Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo

BACKGROUND: Volatile anesthetics protect against cardiac ischemia-reperfusion injury via adenosine triphosphate-dependent potassium channel activation. The authors questioned whether volatile anesthetics can also protect against renal ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate-dependent potassium channels, antiinflammatory effects of volatile anesthetics, or both are involved. METHODS: Rats were anesthetized with equipotent doses of volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of renal ischemia and 3 h of reperfusion during anesthesia. RESULTS: Rats treated with volatile anesthetics had lower plasma creatinine and reduced renal necrosis 24-72 h after injury compared with rats anesthetized with pentobarbital or ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane-treated rats had creatinine (+/- SD) of 2.3 +/- 0.7 mg/dl (n = 12), 1.8 +/- 0.5 mg/dl (n = 6), and 2.4 +/- 1.2 mg/dl (n = 6), respectively, compared with rats treated with pentobarbital (5.8 +/- 1.2 mg/dl, n = 9) or ketamine (4.6 +/- 1.2 mg/dl, n = 8). Among the volatile anesthetics, desflurane demonstrated the least reduction in plasma creatinine after 24 h (4.1 +/- 0.8 mg/dl, n = 12). Renal cortices from volatile anesthetic-treated rats demonstrated reduced expression of intercellular adhesion molecule 1 protein and messenger RNA as well as messenger RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic treatment reduced renal cortex myeloperoxidase activity and reduced nuclear translocation of proinflammatory nuclear factor kappaB. Adenosine triphosphate-dependent potassium channels are not involved in sevoflurane-mediated renal protection because glibenclamide did not block renal protection (creatinine: 2.4 +/- 0.4 mg/dl, n = 3). CONCLUSION: Some volatile anesthetics confer profound protection against renal ischemia-reperfusion injury compared with pentobarbital or ketamine anesthesia by attenuating inflammation. These findings may have significant clinical implications for anesthesiologists regarding the choice of volatile anesthetic agents in patients subjected to perioperative renal ischemia.     

Effects of halothane,isoflurane and sevoflurane on ischemiareperfusion injury in the perfused liver of fasted rats

Background : Although intraoperative ischemia-reperfusion of the liver generally occurs under general anesthesia, little is known about the direct effect of anesthetic agents on hepatic injury due to this phenomenon. The effect of volatile anesthetics on ischemia-reperfusion injury was studied using isolated liver perfusion. Methods : The liver was isolated from 24-h-fasted male Sprague-Dawley rats and perfused through the portal vein with a modified Krebs-Ringer bicarbonate solution in a recirculating perfusion-aeration system. Ischemia was induced by reducing the baseline perfusion pressure from 1.2 to 0.2 kPa followed by reperfusion to baseline level. The ischemia-reperfusion injury was assessed by LDH release from the perfused liver. We studied the effect of halothane, isoflurane and sevoflurane on the ischemia-reperfusion injury during 20 min of control conditions, exposure of the liver to 60 min of ischemia and reperfusion for 90 min. Results : Ischemia was evident by reduced portal vein flow and oxygen consumption, and caused an increase in lactate production. Reperfusion caused a transient reduction in lactate production and a significant increase in LDH release. All anesthetics reduced hepatic oxygen consumption and increased the net lactate production during control conditions. Volatile anesthetics also significantly attenuated LDH release during reperfusion. The suppression of LDH release was observed even when isoflurane was administered during the reperfusion period, but not when it was administered only during ischemia. Conclusion : These results indicate that volatile anesthetics may protect the fasted liver from early, neutrophil-independent, ischemia-reperfusion injury by acting during the reperfusion phase.     

Differential Protective Effects of Volatile Anesthetics against Renal Ischemia-Reperfusion Injury In Vivo

Background: Volatile anesthetics protect against cardiac ischemia-reperfusion injury via adenosine triphosphate-dependent potassium channel activation. The authors questioned whether volatile anesthetics can also protect against renal ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate-dependent potassium channels, antiinflammatory effects of volatile anesthetics, or both are involved.

