Hypertrophic cardiomyopathy: implications for anesthesia.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder and it is recognized as the most common cause of sudden cardiac death in the young, and an important substrate for disability at any age. Anesthetists may be confronted with clinically unrecognized HCM and must be prepared to anticipate the hemodynamic changes and cardiovascular instability that such patients may impose. When HCM patients are subjected to the stress of surgery, perioperative complications occur and can be devastating. Anesthesia providers need to be aware of the relevant pathophysiology and the mechanisms that may trigger or accentuate dynamic left ventricle outflow tract obstruction. Factors that worsen the degree of left ventricle outflow tract obstruction and hemondynamic strategies to improve cardiac outoput are described in the present review. Strategies to respond to hypotension must be promptly instituted to prevent the development of cardiovascular collapse, and subsequent complications. Therefore, a complete understanding of the pathophysiology, hemodynamic changes and anesthetic implications is needed for successful perioperative outcome.

A randomised controlled trial comparing the GlideScope(®) and the Macintosh laryngoscope for double-lumen endobronchial intubation.

Double-lumen endobronchial tubes are the most common method of achieving lung isolation and one-lung ventilation during thoracic anaesthesia and surgery. We compared the clinical performance of the Macintosh laryngoscope and the GlideScope(®) during endobronchial intubation with a double-lumen tube. Seventy patients with no predictors for difficult laryngoscopy were allocated randomly to the Macintosh laryngoscope or GlideScope. The time taken for endobronchial intubation with the Macintosh laryngoscope was significantly shorter compared with that taken for the GlideScope, median (IQR [range]) 33 (22-52 [11-438]) s vs 70 (39-129 [21-242]) s, respectively, p = 0.0013. There was no statistical difference in the rate of success at the first attempt (91% vs 83%, respectively). On a numerical rating scale (scored from 0 to 10), the 30 anaesthetists who took part in the study rated endobronchial intubation overall as easier using the Macintosh compared with the GlideScope, 2 (1-3 [0-8]) vs 3 (2-6 [0-10]), respectively, p = 0.003. Postoperative voice changes were also less common in the Macintosh group (8 (22%) vs 17 (58%), p = 0.045). Anaesthetists found the GlideScope more difficult to use than the Macintosh laryngoscope and endobronchial intubation took longer; therefore, we cannot recommend its routine use with double-lumen tubes in patients who are predicted to have a normal airway.

Cortical responses to speech sounds in 3- and 6-month-old infants fed breast milk, milk formula, or soy formula.

Controversy exists about the safety of soy formula, with the main concern relating to potential estrogenic effects of soy protein. Since estrogens influence early brain development, we compared behavioral development and cortical responses (event-related potentials; ERPs) to speech sounds in infants fed either breast milk or formula (milk- or soy-based). Across-groups ERP measures were generally similar and behavioral measures were within normal ranges, suggesting no important influences of soy formula on behavioral development and brain function during the study period. Analyses relating ERP and behavioral measures revealed diet- and gender-specific emphases that may reflect differences in developmental trajectories of brain-behavior relationships.

RNase L mediated protection from virus induced demyelination.

IFN-alpha/beta plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-alpha/beta dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-alpha/beta pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(-/-)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-alpha/beta expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(-/-) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-alpha/beta mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.

Early infant diet and the omega 3 fatty acid DHA: effects on resting cardiovascular activity and behavioral development during the first half-year of life.

This investigation evaluated variations in resting heart rate (HR) measures during the first half year of life in healthy, full-term infants who were either breast-fed (BF), or fed formula with (milk-based: MF; soy-based: SF) or without (soy-based: SF(-)) commercially supplemented DHA (decosahexaenoic acid). In infants fed the DHA-deficient diet, higher HR and lower values for heart rate variability measures were observed, indicating decreased parasympathetic tone in this group. These effects, appearing at 4 months and continuing for the remainder of the study period, are consistent with suggestions that the 3-5-month postnatal interval may be an important period in the development of cardiovascular regulation. The absence of these effects in SF infants receiving the DHA-supplemented formula suggests that neither soy protein nor the associated phytochemicals in soy formula contribute to these effects to any appreciable extent. In general, the results do not indicate differences in any of the study variables attributable to soy formula per se.

The influence of infant diet on early developmental changes in processing human voice speech stimuli: ERP variations in breast and milk formula-fed infants at 3 and 6 months after birth.

