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Moderate exercise increases postexercise thresholds for vasoconstriction and shivering.

The purpose of this study was to evaluate the effect of exercise on the subsequent postexercise thresholds for vasoconstriction and shivering. On two separate days, with six subjects (3 women), a whole body water-perfused suit slowly decreased mean skin temperature (approximately 7.0 degreesC/h) until thresholds for vasoconstriction and shivering were clearly established. Subjects were then rewarmed by increasing water temperature until both esophageal and mean skin temperatures returned to near-baseline values. Subjects either performed 15 min of cycle ergometry (65% maximal O2 consumption) followed by 30 min of recovery (Exercise) or remained seated with no exercise for 45 min (Control). Subjects were then cooled again. We mathematically compensated for changes in skin temperatures by using the established linear cutaneous contribution of skin to the control of vasoconstriction and shivering (20%). The calculated core temperature threshold (at a designated skin temperature of 30.0 degreesC) for vasoconstriction increased significantly from 36.64 +/- 0.20 to 36.89 +/- 0.22 degreesC postexercise (P < 0.01). Similarly, the shivering threshold increased from 35.73 +/- 0.13 to 36.13 +/- 0.12 degreesC postexercise (P < 0.01). In contrast, sequential measurements, without exercise, demonstrate a time-dependent decrease in both the vasoconstriction (0.10 degreesC) and shivering (0.12 degreesC) thresholds. These data indicate that exercise has a prolonged effect by increasing the postexercise thresholds for both cold thermoregulatory responses.

Adult↗

Pethidine and skin warming to prevent shivering during endovascular cooling.

We tested the efficacy of pethidine and cutaneous warming to prevent shivering during percutaneous cooling in unanaesthetized patients. Ten patients scheduled for cranial neurosurgery received pethidine infusion and skin warming. The Setpoint internal heat-exchanging catheter was inserted and cooling to 33.5 degrees C was started. Clonidine and chlorpromazine were given as "rescue medication" to treat shivering. General anaesthesia was planned to be induced after cooling was complete. Rewarming was initiated at dural closure. Three patients successfully completed the protocol, cooling to 33.8 degrees C at a median rate of 3.6 (range: 3.4-3.8) degrees C/h. Two patients cooled to 33.8 degrees C but required treatment for shivering (cooling rate: 2.9 [2.8-3.1] degrees C/h). Four patients failed to cool adequately because of refractory shivering (cooling rate: 20 [1.5-2.9] degrees C/h). One patient did not shiver and yet failed to cool adequately (cooling rate: 0.76 degrees C/h). Rewarming was at a rate of 26 (1.2-4.3) degrees C/h. There were no significant complications arising from catheter placement. The combination of skin warming and pethidine was not reliable enough to be recommended for use during endovascular cooling in unanaesthetized patients.

Adult↗

The hemodynamic and metabolic effects of shivering during acute normovolemic hemodilution.

UNLABELLED: To assess the hemodynamic and metabolic effects of shivering during extreme normovolemic hemodilution, we anesthetized 16 pigs with fentanyl-midazolam-pancuronium. Mild hypothermia (36.5 degrees +/- 0.1 degrees C) was induced by surface cooling, and the animals were randomized to either a control group (hemoglobin 118 +/- 3 g/L) or a hemodilution group (hemoglobin 52 +/- 2 g/L). In the latter group, blood was replaced with an isotonic Ringer's acetate/dextran 70 solution. Shivering was allowed to occur by a controlled decrease in the infusion rate of pancuronium. Shivering increased oxygen consumption (VO(2)) in both groups (P < 0.001). Initially, this was predominantly compensated for by an increased oxygen extraction ratio (ER), but when VO(2) was 2.3 +/- 0.2 times baseline, critical levels of mixed venous oxygenation (SVO(2) = 18% +/- 2%; PVO(2) = 22.5 +/- 1.5 mm Hg) and ER (82% +/- 3%) were recorded in anemic animals. Control animals did not reach critical levels until VO(2) was maximal (3.7 +/- 0.3 times baseline). Maximal attained VO(2) was less (2.9 +/- 0.1 times baseline) in the anemic animals (P = 0.01), and at this stage two of these pigs had myocardial lactate production, one of which died in ventricular fibrillation. Coronary perfusion pressure was significantly less (P < 0.001) in the anemic animals. We conclude that in this experimental model, maximal shivering as measured by VO(2) was limited in hemodiluted animals, and left ventricular oxygen balance was marginal, as evidenced by a decreased lactate uptake and extraction. IMPLICATIONS: The effect of acute increases in oxygen consumption (shivering) on severely anemic individuals has not been evaluated. In this experimental model, left ventricular oxygen balance was marginal, as evidenced by decreased lactate extraction.

