antiemetic properties of SR 49059 on cisplatin-induced emesis in piglets. Animals receiving an emetic dose of cisplatin (5.5 mg/kg, iv) were observed continuously for 60 h. Piglets acting as controls were iv administered with vehicle 15 min prior to cisplatin infusion (T0(-15min)), while experimental animals received a single iv administration of SR 49059 at the dose of 1 or 3 mg/kg. In additional piglets, we administered SR 49059 (3 mg/kg) every 12 h from T0(-15min) to T48(-15min) (cumulative dose, 15 mg/kg). Another set of animals - observed only during the acute phase - was administered with SR 49059 (10 mg/kg) every 3 h from T0(-15min) to T15(-15min) (cumulative dose, 60 mg/kg). Lastly, 10 piglets were given a bilateral icv injection of SR 49059 (500 microg and 1500 microg/side) 1 h prior to cisplatin infusion. In all groups treated with SR 49059, the latency of the first emetic episode and the incidence of vomiting during the acute, the delayed and the cumulative phases remained statistically similar to that observed in controls, suggesting that V(1a) receptors are not involved in the onset and completion of nausea and vomiting.

Combined effect of heat stress, dehydration and exercise on neuromuscular function in humans.

This study examined the combined effect of exercise induced hyperthermia and dehydration on neuromuscular function in human subjects. Six trained male runners ran for 40 min on a treadmill at 65% of their maximal aerobic velocity while wearing a tracksuit covered with an impermeable jacket and pants to impair the evaporation of sweat. These stressful experimental running conditions led the runners to a physiological status close to exhaustion. On average, the 40 min run ended at a heart rate of 196 (SD 8) beats.min-1, a tympanic temperature of 40 (SD 0.3) degrees C and with a loss of body mass of 2 (SD 0.5)%. Pre- and post-running strength tests included measurements of maximal knee extension and flexion torques in both isometric and isokinetic (at 60 and 240 degrees.s-1) conditions. A 20 s endurance test at 240 degrees.s-1 was also performed. Surface electromyographic (EMG) activity was recorded from six knee extensor and flexor muscles during the entire protocol. The treadmill run led to clear decrements in maximal extension torque and EMG activity both in isometric and at the slowest isokinetic velocity (60 degrees.s-1). However, no differences in these parameters were observed at 240 degrees.s-1. Furthermore, the EMG patterns of the major knee extensor and flexor muscles remained remarkably stable during the treadmill run. These results demonstrate that the exercise-induced hyperthermia and dehydration in the present experiments had only minor effects on the neuromuscular performance. However, it is also suggested that high internal body temperature per se could limit the production of high force levels.

Tympanic temperature and heart rate changes in firefighters during treadmill runs performed with different fireproof jackets.

Six well-trained firefighters performed six treadmill runs at 70% of the velocity at VO2max (Maximal aerobic velocity MAV = 13.2+/-0.3 km h(-1)). A recovery time of 1 week was allowed between trials. The first session was performed by subjects wearing only shorts (i.e. no fire jacket, J0). A similar protocol was applied subsequently to test the physiological effects associated with the wearing of one of five different fire jackets: one leather (J1) and four textile-type jackets: VTN with membrane (J2), VTN without membrane (J3), Vidal with Kermel HTA (Haute Teneur en Aramide i.e. high density in Aramide) (J4); and Rolland with Kermel HTA (J5). All sessions were performed in a randomized order and in laboratory conditions. Exercise with the fireproof jackets resulted in higher tympanic temperature (Tty), heart rate (HR) and body mass loss (BML) changes compared to J0 (p<0.001). The magnitudes of these changes depended on the type of the jacket. Exercise in the leather jacket (J1) resulted in the highest Tty and HR, which differed significantly from values in all other conditions (p<0.001). The exercise-induced increases in Tty wearing jackets J3 and J5 were also significantly (p < 0.05) higher than those observed with jackets J2 and J4. In conclusion, textile jackets induced less HR and Tty stresses than the leather one. The magnitude of the physiological responses induced by textile jackets were correlated to jacket weight. J2 and J4 jackets were more effective in limiting hyperthermia and any potential detrimental effect on the exercise capacity.

