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In the United States, nearly 5% of the population has or has had cancer. Anesthetists frequently encounter patients in all stages of cancer and cancer treatment. This chapter highlights the short term and long term end-organ effects of common chemotherapeutics relevant to the anesthetist and reviews current concepts about how anesthetics may impact cancer and cancer survival.

Background: Several retrospective studies suggest that perioperative care and anesthetic management for cancer resection may influence cancer recurrence or patient survival. Various intraoperative techniques such as paravertebral blocks, decreased opioid use, immunomodulation, and perioperative antiinflammatory administration, have previously been assessed for improved patient survival. The aim of this study was to assess associations between perioperative management and survival in patients undergoing resection of pancreatic adenocarcinoma. Methods: Survival data and anesthetic records for 144 patients who had surgical resection of pancreatic adenocarcinoma from 2001 to 2012 were obtained and associations were sought between survival and 19 predefined variables. The authors performed a propensity weighted multivariable statistical analysis using Cox proportional hazards. Results: Median length of survival was 562 days with 95% confidence interval (471, 680). In a multivariable Cox proportional hazard model of survival, the authors found increased survival in patients who received perioperative epidural analgesia and/or intraoperative dexamethasone. There was a 44% hazard ratio reduction, hazard ratio = 0.56, 95% confidence interval (0.38, 0.87), with dexamethasone. Adjuvant postoperative chemotherapy was associated with longer survival. A decrease in survival was noted in patients who received intraoperative blood transfusions, had poorer histologic grade, and advanced tumor stage. Conclusions: The authors report an association between perioperative dexamethasone administration and improved survival in human pancreatic adenocarcinoma patients. An association between use of epidural anesthesia during primary pancreatic cancer surgery and prolonged survival was also observed. Previously identified associations between perioperative blood transfusions and poor tumor histologic grade and decreased survival were confirmed. Further investigations regarding the use of perioperative dexamethasone and neuraxial anesthesia in this patient population are warranted.

The mechanism by which n-alkanols produce anesthesia and the characteristics relevant to those mechanisms (e.g., lipid solubilities versus potencies) remain unknown. Accordingly, we determined potencies (minimum alveolar anesthetic concentration [MAC]) and solubilities of normal methanol, ethanol, butanol, hexanol, and octanol. We also determined the additivity of these alkanols with a conventional anesthetic (desflurane) and the additivity of methanol with butanol. Finally, we determined whether alkanol metabolism influences alkanol potencies. MAC for methanol, ethanol, butanol, hexanol, and octanol (0.00200, 0.000989, 0.000133, 0.0000214, and 0.00000117 atm, respectively) increased with an increasing solubility in olive oil (olive oil/gas partition coefficients 48.6, 108, 1,650, 11,600, and 93,500, respectively) and octanol (octanol/gas partition coefficients 163, 1,150, 22,900, 135,000, and 4,140,000) to give a product of MAC x solubility for olive oil approximately 10 times less (values of 0.10-0.25) than that expected from the Meyer-Overton hypothesis (compared with conventional inhaled anesthetics). There was less deviation for octanol, but the results were more variable. Inhibition of methanol and butanol metabolism by 4-methylpyrazole did not alter MAC. Methanol, ethanol, butanol, hexanol, and octanol had approximately additive anesthetic effects with desflurane, with some small but statistically significant deviations both above and below additivity. In the presence of 0.5 MAC of desflurane, we needed to add 0.4-0.6 MAC of each alkanol to inhibit the movement of 50% of the rats in response to noxious stimulation. Similarly, the effects of methanol and butanol were additive (with each other). The saline/gas partition coefficient for each alkanol was high (3700, 2650, 1400, 900, and 709 for methanol through octanol), which indicates high polarity. We conclude that the potent anesthetic effects of normal alkanols may result from an affinity to both polar and nonpolar phases. Our finding of additivity of alkanols with each other is consistent with a common mechanism of action. Similarly, the finding of additivity or slight deviations from additivity for alkanols with desflurane is consistent with mechanisms of action that have much in common.

