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Marijuana smoking and cold tolerance in man.

Ten men who were marijuana users served as subjects in a study of the effects of marijuana smoking on response to cold. Cold water (28 degrees C for 60 min) and cold air (20 degrees C for 120 min) mediums were utilized with three exposures in each medium. The three exposures followed smoking marijuana, smoking placebo, and a no-smoking control period. Additionally, a breathhold experiment preceded and followed the four smoking periods. Marijuana and placebo smoke were inhaled from a spirometer with each man receiving the smoke of 0.739 g of marijuana and placebo. Smoking marijuana did not greatly modify body heat content, since rectal temperature and most peripheral temperatures were not altered. However, temperatures over voluntary muscles likely to be involved in shivering were elevated. Heat production also greatly increased after marijuana, suggesting that it had stimulated shivering. Marijuana also produced tachycardia and abolished apneic bradycardia. The mechanism of this action is not clear, but some sympathetic involvement is indicated.

Adaptation, Physiological↗

Rewarming cardiac surgery patients: radiant heat versus forced warm air.

This study compared time required to rewarm, incidence of shivering, and nurses' preferences in hypothermic postoperative cardiac surgery patients treated with a forced air warmer (Bair Hugger) or a noninfrared radiant heater (Thermal Ceiling). Data were collected on 38 subjects and 6 nonsubjects treated with warm blankets. Average minutes to rewarm were: forced air, 100.3; radiant heat, 99.3; and warm blankets, 188.2. The warm air subjects had significantly higher skin temperatures, lower incidence of shivering, and less severe afterdrop, suggesting that rewarming in these patients resulted from heat gained from the environment. Nurses preferred the forced air warmer to the noninfrared radiant heater.

Adult↗

Subarachnoid fentanyl augments lidocaine spinal anesthesia for cesarean delivery.

BACKGROUND AND OBJECTIVES: Fentanyl at doses of 6.25 microgram or more, when to hyperbaric bupivacaine for spinal anesthesia for cesarean delivery, has been reported to markedly increase the duration of analgesia. In this study, subarachnoid fentanyl 15 micrograms was evaluated as the sole adjunct to hyperbaric lidocaine spinal anesthesia in parturients undergoing cesarean delivery at term, to determine its effect on the duration of analgesia and side effects perioperatively. METHODS: Twenty-eight parturients scheduled for elective cesarean delivery at term were randomized to one of two groups in a prospective, double-blind fashion. Patients in group F received 15 micrograms fentanyl in addition to 80 mg hyperbaric lidocaine for subarachnoid anesthesia, while patients in group N received 0.3 mL normal saline in addition to 80 mg hyperbaric lidocaine. Visual analog pain scores were recorded preoperatively and at regular intervals until the first patient request for additional analgesia. The occurrence of side effects (nausea, vomiting, pruritus, shivering) was recorded at intervals for 4 hours postinduction. All patients received patient-controlled analgesia after delivery, and analgesic requirements for 24 hours postinduction were recorded. RESULTS: There was no difference between groups with respect to visual analog pain scores intraoperatively. The mean duration of effective analgesia was increased in the patients receiving fentanyl from 71 minutes to 101 minutes (Student's t-test, P < .01). No difference was observed between groups with regard to 4-hour or 24-hour analgesic requirements. Patients in group F were significantly less likely to experience nausea (Fisher's exact test, P < .05) and vomiting (chi-square test, P < .05) in the immediate perioperative period, but no differences were noted between groups in the incidence of pruritus or shivering. CONCLUSIONS: The addition of fentanyl 15 micrograms to hyperbaric lidocaine for subarachnoid anesthesia for cesarean delivery increases the duration of effective analgesia by approximately 30 minutes compared to plain hyperbaric lidocaine, and provides a protective effect regarding nausea and vomiting in the perioperative period.

Adjuvants, Anesthesia↗

Effect of a radiant heater on post-operative hypothermia: comparison with a reflective blanket.

