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Influence of systemic treatment with cyclooxygenase inhibitors on lipopolysaccharide-induced fever and circulating levels of cytokines and cortisol in guinea-pigs.

Peripheral inflammatory stimuli result in the modification of a number of vital brain-controlled functions including the thermoregulatory set-point (induction of fever) and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. We addressed the question of whether both of these components of the acute-phase response are induced by a common signal pathway. For this purpose we recorded body temperature (by remote radio-telemetry), HPA axis activity (circulating concentrations of cortisol by radio-immunoassay) and levels of the pro-inflammatory cytokines tumour necrosis factor and interleukin-6 (TNF, IL-6, using specific bioassays) in six groups of guinea-pigs. The animals received intra-arterial injections of either 10 microg/kg lipopolysaccharide (LPS) plus saline, 10 microg/kg LPS plus 5 mg/kg meloxicam (an inhibitor of the inducible form of cyclooxygenase), 10 microg/kg LPS plus 5 mg/kg diclofenac (a non-selective cyclooxygenase inhibitor), saline plus solvent, saline plus 5 mg/kg meloxicam or saline plus 5 mg/kg diclofenac. Injection of the cyclooxygenase inhibitors per se had no influence on the investigated parameters. Injection of LPS alone resulted in a biphasic fever, a more than fivefold increase in circulating cortisol and pronounced induction of TNF and IL-6. Treatment with the cyclooxygenase inhibitors either attenuated (meloxicam) or abolished (diclofenac) LPS-induced fever, but had no effect on the LPS-induced rise of plasma cortisol or IL-6. Circulating levels of TNF, in response to LPS, were enhanced by meloxicam and diclofenac, reflecting the negative feedback control exerted by prostaglandins on cytokine (specifically TNF) formation. These results provide the first evidence that the prostaglandin-dependent inflammatory pathway for fever induction is distinct from the pathway of HPA axis activation since fever, but not circulating cortisol, was attenuated by an inhibition of prostaglandin formation.

Animals↗

Individual variation in feeding habitat use by adult female green sea turtles (Chelonia mydas): are they obligately neritic herbivores?

Satellite telemetry and stable isotope analysis were used to confirm that oceanic areas (where water depths are >200 m) are alternative feeding habitats for adult female green sea turtles (Chelonia mydas), which have been thought to be obligate herbivores in neritic areas (where depths are <200 m). Four females were tagged with satellite transmitters and tracked during post-nesting periods from Ogasawara Islands, Japan. Three females migrated to neritic habitats, while transmissions from another female ceased in an oceanic habitat. The overall mean nighttime dive depths during oceanic swimming periods in two females were <20 m, implying that the main function of their nighttime dives were resting with neutral buoyancy, whereas the means in two other females were >20 m, implying that they not only rested, but also foraged on macroplankton that exhibit diel vertical migration. Comparisons of stable carbon and nitrogen isotope ratios between 89 females and the prey items in a three-source mixing model estimated that 69% of the females nesting on Ogasawara Islands mainly used neritic habitats and 31% mainly used oceanic habitats. Out of four females tracked by satellite, two females were inferred from isotope ratios to be neritic herbivores and the two others oceanic planktivores. Although post-nesting movements for four females were not completely consistent with the inferences from isotope ratios, possibly due to short tracking periods (28-42 days), their diving behaviors were consistent with the inferences. There were no relationships between body size and the two isotope ratios, indicating a lack of size-related differences in feeding habitat use by adult female green turtles, which was in contrast with loggerhead sea turtles (Caretta caretta). These results and previous findings suggest that ontogenetic habitat shifts by sea turtles are facultative, and consequently, their life histories are polymorphic.

Animal Migration↗

Field testing a global positioning system (GPS) collar on a Japanese monkey: reliability of automatic GPS positioning in a Japanese forest.

A global positioning system (GPS) collar recorded the locations of an adult female Japanese macaque over a 9-day period in a habitat with mixed suburban and rural land-uses in Chiba Prefecture, Japan. The GPS device acquired positions even in forested areas. The GPS data located the female mostly in forested areas, although the female had ranged through a habitat with inter-mingled fields, orchards, quarries, and residential areas. However, the GPS position acquisition rate was low compared to studies carried out on North American mammals. The GPS fixed a position in 20% of positioning attempts. When the collared female was tracked by radio-telemetry, almost all failures of the GPS to fix a position occurred in forest.

