A conscious septic dog model with hemodynamic and metabolic responses similar to responses of humans

We have developed a conscious septic dog model suitable for in vivo tracer studies. Dogs weighing 10 to 20 kg underwent general anesthesia followed by the insertion of long-term arterial, venous, and portal cannulas and the formation of a long-term tracheostomy. After 7 to 10 days of convalescence, the animals were fed in the morning and 4 hours later 10(10) live Escherichia coli organisms were infused intra-arterially over approximately 30 minutes. One hour later a second dose of 5 X 10(9) bacteria was given, again over 30 minutes. Resuscitation was provided by infusion of 1000 ml of lactated Ringer solution over 3 hours. Twenty-four hours after the induction of sepsis the animals were hemodynamically stable and suitable for study. Cardiac output was increased from the control value of 185 +/- 35 ml/kg X min to 308 +/- 44 ml/kg X min in the septic animals. Heart rate was increased from 98 +/- 10 to 125 +/- 5 beats/min, and arterial pressure was not significantly altered. We employed indirect calorimetry and primed constant infusions of both radioactive and stable isotopes to assess a variety of metabolic parameters. The metabolic rate was increased approximately 25%, and the energy for this increase was primarily provided by the increased oxidation of both free fatty acids and triglyceride. The release of free fatty acids was approximately three times greater than the control value, and triglyceride synthesis increased 500%. The oxidation rate of free fatty acids and the fatty acids contained in very low density lipoproteins-triglyceride increased 40% and 900%, respectively. Glucose production was maintained at approximately the control value, and the rate of glucose oxidation (as measured with 14C-glucose) was also not significantly altered. The plasma insulin concentration was moderately elevated, and plasma glucagon concentration was five to six times greater than the control value. Plasma catecholamine levels were increased significantly. This model is suitable for the performance of metabolic studies in sepsis. The induction of a hyperdynamic septic state in less than 24 hours avoids the complications of starvation and dehydration frequently seen in the various peritonitis and abscess models. Most importantly, the model is predictable in its time course and reproducibly creates a situation that hormonally, hemodynamically, and metabolically resembles what is commonly seen in humans with sepsis.     

Effect of xenon on catecholamine and hemodynamic responses to surgical noxious stimulation in humans

STUDY OBJECTIVE: To determine the effect of xenon in combination anesthesia with sevoflurane on the catecholamine and hemodynamic responses to surgical noxious stimulation in humans. DESIGN: Randomized study. SETTING: A university hospital. PATIENTS: This study involved 32 female ASA physical status I and II patients, age 20-58 years, scheduled for abdominal hysterectomy. INTERVENTIONS: Patients were randomly divided into 4 groups: group X50-S1.5, 50% xenon and 1.5% sevoflurane; group X70-S1.5, 70% xenon and 1.5% sevoflurane; group G70-S1.5, 70% nitrous oxide and 1.5% sevoflurane; and group S2.8, 2.8% sevoflurane. No premedication was administered to the patients, and anesthesia was induced by administration of sevoflurane in oxygen and 0.10 to 0.15 mg/kg of vecuronium. After tracheal intubation, the combination of anesthetics was started, and skin incision was performed after equilibration for more than 15 minutes. MEASUREMENTS: Systolic blood pressure and heart rate (HR) were recorded, and the plasma concentrations of norepinephrine, epinephrine (E), and dopamine were measured 0, 2.5, 5, 7.5, 10, 12.5, and 15 minutes after skin incision. MAIN RESULTS: The maximal increase in the E concentration and the values of the area under the curve for E were significantly smaller in the X50-S1.5 and X70-S1.5 groups compared with that in the S2.8 group (P<0.05). At 1 minute after incision, the HR in X50-S1.5 was significantly lower than those in G70-S1.5 and S2.8 groups and the HR in X70-S1.5 was lower than that in S2.8 group (P<0.01). The systolic blood pressure in S2.8 group at 1 minute was significantly higher than those of other groups (P<0.01). CONCLUSION: Combination anesthesia using xenon and sevoflurane suppresses the plasma E concentration and hemodynamic response after skin incision more effectively than sevoflurane anesthesia alone.     