Methods: Rats were anesthetized with equipotent doses of volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of renal ischemia and 3 h of reperfusion during anesthesia.

Results: Rats treated with volatile anesthetics had lower plasma creatinine and reduced renal necrosis 24-72 h after injury compared with rats anesthetized with pentobarbital or ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane-treated rats had creatinine (+/- SD) of 2.3 +/- 0.7 mg/dl (n = 12), 1.8 +/- 0.5 mg/dl (n = 6), and 2.4 +/- 1.2 mg/dl (n = 6), respectively, compared with rats treated with pentobarbital (5.8 +/- 1.2 mg/dl, n = 9) or ketamine (4.6 +/- 1.2 mg/dl, n = 8). Among the volatile anesthetics, desflurane demonstrated the least reduction in plasma creatinine after 24 h (4.1 +/- 0.8 mg/dl, n = 12). Renal cortices from volatile anesthetic-treated rats demonstrated reduced expression of intercellular adhesion molecule 1 protein and messenger RNA as well as messenger RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic treatment reduced renal cortex myeloperoxidase activity and reduced nuclear translocation of proinflammatory nuclear factor [kappa]B. Adenosine triphosphate-dependent potassium channels are not involved in sevoflurane-mediated renal protection because glibenclamide did not block renal protection (creatinine: 2.4 +/- 0.4 mg/dl, n = 3).     

Neutrophils pretreated with volatile anesthetics lose ability to cause cardiac dysfunction

BACKGROUND: Volatile anesthetics can precondition the myocardium against functional depression and infarction following ischemia-reperfusion. Neutrophil activation, adherence, and release of superoxide play major roles in reperfusion injury. The authors tested the hypothesis that pretreatment of neutrophils with a volatile anesthetic, i.e., simulated preconditioning, can blunt their ability to cause cardiac dysfunction. METHODS: Studies were performed in 60 buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as an index of myocardial contractility. Polymorphonuclear neutrophils and/or drugs were added to coronary perfusate for 10 min, followed by 30 min of recovery. Platelet-activating factor was used to stimulate neutrophils. Pretreatment of neutrophils consisted of incubation with 1.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 15 min, followed by washout. Additional studies were performed with 0.25 MAC isoflurane. Effects of superoxide dismutase were compared to those of volatile anesthetics. Superoxide production was measured by spectrophotometry. Neutrophil adherence to coronary vascular endothelium was estimated from the difference between neutrophils administered and recovered in coronary venous effluent. RESULTS: Activated neutrophils caused marked, persistent reduction (> 50%) in left ventricular developed pressure. Isoflurane and sevoflurane at 1.0 MAC and superoxide dismutase abolished this effect. Isoflurane and sevoflurane reduced superoxide production of activated neutrophils by 29% and 33%, respectively, and completely prevented the platelet-activating factor-induced increases in neutrophil adherence. Isoflurane at 0.25 MAC blunted, but did not abolish, the neutrophil-induced decreases in left ventricular developed pressure. CONCLUSION: Neutrophils pretreated with 1.0 MAC isoflurane or sevoflurane lost their ability to cause cardiac dysfunction, while those pretreated with a concentration of isoflurane as low as 0.25 MAC were partially inhibited. This action of the volatile anesthetics was associated with reductions in superoxide production and neutrophil adherence to the coronary vascular endothelium. Our findings suggest that inhibitory actions on neutrophil activation and neutrophil-endothelium interaction may contribute to the preconditioning effects of volatile anesthetics observed in vivo during myocardial ischemia-reperfusion.     