Potential of substance P antagonists as antiemetics.

The introduction of serotonin 5-HT3 receptor antagonists into clinical practice allowed for a dramatic improvement in the management of nausea and vomiting. Despite this, postoperative and chemotherapy-induced emesis remains a significant, unresolved issue in many patients even when a combination of antiemetic drugs is used. Numerous neurotransmitters have been implicated in triggering emesis; however, the tachykinin substance P, by virtue of its localisation within both the gastrointestinal vagal afferent nerve fibres and brainstem emetic circuitry, and its ability to induce vomiting when administered intravenously, is thought to play a key role in emetic responses. Because substance P is the most likely endogenous ligand for the neurokinin-1 (NK1) receptor, the development of nonpeptide NK1 receptor antagonists led scientists to evaluate these compounds as antiemetics. The five NK1 receptor inhibitors that have been studied initially in humans are: vofopitant (GR-205171), CP-122721, ezlopitant (CJ-11974), MK-869 (L-754030) and its prodrug L-758298. Except for monotherapy in acute cisplatin-induced emesis, this new class of drugs has proven to be highly effective in the control of both chemotherapy-induced nausea and vomiting, and postoperative nausea and vomiting. No major adverse event was reported in the preliminary trials. Further investigation is mandatory in order to assess the optimal treatment regimen and to make sure the wide spectrum activity of the NK1 receptor inhibitors does not cause significant adverse effects in the context of the treatment of nausea and vomiting.

Characterization of lipopolysaccharide-induced emesis in conscious piglets: effects of cervical vagotomy, cyclooxygenase inhibitors and a 5-HT(3) receptor antagonist.

The emetic response to intraperitoneal (i.p., 0.5, 2, 8 mg kg(-1)) and intravenous (i.v., 200 microg kg(-1)) administration of bacterial lipopolysaccharides (LPS) was characterized in conscious piglets observed for 4 h. The latencies and the incidence of the emetic response to LPS (i.p.) decreased and increased, respectively, in a dose-dependent manner. In 14 additional piglets, a bilateral vagotomy performed 4 h prior to LPS administration abolished the vomiting induced by i.p. LPS (2 mg kg(-1)), and decreased its incidence by 77% in the i.v. injected animals. Sham-operated animals (n=6) exhibited a similar emetic pattern to the controls injected intraperitoneally with LPS (2 mg kg(-1)). In 7 piglets, the administration of granisetron, a 5-HT(3) receptor antagonist (i.v., 2 mg kg(-1)), 30 min prior to the i.p. LPS injection (2 mg kg(-1)) failed to reduce significantly the emetic activity; whereas, in 6 animals, a combination of meloxicam (0.3 mg kg(-1)) and indomethacin (5 mg kg(-1)), two cyclooxygenase (COX) inhibitors, administered per os 1.5 h prior to the i.p. LPS (2 mg kg(-1)) abolished the emetic response to endotoxins. The present results show that the activation of the medullary "vomiting centre" in response to i.p. administration of LPS is mediated via vagal afferents and is likely to involve prostaglandins.

Activity of respiratory laryngeal motoneurons during fictive coughing and swallowing.

Membrane potential changes and discharges from 28 laryngeal motoneurons were recorded intracellularly in the caudal nucleus ambiguus of decerebrate, paralyzed and ventilated cats. Electrical activities were recorded from 17 expiratory laryngeal motoneurons (ELMs) with maximal depolarizing membrane potential in early expiration, and from 11 inspiratory laryngeal motoneurons (ILMs) with maximal depolarizing membrane potential in inspiration. Activities during breathing were compared with those observed during fictive coughing and swallowing evoked by electrical stimulation of the superior laryngeal nerves. These non-respiratory behaviors were evidenced in paralyzed animals by characteristic discharge patterns of the phrenic, abdominal nerves and pharyngeal branch of the vagus nerve. We recorded the activity of 11 ELMs and 5 ILMs during coughing in which ELMs, but not ILMs, exhibited increased membrane depolarization and discharge frequencies. Membrane depolarization and discharge frequencies of all ELMs were also significantly increased during swallowing. In addition, membrane depolarization of most ELMs (15/17) was preceded by a short-lasting hyperpolarization due to chloride-dependent inhibitory mechanisms occurring at the onset of swallowing. Out of 10 ILMs tested during swallowing, 7 exhibited membrane depolarization, preceded in 5 cases by a short-lasting hyperpolarization. Discharge frequencies of ILMs were significantly reduced during swallowing. The same pattern of phasic activities of ILMs and ELMs was observed during coughing and breathing, suggesting the involvement of similar excitatory pathways in both behaviors. These results imply that the duration of activation and the discharge frequency of neurons of the central generator for breathing that drive laryngeal motoneurons are enhanced during coughing. During swallowing, in addition to central excitatory mechanisms, laryngeal motoneurons are subjected to an initial inhibition of unknown origin. This inhibition probably contributes to the temporal organization of the swallowing motor sequence.