Thirty patients with post-operative hypothermia following major surgery (thoracic, abdominal, orthopaedic) were allocated randomly to either active warming with a radiant heater (500 W) or passive rewarming with a reflective blanket. Rectal temperature, mean skin temperature (at four measuring sites), continuous haemoglobin saturation and shivering were measured for 2 h post-operatively. Although post-operative heat supply with a radiant heater resulted in faster rewarming, there were no differences between the two groups with respect to haemoglobin saturation and shivering.

Abdomen↗

Accidental hypothermia: an experimental study of practical rewarming methods.

Five rewarming techniques, appropriate for first-aid use in the nonhospital setting, were applied to each of nine subjects whose body temperatures had been lowered to 35 degrees C in a stirred tank of 7.5 degrees C water. The rewarming techniques were: a) inhalation of heated, water-saturated oxygen; b) placement of heating pads over areas of high heat transfer; c) combination of methods a) and b); d) hot whirlpool bath; and e) shivering. Inhalation of heated, water-saturated oxygen was significantly better than the shivering control in minimizing temperature "afterdrop" and is, therefore, preferred over the other techniques as it avoids the physiological hazards of the peripheral vasodilation from external rewarming.

Adult↗

Ultrasonic analysis of tremorine and cold tremor activity in unanesthetized rats.

In order to quantify the tremorine and cold tremor activity in unanesthetized rats, a new ultrasonic motion transducer method was used. Both kinds of activity are reported as vibratory body motion that occurred between 18-32 Hz as determined by spectral analysis. The recorded signal was analyzed and its power spectrum was obtained through a fast Fourier transform operation. It was found that a negative linear relation occurs between shiver amplitude and ambient temperature (r = 0.999). A negative linear relation also occurs between metabolic rate and ambient temperature (r = 0.997). In addition, a positive linear relation between metabolic rate and cold shiver exists (r = 0.999). Both tremorine (30 mg/kg, i.p.) and cold tremor (Ta = 2-22 degrees C) activity monitored by the ultrasonic method were completely abolished by premedication with 1 mg/kg atropine. Thus, it appears that the advantages of this tremor detection method are that is non-invasive and non-contact. Therefore, the ultrasonic method provides a good choice for quantifying tremorine and cold tremor activity in unanesthetized animals during studies of thermoregulatory physiology or motor disorders.

Animals↗

[Resuming of thermoregulation in rats during deep hypothermia with EDTA without rewarming the body].

Administration of the EDTA, a substance binding calcium ions, helped to resume thermoregulation functions after their "cold paralysis" at the rectal temperature 17.1 +/- 0.2 degrees C and the brain temperature 19.2 +/- 0.2 degrees C, without warming up the animal. Enhancement of the muscle electrical activity following the EDTA administration was due both to increase in the number of bursts of shivering and to enhancement of their intensity. The findings suggest that, in hypothermia, improvement of conditions of the calcium ion transport from the cell cytosole into interstitial space helps to restoration of the cold muscle shivering as an important function of the thermoregulation.

Animals↗

Skin temperatures at the nape in infants at high altitude.

Skin temperatures were measured on three Quechua Indian infants resident at 4,000 meters above sea level in Peru. Nape temperatures were warmer than other skin sites, suggesting that the brown adipose tissue associated with non-shivering thermogenesis is metabolically active despite the reduced oxygen availability at high altitude. The question of the role of non-shivering thermogenesis in infant thermoregulation under the covariant stresses of hypoxia and cold is still open.

Adipose Tissue↗

The astrocyte as a locus of carbonic anhydrase in the brains of normal and dysmyelinating mutant mice.