Respiratory gas exchange during total body hyperthermia in man

Respiratory gas exchange was evaluated using indirect calorimetry during total body hyperthermia (TBH) in 7 postoperative patients with disseminated gastric cancer to the peritoneal cavity. TBH was induced using veno-venous bypass and extracorporeal circuit incorporating a heat exchanger to keep pulmonary arterial temperature 42 degrees C. The high temperature was maintained for 3 hours under general anesthesia with droperidol (0.15 mg.kg-1), morphine (1 mg.kg-1) and enflurane (less than 0.5%). Oxygen consumption (VO2) was also calculated using the Fick equation and thermodilution cardiac output. Hyperthermia for three hours increased both VO2 and carbon dioxide output (VCO2) values to 1.5 times as compared to the control values before heating, respectively. VO2 values measured by indirect calorimetry correlated well with the values calculated from the Fick equation when respiratory and cardiovascular system were relatively stable during the procedure. Gradual but statistically insignificant increase in respiratory quotient was observed after recooling started. These results suggest that indirect calorimetry was valuable to measure respiratory gas exchange continuously during hyperthermic state as well as normothermic state. However, RQ value observed in the present study may be modified by several factors including lactate accumulation in the blood, and may not reflect substrate utilization during the hyperthermic state.     

Cerebral oxygen extraction and autoregulation during extracorporeal whole body hyperthermia in humans

BACKGROUND: The effects of hyperthermia on the human brain are incompletely understood. This study assessed the effects of whole body hyperthermia on cerebral oxygen extraction and autoregulation in humans. METHODS: Nineteen patients with chronic hepatitis C virus infection, not responding to interferon treatment, were subjected to experimental therapy with extracorporeal whole body hyperthermia at 41.8 degrees C for 120 min under propofol anesthesia (23 sessions total). During treatment series A (13 sessions), end-tidal carbon dioxide was allowed to increase during heating. During series B (10 sessions), end-tidal carbon dioxide was maintained approximately constant. Cerebral oxygen extraction (arterial to jugular venous difference of oxygen content) and middle cerebral artery blood flow velocity were continuously measured. Cerebral pressure-flow autoregulation was assessed by static tests using phenylephrine infusion and by assessing the transient hyperemic response to carotid compression and release. RESULTS: For treatment series A, cerebral oxygen extraction decreased 2.2-fold and cerebral blood flow velocity increased 2.0-fold during heating. For series B, oxygen extraction decreased 1.6-fold and flow velocity increased 1.5-fold. Jugular venous oxygen saturation and lactate measurements did not indicate cerebral ischemia at any temperature. Static autoregulation test results indicated loss of cerebrovascular reactivity during hyperthermia for both series A and series B. The transient hyperemic response ratio did not decrease until the temperature reached approximately 40 degrees C. Per degree Celsius temperature increase, the transient hyperemic response ratio decreased 0.07 (95% confidence interval, 0.05-0.09; P = 0.000). This association remained after adjustment for variations in arterial partial pressure of carbon dioxide, mean arterial pressure, and propofol blood concentration. CONCLUSION: Profound hyperthermia during propofol anesthesia is associated with decreased cerebral oxygen extraction, increased cerebral blood flow velocity, and impaired pressure-flow autoregulation, indicating transient partial vasoparalysis.     

Endocrine responses to total intravenous anesthesia with droperidol,fentanyl, and ketamine in cardiac patients

Ketamine-induced sympathetic stimulation can be inhibited by administration of sedatives such as benzodiazepines, droperidol, or opioids. We have developed total intravenous anesthesia with ketamine in combination with droperidol and fentanyl (DFK) and have used this anesthetic method in more than 4000 surgical cases. In this study, we compared DFK in cardiac surgery with isoflurane-fentanyl anesthesia (AOI-F). Fourteen patients undergoing aortocoronary artery bypass graft surgery were randomly assigned to the DFK or AOI-F groups. The endocrine responses of the patients were evaluated from the plasma, levels of cortisol, antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), and aldosterone. In both groups, anesthesia per se did not induced any significant changes in the hormones. Although cortisol and ADH increased during surgery, ANP and aldosterone did not change appreciably. All hormones were significantly elevated after the end of cardiopulmonary bypass. There were no significant differences in any of the hormones, blood pressure, and heart rate measured at different points in both groups. These results showed that DFK anesthesia as a total intravenous anesthesia deserves to be studied in more depth.     