The anesthetic concentration just suppressing appropriate response to command (minimum alveolar anesthetic concentration awake [MAC-awake] for volatile anesthetics or plasma concentration to prevent a response in 50% of patients [Cp50]-awake for intravenous anesthetics) provides three important measures. First, along with pharmacokinetics, the ratio of the awakening concentration to the anesthetizing concentration (MAC-awake/MAC or Cp50-awake/Cp50) determines time to awakening. Second, a correlation between MAC-awake and the anesthetic concentration sufficient to prevent learning suggests MAC-awake provides a surrogate measure of amnestic potency. Third, population values for MAC-awake provide evidence for or against commonality in anesthetic mechanisms. We studied 22 male volunteers twice to determine both MAC-awake for desflurane (2.60% +/- 0.46%) and Cp50-awake for propofol (2.69 +/- 0.56 microgram/mL). Awakening with desflurane occurs at a concentration closer to its anesthetizing concentration (36% of MAC) than propofol (18% of Cp50); that is, 1) desflurane requires less of a decrement in anesthetic concentration at the effect site for arousal; and 2) if MAC-awake (Cp50-awake) values reflect the concentrations providing amnesia, propofol is a more potent amnestic. Of interest, the dose response curves of desflurane and propofol were equivalently steep, a finding consistent with a common mechanism of action. In contrast, sensitivity of each volunteer to desflurane did not correlate with sensitivity to propofol (r2 < 0.01, P = 0.98) arguing against a common mechanism.

Whether anesthetized patients register emotionally charged information remains controversial. We tested this possibility using subanesthetic concentrations of propofol or desflurane. Twenty-two volunteers (selected for hypnosis susceptibility) received propofol and desflurane (on separate occasions, and in a random order) at a concentration 1.5-2 times each individual's minimum alveolar anesthetic concentration (MAC)-awake (or equivalent for propofol). We gave vecuronium, intubated the trachea of each volunteer, controlled ventilation, and then presented a neutral (control) drama or a "crisis" drama stating that the oxygen delivery system had failed, assigning crisis and control dramas in a blinded, randomized, and balanced manner. One day later, interviewers blinded to the assigned drama conducted a 2-h structured interview (including hypnosis) to determine whether the contents of the interviews after crisis and control dramas differed. In addition, messages permitting subsequent assessment of learning of matter-of-fact information (Trivial Pursuit-type question task and a behavior task) were presented at the anesthetic concentration just sufficient to prevent response to command in each volunteer. No analyses of the tasks involving matter-of-fact information revealed learning except one which correlated hypnosis susceptibility with behavior task performance. Both propofol and desflurane suppressed memory of the crisis. Consistent with previous findings for isoflurane and nitrous oxide, propofol and desflurane suppressed learning of matter-of-fact information at concentrations just above MAC-awake, except that volunteers' susceptibility to hypnosis correlated with performance of a behavior suggested during anesthesia. Propofol and desflurane suppressed learning of emotionally charged information at anesthetic concentrations 1.5-2 times MAC-awake (less than MAC), a different result from that previously reported for ether.

Anecdotal reports suggest that soda lime and Baralyme brand absorbent can degrade inhaled anesthetics to carbon monoxide (CO). We examined the factors that govern CO production and found that these include: 1) The anesthetic used: for a given minimum alveolar anesthetic concentration (MAC)-multiple, the magnitude of CO production (greatest to least) is desflurane > or = enflurane > isoflurane >> halothane = sevoflurane. 2) The absorbent dryness: completely dry soda lime produces much more CO than absorbent with just 1.4% water content, and soda lime containing 4.8% or more water (standard soda lime contains 15% water) generates no CO. In contrast, both completely dry Baralyme and Baralyme with 1.6% water produce high concentrations of CO, and Baralyme containing 4.7% water produces concentrations equaling those produced by soda lime containing 1.4% water. Baralyme containing 9.7% or more water and standard Baralyme (13% water) do not generate CO.3) The type of absorbent: at a given water content, Baralyme produces more CO than does soda lime. 4) The temperature: an increased temperature increases CO production. 5) The anesthetic concentration: more CO is produced from higher anesthetic concentrations. These results suggest that CO generation can be avoided for all anesthetics by using soda lime with 4.8% (or more) water or Baralyme with 9.7% (or more) water, and by using inflow rates of less than 2-3 L/min. Such inflow rates are low enough to ensure that the absorbent does not dry out.