The purpose of this investigation was to determine if processing of language stimuli during the first half year of life in breast-fed infants differs from that of formula-fed infants. This question was addressed by examining the brain event-related potentials of healthy infants receiving breast milk (n = 15) or milk-based formula (n = 18) recorded in response to consonant vowel syllables presented in an oddball paradigm. The same infants were studied when they were 3-months and 6-months-old. The two groups were comparable on several measures relating to biological and home environment variables previously reported to influence development, including gestation period, birth weight, mother's IQ, and family socioeconomic status, and did not differ in weight or mental or motor development at the times of the visits. In general, ERP response features previously documented in studies of syllable processing in 3-6-month-old infants were observed in this study, including positive components at asymptotically equal to 190 msec (P1), asymptotically equal to 370 msec (P2), and asymptotically equal to 600 msec (P600), and negative components at asymptotically equal to 250 msec (N250), asymptotically equal to 450 msec (N450), and a late, negative going slow wave between 655 and 995 msec (LSW). For both groups there were instances where specific components were either poorly defined, e.g., P1 and N250 to the infrequent syllable at 3 months, N450 and P600 to this syllable at both ages, or not present in many infants, e.g., the P600 to the frequent syllable at 6 months. These variations appeared to be related to individual differences in development or paradigm-related features, i.e., ISI and frequency of syllable occurrence.

Effects of breast milk and milk formula diets on synthesized speech sound-induced event-related potentials in 3- and 6-month-old infants.

Effects of breast milk and milk formula supplemented with docosahexaenoic acid and arachidonic acid on speech processing were investigated by recording event-related potentials (ERPs) to synthesized /pa/ and /ba/ (oddball paradigm, 80%:20%) at 3 and 6 months of age. Behavioral assessment was also obtained. A major positive component (P200) was elicited by both types of sounds. It had a maximal scalp distribution in the fronto-central areas in both groups of infants. The mean latencies did not differ between the groups or between the stimulus types. However, the latencies decreased across age in both groups. The mean P200 amplitude in the formula-fed infants was lower than that in the breast-fed infants, but the difference was not significant. The between-stimulus differences in frontal P200 amplitudes were positively correlated with the behavioral scores of Bayley Index of Infant Development. These data suggest that the processing of the present speech stimuli is not affected by the investigated diets in the early infancy.

Growth status related to brain responses, nutrition, home environment, and behavior in infants and toddlers.

To investigate whether growth status in infants and toddlers affects processes involved in speech perception and discrimination, cortical event-related potentials (ERPs) to consonant-vowel syllables were recorded from 48 healthy babies: 26 low in growth status (LGS, < 25 th percentile in growth measures) and from 22 normal in growth status (NGS, 25t--75 th percentile in growth measures). Food records indicated no significant differences in the amounts of various nutrients consumed in the two groups, but LGS babies consumed slightly more of most nutrients than NGS babies. In response to speech stimuli (either /pa/ or /ba/ presented with 20 and 80% randomized occurrence), brain ERPs showed two prominent post-stimulus components: a large positive wave peaking at about 484 msec and a negative but positive going slow wave (SW) between 867 and 1199 msec. Principal components analysis followed by promax rotation revealed four additional important components. Maximum peak and latency values-for these components showed that NGS and LGS babies differed from one another on all measures in either amplitude, latency, or both. Comparing the two groups of babies, only the LGS group demonstrated a deficit in the phonetic discrimination of speech sounds. The growth deficiencies of the LGS group could not be attributed to the lack of an adequate diet. These negative findings are present in babies generally considered to be healthy (lowest 10-25% in growth measures). This underscores the need for research examining in more detail the relationship between growth status and cognitive growth.

Vaccine-induced memory CD8+ T cells cannot prevent central nervous system virus reactivation.