Anemia↗

The relationship of muscle electrical activity, tremor and heat production to shivering thermogenesis in Japanese quail.

We measured the electrical activity and the tremor of the pectoral muscle and total body heat production in control and cold-acclimated Japanese quail at +26 degrees C, +12 degrees C and +2 degrees C before and after 3 weeks of acclimation, using electromyography, accelerometer recordings, and indirect calorimetry. Japanese quail shiver in 0.2- to 3-s bursts that occur in groups. An increase in both the frequency and the duration of bursts and burst groups contributes to the increase in heat production by shivering at low temperatures. A compilation of shivering patterns in birds is given and its implications for the neural control and phylogeny of shivering are discussed. A rather non-specific increase in electromyographic (EMG) activity and heat production was observed after cold acclimation at all experimental temperatures, although many of the normal signs of cold acclimation (e.g. decrease in gonad mass, increase in heart mass and serum triiodothyronine) were seen. The increase in muscle electrical activity was greater than the increase in oxygen uptake, which resulted in a lower VO2/EMG ratio. The amplitude distribution of muscle electrical activity remained normal, but a shift towards higher frequencies occurred in the EMG spectra of cold-acclimated birds. Despite the increase in muscle electrical activity, power spectra of accelerometer recordings indicated that the amplitude of the muscle tremor was lower in cold-acclimated birds. The increase in the high-frequency components of the EMG indicates that decreased synchronization of motor unit firing may account for the lower tremor amplitude. We suggest that this change is adaptive because it reduces heat loss and/or because more fatigue-resistant motor units are recruited. These results show that temperature acclimation modifies the neural control of shivering in skeletal muscle.

Acclimatization↗

Nitrous oxide decreases shivering threshold in rabbits less than isoflurane.

BACKGROUND: Comparable minimum alveolar concentration (MAC) fractions of volatile anaesthetics produce similar thermoregulatory impairment. Nitrous oxide, however, decreases the vasoconstriction threshold less than sevoflurane or isoflurane. We tested the hypothesis that nitrous oxide also decreases shivering threshold less than isoflurane alone or in combination. METHODS: Twenty-four rabbits were assigned randomly to one of three 0.3 MAC anaesthetic regimens: (i) nitrous oxide 69%; (ii) nitrous oxide 35% and isoflurane 0.3%; or (iii) isoflurane 0.6%. Body temperature was lowered by perfusing 10 degrees C water through a U-shaped thermode positioned in the colon. Shivering was evaluated by inspection. RESULTS: The rabbits anaesthetized with nitrous oxide alone shivered at 37.0 (0.5) degrees C (P<0.01 vs other groups). In those given the nitrous oxide and isoflurane combination, the shivering threshold was 36.4 (0.5) degrees C and that in the isoflurane group was 35.9 (0.4) degrees C. CONCLUSION: This study indicates that nitrous oxide reduces the shivering threshold less than isoflurane.

Anesthetics, Inhalation↗

Thermogenesis induced by inhibition of shivering during cold exposure in exercise-trained rats.