The capacity of desflurane to suppress learning is unknown.We investigated whether a subanesthetic concentration of desflurane (0.6 minimum alevolar anesthetic concentration [MAC]) suppressed learning as much as the same concentration of isoflurane, and whether such suppression differed with increasing duration of anesthesia and intervening changes in anesthetic concentration. Using a cross-over-design study in 18-30 yr-old human volunteers, we supplied answers to Trivial Pursuit Registered Trademark (Selchow & Righter Co., Bay Shore, NY)-like questions at 0.6 MAC desflurane and isoflurane before and after imposing a half-hour period at 1.7 MAC of each anesthetic, and behavioral directions and a category-example task at 0.6 MAC after the period at 1.7 MAC. These volunteers had a third anesthesia in which no information was supplied (control). After anesthesia, we tested whether the provision of answers during anesthesia increased the number of correct answers to Trivial Pursuit Registered Trademark questions. We tested for the number of correct answers for information presented before versus after the 1.7-MAC period, for increased evocation of examples of categories presented during anesthesia, and for exhibition of a behavior suggested during anesthesia. We found that 0.6 MAC of both anesthetics prevented explicit and implicit learning before and after the period at 1.7 MAC. (Anesth Analg 1995;80:568-72)

Background A greater MAC fraction of nitrous oxide than isoflurane is required to prevent response to verbal commands and suppress the capacity to learn. Speculating that this difference between these agents may be caused by nitrous oxide's capacity to increase sympathetic activity, we tested the hypothesis that nitrous oxide may antagonize the suppression of learning found with isoflurane. Methods We administered a combination of isoflurane and nitrous oxide at three subanesthetic test concentrations (0.43, 0.56, and 0.68 MAC) to 24 healthy male volunteers. Assuming additivity of the anesthetics, the first test concentration was selected to suppress learning of new Information by 50% (ED50 for suppression of learning); the second concentration, to suppress the ability to respond appropriately to verbal command by 50% (MAC-awake); and the third, to provide 1.4 times MAC-awake. Three tests of learning were applied. At each test concentration, we provided 7 answers to “trivial pursuit”-type questions, resulting in a set of 21 answered questions for each volunteer; an additional 7 unanswered questions served as controls. At the highest test concentration, each volunteer also heard two examples from each of two categories (4 words) repeated 30 times (the category-example task), and a message instructing them to touch either their nose or their ear during a specified interval in the postanesthetic interview (the behavior task). Results The MAC-awake value for the combination of isoflurane and nitrous oxide was 118 ± 4% of the expected value (i.e., the two anesthetics were antagonistic for this effect). Consistent with antagonism, the anesthetic concentration predicted to suppress learning by 30% permitted significantly more learning, and the ED50 was 105 ± 2% of that predicted. Neither the category task nor the behavior task demonstrated evidence of learning at 1.4 times MAC-awake. Conclusions Our results are consistent with an antagonism between nitrous oxide and isoflurane; however, the degree of antagonism is small.

Nonanesthetic gases or vapors do not abolish movement in response to noxious stimuli despite partial pressures and affinities for lipids that would, according to the Meyer-Overton hypothesis, predict such abolition. We investigated whether nonanesthetics depress learning and memory (i.e., provide amnesia). To define learning, we used a "fear-potentiated startle paradigm": rats trained to associate light with a noxious stimulus (footshock) will startle more, as measured by an accelerometer, when a startle-eliciting stimulus (e.g., a noise) is paired with light than when the startle-eliciting stimulus is presented alone. We imposed light-shock pairings on 98 rats under three conditions: no anesthesia (control); 0.20, 0.29, and 0.38 times the minimum alveolar anesthetic concentration (MAC) of desflurane; or two nonanesthetics (1,2-dichloroperfluorocyclobutane and perfluoropentane) at partial pressures predicted from their lipid solubilities to be between 0.2 and 1 MAC. Desflurane produced a dose-related depression of learning with abolition of learning at 0.28 MAC. Perfluoropentane at 0.2-predicted MAC had the same effect as 0.28 MAC desflurane. 1,2-Dichloroperfluorocyclobutane at 0.5- to 1-predicted MAC abolished learning. Because nonanesthetics suppress learning but not movement (the two critical components of anesthesia), they may prove useful in discriminating between mechanisms and sites of action of anesthetics.