麻醉药物对心肌缺血再灌注损伤的保护研究进展

心肌缺血再灌注损伤(MIRI)是临床上一类非常常见而严重的并发症,被麻醉学界广泛关注.实际上,自从1985年Freedman首次报道安氟醚能改善缺血后心功能以来,如何找到防治MIRI经济有效的方法,已经成为这个领域多年来研究的方向.大量实验证明,多种麻醉药物对MIRI具有不同方面的保护作用.此文综述了国内外关于麻醉药物以及具有中国特色和优势的中药复方制剂对MIRI保护研究的进展,其中重点综述几种代表性药物,如瑞芬太尼、丙泊酚、咪达唑仑、参附注射液等,并总结了近年来这一方向的研究成果.     

Comparison of seven anesthetic agents on outcome after experimental traumatic brain injury in adult, male rats

Isoflurane is commonly used in experimental traumatic brain injury (TBI), both before and early after injury, yet it is rarely used clinically. Narcotics and benzodiazepines are frequently used after injury in clinical TBI. We compared seven anesthetic/sedative agents applied after injury in the controlled cortical impact model: diazepam, fentanyl, isoflurane, ketamine, morphine, pentobarbital, and propofol. Our objective was to provide insight into the relative degrees of neuroprotection provided by these agents in a standard model of TBI. We hypothesized that the choice of anesthetic/sedative early after experimental TBI critically impacts outcome and that the agents most commonly used clinically may be less neuroprotective than isoflurane. Rats treated with isoflurane had the best cognitive recovery (p < 0.05) and hippocampal neuronal survival (p < 0.05). Conversely, rats treated with ketamine had the most hippocampal neuronal death (p < 0.05). Morphine or propofol, two agents commonly used clinically, were associated with the poorest motor function on post-trauma day 1-5 (p < 0.05). Our data support beneficial effects of isoflurane early after experimental TBI. Our data suggest that the early post-TBI use of isoflurane, despite practical logistical issues, could potentially provide clinical benefits in TBI--versus other commonly used sedatives or analgesics. Furthermore, the choice of post-injury sedation and analgesia could have important implications on attempts to translate novel therapies from bench to field or bedside.     

Differential Effects of Anesthetic Agents on Outcome from Near-complete but Not Incomplete Global Ischemia in the Rat

Background: It has been postulated that anesthetic agents that reduce cerebral metabolic rate will protect the brain against ischemia when electroencephalographic (EEG) activity is persistent, but will provide no protection when ischemia is severe enough to cause EEG isoelectricity. No outcome studies have addressed this issue. The authors studied anesthetic agents to determine if they provide differential effects on outcome from global cerebral ischemic insults that cause either an attenuated or isoelectric EEG.

Methods: Fasted rats were subjected to either (1) incomplete ischemia (attenuated EEG; 20 min of mean arterial pressure [MAP] = 50 mmHg and bilateral carotid occlusion) or (2) near-complete ischemia (isoelectric EEG; 10 min of MAP = 30 mmHg and bilateral carotid occlusion) while anesthetized with 1.4% isoflurane, 1 mg [middle dot] kg-1 [middle dot] min-1 ketamine, or 25 [micro sign]g [middle dot] kg-1 [middle dot] h-1 70% nitrous oxide and fentanyl. The brain was maintained at normothermia during ischemia and for 22 h after ischemia. Five days later, hippocampal CA1 and cortical injury were measured.

Results: There was no difference among anesthetic agents during incomplete ischemia for mean +/- SD percentage dead CA1 neurons (fentanyl, 38% +/- 20%; isoflurane, 31% +/- 10%; ketamine, 40% +/- 19%; P = 0.38). During near-complete ischemia, there was a difference among anesthetic agents (fentanyl, 88% +/- 9%; isoflurane, 37% +/- 20%; ketamine, 70% +/- 28%; P = 0.00008). Isoflurane was protective compared with fentanyl (P = 0.00007) and ketamine (P = 0.0061). There was no difference between fentanyl and ketamine (P = 0.143). Similar observations were made in the cortex. Neurologic function correlated with histologic damage.     