The influence of total body hyperthermia on brain haemodynamics and blood-brain barrier in dogs

Summary To determine the incidence of induced systemic hypotension in patients after aneurysmal subarachnoid haemorrhage (SAH) and nimodipine treatment 87 consecutive cases were reviewed.The patients were managed according to the same Nimodipine treatment protocol. After confirmation of SAH the nimodipine treatment was started as a continuous intravenous perfusion at a dosage of 0.5 mg/h and gradually increased every 6 hours if haemodynamically tolerated until the maintenance dose of 2 mg/h was reached. Median systemic pressure was continuously measured and tolerated until a lowest limit of 75 mmHg. In 31 patients (36%) hypotension with values below 75 mmHg during at least 30 minutes was noted and needed Nimodipine reduction. Intravenous Nimodipine administration was responsible for hypotension in 26 cases as compared to 5 cases due to oral administration. 38% of all patients required support by vaso-active agents (Dopamine or Noradrenaline).There was no statistically significant difference of incidence of delayed ischaemic deterioration comparing the Nimodipine-reduction group with the normal dose group.This study demonstrates that a considerable risk exists of Nimodipine induced hypotension in intravenous administration despite gradually increasing the doses. Correction of hypotension through further induced hypervolaemia accompanied by vasoactive agents can lead to critical haemodynamic situations. We therefore recommend oral Nimodipine administration.     

Pulmonary and systemic hemodynamic responses to fentanyl in infants

Pulmonary and systemic hemodynamic responses to fentanyl were studied in 12 infants after repair of congenital heart defects. During controlled ventilation, hemodynamic responses to 25 micrograms/kg of fentanyl were measured. No significant changes were found in heart rate, cardiac index, mean pulmonary artery pressure, or pulmonary vascular resistance index 5 min after the fentanyl had been given. There were small but statistically significant decreases in mean arterial pressure and systemic vascular resistance index after fentanyl. We conclude that under the conditions of this study, pulmonary and systemic hemodynamics in infants are minimally altered by 25 micrograms/kg of fentanyl.     

Efficacy of landiolol in attenuating hemodynamic responses to local epinephrine infiltration in patients undergoing vaginal total hysterectomy

Purpose Local epinephrine infiltration often causes ₁-adrenoceptor-mediated tachycardia, hypertension, and arrhythmia. Landiolol, a short acting ₁-adrenoceptor blocker, may represent the most ideal agent to attenuate these adverse effects. In this study, we examined the effects of landiolol on the hemodynamic changes resulting from local infiltration of epinephrine.Methods Thirty-six patients undergoing vaginal total hysterectomy under general anesthesia were randomly assigned to one of three groups: control group (n = 12), L5 group (n = 12), and L10 group (n = 12). In the control, L5, and L10 groups, the patients were given saline, landiolol 5mg, and 10mg, respectively, just before infiltration of epinephrine(1:300000; total dose, about 100µg) into the surgical field. Blood pressure and heart rate was assessed before and 5, 10, 15, 20, 25, 30min after the initiation of epinephrine infiltration. If systolic blood pressure and heart rate exceeded 160mmHg and 120 beats·min^–1, respectively, Ca blockers of either diltiazem 5mg or nicardipine 1mg and/or 2% sevoflurane were given.Results Epinephrine infiltration significantly increased systolic blood pressure from 122 ± 15 to 170 ± 29mmHg and heart rate from 63 ± 8 to 106 ± 10 beats·min^–1. In both the L5 and L10 groups, the increase in heart rate (from 69 ± 16 to 87 ± 16 beats·min^–1, P < 0.01, and from 70 ± 18 to 76 ± 9 beats·min^–1, P < 0.01, respectively) was significantly smaller compared to the control group, but the increase in systolic blood pressure was significantly attenuated in the L10 group (from 116 ± 18 to 140 ± 27mmHg, P < 0.01). The number of patients given either Ca blockers or sevoflurane in the control group was significantly higher than that in the landiolol groups (P < 0.01).Conclusion The present study suggests that landiolol 10mg may be a more suitable dose than landiolol 5mg to antagonize hyperdynamic states induced by local administration of epinephrine.     