The present investigation was conducted to examine the role of nonshivering and shivering thermogenesis caused by cold exposure in exercise-trained rats. Wistar rats were divided into warm-acclimated (WA), exercise-trained (ET) and cold-acclimated (CA) groups. The trachea was cannulated and a ventilator was connected under light anesthesia and in the supine position. Shivering, oxygen consumption, colonic temperature, blood glucose, and free-fatty acids were measured at 25 degrees C and then at 0 degrees C room temperatures. D-tubocurarine chloride (curare, 0.04 mg/100 g body weight, ip) was given to inhibit muscular activity. Cold-induced oxygen consumption in the ET and WA groups did not decrease when shivering was inhibited, whereas it increased in the CA. The magnitude just after shivering onset for the ET and CA groups as significantly greater than for the WA group. Colonic temperature at the onset of shivering was significantly higher in the WA group than in the ET and the CA groups. The blood glucose concentration during cold exposure and curarization was elevated in the ET group, and did not change in the CA or WA groups. The present results suggest that endurance training at a thermoneutral environment increases cold-induced thermogenic capacity in rats, which may be attributed to preferential carbohydrate utilization.

Acclimatization↗

[Effect of halothane on the peripheral cutaneous vasoconstriction and shivering induced by internal body cooling in rabbits].

Although suppression of thermoregulatory mechanisms by anesthetics is generally assumed, the extent to which thermoregulatory responses are active during general anesthesia is not known. To evaluate the effect of anesthetics on thermoregulation, we investigated the threshold body core temperatures to induce peripheral cutaneous vasoconstriction and shivering in spontaneously breathing rabbits. Rabbits are anesthetized with halothane at 0.05, 0.2 and 0.4 MAC (minimum alveolar concentration). Internal whole body cooling was performed by perfusing the cool water through an intestinal U-shaped thermode placed in the colon. Core (esophagus) and peripheral (ear) temperatures were measured with thermistors. The esophageal temperatures at the beginning of peripheral cutaneous vasoconstriction and shivering induced by internal whole body cooling were determined. Peripheral cutaneous vasoconstriction was not significantly affected by halothane. However, the incidence of shivering was significantly decreased by halothane dose-dependently. Threshold of shivering (37.3 +/- 0.8 degrees C) was significantly lower than that of peripheral cutaneous vasoconstriction (38.9 +/- 1.1 degrees C). We conclude that the halothane can exert an influence on shivering.

Animals↗

[Shivering during recovery after cardiac surgery under extracorporeal circulation. Inconveniences and methods of prevention].

Among 109 subjects who had undergone cardiac surgery under ECC, the authors recorded 50 (45 p. 100) who suffered from shivering during the coming round period. Comparing the series of patients who shivered, with that of the subjects who did not shiver, the authors demonstrate in the first case, an increase in cellular metabolism, the cardiac index, heart rate, central venous pressure and cardiac work. They subsequently note the apprearance of mixed acidosis and an increase in the lactate-pyruvate ratio. Certain patients, in whom the cardiac output did not keep up with the metabolic demand considerably increased the arterio-venous oxygen difference. Blood loss is increased as well as coagulation time showing a more intense heparin rebound. The study of the drugs used during anesthesia showed that the patients who had received chlorprotixene, as the neuroleptic, a neuroleptic with adrenolytic properties, had a very decreased frequency of shivering in comparison with those who had received droperidol. The placing of the patient at the end of the intervention on a heating mattress, combined with the administration of chlorprotixene during anesthesia, prevented the appearance of shivering.

Adult↗

[A comparison of three drugs (pethidine, magnesium sulfate and droperidol) in patients with post-anesthesia shivering].