There is some controversy in the literature whether carbonic anhydrase occurs in astrocytes, as well as in oligodendrocytes and myelin, in the mammalian brain. In the present study this issue was addressed by double immunostaining for carbonic anhydrase and two astrocytic "markers" in the brains of normal mice and two dysmyelinating mutants, jimpy and shiverer. In the brains of young mice, carbonic anhydrase and glutamine synthetase were colocalized in astrocytes in the cortical gray matter. In gray matter of the adult mouse brain, it was possible to immunostain both carbonic anhydrase and glial fibrillary acidic protein (GFAP) in the same cells. However, in contrast to the findings in gray matter, in and near subcortical white matter carbonic anhydrase could be detected only in oligodendrocytes and myelinated fibers. In the brains of jimpy mice, virtually all the carbonic-anhydrase-positive cells were also GFAP positive, even in regions normally occupied by white matter. In the brains of young and adult shiverer mice, carbonic anhydrase was localized in astrocytes in the gray matter, but in and near the tracts normally occupied by white matter carbonic anhydrase could be detected only in oligodendrocytes and their abundant processes. The findings confirmed the oligodendrocyte-myelin unit to be the primary locus of carbonic anhydrase in the normal mouse brain and showed the astrocytes in gray matter normally to be a secondary locus of carbonic anhydrase. The immunostaining in the jimpy mouse brain suggested further that reactive astrocytes, in particular, might be rich in carbonic anhydrase.

Animals↗

Differential myelinogenic capacity of specific developmental stages of the oligodendrocyte lineage upon transplantation into hypomyelinating hosts.

The capacity of oligodendrocytes (OLs) and their progenitors to migrate, proliferate, and differentiate in vivo was evaluated by transplanting highly enriched populations of sequential stages of the OL lineage (A2B5+O4-, O4+GalC-, and GalC+) into the telencephalon of the hypomyelinating mouse, shiverer. The shiverer mouse neither expresses the major myelin basic protein (MBP) nor makes normal myelin due to a large deletion in the gene for MBP. Thirty days after transplantation, serial 225 micron sections of the host brain were immunostained with antiserum to MBP and analyzed by confocal microscopy. The presence of MBP+ patches of myelin in the otherwise MBP- host brain allowed a retrospective analysis of the myelinogenic activity of the transplanted progenitors cells. Both the extent of MBP+ myelin and the location of MBP+ structures relative to the initial site of cell deposition were highly dependent on the developmental stage of the transplanted cells. Specifically, A2B5+O4- OL progenitors migrated distances of > or = 600 microns and produced MBP+ patches in nearly every slice of the host brain. An average of over 250 separate patches were found per host brain, some of which had cross-sectional areas of > 250,000 microns2 containing as many as 60 MBP+ OL cell bodies, and with densities of myelination rivaling that of normal brain. In marked contrast, transplantation of O4+GalC- cells produced only small (1,000-25,000 microns2), scattered (25-40 per brain) patches of MBP+ myelin containing one to five cell bodies, all of which were within 50 microns of the needle track or the nearest ventricular surface. GalC+ cells produced MBP+ myelin at a level similar to that of O4+CalC- cells. These data suggest that the developmental transition of OL progenitors from the O4- to the O4+ phenotype is accompanied by a dramatic reduction in the innate capacity of the cells to migrate and survive in vivo. The use of developmentally identified, enriched populations of OL progenitor cells offers the opportunity for more precise analyses of transplantation and remyelination behavior, and relates to clinically relevant studies indicating that contaminant cell types can seriously interfere with the stable integration of donor tissue into the host.

Animals↗

Insertional mutagenesis inducing hypomyelination in transgenic mice.

Investigations of myelin disorders, in particular multiple sclerosis (MS), have concentrated on immunemediated damage to formed myelin, while there has been less emphasis on the molecular genetics of myelin formation. We have generated a transgenic mouse mutant (designated 2-50) which carries an insertional mutation in a locus regulating myelination. These mice carry a transgene comprising 1.3 Kb of the mouse myelin basic protein (MBP) promoter conjugated to a fragment containing exons 2 and 3 of the human c-myc gene. Positive mice show a significant reduction in myelin compared to controls and a shivering phenotype. Unlike other myelin mutants, all 2-50 mice lose the shivering phenotype and breed normally. Expression of c-myc is detectable in only 65% of transgene-carrying mice, and when present occurs at extremely low levels. This shows that the phenotype is caused by insertional inactivation of a gene necessary for myelination rather than ectopic expression of the transgene. The transgene was found by in situ hybridization to be inserted into a single site which is very distally located on chromosome 9. The 2-50 mice represent a unique model which will be ideal for investigating the molecular basis of myelin assembly and for developing gene therapy to promote remyelination in conditions such as MS.