Neither lipophilicity nor vapor pressure of larger n-alkanes appear to correlate with their anesthetizing partial pressures in inspired gas. Such results suggest that the Meyer-Overton hypothesis and Ferguson's rule may not apply to these compounds. An alternative explanation might be that a large difference in inspired-to-arterial partial pressure exists, i.e., that the inspired partial pressure misrepresents the effective partial pressure. To test this explanation, we investigated the kinetics of five consecutive even-numbered n-alkanes (C2H6 to C10H22) in rats. The ratio of end-tidal-to-inspired (PA/PI), arterial-to-end-tidal (Pa/PA), and arterial-to-inspired (Pa/PI) partial pressures decreased with increasing carbon chain length, consistent with our separate finding that blood solubility increased. Using Pa/PI and the minimum inspired concentration (MIC) obtained previously, we calculated the true effective potency, minimum alveolar anesthetic concentration (MAC); of these n-alkanes as (Pa/PI)(MIC). This markedly improved, but did not perfectly correct, the correlation of MAC with lipid solubility (the Meyer-Overton hypothesis) and vapor pressure (Ferguson's rule). A coefficient of variation of 76.7% was found for the product of MAC and the olive oil/gas partition coefficient. More importantly, the correlation of the logarithm of MAC and oil solubility had a slope of -0.724 (i.e., deviated from -1.0), whereas the slope for eight conventional anesthetics was -1.046 (approached-1.0). These data imply that olive oil does not adequately mimic the nature of the anesthetic site of action of n-alkanes.

Anesthetic potencies (minimum alveolar anesthetic concentration [MAC]) of perfluoroalkanes from perfluoromethane to perfluorooctane were assessed in male rats to determine whether a cutoff in anesthetic effect (i.e., an absence of any anesthetic effect) exists for the larger compounds in this series. Although hyperbaric measurements suggested a MAC of 38.9 +/- 6 atm (mean +/- SD) for CF4, this pressure was nearly identical to the lethal pressure of 41.1 +/- 5.8 atm. Hyperbaric studies of C2F6 caused death without causing anesthesia, the lethal pressure being 23.8 +/- 2.6 atm. Results from studies of additivity with desflurane suggested that the MAC of CF4 was 66.5 +/- 13.4 atm at an average CF4 test partial pressure of 17.7 +/- 4.0 atm (i.e., 17.7 atm of CF4 decreased the MAC of desflurane by 26.6%). Studies of additivity with desflurane, isoflurane, or halothane did not reveal an anesthetic effect of C2F6 at a pressure of 7.2 +/- 0.4 atm, or of larger perfluoroalkanes near to or at their saturated vapor pressures. We conclude that a cutoff in anesthetic potency for perfluoroalkanes exists between perfluoromethane and perfluoroethane.

Previously, we found unconscious (implicit) learning in subjects given subanesthetic, but not anesthetic, concentrations of isoflurane. Other investigators, using different learning tasks, have reported implicit learning at anesthetic concentrations. We investigated whether one of these tasks might provide a more sensitive test of implicit learning. In addition, to determine whether suppression of explicit or implicit learning is dose-dependent, we studied one of the tasks at three subanesthetic concentrations.We applied a category-example task at 0.15, 0.28, and 0.4 minimum alveolar concentration (MAC) of isoflurane, and a behavior task only at 0.4 MAC. After anesthesia, we determined whether volunteers more frequently listed an example of a category (e.g., flute as an example of musical instrument) presented during anesthesia and/or demonstrated a behavior (touching ear, chin, or knee) suggested to them at 0.4 MAC.Results from the category task indicated implicit learning only at 0.15 MAC, a concentration that also permitted significant explicit learning. Explicit learning was demonstrated at 0.28 but not at 0.4 MAC (ED50 of 0.20 MAC and ED95 of 0.4 MAC). Results from the behavior task revealed neither implicit nor explicit learning.The ED50 that suppressed explicit learning in our volunteers equaled that previously reported (0.2 MAC) for implicit learning in volunteers measured using a different task. Combined, these results suggest that less than 0.45 MAC isoflurane suppresses learning in volunteers.

