Preconditioning by isoflurane is mediated by reactive oxygen species generated from mitochondrial electron transport chain complex III

Reactive oxygen species (ROS) mediate volatile anesthetic preconditioning. We tested the hypothesis that isoflurane (ISO) generates ROS from electron transport chain complexes I and III. Rabbits (n = 55) underwent 30 min coronary artery occlusion followed by 3 h reperfusion and received 0.9% saline, the complex I inhibitor diphenyleneiodonium (DPI; 1.5 mg/kg bolus followed by 1.5 mg/kg over 1 h), or the complex III inhibitor myxothiazol (MYX; 0.1 mg/kg bolus followed by 0.3 mg/kg over 1 h) in the absence and presence of 1.0 minimum alveolar concentration ISO. ISO was administered for 30 min and discontinued 15 min before coronary occlusion. Infarct size and ROS production (n = 32) were determined using triphenyltetrazolium staining and ethidium-DNA fluorescence, respectively. Adenosine triphosphate (ATP) synthesis in mitochondria obtained from rabbit hearts (n = 24) subjected to drug interventions was measured by luciferin-luciferase luminometry. ISO significantly (P < 0.05) reduced infarct size (19% +/- 4%) as compared with control (39% +/- 4%). MYX (35% +/- 4%), but not DPI (24% +/- 2%), abolished this protection. ISO increased ethidium-DNA fluorescence (83 +/- 11 U) as compared with control (40 +/- 12 U). MYX (35 +/- 3 U), but not DPI (78 +/- 9 U), abolished ROS generation. DPI and MYX selectively reduced complex I- and complex III-mediated ATP synthesis, respectively. ROS generated from electron transport chain complex III mediate ISO-induced cardioprotection.     

Mitochondrial adenosine triphosphate-regulated potassium channel opening acts as a trigger for isoflurane-induced preconditioning by generating reactive oxygen species

BACKGROUND: Whether the opening of mitochondrial adenosine triphosphate-regulated potassium (K(ATP)) channels is a trigger or an end effector of anesthetic-induced preconditioning is unknown. We tested the hypothesis that the opening of mitochondrial K(ATP) channels triggers isoflurane-induced preconditioning by generating reactive oxygen species (ROS) in vivo. METHODS: Pentobarbital-anesthetized rabbits were subjected to a 30-min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive a vehicle (0.9% saline) or the selective mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD) alone 10 min before or immediately after a 30-min exposure to 1.0 minimum alveolar concentration (MAC) isoflurane. In another series of experiments, the fluorescent probe dihydroethidium was used to assess superoxide anion production during administration of 5-HD or the ROS scavengers N-acetylcysteine or N-2-mercaptopropionyl glycine (2-MPG) in the presence or absence of 1.0 MAC isoflurane. Myocardial infarct size and superoxide anion production were measured using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively. RESULTS: Isoflurane (P < 0.05) decreased infarct size to 19 +/- 3% (mean +/- SEM) of the left ventricular area at risk as compared to the control (38 +/- 4%). 5-HD administered before but not after isoflurane abolished this beneficial effect (37 +/- 4% as compared to 24 +/- 3%). 5-HD alone had no effect on infarct size (42 +/- 3%). Isoflurane increased fluorescence intensity. Pretreatment with N-acetylcysteine, 2-MPG, or 5-HD before isoflurane abolished increases in fluorescence, but administration of 5-HD after isoflurane only partially attenuated increases in fluorescence produced by the volatile anesthetic agent. CONCLUSIONS: The results indicate that mitochondrial K(ATP) channel opening acts as a trigger for isoflurane-induced preconditioning by generating ROS in vivo.     

An outbreak of food poisoning in a military establishment

Background: An outbreak of food poisoning in a military establishment mess was investigated and remedial measures suggested.     

Facilitating the transition to practice: a weekend retreat curriculum for business-of-medicine education of United States anesthesiology residents

Anesthesiology residents in the United States (US) not only must develop the clinical skills needed to provide independent patient care, but also are required to become familiar with the business aspects of the modern health care system. Unfortunately, practice management education may be inadequate during anesthesiology residency training. The authors describe the design and implementation of a weekend retreat curriculum in business-of-medicine education for anesthesiology residents. Experts were recruited to discuss interviewing skills, contract law and negotiation, billing and reimbursement, insurance, malpractice, and financial planning. A strict lecture didactic format was avoided, and presentations were designed to encourage speaker–audience interaction. The program was relatively simple to design and implement, satisfied several Accreditation Council of Graduate Medical Education core competencies for US anesthesiology education, may be altered as practice management evolves, and may be adapted to accommodate the needs of programs in other countries.     

The Heartsink Patient: A Preliminary Study

Eight GPs identified 78 heartsink patients; in an open-endedinterview they were asked to explain why they regarded themin this way. A GP's definition of a heartsink patient was influencedby GP sex, practice location, and time of surgery, althoughthe number of participating GPs was too low to make any definiteassertions. Practitioners' anticipations of heartsink consultationswere generally over-exaggerated, with most of the encountersgoing better than expected. GPs expressed the view that thesepatients raised serious professional issues for them, whilstthere was also a dislike for these patients' personalities andbehaviour. Two levels of the heartsink state are hypothesized:one, a state of inertia, is when the heartsink patient has beena chronic high user of the primary health care system, and aGP has exhausted all avenues. The other is an acute situationwith those heartsink patients who have been low users of thesystem in the past. Recent, new events in these patients' liveshave raised an issue that is just as much to do with patientand doctor reaction to these events, as it is about findinga diagnosis or solution to the problem. We present the results and hypotheses to provoke further discussionand research.