Animals↗

Migration and multipotentiality of PSA-NCAM+ neural precursors transplanted in the developing brain.

By optimizing the previously described strategy for obtention of spheres enriched in PSA-NCAM+ precursors, we prepared PSA-NCAM-immunoselected cell populations from cerebral hemispheres of neonatal MBP-LacZ transgenic mice. These cells expressed Nestin, exhibited clonal expansion potential and formed spheres, which were initially enriched in PSA-NCAM+ cells but became enriched in GD3+ oligodendrocyte progenitors after 1 week in B104 contionned medium. One month after their periventricular transplantation into the brain of wild-type and/or shiverer newborn mice, cells from PSA-NCAM+ spheres exhibited a higher rostral migration potential than cells from GD3+ spheres, and clearly contributed to myelination in the olfactory bulb. In shiverer hosts, both sphere populations generated oligodendrocytes with similar myelination potential. In addition PSA-NCAM+ sphere cells generated GFAP+ astrocytes and NeuN+ neurons, depending on their site of insertion. These results evidence the high plasticity of newborn PSA-NCAM+ neural precursors and suggest that they are promising tools for cell therapy of CNS diseases, including myelin disorders.

Animals↗

Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water.

Myelin loss and axonal damage are both observed in white matter injuries. Each may have significant impact on the long-term disability of patients. Currently, there does not exist a noninvasive biological marker that enables differentiation between myelin and axonal injury. We describe herein the use of magnetic resonance diffusion tensor imaging (DTI) to quantify the effect of dysmyelination on water directional diffusivities in brains of shiverer mice in vivo. The principal diffusion eigenvalues of eight axonal fiber tracts that can be identified with certainty on DTI maps were measured. The water diffusivity perpendicular to axonal fiber tracts, lambda(perpendicular), was significantly higher in shiverer mice compared with age-matched controls, reflecting the lack of myelin and the increased freedom of cross-fiber diffusion in white matter. The water diffusivity parallel to axonal fiber tracts, lambda(parallel), was not different, which is consistent with the presence of intact axons. It is clear that dysmyelination alone does not impact lambda(parallel). The presence of intact axons in the setting of incomplete myelination was confirmed by electron microscopy. Although further validation is still needed, our finding suggests that changes in lambda(perpendicular) and lambda(parallel) may potentially be used to differentiate myelin loss versus axonal injury.

Animals↗

Hypothermia produced by tributyl S,S,S-phosphorotrithioate (DEF).

Tributyl S,S,S-phosphorotrithioate (DEF) produces profound hypothermia in rats, mice and guinea pigs by inhibition of thermogenesis. Its actions on heat conservation and motor control are, however, minimal. It is effective against both shivering and non-shivering thermogenesis and completely blocks the increase in body temperature evoked by anterior hypothalamic stimulation. A number of other measures indicated that this is unlikely to be due to a lack of peripheral thermogenic capacity: thus plasma concentrations of glucose, free fatty acids, and ketone bodies remained normal or rose after DEF, and in vitro noradrenaline-stimulated lipolysis was normal in the presence of DEF. The metabolic response to the uncoupler, 2,4-dinitrophenol was unchanged by DEF, and the increase in temperature of brown fat evoked in vivo by nerve stimulation or noradrenaline was also unaffected. It is suggested that DEF (or more likely a DEF metabolite) acts selectively on a central thermogenic control process.

Acclimatization↗

Oligodendrocytes from optic nerves subjected to long term Wallerian degeneration retain the capacity to myelinate.