Anesthetic protection against hepatic injury

In this review article, hepatocyte injury by volatile anesthetics, effects of anesthetics on hepatic perfusion, protection offered by either ischemic preconditioning or anesthetic preconditioning against hepatic ischemia-reperfusion injury and effects of anesthetics on sepsis-induced hepatic injury are discussed. Halothane poses significant risk of immunologically-mediated hepatocyte injury and disturbances of hepatic blood supply. Other modern volatile anesthetics such as isoflurane, sevoflurane and desflurane seem to have only minor risks. Several animal studies demonstrate that volatile anesthetics offer more protection against ischemia-reperfusion injury than intravenous anesthetics. On the contrary, intravenous anesthetics may be more protective against sepsis-induced hepatic injury than volatile anesthetics.     

Sevoflurane and isoflurane do not enhance the pre- and postischemic eicosanoid production in guinea pig hearts

Eicosanoids and volatile anesthetics can influence cardiac reperfusion injury. Accordingly, we analyzed the effects of sevoflurane and isoflurane applied in clinically relevant concentrations on the myocardial production of prostacyclin and thromboxane A2 (TxA2) and on heart function. Isolated guinea pig hearts, perfused with crystalloid buffer, performed pressure-volume work. Between two working phases, hearts were subjected to 15 min of global ischemia followed by reperfusion. The hearts received no anesthetic, 1 minimum alveolar anesthetic concentration (MAC) isoflurane (1.2 vol%), or 0.5 and 1 MAC sevoflurane (1 vol% and 2 vol%), either only preischemically or pre- and postischemically. In additional groups, cyclooxygenase function was examined by an infusion of 1 microM arachidonic acid (AA) in the absence and presence of sevoflurane. The variables measured included the myocardial production of prostacyclin, TxA2 and lactate, consumption of pyruvate, coronary perfusion pressure, and the tissue level of isoprostane 8-iso-PGF2alpha. External heart work, determined pre- and postischemically, served to assess recovery of heart function. Volatile anesthetics had no impact on postischemic recovery of myocardial function (50%-60% recovery), perfusion pressure, lactate production, or isoprostane content. Release of prostacyclin and TxA2 was increased in the early reperfusion phase 5-8- and 2-4-fold, respectively, indicating enhanced AA liberation. Isoflurane and sevoflurane did not augment the eicosanoid release. Only 2 vol% sevoflurane applied during reperfusion prevented the increased eicosanoid formation in this phase. Infusion of AA increased prostacyclin production approximately 200-fold under all conditions, decreased pyruvate consumption irreversibly, and markedly attenuated postischemic heart work (25% recovery). None of these effects were mitigated by 2 vol% sevoflurane. In conclusion, only sevoflurane at 2 vol% attenuated the increased liberation of AA during reperfusion. Decreased eicosanoid formation had no effect on myocardial recovery in our experimental setting while excess AA was deleterious. Because eicosanoids influence intravascular platelet and leukocyte adhesion and activation, sevoflurane may have effects in reperfused tissues beyond those of isoflurane. IMPLICATIONS: In an isolated guinea pig heart model, myocardial eicosanoid release was not increased by isoflurane or sevoflurane, either before or after ischemia. Sevoflurane (2 vol%) but not isoflurane attenuated the increased release of eicosanoids during reperfusion.     