Noncytopathic viruses use multiple strategies to evade immune detection, challenging a role for vaccine induced CTL in preventing microbial persistence. Recrudescence of neurotropic coronavirus due to loss of T cell-mediated immune control provided an experimental model to test T cell vaccination efficacy in the absence of Ab. Challenge virus was rapidly controlled in vaccinated Ab-deficient mice coincident with accelerated recruitment of memory CD8+ T cells and enhanced effector function compared with primary CD8+ T cell responses. In contrast to primary effectors, reactivated memory cells persisted in the CNS at higher frequencies and retained ex vivo cytolytic activity. Nevertheless, despite earlier and prolonged T cell-mediated control in the CNS of vaccinated mice, virus ultimately reactivated. Apparent loss of memory CD8+ effector function in vivo was supported by a prominent decline in MHC expression on CNS resident target cells, presumably reflecting diminished IFN-gamma. Severely reduced MHC expression on glial cells at the time of recrudescence suggested that memory T cells, although fully armed to exert antiviral activity upon Ag recognition in vitro, are not responsive in an environment presenting few if any target MHC molecules. Paradoxically, effective clearance of viral Ag thus affords persisting virus a window of opportunity to escape from immune surveillance. These studies demonstrate that vaccine-induced T cell memory alone is unable to control persisting virus in a tissue with strict IFN-dependent MHC regulation, as evident in immune privileged sites.

A new scaling method for topographical comparisons of event-related potentials.

Recent studies have demonstrated that comparisons of scalp topographical distributions of event-related potentials (ERPs) between experiment conditions may not correctly indicate underlying changes in neural sources if the signals are not scaled prior to the comparisons. This important issue was re-evaluated in this paper using both simulated and experimental data. Simulated data were generated according to 16 different brain models containing 2-4 dipole sources varying in strength, orientation, origin and number. The changes made in the strength, orientation and origin included relative changes between the sources or symmetrical changes in the sources. Experimental data were ERPs collected from 45 infants at 3 months of age. Influences of linked-ear and average references were examined. A scaling method based on relations of signal amplitudes between conditions was devised and compared with the vector method (McCarthy and Wood, 1985). While real topographic differences generated by complex changes in underlying sources were preserved, interactions between condition and electrode site due to mere strength changes were successfully identified by the new method, irrespective of reference method used. However, the vector method was not always reliable because failure to differentiate or mistakenly indicate changes in sources may occur when a linked-mastoid reference was used. The method presented in this paper is reliable and recommended prior to topographic comparisons to distinguish different types of changes in underlying neural sources.

Differential regulation of primary and secondary CD8+ T cells in the central nervous system.

T cell accumulation and effector function following CNS infection is limited by a paucity of Ag presentation and inhibitory factors characteristic of the CNS environment. Differential susceptibilities of primary and recall CD8+ T cell responses to the inhibitory CNS environment were monitored in naive and CD8+ T cell-immune mice challenged with a neurotropic coronavirus. Accelerated virus clearance and limited spread in immunized mice was associated with a rapid and increased CNS influx of virus-specific secondary CD8+ T cells. CNS-derived secondary CD8+ T cells exhibited increased cytolytic activity and IFN-gamma expression per cell compared with primary CD8+ T cells. However, both Ag-specific primary and secondary CD8+ T cells demonstrated similar contraction rates. Thus, CNS persistence of increased numbers of secondary CD8+ T cells reflected differences in the initial pool size during peak inflammation rather than enhanced survival. Unlike primary CD8+ T cells, persisting secondary CD8+ T cells retained ex vivo cytolytic activity and expressed high levels of IFN-gamma following Ag stimulation. However, both primary and secondary CD8+ T cells exhibited reduced capacity to produce TNF-alpha, differentiating them from effector memory T cells. Activation of primary and secondary CD8+ T cells in the same host using adoptive transfers confirmed similar survival, but enhanced and prolonged effector function of secondary CD8+ T cells in the CNS. These data suggest that an instructional program intrinsic to T cell differentiation, rather than Ag load or factors in the inflamed CNS, prominently regulate CD8+ T cell function.

Effects of a carbohydrate supplement upon resting brain activity.

