Sevoflurane induces cardioprotection through reactive oxygen species-mediated upregulation of autophagy in isolated guinea pig hearts.

PURPOSE: Sevoflurane increases reactive oxygen species (ROS), which mediate cardioprotection against myocardial ischemia-reperfusion injury. Emerging evidence suggests that autophagy is involved in cardioprotection. We examined whether reactive oxygen species mediate sevoflurane preconditioning through autophagy. METHODS: Isolated guinea pigs hearts were subjected to 30 min ischemia followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2 % sevoflurane for 10 min before ischemia (SEVO). The ROS-scavenger, N-(2-mercaptopropionyl) glycine (MPG, 1 mmol/l), was administered starting 30 min before ischemia to sevoflurane-treated (SEVO + MPG) or non-sevoflurane-treated (MPG) hearts. Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained after reperfusion to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, -II) and 5\u27 AMP-activated protein kinase (AMPK) expression using Western blot analysis. Electron microscopy was used to detect autophagosomes. RESULTS: Infarct size was significantly reduced and there were more abundant autophagosomes in SEVO compared with control. Western blot analysis revealed that the ratio of LC3-II/I and phosphorylation of AMPK were significantly increased in SEVO. These effects were abolished by MPG. CONCLUSIONS: Sevoflurane induces cardioprotection through ROS-mediated upregulation of autophagy

Sevoflurane confers additive cardioprotection to ethanol preconditioning associated with enhanced phosphorylation of glycogen synthase kinase-3β and inhibition of mitochondrial permeability transition pore opening.

OBJECTIVE: The purposes of this study were to investigate whether sevoflurane (SEVO) enhances moderate-dose ethanol (EtOH) preconditioning and whether this additional cardioprotection is associated with glycogen synthase kinase-3β (GSK-3β), protein kinase B (Akt), mammalian target of rapamycin (mTOR), 70-kDa ribosomal s6 kinase-1 (p70s6K), and/or mitochondrial permeability transition pore (MPTP) opening. DESIGN: In vitro study using an isolated heart Langendorff preparation. SETTING: University research laboratory. PARTICIPANTS: Male guinea pigs (n = 170). INTERVENTIONS: Isolated perfused guinea pig hearts underwent 30-minute ischemia and 120-minute reperfusion (control). The EtOH group received 5% EtOH in the drinking water for 8 weeks. Anesthetic preconditioning was elicited by a 10-minute exposure to 2% SEVO in EtOH (EtOH + SEVO group) or non-EtOH (SEVO group) hearts. The inhibition of GSK-3β phosphorylation and mTOR was achieved with LY294002 and rapamycin, respectively. GSK-3β, Akt, mTOR, and p70s6K expressions were determined by western blot. Calcium-induced MPTP opening was assessed in isolated calcein-loaded mitochondria. MEASUREMENTS AND MAIN RESULTS: After ischemia-reperfusion, the EtOH, SEVO, and EtOH + SEVO groups had higher left ventricular developed pressure recovery and lower end-diastolic pressure versus the control group. Infarct size was smaller in the EtOH and SEVO groups versus control and even smaller in the EtOH + SEVO group. Phosphorylation of GSK-3β and Akt, but not mTOR and p70s6K, was increased in the EtOH and SEVO groups. Phosphorylation of GSK-3β, but not mTOR and p70s6K, was further increased in the EtOH + SEVO group. The EtOH and SEVO groups exhibited a smaller calcium-induced MPTP opening, and the EtOH + SEVO presented an even smaller MPTP opening. CONCLUSIONS: SEVO and chronic EtOH preconditioning offer additive cardioprotection. This effect is associated with an increased GSK-3β phosphorylation and an inhibition of MPTP opening

Induction of autophagy restores the loss of sevoflurane cardiac preconditioning seen with prolonged ischemic insult.

Sevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We examined whether induction of autophagy prolongs sevoflurane preconditioning protection during a longer ischemic insult. Isolated guinea pigs hearts were subjected to 30 or 45 min ischemia, followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2% sevoflurane for 10 min prior to ischemia (SEVO-30, SEVO-45). Chloramphenicol (autophagy upregulator, 300 µM) was administered starting 20 min before ischemia and throughout reperfusion in SEVO-45 (SEVO-45+CAP). To inhibit autophagy, 3-methyladenine (10 μM) was administered during sevoflurane administration in SEVO-45+CAP. Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained before ischemia to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, II), Akt and glycogen synthase kinase 3β (GSK3β) expression using Western blot analysis. The effect of autophagy on calcium-induced mitochondrial permeability transition pore (MPTP) opening in isolated calcein-loaded mitochondria was assessed. Electron microscopy was used to detect autophagosomes. Infarct size was significantly reduced in SEVO-30, but not in SEVO-45. Chloramphenicol restored sevoflurane preconditioning lost by 45 min ischemia. There were more abundant autophagozomes and LC3-II expression was significantly increased in SEVO-45+CAP. Induction of autophagy before ischemia enhanced GSK3β phosphorylation and inhibition of calcium-induced MPTP opening. These effects were abolished by 3-methyladenine. Pre-ischemic induction of autophagy restores sevoflurane preconditioning lost by longer ischemic insult. This effect is associated with enhanced inhibition of MPTP by autophagy

Severe Hyponatremia due to Phlegmonous Trismus

We describe a patient with dysphagia and trismus associated with lower jaw inflammation due to phlegmon who developed severe hyponatremia from water intoxication due to excessive water intake after diaphoresis caused by abnormally hot weather. A 63-year-old woman presented with severe swelling of the floor of the mouth and trismus. As she had spasms and numbness of the extremities and restlessness and water intoxication caused by excessive water intake was suspected, she was hospitalized for the treatment of inflammation and electrolyte disorder. Although swelling of the floor of the mouth subsided over time after antimicrobial therapy, vomiting, diarrhea, and numbness of the extremities continued. On day 5 of hospitalization, severe vomiting and diarrhea recurred, and serum sodium levels decreased to 108 mEq/L. Decrease in water intake is essential in the treatment of hyponatremia. However, in patients with severe vomiting and diarrhea who can swallow only liquids because of hot weather and eating disorder, the risk of sodium depletion is high. It is important to restore electrolyte balance and fluid volume through supplementation with sodium, chlorine, potassium, and glucose among others, the reduction of intravenous fluid volume, and diuresis in order to correct the sodium level slowly

Changes in Blood Pressure During Induction of Anesthesia and Oral and Maxillofacial Surgery by Type and Timing of Discontinuation of Antihypertensive Drugs

The purpose of this study was to evaluate the effects of an antihypertensive drug class and the timing of discontinuation of antihypertensive therapy on blood pressure during oral and maxillofacial surgery for 129 patients on antihypertensive therapy receiving general anesthesia. Blood pressures at loss of response to stimulation and 5–15 minutes after intubation were significantly lower than those before induction, although the type of antihypertensive therapy did not affect changes in blood pressure. No significant correlation was observed between systolic blood pressure (SBP) on the ward and change in SBP during surgery, though patients with higher blood pressure on the ward tended to exhibit larger differences between SBP on the ward and the lowest SBP during surgery. Frequency of use of vasopressors during surgery was significantly higher in patients who discontinued antihypertensive therapy on the day before surgery than in those who continued antihypertensive therapy on the day of surgery. These findings suggest that appropriate preoperative antihypertensive therapy is important for minimizing change in blood pressure during surgery and preventing perioperative complications. Patients undergoing antihypertensive therapy should be carefully monitored perioperatively by observation for interactions between antihypertensive and anesthetic agents and minimizing interruption schedules for antihypertensive therapy