Animals↗

Effect of magnetic resonance imaging on DDD pacemakers.

A previous study suggested the safety of exposing patients with certain pacemakers models to magnetic resonance imaging (MRI). However, the function of a variety of more advanced DDD pacemakers and the effect of higher magnetic and radio-frequency (rf) field strengths has not been reported. In the present study 4 different DDD pacemakers (Cordis 233F, Intermedic 283-01, Medtronic 7000A, and Pacesetter 283) were tested in a saline phantom under several conditions and with various imaging sequences. Pacemaker output was monitored using electrocardiographic telemetry. All units paced normally in the static magnetic field. However, during imaging, all units malfunctioned, with total inhibition of atrial and ventricular output in 3 of the pacemakers. In the fourth pacemaker, ventricular backup pacing was activated at high rf pulse repetition rates. However, the MRI scanner could trigger atrial output in this pacemaker at rates of up to 800/minute. All malfunctions were a result of rf interference, whereas gradient and static magnetic fields had no effect. Thus, despite magnetic fields had no effect. Thus, despite magnetic field strengths adequate to close pacemaker reed switches, rf interference during MRI may cause total inhibition of atrial and ventricular output in DDD pacemakers, and can also cause dangerous atrial pacing at high rates. MRI should be avoided in patients with these DDD pacemakers.

Electrocardiography↗

Arrhythmias after cardiac transplantation.

The etiology and clinical significance of sustained arrhythmias, and atrial and ventricular premature complexes (APCs and VPCs, respectively) after heart transplantation are controversial. Fifty adult recipients surviving > 2 weeks were studied by continuous telemetry while in the hospital and by ambulatory electrocardiographic monitoring at 2, 4, 6, 12 and 24 weeks after transplantation. The median APC frequency was greater among subjects who experienced allograft rejection in the early postoperative period (0.7/hour, range 0 to 23) than among those who did not (0.2/hour, range 0 to 10.4) (p = 0.04). The APC frequency in all subjects decreased from 0.25/hour (range 0 to 23) early to 0/hour (0 to 14) later (p = 0.04). Atrial flutter was the most frequent sustained arrhythmia; it was recorded in 5 of 21 rejectors and in 1 of 29 nonrejectors (p = 0.04), and 11 of 16 episodes (69%) were related to acute rejection temporally. VPCs were recorded in all patients early after transplantation, but the median frequency subsequently decreased from 4.6/hour (range 0.5 to 470) early to 1.25/hour (range 0 to 225) later (p < 0.001). VPC frequency was unrelated to rejection. Sustained ventricular tachycardia was recorded once and was caused by the proarrhythmic effect of flecainide. Thus, APCs and VPCs occur frequently after transplantation. Frequent APCs are associated with rejection, whereas the main determinant of VPC frequency is time after transplantation. Atrial flutter is closely associated with rejection and should be regarded as an indication for endomyocardial biopsy. Ventricular tachycardia occurs seldom, and in this study was due to proarrhythmic drug effects.

Adult↗

Automated remote temperature measurement in small animals using a telemetry/microcomputer interface.

Temperatures can be obtained from small animals by implanting commercially available radio-telemetry probes (Mini-Mitters), thereby avoiding handling-induced artifacts. We have developed an inexpensive microcomputer interface to automatically collect data from Mini-Mitters. The interface hardware detects the signal and converts it to a TTL pulse train compatible with the Commodore PET microcomputer. The software converts the frequency to temperature, controls the sampling schedule, and can selectively measure any one of eight cages. Temperature measurements can thus be made around the clock with no technician present.

Animals↗

[Rhythmic slow waves and multi-unit activity during sleep-waking cycle in the rat ventral tegmentum].

1. Multi-unit activity (MUA) was recorded together with gross activity in different structures during various states of sleep in 43 rats. The records were made by means of telemetry from lateral hypothalamus, nucleus ruber, formatio reticularis, dorsal hippocampus and the ventral mesencephalic tegmentum (VMT) surrounding the nucleus interpeduncularis. 2. The records during paradoxical sleep showed slow rhythmic theta waves located in the VMT and the dorsal hippocampus. In these two structures the MUA was mainly organized in periodic patterns of discharges. In the other structures a continuous increment of the basic level of discharge was superimposed on the periodic patterns. 3. The similarity of the hippocampal and VMT records strengthens the hypothesis that the VMT region has anatomical and functional connections with the limbic system.