Background Suppression of response to command commonly indicates unconsciousness and generally occurs at anesthetic concentrations that suppress or eliminate memory formation. The authors sought midlatency auditory evoked potential indices that successfully differentiated wakeful responsiveness and unconsciousness. Methods The authors correlated midlatency auditory evoked potential indices with anesthetic concentrations permitting and suppressing response in 22 volunteers anesthetized twice (5 days apart), with desflurane or propofol. They applied stepwise increases of 0.5 vol% end-tidal desflurane or 0.5 microg/ml target plasma concentration of propofol to achieve sedation levels just bracketing wakeful response. Midlatency auditory evoked potentials were recorded, and wakeful response was tested by asking volunteers to squeeze the investigator's hand. The authors measured latencies and amplitudes from raw waveforms and calculated indices from the frequency spectrum and the joint time-frequency spectrogram. They used prediction probability (PK) to rate midlatency auditory evoked potential indices and concentrations of end-tidal desflurane and arterial propofol for prediction of responsiveness. A PK value of 1.00 means perfect prediction and a PK of 0.50 means a correct prediction 50% of the time (e.g., by chance). Results The approximately 40-Hz power of the frequency spectrum predicted wakefulness better than all latency or amplitude indices, although not all differences were statistically significant. The PK values for approximately 40-Hz power were 0.96 during both desflurane and propofol anesthesia, whereas the PK values for the best-performing latency and amplitude index, latency of the Nb wave, were 0.86 and 0.88 during desflurane and propofol (P = 0.10 for -40-Hz power compared with Nb latency), and for the next highest, latency of the Pb wave, were 0.82 and 0.84 (P < 0.05). The performance of the best combination of amplitude and latency variables was nearly equal to that of approximately 40-Hz power. The approximately 40-Hz power did not provide a significantly better prediction than anesthetic concentration; the PK values for concentrations of desflurane and propofol were 0.91 and 0.94. Changes of 40-Hz power values of 20% (during desflurane) and 16% (during propofol) were associated with a change in probability of nonresponsiveness from 50% to 95%. Conclusions The approximately 40-Hz power index and the best combination of amplitude and latency variables perform as well as predictors of response to command during desflurane and propofol anesthesia as the steady-state concentrations of these anesthetic agents. Because clinical conditions may limit measurement of steady-state anesthetic concentrations, or comparable estimates of cerebral concentration, the approximately 40-Hz power could offer advantages for predicting wakeful responsiveness.

Background Increases in desflurane and isoflurane concentrations can transiently increase arterial blood pressure or heart rate or both during induction of anesthesia. The current study tested the hypothesis that a rapid increase of desflurane concentration in humans increases sympathetic activity and hormonal variables and heart rate and arterial blood pressure more than does an equivalent increase in isoflurane concentration. Methods Twelve healthy male volunteers were assigned randomly to receive desflurane and on a separate occasion isoflurane. After induction of anesthesia with propofol 2 mg/kg, anesthesia was maintained at 0.55 MAC (desflurane, 4.0%; isoflurane 0.71% end-tidal) for 32 min. Mechanical ventilation maintained normocapnia throughout anesthesia. Mean arterial blood pressure and heart rate were recorded continuously, and arterial blood was sampled for plasma catecholamine and vasopressin (AVP) concentrations, and plasma renin activity. Anesthetic concentration was increased rapidly to 1.66 MAC (desflurane, 12.0%; isoflurane 2.12% end-tidal), and maintained at this concentration for 32 min, and then rapidly decreased to and maintained at 0.55 MAC for an additional 32 min. Results Neither anesthetic produced sympathetic or cardiovascular stimulation during their initial rapid wash-in to 0.55 MAC. The rapid increase to 1.66 MAC increased mean arterial blood pressure, heart rate, and plasma epinephrine and norepinephrine concentrations, and plasma renin activity with both desflurane and isoflurane, the former usually producing a response of greater magnitude than the latter. Plasma AVP concentration increased with desflurane only. Increased mean arterial blood pressure returned to control in 4 min. Heart rate decreased 50% of the difference between its peak and the value at 32 min at 1.66 MAC in 2 min with desflurane and in 4 min with isoflurane but did not return to the value at 0.55 MAC with either anesthetic. With desflurane, plasma epinephrine and AVP concentrations decreased quickly from their peak values, remaining elevated for 8 min. Decrease of concentrations of desflurane and isoflurane from 1.66 MAC to 0.55 MAC rapidly decreased heart rate and increased mean arterial blood pressure with both anesthetics. Thirty-two minutes after return to 0.55 MAC, with both anesthetics, only heart rate remained increased relative to the values at 32 min of the initial period of 0.55 MAC anesthesia. Conclusions In healthy male volunteers, rapid increases of desflurane or isoflurane from 0.55 to 1.66 MAC increase sympathetic and renin-angiotensin system activity, and cause transient increases in arterial blood pressure and heart rate. Desflurane causes significantly greater increases than isoflurane, and also causes a transient increase in plasma AVP concentration. The temporal relationships suggest that the increased sympathetic activity increases mean arterial blood pressure and heart rate, with mean arterial blood pressure also increased by increased plasma AVP concentration, whereas the delayed, increased plasma renin activity is likely a response to the ensuing hypotension, or earlier inhibition by AVP, or both.