Cardioprotection by anesthetics

Perioperative myocardial ischemia is one of the most important complications associated with significant risk of perioperative cardiac event. Ischemic preconditioning is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the myocardium against a more prolonged ischemic insult, the result of which is a marked reduction in myocardial infarct size, severity of myocardial stunning, or incidence of cardiac arrhythmias. Myocardial stunning is a clinically important ischemia-reperfusion injury described as a prolonged postischemic contractile dysfunction of myocardium salvaged by reperfusion. Experimental data indicate that general anesthetics protect the myocardium against ischemia-reperfusion injury, as shown by decreased infarct size and a more rapid recovery of contractile function on myocardial stunning. This phenomenon is called anesthetic preconditioning. Volatile anesthetics and morphine have a strong preconditioning like effect. The cardioprotective effect of volatile anesthetics has been supported by some clinical studies. Although the cellular mechanism of anesthetic preconditioning is not fully investigated, possible mechanism involves adenosine, adenosine receptors, the ATP-dependent potassium (K(ATP)) channels, protein kinase C, reactive oxygen species and other mediators or substances. Further, mitochondrial K(ATP) channels play the central role in anesthetic preconditioning.     

The effect of sevoflurane and propofol on cerebral neurotransmitter concentrations during cerebral ischemia in rats

Sevoflurane and propofol are neuroprotective possibly by attenuating central or peripheral catecholamines. We evaluated the effect of these anesthetics on circulating catecholamines and brain neurotransmitters during ischemia in rats. Forty male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: fentanyl and N(2)O/O(2) (control), 2.0% sevoflurane, 0.8-1.2 mg x kg(-1) x min(-1) of propofol, and sham-operated rats with fentanyl and N(2)O/O(2). Ischemia (30 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 32 +/- 2 mm Hg. Pericranial temperature, arterial blood gases, and pH value were maintained constant. Cerebral catecholamine and glutamate concentrations, sampled by microdialysis, and plasma catecholamine concentrations were analyzed using high-pressure liquid chromatography. During ischemia, circulating catecholamines were almost completely suppressed by propofol but only modestly decreased with sevoflurane. Sevoflurane and propofol suppressed brain norepinephrine concentration increases by 75% and 58%, respectively, compared with controls. Intra-ischemia cerebral glutamate concentration was decreased by 60% with both sevoflurane and propofol. These results question a role of circulating catecholamines as a common mechanism for cerebral protection during sevoflurane and propofol. A role of brain tissue catecholamines in mediating ischemic injury is consistent with our results. IMPLICATIONS: During incomplete cerebral ischemia, the neuroprotective anesthetics sevoflurane and propofol suppressed cerebral increases in norepinephrine and glutamate concentrations. In contrast, propofol, but not sevoflurane, suppressed the ischemia-induced increase in circulating catecholamines to baseline levels. The results question a role for plasma catecholamines in cerebral ischemic injury.     

Pulmonary-to-systemic blood flow ratio effects of sevoflurane,isoflurane, halothane,and fentanyl/midazolam with 100% oxygen in children with congenital heart disease

The cardiovascular effects of volatile anesthetics in children with congenital heart disease have been studied, but there are limited data on the effects of anesthetics on pulmonary-to-systemic blood flow ratio (Qp:Qs) in patients with intracardiac shunting. In this study, we compared the effects of halothane, isoflurane, sevoflurane, and fentanyl/midazolam on Qp:Qs and myocardial contractility in patients with atrial (ASD) or ventricular (VSD) septal defects. Forty patients younger than 14 yr old scheduled to undergo repair of ASD or VSD were randomized to receive halothane, sevoflurane, isoflurane, or fentanyl/midazolam. Cardiovascular and echocardiographic data were recorded at baseline, randomly ordered 1 and 1.5 mean alveolar anesthetic concentration (MAC) levels, or predicted equivalent fentanyl/midazolam plasma levels. Ejection fraction (using the modified Simpson's rule) was calculated. Systemic (Qs) and pulmonary (Qp) blood flow was echocardiographically assessed by the velocity-time integral method. Qp:Qs was not significantly affected by any of the four regimens at either anesthetic level. Left ventricular systolic function was mildly depressed by isoflurane and sevoflurane at 1.5 MAC and depressed by halothane at 1 and 1.5 MAC. Sevoflurane, halothane, isoflurane, or fentanyl/midazolam in 1 or 1.5 MAC concentrations or their equivalent do not change Qp:Qs in patients with isolated ASD or VSD. IMPLICATIONS: Sevoflurane, halothane, isoflurane, and fentanyl/midazolam do not change pulmonary-to-systemic blood flow ratio in children with atrial and ventricular septal defects when administered at standard anesthetic doses with 100% oxygen.     