Action Potentials↗

Seizure moitoring: a new tool in electroencephalography.

A seizure monitoring system, based on telemetry and computer techniques, has been developed to provide a reliable means of recording the patient's spontaneous seizures. It allows a patient's EEG to be monitored for hours or days with 16 channels of EEG from surface, sphenoidal or stereotaxically implanted depth electrodes, from any ward or room within the hospital. The EGG is delayed in time by up to 4 min by a mini-computer so that either the patient can push a button when he experiences his aura or others can push the button when they observe his seizure. Since the delayed EEG is written out, the preictal, ictal and postictal are recorded on paper, without many pages of uneventful interictal information. During the past 16 months, the seizure monitoring system has been used as a clinical service to examine patients with surface electrodes (42), sphenoidal wires (25) and depth electrodes (7) during 146 recording sessions for over 3200 h of monitoring time while over 200 seizures have been recorded.

Amplifiers, Electronic↗

A portable pulse-interval modulation telemetry/multiplexing EEG recording system for use in the home.

A portable 6-channel recording system employing time-division multiplexing with cable or radio-telemetry has been developed. The system is very compact and has proved to be reliable when used in a domestic environment. The use of multiplexing, in general, permits an expansion in the number of available channels and a reduction in equipment and tape costs, while the use of pulse interval modulation, in particular, overcomes tape recording limitations which may be encountered with the more common amplitude modulation techniques.

Electroencephalography↗

Telemetering in vivo loads from nail plate implants.

A system of multi-channel telemetry capable of broadcasting in vivo loading from orthopaedic implants is presented. Its use to monitor the two orthogonal bending moments about the nail plate junction of three implanted hip nails is described. Typical results from these cases in which the telemeterized implant was employed to treat proximal femoral fixation and osteotomy are given.

Biomechanical Phenomena↗

A spinal fixation device for in vivo load measurement.

An instrumented spinal fixation device has been developed that allows in vivo measurement of the forces and moments acting on the implant. The telemetry is inductively powered, hermetically sealed by electron beam welding and is active only during the measurements. The instrumented fixateur interne is similar in size to the original Dick internal fixator implant and has the strength of the original implant. Laboratory tests with paired implants mounted in plastic vertebrae show that small changes in the position of the implants have a strong influence on the distribution of the loads on the implants.

Activities of Daily Living↗

Hippocampal electrical activity during social interactions in rabbits living in a seminatural environment.

The aim of the present experiment was to study the effect on the electrical activity of the hippocampus of interactions between male rabbits. The behavioral and electrical correlates of social interactions were studied in 13 animals living in a seminatural environment. Rabbits carrying chronic microelectrodes implanted in the hippocampus were introduced singly into a large, natural open air enclosure and their spontaneous behavior observed until they had adapted to the environment. Hippocampal EEG was recorded by telemetry. Subsequently, a second rabbit (intruder) was introduced into the enclosure. Hippocampal EEG and the concomitant behavior of the resident were stored and analyzed. Alerting reactions, approaching and conflictual elements were characterized by typical electrical patterns and parameters. Power spectra of hippocampal EEG showed a significant increase in frequency passing progressively from environment-related behaviors to more specific elements directed towards the intruder. Behavioral elements belonging to the same modality, such as running, chase and flight had different hippocampal EEG frequency distributions. Seven residents showed a clear prevalence of offensive reactions (offensive rabbits) and six defensive elements (defensive rabbits). Defensive animals showed very high frequency levels during nose and flight. Exploration of offensive rabbits in the period preceding and following the introduction of the intruder was characterized by higher EEG frequency values than exploration of defensive animals.

Aggression↗

Behavioral and electrocardiographic responses to social stress in male rats.

Telemetry ECGs were recorded from Wistar male rats during social stress induced by exposure to aggressive lactating female rats. Behavioral response to maternal attack was evaluated in terms of relative duration of passive submissive (p/s) and active/nonsubmissive (a/ns) patterns. A decrease of R-R interval (R-R) compared to baseline conditions was found, significantly more pronounced than that observed in control animals exposed just to novel environment. R-R variability during social stress was positively correlated with the amount of p/s behavior. R-R fluctuations, episodes of II degree A-V block, and ventricular arrhythmias were also observed. Most R-R fluctuations and II degree A-V blocks were temporally associated with phases of p/s behavior and periods of high R-R variability. Ventricular arrhythmias generally appeared during a/ns behavior and were temporally linked with periods of low R-R variability. Ventricular arrhythmias, low R-R variability, and concomitant a/ns behavior might be related to an increased sympathetic activity. R-R fluctuations and II degree A-V blocks, associated with high R-R variability and p/s behavior, might be related to a predominant inhibitory effect of vagal activation (accentuated antagonism).