Bone hemodynamic responses to changes in external pressure

Adequate blood supply and circulation to the bones is required to maintain a healthy skeleton. Inadequate blood perfusion is associated with numerous bone pathologies and a decrease in bone mineral density, yet bone hemodynamics remains poorly understood. This study aims to 1) quantify bone hemodynamic responses to changes in external pressure, and 2) identify the predominant mechanisms regulating bone hemodynamic responses to pressure changes. Photoplethysmography was used to measure bone and skin perfusion in response to changes in external pressure. Single-limb pressure chamber experiments were performed over a pressure range of ? 50 to + 50 mm Hg. Bone perfusion is decreased at all negative pressures, and larger decrements in perfusion are observed at the more extreme pressure differences. At positive pressures we observed an initial increase in perfusion followed by activation of intramuscular pressure receptors at + 30 mm Hg, which overrides the initial response and results in decreased perfusion at the highest positive pressure levels. The myogenic effect is observed and is shown to be the predominant control mechanism in bone over a wide range of pressure exposures. Greater understanding of these hemodynamic mechanisms may be important in developing new drugs and therapies to treat various bone disorders.     

Wheal and flare responses to opioids in humans

Certain opioids release histamine from cutaneous mast cells to produce local wheal and flare responses and adverse hemodynamic effects. In vivo responses to opioids suggest that cutaneous responses result from the interaction of opioids with opioid receptors on human mast cells. There are no data evaluating or comparing the opioids currently used in anesthesia. Volunteers were injected intradermally with different opioids as well as with naloxone and antihistamines to evaluate their effects on cutaneous mast cell reactivity and cutaneous vascular responses. Fentanyl and morphine produced concentration-dependent wheal and flare responses in the range of 5 X 10(-6) M to 1.5 X 10(-3) M. Volunteers were then tested intradermally with different opioids and histamine at a 5 X 10(-4) M concentration to determine their relative cutaneous effects. Morphine, meperidine, fentanyl, and sufentanil produced both wheal and flare responses that were significantly greater than those due to saline (P less than 0.05). Naloxone, alfentanil, and nalbuphine did not produce significant wheal or flare responses. Butorphenol was followed by a significant wheal but no flare. Naloxone attentuated cutaneous wheal and flare responses to fentanyl and the flare response to morphine. Intradermal antihistamines (diphenhydramine and cimetidine) produced significant wheal and flare responses. Electron micrographs of biopsies from fentanyl-induced wheals demonstrated normal mast cell architecture with no evidence of mast cell degranulation. Opioid effects on wheal and flare responses and mast cell degranulation appear independent of opioid analgesic potency. Opioids produce cutaneous vascular responses dependent on both histamine release from mast cells and direct effects on the vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine and immune responses to resistance training in prostate cancer patients

This study examined the effect of 20 weeks resistance training on a range of serum hormones and inflammatory markers at rest, and following acute bouts of exercise in prostate cancer patients undergoing androgen deprivation. Ten patients exercised twice weekly at high intensity for several upper and lower-body muscle groups. Neither testosterone nor prostate-specific antigen changed at rest or following an acute bout of exercise. However, serum growth hormone (GH), dehydroepiandrosterone (DHEA), interleukin-6, tumor necrosis factor-alpha and differential blood leukocyte counts increased (P < 0.05) following acute exercise. Resistance exercise does not appear to compromise testosterone suppression, and acute elevations in serum GH and DHEA may partly underlie improvements observed in physical function.     

Hyperoxia and the cerebral hemodynamic responses to moderate hyperventilation

BACKGROUND: A reduction in the arterial partial pressure of CO2 (PaCO2) leads to a rapid reduction in cerebral blood flow (CBF). However, despite continuing hypocapnia there is secondary recovery of CBF over time as a result of increases in lactic acid production. Hyperoxia is thought to modulate the production of lactic acid. This study examined the kinetics of middle cerebral artery flow velocity (MCA FV) reduction during hyperventilation, and its modulation by hyperoxia. METHODS: Cerebral blood flow was assessed using transcranial Doppler ultrasound in nine healthy, awake human volunteers. Subjects were ventilated, via a mouthpiece, to achieve a stable end-tidal CO2 (PETCO2). After a 20-min baseline period the minute volume on the ventilator was passively increased by approximately 20% to reduce PETCO2 by 0.75-1 kPa. After a 10-min stabilization period the new PETCO2 level was maintained at a constant level for 20 min, and MCA FV recovery was measured during this 20-min period. Subjects undertook the protocol breathing air and breathing 100% oxygen. RESULTS: The PETCO2 level was (mean +/- SD) 4.9 +/- 0.4 kPa (normoxia baseline), 4.0 +/- 0.3 kPa (normoxia hyperventilation), 4.6 +/- 0.4 kPa (hyperoxia baseline) and 3.9 +/- 0.4 kPa (hyperoxia hyperventilation). CO2 reactivity was significantly lower with normoxia than hyperoxia (16.5 +/- 3.8 vs. 21.2 +/- 4.6 % kPa-1; P< 0.05). Middle cerebral artery FV recovery was significantly more rapid with normoxia than hyperoxia (0.23 +/- 0.17 vs. 0.08 +/- 0.1 % baseline min-1; P< 0.01). CONCLUSIONS: Our results suggest that cerebral hemodynamic responses to moderate hyperventilation are different in normoxic and hyperoxic conditions. Clinical assessment of CO2 reactivity and CBF recovery during hyperventilation should take the degree of arterial oxygenation into account.     