Neutrophils Pretreated with Volatile Anesthetics Lose Ability to Cause Cardiac Dysfunction

Background: Volatile anesthetics can precondition the myocardium against functional depression and infarction following ischemia-reperfusion. Neutrophil activation, adherence, and release of superoxide play major roles in reperfusion injury. The authors tested the hypothesis that pretreatment of neutrophils with a volatile anesthetic, i.e., simulated preconditioning, can blunt their ability to cause cardiac dysfunction.

Methods: Studies were performed in 60 buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as an index of myocardial contractility. Polymorphonuclear neutrophils and/or drugs were added to coronary perfusate for 10 min, followed by 30 min of recovery. Platelet-activating factor was used to stimulate neutrophils. Pretreatment of neutrophils consisted of incubation with 1.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 15 min, followed by washout. Additional studies were performed with 0.25 MAC isoflurane. Effects of superoxide dismutase were compared to those of volatile anesthetics. Superoxide production was measured by spectrophotometry. Neutrophil adherence to coronary vascular endothelium was estimated from the difference between neutrophils administered and recovered in coronary venous effluent.

Results: Activated neutrophils caused marked, persistent reduction (> 50%) in left ventricular developed pressure. Isoflurane and sevoflurane at 1.0 MAC and superoxide dismutase abolished this effect. Isoflurane and sevoflurane reduced superoxide production of activated neutrophils by 29% and 33%, respectively, and completely prevented the platelet-activating factor-induced increases in neutrophil adherence. Isoflurane at 0.25 MAC blunted, but did not abolish, the neutrophil-induced decreases in left ventricular developed pressure.     

Isoflurane-sevoflurane adminstration before ischemia attenuates ischemia-reperfusion-induced injury in isolated rat lungs

BACKGROUND: The effects of volatile anesthetics on ischemia-reperfusion (IR)-induced lung injury are not clear. The authors investigated the effects of preadministration of isoflurane and sevoflurane on IR-induced lung injury in an isolated buffer-perfused rat lung model. METHODS: Isolated rat lungs were designated into four groups: control group (n = 6): perfusion for 120 min without ischemia; IR group (n = 6): interruption of perfusion and ventilation for 60 min followed by reperfusion for 60 min; sevoflurane (SEVO)-IR (n = 6) and isoflurane (ISO)-IR (n = 6) groups: 1 minimum alveolar concentration (MAC) isoflurane or sevoflurane was administered for 30 min, followed by 60 min ischemia, then 60 min reperfusion. The authors measured the coefficient of filtration (Kfc) of the lung, lactate dehydrogenase (LDH) activity, tumor necrosis factor alpha, and nitric oxide metabolites (nitrite + nitrate) in the perfusate and the wet-to-dry lung weight ratio. RESULTS: IR caused significant increases in the coefficient of filtration (approximately sevenfold at 60 min of reperfusion compared with baseline; P < 0.01), the wet-to-dry lung weight ratio, the rate of increase of lactate dehydrogenase activity, and tumor necrosis factor a in the perfusate, and caused a significant decrease in nitric oxide metabolites in the perfusate. Administration of 1 MAC isoflurane or sevoflurane before ischemia significantly attenuated IR-induced increases in the coefficient of filtration and the wet-to-dry lung weight ratio, inhibited increases in the rate of increase of lactate dehydrogenase activity and tumor necrosis factor alpha in the perfusate, and abrogated the decrease in nitric oxide metabolites in the perfusate. No difference was found between the SEVO-IR and ISO-IR groups. CONCLUSION: Isoflurane and sevoflurane administered before ischemia can attenuate IR-induced injury in isolated rat lungs.     