Aggression↗

Stress induced disorganization of circadian and ultradian rhythms: comparisons of effects of surgery and social stress.

Persistent autonomic disturbances following stressful events suggest that the rhythmical nature of homeostatic functioning may be disrupted by these experiences. We assessed the effects of two different stressors on circadian and ultradian rhythms of Long-Evans rats by using nonlinear multi-oscillator cosinor analysis. Heart rate and intraperitoneal temperature were monitored continuously in 5-min intervals in two groups of animals via radio-telemetry for 15 days after surgery (n = 9) and 15 days following social defeat (n = 6). Circadian amplitude of heart rate and temperature increased significantly for the first nine days of the recovery from surgery but only circadian temperature amplitude increased following social defeat. Circadian acrophase of temperature but not heart rate changed significantly for a similar period following the surgery but not after the social defeat. A mathematical model incorporating the first five harmonics of the circadian rhythm was found to fit the data significantly better than a circadian model alone with rhythms of 3 and 5 cycles/day in temperature and heart rate entraining significantly to the light-dark schedule. Full recovery of the circadian and ultradian rhythms did not occur until a minimum of nine to twelve days after surgery or social defeat. The results suggest that rhythms with multiple periodicities are involved in homeostatic functioning and that models incorporating these rhythms may aid in understanding an organisms adaptive response to surgical intervention and social defeat, long after the challenges have terminated.

Activity Cycles↗

Genetic selection alters thermoregulatory response to ethanol.

The present study examined the effect of ethanol on the regulated temperature of two lines of mice selected in replicate for a smaller (HOT1 and HOT2) or greater (COLD1 and COLD2) decline in rectal temperature after IP ethanol. Mice were implanted with indwelling telemetry devices for remote monitoring of internal temperature and trained in a temperature gradient (8-40 degrees C). Both internal and selected temperature were tracked and recorded with a computer after injections of NaCl or various doses of ethanol. All animals responded similarly to control injections, with a transient rise in body temperature. After an effective dose of ethanol, mice showed clear evidence of a regulated decline in body temperature, as evidenced by selection of low temperatures in the gradient at the same time internal temperatures were falling. COLD mice were more sensitive than HOT mice; this was apparent in both replicates of the selected lines, indicating that a difference in the CNS regulator of body temperature has been selected for in these animals.

Animals↗

PHYSIOLAB: a new laboratory for the study of the cardio-vascular system.

On the basis of the experience gained during the previous french-russian missions on board MIR about the adaptation processes of the cardio-vascular system, a new laboratory has been designed. The objective of this "PHYSIOLAB" is to have a better understanding of the mechanisms underlying the changes in the cardio-vascular system, with a special emphasis on the phenomenon of cardio-vascular deconditioning after landing. Beyond these scientific objectives, it is also intended to use PHYSIOLAB to help in the medical monitoring on-board MIR, during functional tests such as LBNP. PHYSIOLAB will be set up in MIR by the French cosmonaut during the next french-russian CASSIOPEE mission in 1996. Its architecture is based on a central unit, which controls the experimental protocols, records the results and provides an interface for transmission to the ground via telemetry. Different specific modules are used for the acquisition of various physiological parameters. This PHYSIOLAB under development for the CASSIOPEE mission should evolve towards a more ambitious laboratory, whose definition would take into account the results obtained with the first version of PHYSIOLAB. This "second generation" laboratory should be developed in the frame of wide International cooperation.

Aerospace Medicine↗

Prevalence and prognostic significance of atrial arrhythmias after orthotopic cardiac transplantation.