Dexmedetomidine and hemodynamic responses to simulated hemorrhage in experimental heart failure

alpha(2)-Adrenoreceptor agonists may counteract the increased basal sympathetic nervous activity in patients with congestive heart failure (CHF), but they may also compromise reflex responses to hypovolemia. We have tested responses to simulated hemorrhage (central hypovolemia) after IV dexmedetomidine in normal animals and in experimental chronic CHF. Rabbits (n = 14) were treated with IV doxorubicin (or control saline) for 8 weeks inducing biventricular dilatation and myocardial damage. Cardiac output (CO) was measured continuously with a transit-time Doppler implanted on the ascending aorta. Progressive inflation of a cuff around the inferior vena cava (simulated hemorrhage) was used to reduce cardiac index at a constant rate. Arterial baroreceptor-mediated vasoconstrictor and heart rate responses were tested with repeated cuff inflations. Although resting CO was reduced in CHF, the blood pressure and heart rate changes with dexmedetomidine were not exaggerated. The slope of the vasoconstrictor response to graded hypovolemia was attenuated by dexmedetomidine with an earlier onset of decompensation. There was no added effect of CHF on the response until the dose of dexmedetomidine was sufficient to reduce resting CO in addition to arterial blood pressure and heart rate. Implications: As an adjunct to anesthesia, dexmedetomidine may be useful in reducing basal sympathetic nervous activity. This study in experimental animals suggests this may be achieved without compromising protective responses to decreased blood volume.     

Hormonal and hemodynamic responses to halothane and enflurane in spontaneously hypertensive rats

Forty-two spontaneously hypertensive rats (SHR) and 42 normotensive Wistar-Kyoto rats (WKY) were anesthetized with either halothane or enflurane. Blood pressure, heart rate, cardiac output, distribution of blood flow, plasma renin activity, and plasma catecholamines were measured to determine in what manner the hypertensive animal responded to these two anesthetics. Major findings of the study were that plasma renin activity did not increase in the SHR despite a 25% reduction in MAP. The infusion of saralasin, an angiotensin II antagonist, resulted in a further decrease in blood pressure in SHR anesthetized with halothane but not with enflurane. Plasma catecholamine concentrations were elevated in the awake SHR and were decreased in SHR anesthetized with enflurane. Both halothane and enflurane anesthesia resulted in similar alterations in blood flow in the SHR. The normotensive WKY responded to halothane and enflurane in a different manner than the SHR. Plasma renin activity increased with the decrease in blood pressure with both agents. A further decrease in blood pressure occurred with saralasin infusion in WKY anesthetized with halothane or enflurane. Significant blood flow alterations occurred in the WKY anesthetized with both agents, but enflurane caused the greatest changes. The SHR may prove useful in examining the effects of anesthetic agents and other drugs so that we may have a better understanding of the perioperative management of the patients with essential hypertension.     