Shivering is one of the common complications after general anesthesia. It increases metabolic rate markedly and may cause myocardial ischemia in patients with decreased cardiopulmonary function. We investigated, therefore, the effects of three drugs (pethidine, magnesium sulfate and droperidol) on shivering in 30 patients under enflurane anesthesia. The patients were of ASA class I or II physical status and had no cardiovascular or respiratory disease. For post-anesthesia shivering, every patient was administered with pethidine 0.5 mg.kg-1, MgSO4 30 mg.kg-1 or droperidol 0.15 mg.kg-1. Their VO2 and VCO2 were measured for 5 minutes during shivering and 15 minutes after drug administration. We also evaluated the therapeutic efficacy of each drug for the treatment of shivering by examining VO2 and VCO2 before and after drug administration. With pethidine and MgSO4, both VO2 and VCO2 decreased significantly after each drug administration. With pethidine, VO2 and VCO2 decreased significantly more than that in MgSO4 (P less than 0.01 vs P less than 0.05). But with droperidol, there was no significant change. These results suggest that pethidine is most effective followed by MgSO4.

Adult↗

Shivering during regional anaesthesia and its control with pethidine.

Ninety-seven consecutive patients who underwent four different types of regional anaesthesia such as lumbar epidural, spinal, caudal and brachial blocks were studied for their incidence of shivering. Fifty percent of patients who received epidural anaesthesia shivered compared to 19% of patients who received either spinal or caudal anaesthesia. None of the patients who had brachial block shivered. Intravenous injection of 25 mg pethidine would stop shivering in almost all patients who shivered during regional blocks.

Adult↗

Factors related to amphotericin-B-induced rigors (shivering)

Amphotericin-B is the only parenteral agent currently available to treat systemic fungal infections. Pyrogenesis, accompanied by severe shivering, is a distressing side effect. Possible risk factors of developing this reaction have not been reported. A case series was developed to document the occurrence and duration of shivering in patients who received amphotericin-B and to investigate whether these responses were associated with a diagnosis of diabetes mellitus, receipt of insulin or beta blockers, the amount of body fat content, an immunocompromised state, age, and gender. Medical records were reviewed and abstracted for patients who received 20 milligrams or more of amphotericin-B per day for at least 10 consecutive days between January 1, 1984, and September 1, 1988. Results indicated that a diagnosis of diabetes, insulin therapy, and advancing age were inversely associated with the amphotericin-B-induced rigors response. Shivering was noted to occur first at the test dose, with the percentage of patients who shivered increasing with each successive dose (this peaked at the fifth therapeutic dosage). Of the factors under study, only advancing age appeared to be related to the duration of shivering. It is possible that identification of the descriptive characteristics of amphotericin-B-induced rigors will facilitate the nursing care of patients who receive this treatment; it also may be an important first step in the identification of risk factors for this clinical complication.

Adipose Tissue↗

Effect of meperidine on oxygen consumption, carbon dioxide production, and respiratory gas exchange in postanesthesia shivering.

Meperidine has been used to suppress postanesthesia shivering. However, its efficacy to date has only been assessed by observation of visible shivering. We measured the effect of meperidine on oxygen consumption (VO2), carbon dioxide production (VCO2) and pulmonary gas exchange in 14 otherwise healthy patients shivering after general anesthesia. Meperidine successfully suppressed visible shivering in all patients and was associated with significant decreases in VO2, and VCO2 and minute ventilation (VE) but not with return to basal levels. Arterial PCO2 levels remained unchanged at normal, whereas significant improvements occurred in pH and bicarbonate levels. Meperidine is an effective method of reducing the elevated metabolic demand of shivering.

Acidosis↗

Physiologic requirements during rewarming: suppression of the shivering response.