OBJECTIVES: We studied the duration and prognostic significance of atrial arrhythmias in the denervated transplanted heart, specifically the occurrence of atrial fibrillation in the absence of vagal modulation. BACKGROUND: Substantial animal data indicate that vagally induced dispersion of atrial refractoriness plays a central role in the induction and maintenance of atrial fibrillation. METHODS: We studied the occurrence of atrial arrhythmias in the denervated hearts of 88 consecutive orthotopic transplantations in 85 patients by means of continuous telemetry and all available electrocardiographic tracings. RESULTS: Fifty percent of recipients (44 of 88) developed at least one atrial arrhythmia. Atrial fibrillation occurred 23 times (21 recipients), atrial flutter 39 times (26 recipients), ectopic atrial tachycardia 3 times (3 recipients) and supraventricular tachycardia 18 times (11 recipients). The number of atrial fibrillation and atrial flutter episodes did not differ (23 vs. 39, p = 0.072), but the mean duration of atrial flutter was longer than that of atrial fibrillation (37.0 +/- 10 vs. 6.6 +/- 3.6 h, p = 0.014). Atrial fibrillation was associated with an increased risk of subsequent death (10 of 21 recipients with vs. 15 of 67 without atrial fibrillation, risk ratio 3.15 +/- 0.18, p = 0.005 by Cox proportional hazards model). All 5 recipients who developed "late" atrial fibrillation (> 2 weeks after transplantation) died versus 5 of 16 who developed atrial fibrillation within the first 2 weeks (p = 0.007). Causes of death included rejection (three recipients), allograft failure (two recipients), infection (three recipients) and multiorgan failure (two recipients). Atrial fibrillation was not associated with age, gender, ischemic time, reason for transplantation, echocardiographic variables, invasive hemodynamic variables or biopsy grade. Mean time from atrial arrhythmia to echocardiography was 2.7 +/- 3.3 days; that to biopsy was 4.8 +/- 6.3 days. Atrial flutter was not associated with subsequent death. Only 7 (15.9%) of 44 recipients demonstrated moderate or severe allograft rejection at the time of the arrhythmia. CONCLUSIONS: Atrial arrhythmias occur frequently in the denervated transplanted heart, often in the absence of significant rejection. Late atrial fibrillation may be associated with an increased all-cause mortality.

Actuarial Analysis↗

Electromagnetic interference from welding and motors on implantable cardioverter-defibrillators as tested in the electrically hostile work site.

OBJECTIVES: This study was designed to determine the susceptibility of an implanted cardioverter-defibrillator to electromagnetic interference in an electrically hostile work site environment, with the ultimate goal of allowing the patient to return to work. BACKGROUND: Normal operation of an implanted cardioverter-defibrillator depends on reliable sensing of the heart's electrical activity. Consequently, there is concern that external electromagnetic interference from external sources in the work place, especially welding equipment or motor-generator systems, may be sensed and produce inappropriate shocks or abnormal reed switch operation, temporarily suspending detection of ventricular tachycardia or ventricular fibrillation. METHODS: The effects of electromagnetic interference on the operation of one type of implantable cardioverter-defibrillator (Medtronic models 7217 and 7219) was measured by using internal event counter monitoring in 10 patients operating arc welders at up to 900 A or working near 200-hp motors and 1 patient close to a locomotive starter drawing up to 400 A. RESULTS: The electromagnetic interference produced two sources of potential interference on the sensing circuit or reed switch operation, respectively: 1) electrical fields with measured frequencies up to 50 MHz produced by the high currents during welding electrode activation, and 2) magnetic fields produced by the current in the welding electrode and cable. The defibrillator sensitivity was programmed to the highest (most sensitive) value: 0.15 mV (model 7219) or 0.3 mV (model 7217). The ventricular tachycardia and ventricular fibrillation therapies were temporarily turned off but the detection circuits left on. CONCLUSIONS: None of the implanted defibrillators tested were affected by oversensing of the electric field as verified by telemetry from the detection circuits. The magnetic field from 225-A welding current produced a flux density of 1.2 G; this density was not adequate to close the reed switch, which requires approximately 10 G. Our testing at the work site revealed no electrical interference with this type of defibrillator. Patients were allowed to return to work. The following precautions should be observed by the patient: 1) maintain a minimal distance of 2 ft (61 cm) from the welding arc and cables or large motors, 2) do not exceed tested currents with the welding equipment, 3) wear insulated gloves while operating electrical equipment, 4) verify that electrical equipment is properly grounded, and 5) stop welding and leave the work area immediately if a therapy is delivered or a feeling of lightheadedness is experienced.

Defibrillators, Implantable↗