Potent inhibition of both the acute and delayed emetic responses to cisplatin in piglets treated with GR205171, a novel highly selective tachykinin NK1 receptor antagonist.

The effects of GR205171, a selective tachykinin NK1 receptor antagonist, were investigated on both the acute and delayed phases of cisplatin-induced nausea-like behaviour and vomiting in the conscious piglet. Animals receiving cisplatin (5.5 mg kg(-1), i.v.) were observed for 60 h. Fifteen min prior to cisplatin infusion (T0(-15 min)), eight piglets acting as controls received an intravenous injection of saline solution (1 ml kg(-1)), whereas experimental animals received a single i.v. administration of GR205171 (1 ml kg(-1)) at a dose of 0.01 (n=8), 0.03 (n=8), 0.1 (n = 8), 0.3 (n = 16) or 1.0 (n = 13) mg kg(-1). In eight additional piglets, GR205171 (1 mg kg(-1)) was administered 15 min before the onset of the delayed phase (T16(-15 min)). A further five piglets received GR205171 (1 mg kg(-1)) every 6 h throughout the experiment. The latencies of the first emetic episode (EE) and nausea-like behavioural episode (NE) increased in all experimental groups treated at T0(-15 min), and the total number of both EE and NE during the 60 h was reduced in a dose-dependent manner. In piglets treated at T0(-15 min) with GR205171 1 mg kg(-1), eight out of 13 (62%) did not vomit throughout the experiment. Animals treated with GR205171 (1 mg kg(-1)) at T16(-15 min) exhibited an acute response to cisplatin but did not vomit during the delayed phase. The greatest inhibition of both nausea-like behaviour and vomiting was observed in piglets receiving multiple injections of GR205171. These results demonstrate the long-lasting anti-emetic effects of GR205171, and confirm the key role of substance P within the emetic reflex.

Differential brainstem Fos-like immunoreactivity after laryngeal-induced coughing and its reduction by codeine.

We used the expression of the immediate-early gene c-fos, a marker of neuronal activation, to localize brainstem neuronal populations functionally related to fictive cough (FC). In decerebrate, paralyzed, and ventilated cats, the level of Fos-like immunoreactivity (FLI) was examined in five groups of animals: (1) controls, sham-operated unstimulated animals; (2) coughing cats, including both animals in which FC was elicited by unilateral electrical stimulation of the superior laryngeal nerve (SLN) and (3) those in which FC was elicited by bilateral SLN stimulation; (4) stimulated-treated cats, in which bilateral SLN stimulation was applied after selective blockade of FC by codeine; and (5) codeine controls, sham-operated unstimulated cats subjected to administration of codeine. Fifteen brainstem structures were compared for numbers of labeled cells. Because codeine selectively blocks FC, brainstem nuclei activated specifically during FC were identified as regions showing increased FLI after FC and significant reductions in FLI after FC suppression by codeine in stimulated-treated cats. In coughing animals, we observed a selective immunoreactivity in the interstitial and ventrolateral subdivisions of the nucleus of the tractus solitarius, the medial part of the lateral tegmental field, the internal division of the lateral reticular nucleus, the nucleus retroambiguus, the para-ambigual region, the retrofacial nucleus, and the medial parabrachial nucleus. FLI in all these nuclei was significantly reduced in stimulated-treated cats. Our results are consistent with the involvement of neurons overlapping the main brainstem respiratory-related regions as well as the lateral tegmental field and the lateral reticular nucleus in the neural processing of laryngeal-induced FC.