Glucose is a major energy source for the brain, and along with several monosaccharide derivatives as components of brain gangliosides, they play important roles in neurologic function. However, there is little information available on the role of glucose and other monosaccharides on resting brain activity. This study was designed to evaluate the effects of a single dose of a carbohydrate supplement containing glucose and several of its derivatives on resting brain activity in 20 healthy male college students. The supplement provided an insignificant amount of carbohydrate (3.9 g), protein (0.28 g), fat (0 g), and calories (14 kcal). The amount of glucose in the supplement was 0.5 g (1% the amount of glucose used in adult studies of cognitive functioning and memory). We hypothesized that the glyconutrient supplement would enhance brain activity associated with alertness and attention. The study design was double blind, with subjects randomly assigned to one of two orders, either carbohydrate supplement week one followed by placebo a week later, or the opposite. Electrical brain activity was monitored by 15 electrodes positioned at nine standard international 10-20 system locations, including three bilateral pairs at frontal, parietal, and occipital sites. Thirty minutes following ingestion of a placebo or carbohydrate supplement drink, EEG activity was recorded for 10-mins while subjects focused on a stationary visual target. Spectral power of resting brain activity was computed and analyzed contrasting the placebo and supplement groups. Relative to placebo, the carbohydrate supplement significantly enhanced power in three brain wave frequencies (theta, alpha, and beta) that are known to be associated with attention and arousal. Since changes were observed in the supplement but not placebo group, our study suggests that additional sugars in the glyconutritional supplement facilitate enhancement of brain electrical activity. Whether the apparent enhancement of arousal in baseline recordings is associated with improved task performance remains to be determined.

A survey of peri-operative use of magnesium sulphate in adult cardiac surgery in the UK.

We conducted a postal survey of cardiac anaesthetists in the UK, to determine the extent of magnesium sulphate (MgSO4) use and the main indications for its administration. Questionnaires were sent to anaesthetists at 35 UK hospitals undertaking adult cardiac surgery. Responses were received from 24 hospitals (69%) totalling 124 individual responses. Twenty-five (20%) of the anaesthetists responding to the questionnaire routinely gave magnesium other than in cardioplegia. The most common indications for administration were arrhythmia prophylaxis and treatment, myocardial protection, and the treatment of hypomagnesaemia.

Parental perception and factors associated with glycemic control in pediatric patients with type 1 diabetes.

OBJECTIVE: To compare subjective parental perceptions of short-term diabetes control with objective glycated hemoglobin (HbA1c) measurements in a pediatric population. METHODS: Parents of 159 children and adolescents with type 1 diabetes anonymously completed a questionnaire concerning demographics, parental perception of the child's recent glycemic control, concern about nocturnal blood glucose levels, and factors related to severity of the child's diabetes. Nonparametric correlations were performed among all variables and the child's current HbA1c measurement. Good short-term glycemic control was defined as an HbA1c value of < or = 8.5%. RESULTS: Five factors were found to correlate significantly with good glycemic control, and these variables were subjected to a logistic regression analysis. With use of a cutoff value of 0.58, results explained 26% of the variance and had an overall 71% correct classification rate. Children with good glycemic control were younger, had a shorter duration of diabetes, lived in families with higher socioeconomic status, were less likely to experience hospitalizations due to their diabetes, and had parents who "always worried" about nocturnal blood glucose variations. Parental perception and HbA1c values were not significantly related (P>0.19); 60% of the parents correctly perceived the status of diabetes in their children, and 40% misperceived the level of glycemic control. Further analysis suggested that accuracy of parental perception was highly dependent on the child's level of glycemic control. Parents whose children had lower HbA1c values (< or = 7.5%) correctly perceived the status of blood glucose control in their children, whereas parents whose children had poorer glycemic control (HbA1c > or = 9.5%) had inaccurate perceptions. CONCLUSION: Subjective parental perceptions of diabetes control in their children may not correspond to objective assessments. Our findings suggest a need for more educational feedback concerning HbA1c levels and recommended goals for glycemic control.

Isoflurane, but not halothane, induces protection of human myocardium via adenosine A1 receptors and adenosine triphosphate-sensitive potassium channels.

BACKGROUND: Volatile anesthetics produce differing degrees of myocardial protection in animal models of ischemia. The purpose of the current investigation was to determine the influence of isoflurane and halothane on myocardial protection in a human model of simulated ischemia and the role of adenosine A1 receptors and adenosine triphosphate-sensitive potassium (KATP) channels in the anesthetic pathway. METHODS: Human atrial trabecular muscles were superfused with oxygenated Krebs-Henseleit buffer and stimulated at 1 Hz, with recording of maximum contractile force. Fifteen minutes before a 30-min anoxic insult, muscles were pretreated for 5 min with either anoxia, the A1 agonist N6-cyclohexyladenosine, 1% halothane or 1.2% isoflurane. These treatments were also performed in the presence of either the KATP channel antagonist glibenclamide or the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Anesthetic effects were also determined on KATP currents in isolated whole cell voltage-clamped human atrial myocytes. RESULTS: Recovery of force (recorded 60 min after anoxia) in isoflurane-pretreated muscles was reduced from 76.6 +/- 7.5% of baseline to 43.7 +/- 7.1% by pretreatment with glibenclamide, and to 52.5 +/- 6.2% by pretreatment with DPCPX. Halothane treatment provided no cardioprotection and seemed to inhibit protection by anoxic preconditioning. Halothane decreased whole cell KATP currents in atrial myocytes, whereas isoflurane had no effects. CONCLUSIONS: This study demonstrates the cardioprotective effects of isoflurane in contrast to the effects of halothane. Furthermore, A1 receptors and KATP channels seem to mediate the beneficial effects of anoxia and isoflurane in human myocardium.

