Long-term administration of magnesium after acoustic trauma caused by gunshot noise in guinea pigs.

In a previous study we observed that a 7-day post-trauma magnesium treatment significantly reduced auditory threshold shifts measured 7 days after gunshot noise exposure. However this improvement was only temporary, suggesting that it could be potentially beneficial to prolong this treatment. The aim of the present study was to evaluate the efficacy of a long-term (1 month) magnesium treatment after an impulse noise trauma, in comparison with either a 7-day magnesium treatment, an administration of methylprednisolone (conventional treatment), or a placebo (NaCl). Guinea pigs were exposed to impulse noise (three blank gunshots, 170 dB SPL peak). They received one of the four treatments, 1 h after the noise exposure. Auditory function was explored by recording the auditory brainstem response (ABR) and measuring the distortion product otoacoustic emissions (DPOAE) over a 3-month recovery period after the gunshot exposure. The functional hearing study was supplemented by a histological analysis. The results showed that a 1-month treatment with magnesium was the most effective treatment in terms of hair cell preservation. The DPOAE confirmed this effectiveness. Methylprednisolone accelerated recovery but its final efficacy remained moderate. It is probable that magnesium acts on the later metabolic processes that occur after noise exposure. Multiple mechanisms could be involved: calcium antagonism, anti-ischaemic effect or NMDA channel blockage. Regardless of the specific mechanism, a 1-month treatment with magnesium clearly attenuates NIHL, and presents the advantage of being safe for use in humans.

Therapeutic efficacy of intra-cochlear administration of methylprednisolone after acoustic trauma caused by gunshot noise in guinea pigs.

The therapeutic efficacy of cochlear infusion of methylprednisolone (MP) after an impulse noise trauma (170dB SPL peak) was evaluated in guinea pigs. The compound action potential threshold shifts were measured over a 14 days recovery period after the gunshot exposure. For each animal, one of the cochlea was perfused directly into the scala tympani with MP during 7 days via a mini-osmotic pump, whereas the other cochlea was not pump-implanted. The functional study of hearing was supplemented by histological analysis. Forty eight hours after the trauma, significant differences between auditory threshold shifts in the implanted and non-implanted ears were observed for frequencies above 8kHz. At day 7, the difference was significant for only one frequency and no difference was observed after 14 days recovery. Cochleograms showed that the hair cell losses were significantly lower in the MP treated ears. This work indicates that direct infusion of MP into perilymphatic space accelerates hearing recovery, reduces hair cell losses after impulse noise trauma but does not limit permanent threshold shifts.

Spectrum of neural electrical activity in guinea pig cochlea: effects of anaesthesia regimen, body temperature and ambient noise.

Spectral analysis of electric noise recorded from the round window of the cochlea is thought to represent the summed spontaneous activity of the auditory nerve. It has been postulated that it could provide a possible tinnitus index. Because experimental conditions could change this neural activity, the effect of anaesthesia regimen, body temperature and ambient noise on the spectrum of spontaneous neural noise (SNN) were investigated in guinea pig cochlea. SNN was studied in awake guinea pigs and after anaesthesia with pentobarbital (P), xylazine/ketamine (XK) or xylazine/tiletamine-zolazepam (XTZ). Body temperature varied gradually from 33 to 41 degrees C under XK regimen. In awake animals, broadband noise was generated with intensity varying from 0 to 50 dB. The SNN consisted in a broad peak at approximately 900 Hz. With ambient broadband noise, it increased exponentially with the sound level with no shift in frequency. Soon after anaesthetic induction, the lowest frequencies were constantly decreased, and gradually the 900 Hz peak either increased moderately (P) or dropped steeply (XTZ) or remained unchanged (XK). Peak frequency increased linearly with body temperature whereas the amplitude reached a maximum at around 39.5 degrees C. In conclusion, these data indicate that experimental conditions such as anaesthesia regimen, body temperature and ambient noise modify the spontaneous neural outflow of the cochlea and must be taken into account when studying SNN.

Magnesium therapy in acoustic trauma.

Acoustic trauma is one of the major causes of hearing loss and tinnitus, particularly in industrial environments. Noise-induced hearing loss (NIHL) results in direct mechanical damage as well as in indirect metabolic processes. Metabolic disorders have multiple origins: ionic, ischemic, excitotoxic and production of cochlear free radicals causing cell death, due to necrosis or apoptosis. The efficacy of magnesium, administered either to prevent or to treat NIHL has been demonstrated in several studies in animals and in humans. Magnesium, which easily crosses the hematocochlear barrier, presents neuroprotective and vasodilatory effects, and thus, is able to limit the cochlear damage. Magnesium therapy is well documented because it is usually prescribed in other pathologies. Its side effects and contraindications are few and it is cheap. This article presents also some arguments that emphasize the interest of magnesium therapy in acoustic trauma.

Positive end expiratory pressure (PEEP) slightly modifies ventilatory response during incremental exercise.

To clarify the ventilatory effects of a 5-cm H2O positive end expiratory pressure (PEEP) in healthy men during incremental exercise in normoxic conditions, 22 subjects were subjected to a constant workload (0 W, 50 W, 100 W, 150 W and 200 W) on a cycle ergometer for periods of 8 min each, both with and without 5-cm H2O PEEP. Results show that PEEP increases inspiratory (TI) and expiratory (TE) duration and tidal volume (VT) and decreases breathing frequency (fB) at rest (p < 0.05). During exercise, TI is higher at 50 W and 100 W (p < 0.05), but not at 150 and 200 W. TE only increases at 50 W (p < 0.05). An increased VT (p < 0.05 at 50, 100 and 150 W) and a decreased fB (p < 0.05 throughout the experiment) were observed. However, mean inspiratory flow (VT/T1) and duty cycle (TI/TT) were unaffected by PEEP. In conclusion, this study shows that a 5-cm H2O PEEP slightly modifies the ventilatory parameters in healthy subjects during incremental exercise in normoxic conditions.