Repeated administration of the 5-HT3 receptor antagonist granisetron reduces the incidence of delayed cisplatin-induced emesis in the piglet.

We analyzed the effects of the 5-HT3 receptor antagonist granisetron on both acute and delayed phases of cisplatin-induced emesis in the conscious piglet. Animals that received a high dose of cisplatin (5.5 mg/kg i.v.) were observed continuously for 60 h. Seventeen piglets were treated with cisplatin only and acted as controls. In experimental animals, granisetron (administered before cisplatin) was administered either as a single initial injection (7 mg/kg), alone or in combination with dexamethasone (40 mg), or as multiple injections (1 mg/kg) given every 5 h during the first 30 h of the experiment (cumulative dose: 7 mg/kg). Two other groups of piglets were treated with dexamethasone (40 mg) alone or with multiple injections of ondansetron (7 injections at 3.5 mg/kg), respectively. The latency to the first emetic episode was significantly increased in all groups that received a 5-HT3 receptor antagonist, whatever the agent and the protocol of administration. Piglets treated solely with dexamethasone exhibited a latency similar to that of controls. The total number of emetic events during the 60 h was significantly reduced only in the group of piglets treated repeatedly with granisetron and in the group that received an initial dose (7 mg/kg) of granisetron in combination with dexamethasone. We observed that 3 out of 8 piglets treated repeatedly with granisetron did not vomit throughout the experiment. These results demonstrate that granisetron, when administered repeatedly, is efficacious against delayed emesis. They also suggest that serotonin may be involved in the production of the delayed phase of cisplatin-induced emesis.

Activity of dorsal respiratory group inspiratory neurons during laryngeal-induced fictive coughing and swallowing in decerebrate cats.

Membrane potential changes and/or discharges from 36 inspiratory neurons were recorded intracellularly in the dorsal respiratory group (DRG; i.e., the ventrolateral subdivision of the nucleus tractus solitarii) in decerebrate, paralyzed, and ventilated cats. Electrical activities were recorded from both somata (n = 10) and axons (n = 26). Activities during quiet breathing were compared with those observed during fictive coughing and swallowing evoked by repetitive electrical stimulation of afferent fibers of the superior laryngeal nerve (SLN). These nonrespiratory behaviors were evident in paralyzed animals as characteristic discharge patterns of the phrenic, abdominal, and hypoglossal nerves. Twenty-six neurons exhibiting antidromic action potentials in response to electrical stimuli applied to the cervical (C3-5) spinal cord were classified as inspiratory bulbospinal neurons (IBSNs). These neurons were considered as premotoneurons. The remaining 10 inspiratory neurons (I-NAA) were not antidromically activated by electrical stimuli applied to either cervical spinal cord or ipsilateral cervical vagus. These neurons are thought to be propriobulbar neurons. We recorded the activity of 31 DRG inspiratory neurons (24 IBSNs and 7 I-NAA) during coughing. All but one (a late-recruited IBSN) discharged a burst of action potentials during the coughing-related phrenic nerve activity. Typically, ramp-like membrane depolarization trajectories and discharge frequencies during coughing were similar to those observed during inspiration. We recorded the activity of 33 DRG inspiratory neurons (23 IBSNs and 10 I-NAA) during swallowing. Most (28/33) neurons were briefly activated, i.e., discharged a burst of action potentials during swallowing, but peak discharge frequency decreased compared with that measured during inspiration. The membrane potentials of nine somata exhibited a brief bell-shaped depolarization during swallowing, the amplitude of which was similar to that observed during inspiration. These results suggest that some inspiratory premotoneurons and propriobulbar neurons of the DRG might be involved in nonrespiratory motor activities, even if clearly antagonistic to breathing (e.g., swallowing). We postulate the existence in the medulla oblongata of adult mammals of neurons exhibiting a "functional flexibility".