Inhibition of neuronal Na+ channels by antidepressant drugs.

Although tricyclic antidepressant (TCA) blockade of cardiac Na+ channels is appreciated, actions on neuronal Na+ channels are less clear. Therefore, the effects of TCAs (amitriptyline, doxepin and desipramine) as well as trazdone and fluoxetine on voltage-gated Na+ current (INa) were examined in bovine adrenal chromaffin cells using the whole-cell patch-clamp method. Amitriptyline produced concentration-dependent depression of peak INa evoked from a holding potential of -80 mV with KD value of 20.2 microM and a Hill coefficient of 1.2. Although 20 microM amitriptyline induced no change in the rate or voltage dependence of INa activation, steady-state inactivation demonstrated a 15-mV hyperpolarizing shift. Similar results were observed for doxepin and desipramine. This shift in steady-state inactivation was associated with a slowed rate of recovery from the inactivated state. Contrasting results were observed with the atypical antidepressants: while 20 microM fluoxetine depressed peak INa by 61% and caused a 7-mV hyperpolarizing shift in steady-state inactivation, 100 microM trazodone decreased peak INa by only 19% and caused only a 3-mV shift. Although the magnitude of fluoxetine effects was similar to those of the TCAs, the onset of fluoxetine effects was substantially slower than for amitriptyline. In voltage-clamp and current-clamp measurements from neonatal rat dorsal root ganglion neurons, 20 microM amitriptyline decreased INa by 52% and depressed action potential dynamics consistent with enhanced Na+ channel inactivation. The effects of the TCAs on INa are similar to local anesthetic behavior and could contribute to certain analgesic actions.

Neuropeptide Y perfused in the preoptic area of rats shifts extracellular efflux of dopamine, norepinephrine, and serotonin during hypothermia and feeding.

This study examined the localized action of neuropeptide Y (NPY) on monoamine transmitter activity in the hypothalamus of the unrestrained rat as this peptide induced hypothermia, spontaneous feeding or both responses simultaneously. A guide tube was implanted in the anterior hypothalamic pre-optic area (AH/POA) of Sprague-Dawley rats. Then either control CSF vehicle or NPY in a dose of either 100 ng/microliter or 250 ng/microliter was perfused by push-pull cannulae in this structure in the fully sated, normothermic rat. Successive perfusions were carried out at a rate of 20 microliters/min for 6.0 min with an interval of 6.0 min elapsing between each. Samples of perfusate were assayed by HPLC for their levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their respective metabolites. Whereas control CSF was without effect on body temperature (Tb) or feeding, repeated perfusions of NPY over 3.0 hr caused dose-dependent eating from 4 to 39 g of food, hypothermia of 0.9 to 2.3 degrees C or both responses concurrently. As the rats consumed 11-39 g of food, the efflux of NE, MHPG, DOPAC and 5-HT was enhanced significantly, whereas during the fall in Tb the efflux of NE, DOPAC and 5-HIAA from the AH/POA increased. When the Tb of the rat declined simultaneously with eating behavior, the levels in perfusate of DOPAC and HVA increased significantly while MHPG declined. During perfusion of the AH/POA with NPY the turnover of NE declined while DA and 5-HT turnover increased during hypothermia alone or when accompanied by feeding. These results demonstrate that the sustained elevation in NPY within the AH/POA causes a selective alteration in the activity of the neurotransmitters implicated in thermoregulation, satiety and hunger. These findings suggest that both DA and NE comprise intermediary factors facilitating the action of NPY on neurons involved in thermoregulatory and ingestive processes. The local activity of NPY on hypothalamic neurons apparently shifts the functional balance of serotonergic and catecholaminergic neurons now thought to play a primary role in the control of energy metabolism and caloric intake.