Sympathetic stimulation induced by hand cooling alters cold-induced vasodilatation in humans.

Hand cooling is a cold pressor test, which induces general sympathetic stimulation. This cooling procedure is often performed to investigate cold induced vasodilatation (CIVD) in one finger. To investigate the effects of this sympathetic stimulation on local CIVD, 12 subjects immersed either the right index finger (T1), right hand (T2) or left hand and right index finger (T3) for 30 min in water at 5 degrees C followed by 15-min recovery. Skin temperature and skin blood flow (Q(sk)) measured by laser Doppler flowmetry on the right index finger, as well as heart rate (f(c)) and mean arterial blood pressure (BP(a)), were continuously monitored during the three tests. Cutaneous vascular conductance was calculated as Q(sk)/(BP(a)). Concentrations of plasma noradrenaline (NA) and adrenaline (AD) were measured at different times during the tests. The results showed no cardiovascular change in T1, whereas f(c) and (BP(a)) increased significantly at the beginning of both T2 and T3. Similarly, sympathetic stimulation was reflected in the NA concentrations, which increased significantly (P < 0.01) during T2 and T3 after 5 min of immersion, and remained elevated until the recovery period. The AD concentration did not change during the three tests. During T2, the CIVD appeared later and slower in comparison with T1 [CIVD onset: 12.81 (SEM 2.30) min in T2 and 5.62 (SEM 0.33) min in T1]. During T3, the CIVD onset was not delayed compared to T1 [6.38 (SEM 0.67) min], but the rewarming was lower [+5.40 (SEM 0.86) degrees C in T3 and +9.10 (SEM 1.31) degrees C in T1]. These results showed that CIVD could be altered by sympathetic stimulation but it also appeared that the onset of CIVD could be influenced by local cooling, independently of the general sympathetic stimulation.

Cold induced vasodilatation and cardiovascular responses in humans during cold water immersion of various upper limb areas.

To study the physiological responses induced by immersing in cold water various areas of the upper limb, 20 subjects immersed either the index finger (T1), hand (T2) or forearm and hand (T3) for 30 min in 5 degrees C water followed by a 15-min recovery period. Skin temperature of the index finger, skin blood flow (Qsk) measured by laser Doppler flowmetry, as well as heart rate (HR) and mean arterial blood pressure (BPa) were all monitored during the test. Cutaneous vascular conductance (CVC) was calculated as Qak/BPa. Cold induced vasodilatation (CIVD) indices were calculated from index finger skin temperature and CVC time courses. The results showed that no differences in temperature, CVC or cardiovascular changes were observed between T2 and T3. During T1, CIVD appeared earlier compared to T2 and T3 [5.90 (SEM 0.32) min in T1 vs 7.95 (SEM 0.86) min in T2 and 9.26 (SEM 0.78) min in T3, P < 0.01]. The HR was unchanged in T1 whereas it increased significantly at the beginning of T2 and T3 [+13 (SEM 2) beats.min-1 in T2 and +15 (SEM 3) beats.min-1 in T3, P < 0.01] and then decreased at the end of the immersion [-12 (SEM 3) beats.min-1 in T2, and -15 (SEM 3) beats.min-1 in T3, P < 0.01]. Moreover, BPa increased at the beginning of T1 but was lower than in T2 and T3 [+9.3 (SEM 2.5) mmHg in T1, P < 0.05; +20.6 (SEM 2.6) mmHg and 26.5 (SEM 2.8) mmHg in T2 and T3, respectively, P < 0.01]. The rewarming during recovery was faster and higher in T1 compared to T2 and T3. These results showed that general and local physiological responses observed during an upper limb cold water test differed according to the area immersed. Index finger cooling led to earlier and faster CIVD without significant cardiovascular changes, whereas hand or forearm immersion led to a delayed and slower CIVD with a bradycardia at the end of the test.

Biometrical characteristics and physiological responses to a local cold exposure of the extremities.

The aim of this study was firstly to describe the physiological responses observed in 19 subjects during immersion of the arm up to the elbow in water at 5 degrees C (5 min) followed by a 10-min recovery and secondly, to correlate the observed physiological responses with biometrical characteristics of the subjects (maximal oxygen uptake, VO2max, percentage fat content of whole body, BF, and arm, forearm and hand skinfold thickness). The results showed that the time courses of changes in forearm and hand skin temperature were different compared to those of finger skin temperatures both during local cooling and during rewarming (P < 0.05). Cardiovascular responses (heart rate, systolic and diastolic blood pressures) and finger skin temperatures were not related to the biometrical characteristics of the subjects. However, at the end of the immersion, decreased hand skin temperature was correlated to VO2max (r = 0.45, P < or = 0.05) whereas decreased forearm skin temperature was correlated both to VO2max (r = 0.44, P < or = 0.05) and to skinfold thickness (r = -0.44, P < or = 0.05) but not to BF. During the beginning of the recovery period only, outside, inside forearm and hand skin temperatures were related to VO2max (r = 0.54, P < or = 0.05; r = 0.66, P < or = 0.01 and r = 0.45, P < or = 0.05, respectively) and all the skinfold thicknesses (r = -0.47 to -0.71, P < or = 0.05). It was concluded that the local skin temperature profiles differed according to the upper limb segment both during cooling and during early rewarming. Moreover, VO2max and upper limb skinfold thickness but not BF did influence the forearm and hand skin temperature changes during cooling and early rewarming but not the finger skin temperature changes and cardiovascular responses.