Fructose amplifies counterregulatory responses to hypoglycemia in humans

Glucokinase (GK) is required for cellular glucose sensing, although there is a paucity of data regarding its role in the counterregulatory response to hypoglycemia in humans. Because fructose has been shown to modulate GK activity, we examined the effects of an acute infusion of fructose on hypoglycemia counterregulation in seven lean nondiabetic subjects. Using stepped hypoglycemia clamp studies (5.0, 4.4, 3.9, and 3.3 mmol/l target plasma glucose steps, 50 min each), subjects were studied on two separate occasions, without (control) or with co-infusion of fructose (1.2 mg.kg(-1).min(-1)). Fructose induced a resetting of the glycemic thresholds for secretion of epinephrine (3.8 +/- 0.1 mmol/l) and glucagon (3.9 +/- 0.2 mmol/l) to higher plasma glucose concentrations (4.0 +/- 0.1 mmol/l [P = 0.006] and 4.1 +/- 0.1 mmol/l [P = 0.03], respectively). In addition, the magnitude of increase in epinephrine and glucagon concentrations was higher after administration of fructose (48 and 39%, respectively, P < 0.05 for both). The amplification of these hormonal responses was specific because plasma norepinephrine, growth hormone, and cortisol were comparable in both sets of studies. Endogenous glucose production, measured with [3-(3)H]glucose, increased by 47% (P < 0.05) in the fructose infusion studies compared with 14% (P = NS) in the control studies. In addition, glucose uptake was more suppressed with fructose infusion (by 33%, P < 0.05). In concert with these effects of fructose on glucose kinetics, average glucose infusion rate was markedly reduced in the fructose infusion studies during the 3.9-mmol/l glucose step (4.6 +/- 0.9 vs. 7.4 +/- 1.1 micromol.kg(-1).min(-1), respectively, P = 0.03) and during the 3.3-mmol/l glucose step (0.5 +/- 0.1 vs. 5.2 +/- 1.2 micromol.kg(-1).min(-1), respectively, P < 0.001), suggesting more potent glucose counterregulation and improved recovery from hypoglycemia with fructose infusion. We conclude that infusion of a catalytic dose of fructose amplifies the counterregulatory response to hypoglycemia by both increases in hormonal activation and augmentation of glucose counterregulation in humans.     

Physiologic responses to mild perianesthetic hypothermia in humans

To evaluate physiologic responses to mild perianesthetic hypothermia, we measured tympanic membrane and skin-surface temperatures, peripheral vasoconstriction, thermal comfort, and muscular activity in nine healthy male volunteers. Each volunteer participated on three separate days: 1) normothermic isoflurane anesthesia; 2) hypothermic isoflurane anesthesia (1.5 degrees C decrease in central temperature); and 3) hypothermia alone (1.5 degrees C decrease in central temperature) induced by iced saline infusion. Involuntary postanesthetic muscular activity was considered thermoregulatory when preceded by central hypothermia and peripheral cutaneous vasoconstriction. Tremor was considered normal shivering when electromyographic patterns matched those produced by cold exposure in unanesthetized individuals. During postanesthetic recovery, central temperatures in hypothermic volunteers increased rapidly when residual end-tidal isoflurane concentrations were less than or equal to 0.3% but remained 0.5 degree C less than control values throughout 2 h of recovery. All volunteers were vasodilated during isoflurane administration. Peripheral vasoconstriction occurred only during recovery from hypothermic anesthesia, at end-tidal isoflurane concentrations of less than approximately 0.4%. Spontaneous tremor was always preceded by central hypothermia and peripheral vasoconstriction, indicating that muscular activity was thermoregulatory. Maximum tremor intensity during recovery from hypothermic anesthesia occurred when residual end-tidal isoflurane concentrations were less than or equal to 0.4%. Three patterns of postanesthetic muscular activity were identified. The first was a tonic stiffening that occurred in some normothermic and hypothermic volunteers when end-tidal isoflurane concentrations were approximately 0.4-0.2%. This activity appeared to be largely a direct, non-temperature-dependent effect of isoflurane anesthesia. In conjunction with lower residual anesthetic concentrations, stiffening was followed by a synchronous, tonic waxing-and-waning pattern and spontaneous electromyographic clonus, both of which were thermoregulatory. Tonic waxing-and-waning was by far the most common pattern and resembled that produced by cold-induced shivering in unanesthetized volunteers; it appears to be thermoregulatory shivering triggered by hypothermia. Spontaneous clonus resembled flexion-induced clonus and pathologic clonus and did not occur during hypothermia alone; it may represent abnormal shivering or an anesthetic-induced modification of normal shivering. We conclude that among the three patterns of muscular activity, only the synchronous, tonic waxing-and-waning pattern can be attributed to normal thermoregulatory shivering.