It has previously been shown in the adult rat optic nerve that cells with many features of oligodendrocytes are capable of surviving for extended periods of time in the absence of axons. This is in contrast to the situation in the developing nervous system, where removal of axons leads to the failure of differentiation and to the death of oligodendrocytes. In the adult, these surviving oligodendrocytes were not typical in their appearance, and could only be identified with certainty using cell specific markers. In the present experiments, the functional capacity of these long-term quiescent cells to regenerate and myelinate was tested using the Shiverer mouse, a mutant lacking the gene for myelin basic protein (MBP), as a host animal. Fragments of optic nerve from adult rats which had been enucleated up to 2 years previously, were implanted into neonatal Shiverer mice. Four weeks later, the brains were removed and the formation of myelin investigated with antibodies to MBP, to ensure that this was of donor origin. Axons were demonstrated to have grown into the implants, and may have provided the stimulus for the production of MBP by the oligodendrocytes, which were stained positively within the implant. Myelin was demonstrated both within and adjacent to the implant. This study indicates that in the adult central nervous system, cells can survive for extended periods of time in the absence of axons, albeit in an inactive state, and are then capable of functional regeneration when placed in contact with unmyelinated axons. The origin of these cells, either from surviving oligodendrocytes which had previously myelinated the axons, or from progenitors lying within the adult nerve is unclear. The implications of these results are of importance in the further investigation of the potential for central nervous system regeneration.

Animals↗

Effects of acclimatization to cold baths on men's responses to whole-body cooling in air.

The purpose of this study was to investigate the thermoregulatory mechanisms underlying artificial acclimatization to cold and to compare them with those of naturally acclimatized men. Six white men were cooled, nude, in air at 10 degrees C for 2 h before and after they had been acclimatized by ten daily cold (15 degrees C) baths of 30-60 min followed by rapid rewarming in hot (38-42 degrees C) water, and again 4 months later after acclimatization had decayed. Six control subjects also underwent the same tests, providing an opportunity to discriminate between changes caused by the immersions and those caused by extraneous influences. Acclimatization significantly reduced heat production and heat loss (P < 0.05) but did not change heat debt. The reduced heat production was accompanied by reductions in shivering (P < 0.10) and in cold-induced muscle tenseness; no evidence of nonshivering thermogenesis or active brown fat was found. These findings are attributed to increased tissue insulation, mediated by an enhanced vascular response to cold that did not involve the cutaneous circulation and was probably located in skeletal muscle. Thermal sensation and discomfort did not change, although perceived strain tended to increase (P = 0.08). Acclimatization was accompanied by, but was unrelated to, slower cooling of the finger and toe. The main conclusions, and many specific findings, agree with those of two previous studies made by the same techniques in naturally acclimatized men wintering in Antarctica. Other significant findings included changes--in particular reduced thermoneutral rectal temperature and a delayed onset of shivering--that are commonly regarded as evidence of acclimatization but were in fact unrelated to it as they also occurred in the control group. They are attributed to extraneous influences, in particular the relaxation of heightened arousal ('first-time effects') found in the baseline tests.

Acclimatization↗

Central thermosensitivity in conscious goats: hypothalamus and spinal cord versus residual inner body.

Experiments were performed on conscious goats to confirm the suggestion that in this species the inner body contains more thermosensitive structures than those residing in the hypothalamus and spinal cord. For this purpose goats were chronically implanted with local thermodes and intravascular heat exchangers to allow independent temperature control of the hypothalamus, spinal cord and residual inner body. With the hypothalamus and spinal cord clamped simultaneously at different levels between 32 degrees C and 40 degrees C, residual internal temperature was lowered by subtracting heat via the intravascular heat exchanger. The residual internal temperature at which shivering and increased heat production occured due to heat extraction, was directly related to the value of the combined hypothalamic and spinal cord clamp temperature. The higher hypothalamic and spinal cord clamp temperatures were, the lower residual internal temperature fell before shivering occurred and heat production rose. Plots relating residual internal temperature to hypothalamic and spinal cord temperature at different levels of heat production showed the signal input generated within the residual inner body to be of nearly the same order of magnitude as that from the hypothalamus and spinal cord.

Animals↗