Cardioprotective effects of propofol and sevoflurane in ischemic and reperfused rat hearts: role of K(ATP) channels and interaction with the sodium-hydrogen exchange inhibitor HOE 642 (cariporide).

BACKGROUND: Sodium ion-hydrogen ion (Na(+)-H(+)) exchange inhibitors are effective cardioprotective agents. The N(+)-H(+) exchange inhibitor HOE 642 (cariporide) has undergone clinical trials in acute coronary syndromes, including bypass surgery. Propofol and sevoflurane are also cardioprotective via unknown mechanisms. The authors investigated the interaction between propofol and HOE 642 in the ischemic reperfused rat heart and studied the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels in the myocardial protection associated with propofol and sevoflurane. METHODS: Isolated rat hearts were perfused by the Langendorff method at a constant flow rate, and left ventricular function and coronary pressures were assessed using standard methods. Energy metabolites were also determined. To assess the role of K(ATP) channels, hearts were pretreated with the K(ATP) blocker glyburide (10 microM). Hearts were then exposed to either control buffer or buffer containing HOE 642 (5 microM), propofol (35 microM), sevoflurane (2.15 vol%), the K(ATP) opener pinacidil (1 microM), or the combination of propofol and HOE 642. Each heart was then subjected to 1 h of global ischemia followed by 1 h of reperfusion. RESULTS: Hearts treated with propofol, sevoflurane, pinacidil, or HOE 642 showed significantly higher recovery of left ventricular developed pressure and reduced end-diastolic pressures compared with controls. The combination of propofol and HOE 642 provided superior protection toward the end of the reperfusion period. Propofol, sevoflurane, and HOE 642 also attenuated the onset and magnitude of ischemic contracture and preserved high-energy phosphates (HEPs) compared with controls. Glyburide attenuated the cardioprotective effects of sevoflurane and abolished the protection observed with pinacidil. In contrast, glyburide had no effect on the cardioprotection associated with propofol treatment. CONCLUSION: HOE 642, propofol, and sevoflurane provide cardioprotection via different mechanisms. These distinct mechanisms may allow for the additive and superior protection observed with the combination of these anesthetics and HOE 642.     

Sevoflurane inhalation at sedative concentrations provides endothelial protection against ischemia-reperfusion injury in humans

BACKGROUND: Endothelial cells can be protected against cytokine-induced toxicity by volatile anesthetics. The authors tested whether inhalation of sevoflurane at subanesthetic concentrations provides protection against postocclusive endothelial dysfunction induced by ischemia-reperfusion injury of the forearm in humans. METHODS: Five healthy male volunteers were enrolled in this study with crossover design. Each subject was randomly exposed to 15 min of forearm ischemia in the presence or absence of sevoflurane. Sevoflurane was inhaled at 0.5-1 vol% end-tidal concentrations from 15 min before ischemia until 5 min after the onset of reperfusion. Hyperemic reaction, an indicator of ischemic injury and endothelial function, was determined at 15 and 30 min of reperfusion using venous occlusion plethysmography. Also, markers of leukocyte activation (CD11b, CD42b) were measured by flow cytometry during reperfusion. RESULTS: Fifteen minutes of forearm ischemia followed by reperfusion diminished postocclusive endothelium-dependent hyperemic reaction at 15 and 30 min of reperfusion. Peri-ischemic inhalation of sevoflurane, targeted at 0.5-1 vol% end-tidal concentrations, markedly improved postocclusive hyperemic reaction. In addition, inhalation of sevoflurane attenuated activation of leukocytes, as measured by CD11b expression, after ischemia-reperfusion injury. No changes in CD42b expression were observed after ischemia-reperfusion of the forearm. CONCLUSIONS: These data suggest that human endothelium, a key component of all vital organs, is receptive to protection by sevoflurane in vivo. Peri-ischemic administration of sevoflurane mimics a combination of pharmacologic preconditioning and postconditioning and protects at even low sedative concentrations (< 1 vol%). Inhibition of leukocyte adhesion is likely to be involved in the protection.     