Fourteen polyhalogenated, completely halogenated (perhalogenated), or perfluorinated compounds were examined for their anesthetic effects in rats. Anesthetic potency or minimum alveolar anesthetic concentration (MAC) was quantified using response/nonresponse to electrical stimulation of the tail as the end-point. For compounds that produced excitable behavior, and/or did not produce anesthesia when given alone, we determined MAC by additivity studies with desflurane. Nine of 14 compounds had measurable MAC values with products of MAC x oil/gas partition coefficient ranging from 3.7 to 24.8 atm. Because these products exceed that for conventional inhaled anesthetics (1.8 atm), they demonstrate a deviation from the Meyer-Overton hypothesis. Five compounds (CF3CCIFCF3, CF3CCIFCCIFCF3, perfluorocyclobutane, 1,2-dichloroperfluorocyclobutane, and 1,2-dimethylperfluorocyclobutane) had no anesthetic effect when given alone, had excitatory effects when given alone, and tended to increase the MAC for desflurane. These five compounds had no anesthetic properties in spite of their abilities to dissolve in lipids and tissues, to penetrate into the central nervous system, and to be administered at high enough partial pressures so that they should have an anesthetic effect as predicted by the Meyer-Overton hypothesis. Such compounds will be useful in identifying and differentiating anesthetic sites and mechanisms of action. Any physiologic or biophysical/biochemical change produced by conventional anesthetics and deemed important for the anesthetic state should not be produced by nonanesthetics.

We examined 35 unfluorinated, partially fluorinated, and perfluorinated methanes, ethanes, propanes, and butanes to define those molecular properties that best correlated with optimum solubility (low) and potency (high). Limited additional data were obtained on longer-chained alkanes. Using standard techniques, we assessed anesthetic potency (minimum alveolar anesthetic concentration [MAC] in rats); vapor pressure; stability in soda lime; and solubility in saline, human blood, and oil. If nonflammability, stability, low solubility in blood, clinically useful vapor pressures, and potency permitting delivery of high concentrations of oxygen are essential components of an anesthetic that might supplant those presently available, our data indicate that such a drug would have three or four carbon atoms with single or dual hydrogenation of two carbons, especially terminal carbons. We conclude that: 1) smaller and larger molecules and lesser hydrogenation provide insufficient potency; 2) high vapor pressures of smaller molecules do not permit the use of variable bypass vaporizers; 3) greater hydrogenation enhances flammability, and complete hydrogenation decreases potency; 4) internal hydrogenation decreases stability; and 5) greater hydrogenation increases blood solubility.

In conflict with the prediction of the Meyer-Overton hypothesis, perfluoropropane (C3F8) and perfluoropentane (C5F12) have no anesthetic effect in rats. To test whether this resulted from a failure of the inspired drugs to reach the brain, we determined the increase in partial pressures of C3F8 and C5F12 in the blood and brains of rats exposed to 0.65 ata of each drug. C3F8 and C5F12 blood/gas partition coefficients equaled 0.00125 +/- 0.00037 (mean +/- SD, n = 9) and 0.00277 +/- 0.00082 (n = 4), and brain/gas partition coefficients equaled 0.0119 +/- 0.0002 (n = 4) and 0.0229 +/- 0.0055 (n = 7), respectively. As a fraction of the inspired value (Pa/PI), the partial pressures of C3F8 and C5F12 in blood (Pa) were 0.99 +/- 0.12 and 0.69 +/- 0.19, respectively, 30 min after administration. The increases in cerebral (Pb) partial pressures of both drugs paralleled the arterial increases (Pb/PI = 0.85 +/- 0.02, and 1.05 +/- 0.03, respectively at 30 min), with C3F8 reaching a plateau at 2 h of 96% +/- 4% of the partial pressure of inspired gas. We conclude that failure of C3F8 and C5F12 to reach the brain does not account for the absence of an anesthetic effect of these compounds.

The total number of bifurcated and nonbifurcated fibers were counted in rat soleus muscles induced to hypertrophy by surgical ablation of the gastrocnemius and plantaris muscles. Sham-operated and normal soleus muscles served as controls. Every muscle fiber within the entire muscle was individually examined and counted with the aid of a dissecting microscope following a 10-12 hour nitric acid digestion of the connective tissue. The results show that the total number of muscle fibers in the hypertrophic soleus did not differ significantly from the control. The frequency of bifurcated fibers observed in the control muscles was significantly greater than has been previously reported, and their frequency in the hypertrophic muscles, although slightly increased, was not significantly different from control values. These data confirm that fiber hypertrophy is not accompanied by hyperplasia, and they further suggest that bifurcated fibers probably play an insignificant role during muscle adaptation to hypertrophy due to their very low frequency.