Intraoperative hypothermia has become a common occurrence. Postoperative rewarming often is accompanied by shivering and results in increased metabolic and circulatory demands. We examined the metabolic, hemodynamic, and biochemical variables in 2 groups of hypothermic (greater than 35.8 degrees C) patients requiring mechanical ventilation after a major operation. One was observed during routine medical management whereas the other group received 40 mg of metocurine iodide and then observed during routine medical management. All patients were allowed to rewarm passively. O2 consumption (VO2, ml/min, STPD), CO2 production (VCO2, ml/min, STPD) and respiratory quotient (RQ) measurements were made every 15 min using a Beckman Metabolic Measurement Cart. Esophageal temperature, arterial blood pressure, heart rate (HR), rate pressure product, CVP, arterial blood gases, serum lactate concentration, and duration of shivering also were recorded. Suppression of the shivering by metocurine increased rewarming time significantly and decreased VCO2, VO2, HR, rate pressure product, mean arterial pressure (MAP), and the O2 cost of rewarming. Thus, the elimination of shivering during postoperative rewarming is associated with a decrease in caloric, metabolic demands and myocardial work (as assessed by the rate pressure product) while rewarming time is prolonged. In the postoperative, hypothermic, critically ill patient, suppression of the shivering response in selected patients may be indicated.

Adult↗

[The evaluation of the anti-shivering effect of tramadol during epidural anesthesia].

60 patients (except parturients) suffering from shivering after receiving epidural anesthesia were randomly divided into 2 equal groups. In order to evaluate the effect of Tramadol on the shivering, i.v. Tramadol (1 mg/Kg), in contrast to distilled water (20 ml) for the control group, was administered to the patients in the experimental group. We compared the arrest time between the two groups in addition to systolic blood pressure, diastolic blood pressure, heart rate, arterial O2 saturation, respiratory rate and body surface temperature. Furthermore, the degree of shivering was also compared sequentially. The systolic pressure of the control group declined significantly in the first 30 minutes (P < 0.05). The other data, including the diastolic pressure, heart rate, arterial O2 saturation, respiratory rate and body surface temperature, showed no significant difference (P > 0.05). The arrest time in the experimental group was 179 +/- 71.25 seconds in contrast to 2790 +/- 440.23 seconds in the control group, a large significant difference (P < 0.001). 10% of the patients in the experimental group experienced nausea or vomiting and 6.67% of the patients showed sedation which did not disturb consciousness level of psychomotor status. Since the exact mechanism of shivering during epidural anesthesia is not established, we sincerely hope more information about the effect to Tramadol on shivering can be uncovered.

Adult↗

Hypercapnia lowers the shivering threshold and increases core cooling rate in humans.

BACKGROUND: Hypercapnia, which may be encountered during diving operations or by patients under general anesthesia with spontaneous respiration, alters the basic thermoregulatory responses of animals and humans. In cold-exposed animals, 3-10% inspired CO2 impairs thermal homeostasis by attenuating shivering and promoting heat loss through peripheral vasodilation. Experimental results with humans are equivocal. PURPOSE: To determine the effects of hypercapnia on warm and cold thermoregulatory responses and core cooling rates during mild cold stress, we examined the core temperature (TCO) thresholds for sweating, vasoconstriction and shivering, as well as core cooling rates of eight subjects immersed in 28 degrees C water under hypercapnic conditions. METHODS: On two separate days, subjects exercised on an underwater cycle ergometer to elevate TCO above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects inspired humidified room air during the control trial and 4% CO2/20.9% O2/balance N2 during the hypercapnia trial. RESULTS: Hypercapnia lowered the threshold for shivering by 0.13 degrees C and increased the core cooling rate by 0.35 degrees C.h-1 (25%). Minute ventilation was approximately 12.0 L.min-1 throughout cooling during control and increased from 25.3 to 28.7 L.min-1 during hypercapnia. CONCLUSIONS: Therefore, hypercapnia enhances the core cooling rate during mild cold stress. This may be attributed in part to a delay in shivering onset, as well as increased respiratory heat loss during hypercapnic hyperventilation.

Adult↗

Myelin deficiencies visualized in vivo: visually evoked potentials and T2-weighted magnetic resonance images of shiverer mutant and wild-type mice.

