Age-associated changes in cardiac gene expression after preconditioning.

BACKGROUND: Cardiac protection afforded by ischemic preconditioning (IPC) and anesthetic preconditioning (APC) are significantly reduced in the senescent myocardium. The authors hypothesized that age would differentially modulate gene expression induced by IPC and APC in vivo. METHODS: Affymetrix RAT EXON ST 1.0 gene chips (Affymetrix, Santa Clara, CA) were used to explore the transcriptional response to IPC and APC in Fisher 344 male rats (young, 3-5 months, and old, 20-24 months, respectively). Both cohorts, young and old, were divided into three groups: (1) sham control, (2) IPC, and (3) APC. After a total of 90 min, the heart was removed, and the total RNA and protein were extracted. RESULTS: Thirty-one transcripts were increased in the young animals subjected to IPC, particularly transcriptional regulators (Atf3, Egr-1, Btg2, Egr2), cytokines (interleukin 6, CSF1, Myd88), chemokines (Cxcl10, Ccl2, Ccl7), regulators of growth and inflammation (Reg3g, Hamp), remodeling and cell adhesion migration (Cyr61, Tfpi2, Timp1), regulators of apoptosis/cell death (Birc3, Arntl, Hamp, Phlda1), and cell cycle control/DNA repairs (Rrad, Gadd45b, Gadd45g). In contrast, only one transcript increased (Atf3) in the old animals subjected to IPC. No changes in gene expression were found in the young or the old animals subjected to APC. CONCLUSIONS: Early-phase IPC and APC induced different genomic responses. The absence of detectable changes associated with early-phase APC suggests a posttranscriptional or posttranslational mechanism. The absence of a genomic response in the senescent myocardium (except for IPC-induced Atf3) could underlie the failure of IPC to provide any cardiac protective benefit to older animals.

Spectral entropy predicts auditory recall in volunteers.

BACKGROUND: From a patient's perspective, intraoperative amnesia is an essential component of general anesthesia. Without specific strategies to reduce recall, its incidence is approximately 0.2% in the general surgical population and may be higher in certain subpopulations. We sought to test the validity for predicting recall of a new spectral entropy-based clinical electroencephalogram monitor. METHODS: We studied 16 volunteers in an unblinded crossover design to assess the correlation of entropy values with behavioral end points during sedation with either propofol or sevoflurane. The end points we considered included word recall, and motor response to verbal command. We also examined the stimulatory effect of verbal commands on electroencephalogram entropy. Logistic regression, receiver operating characteristics, and prediction probability were used to analyze the data. RESULTS: Both State Entropy and Response Entropy were closely correlated with both behavioral end points. The prediction probability of these parameters under a variety of conditions ranged from 0.85 to 0.96. Verbal command to move increased entropy in a dose and drug-dependent fashion. CONCLUSIONS: Entropy parameters in this group of young, healthy volunteers appear to be reliable predictors of recall. These results justify extending these studies to additional anesthetics and to surgical patients.

Isoflurane modulates genomic expression in rat amygdala.

General anesthesia, at a minimum, provides amnesia and unresponsiveness. Although anesthetics have many modulatory effects on neuronal ionophore protein complexes, it is not clear that the resulting electrophysiologic changes are the sole mechanisms of clinical anesthetic action. Cells respond to environmental changes in several ways, including alterations in DNA transcription leading to changes in the cell's proteins. We sought to expose the changes in global genomic expression, seeking potential targets involved in the processes of anesthetic-induced amnesia, and persistent long-term side effects of general anesthesia, including nausea and postoperative cognitive decline. Using Affymetrix GeneChips, we surveyed changes in expression across the entire expressed genome of Sprague-Dawley rat (n = 10 baseline, n = 6 isoflurane) basolateral amygdala 6 h after exposure to 15 min of 2% (1.4 MAC) isoflurane. Isoflurane administration was associated with altered expression in 269 unique genes possessing functional annotation. Affected genes were related to DNA transcription, protein synthesis, metabolism, signaling cascades, cytoskeletal structural proteins, and neural-specific proteins, among others. Even brief exposure to isoflurane leads to widespread changes in the genetic control in the amygdala 6 h after exposure. Gene expression is a dynamic process that may explain some long-term effects of anesthesia and that has the potential to modulate some of those effects using specific molecular therapeutics.

Communication in critical care environments: mobile telephones improve patient care.

Most hospital policies prohibiting the use of wireless devices cite reports of disruption of medical equipment by cellular telephones. There have been no studies to determine whether mobile telephones may have a beneficial impact on safety. At the 2003 meeting of the American Society of Anesthesiologists 7878 surveys were distributed to attendees. The five-question survey polled anesthesiologists regarding modes of communication used in the operating room/intensive care unit and experience with communications delays and medical errors. Survey reliability was verified using test-retest analysis and proportion agreement in a convenience sample of 17 anesthesiologists. Four-thousand-eighteen responses were received. The test-retest reliability of the survey instrument was excellent (Kappa = 0.75; 95% confidence interval, 0.56-0.94). Sixty-five percent of surveyed anesthesiologists reported using pagers as their primary mode of communications, whereas only 17% used cellular telephones. Forty-five percent of respondents who use pagers reported delays in communications compared with 31% of cellular telephone users. Cellular telephone use by anesthesiologists is associated with a reduction in the risk of medical error or injury resulting from communication delay (relative risk = 0.78; 95% confidence interval, 0.6234-0.9649). The small risks of electromagnetic interference between mobile telephones and medical devices should be weighed against the potential benefits of improved communication.

The incidence of awareness during anesthesia: a multicenter United States study.

Awareness with recall after general anesthesia is an infrequent, but well described, phenomenon that may result in posttraumatic stress disorder. There are no recent data on the incidence of this complication in the United States. We, therefore, undertook a prospective study to determine the incidence of awareness with recall during general anesthesia in the United States. This is a prospective, nonrandomized descriptive cohort study that was conducted at seven academic medical centers in the United States. Patients scheduled for surgery under general anesthesia were interviewed in the postoperative recovery room and at least a week after anesthesia and surgery by using a structured interview. Data from 19,575 patients are presented. A total of 25 awareness cases were identified (0.13% incidence). These occurred at a rate of 1-2 cases per 1000 patients at each site. Awareness was associated with increased ASA physical status (odds ratio, 2.41; 95% confidence interval, 1.04-5.60 for ASA status III-V compared with ASA status I-II). Age and sex did not influence the incidence of awareness. There were 46 additional cases (0.24%) of possible awareness and 1183 cases (6.04%) of possible intraoperative dreaming. The incidence of awareness during general anesthesia with recall in the United States is comparable to that described in other countries. Assuming that approximately 20 million anesthetics are administered in the United States annually, we can expect approximately 26,000 cases to occur each year.