Visually evoked potentials (VEPs) and micro magnetic resonance imaging (micro MRI) are widely used as noninvasive techniques for diagnosis of central nervous system (CNS) diseases, especially myelin diseases, such as multiple sclerosis. Here we use these techniques in tandem to validate the in vivo data in mouse models. We used the shiverer mutant mouse, which has little or no CNS myelin, as a test model. These data show that shiverer (MBP(shi)/MBP(shi)) has a VEP latency that is 30% longer than that of its wild-type sibling. Surprisingly, the heterozygous (MBP(shi)/+) mouse, with apparently normal myelin, nevertheless has a 7% increase in its VEP latency vs. wild type. The micro MRIs of the same animals show that myelinated white matter is hypointense compared with gray matter as a result of the shorter T2 in myelinated regions of the CNS. T2-weighted images of wild-type and heterozygous shiverer mice show regions of hypointensity corresponding to the major myelinated tracts, including the optic nerve and the optic tract of the CNS, whereas shiverer mice have no regions of low intensity and therefore no detectable myelinated areas. In shiverer mice, micro MRI can discern hypomyelination throughout the brain, including the optic tract, and these changes correlate with longer VEP latencies. In addition, VEPs can also detect changes in the molecular make up of myelin that are not discernible with histology or micro MR. These data show the potential of using micro MRI in combination with VEPs to follow changes in both the quality and the quantity of myelin in vivo. These combined methods would be useful for longitudinal studies and therapy testing.

Animals↗

Developmental dissociation of myelin synthesis and "myelin-associated" enzyme activities in the shiverer mouse.

Developmental changes in three enzymes associated with myelin lipids were studied in the shiverer mouse, a murine mutant showing a severe deficiency of CNS myelin. Age-related changes in cerebroside sulfotransferase (measured in brain) and arylsulfatase A and cerebroside B-galactosidase (measured in brain and liver) were the same for shiverer and control mice. The shiverer mouse, therefore, demonstrates a dissociation between the genetic mechanisms regulating myelination in the CNS and developmental changes in enzyme activities thought to be closely related to the synthesis of myelin. In addition, we found no defect in the shiverer mouse in the incorporation of glycine-labeled basic protein into CNS myelin, indicating an important metabolic difference between the morphologically similar shiverer and quaking mutants.

Aging↗

Effects of ZnCl2 on membrane interactions in myelin of normal and shiverer mice.

X-ray diffraction was used to record the effects of metal cations on the structure of peripheral nerve myelin. Acidic saline (pH 5.0) either with or without added metal cations caused myelin to swell by 10-20 A from its native period of 178 A. The X-ray patterns usually showed broad reflections, and higher orders were either weak or unobserved. With added ZnCl2, however, the swollen myelin gave diffraction patterns that retained sharp reflections to approx. 15 A spacing. Alkaline saline (pH 9.7) containing ZnCl2 produced a reduction of the myelin period by approx. 5 A which was at least twice as much as that produced by other metals. To examine the underlying chemical basis for these unique interactions of Zn2+ with myelin, we carried out parallel X-ray experiments on sciatic nerve from the shiverer mutant mouse, which lacks the major myelin basic proteins. Shiverer myelin responded like normal myelin to ZnCl2 in acidic saline; however, in alkaline saline shiverer myelin showed broadened X-ray reflections which indicated disordering of the regularity of the membrane arrays, and additional reflections were recorded which indicated lipid phase separation. This breakdown may come about by the binding of Zn2+ to negatively-charged lipids which could be more exposed due to the absence of myelin basic proteins. Electron density profiles were calculated on the assumption that, except for changes in their packing, the myelin membranes were minimally altered in structure. For both normal and shiverer myelins, treatments under acidic conditions resulted in swelling at the extracellular apposition and a slight narrowing of the cytoplasmic space. This swelling is likely due to adsorption of protons and divalent cations. Interaction between Zn2+ and myelin P0 glycoprotein could preserve an ordered arrangement of the apposed membrane surfaces. Alkaline saline containing ZnCl2 produced compaction at the cytoplasmic apposition in both normal and shiverer myelins possibly through interactions with a portion of P0 glycoprotein which extends into the cytoplasmic space between membranes.

Animals↗