Sevoflurane but not propofol preserves myocardial function during minimally invasive direct coronary artery bypass surgery

Volatile anesthetics exert cardioprotective properties in experimental and clinical studies. We designed this study to investigate the effects of sevoflurane on left ventricular (LV) performance during minimally invasive direct coronary artery bypass grafting (MIDCAB) without cardiopulmonary bypass. Fifty-two patients scheduled for MIDCAB surgery were randomly assigned to a propofol or a sevoflurane group. Apart from the anesthetics used, there was no difference in surgical and anesthetic management. After determination of cardiac troponin T, creatine kinase, and creatine kinase MB, electrocardiographic (ECG) data and echocardiography variables (myocardial performance index and early to atrial filling velocity ratio) the left anterior descending coronary artery (LAD) was clamped until anastomosis with the left internal mammary artery was completed. During LAD occlusion and during reperfusion, echocardiography measurements were repeated. Blood samples were obtained repeatedly for up to 72 h. After LAD occlusion, myocardial performance index and early to atrial filling velocity ratio in the propofol group deteriorated significantly from 0.40 +/- 0.12 and 1.29 +/- 0.35 to 0.49 +/- 0.10 and 1.13 +/- 0.22, respectively, whereas there was no change in the sevoflurane group. In the propofol group myocardial performance index remained increased (0.47 +/- 0.11) compared with baseline during reperfusion. There were no significant differences in ECG and laboratory values between groups. In conclusion, during a brief period of ischemia in patients undergoing MIDCAB surgery, sevoflurane preserved myocardial function better than propofol.     

Ischemic Preconditioning Produces Comparable Protection Against Hepatic Ischemia/Reperfusion Injury Under Isoflurane and Sevoflurane Anesthesia in Rats

Background

Various volatile anesthetics and ischemic preconditioning (IP) have been demonstrated to exert protective effect against ischemia/reperfusion (I/R) injury in liver. We aimed to determine whether application of IP under isoflurane and sevoflurane anesthesia would confer protection against hepatic I/R injury in rats.

七氟醚对心肌缺血/再灌注损伤的临床研究进展

背景 七氟醚的心肌保护作用得到广泛关注,大量基础研究表明七氟醚对心肌缺血/再灌注损伤(myocardial ischemia/reperfusion injury,MI/RI)具有确切的保护作用.然而,临床中关于七氟醚具有心肌保护作用的结论尚未完全统一.目的 通过总结近年的研究进展对七氟醚的心肌保护作用进行阐述.内容 不同心脏手术及非心脏手术中七氟醚药物处理的心肌保护效果.趋向 今后仍需加强对七氟醚心肌保护作用的临床研究,为围手术期患者的心肌保护提供更为可靠的理论依据.     

Sevoflurane Inhalation at Sedative Concentrations Provides Endothelial Protection against Ischemia-Reperfusion Injury in Humans

Background: Endothelial cells can be protected against cytokine-induced toxicity by volatile anesthetics. The authors tested whether inhalation of sevoflurane at subanesthetic concentrations provides protection against postocclusive endothelial dysfunction induced by ischemia-reperfusion injury of the forearm in humans.

Methods: Five healthy male volunteers were enrolled in this study with crossover design. Each subject was randomly exposed to 15 min of forearm ischemia in the presence or absence of sevoflurane. Sevoflurane was inhaled at 0.5-1 vol% end-tidal concentrations from 15 min before ischemia until 5 min after the onset of reperfusion. Hyperemic reaction, an indicator of ischemic injury and endothelial function, was determined at 15 and 30 min of reperfusion using venous occlusion plethysmography. Also, markers of leukocyte activation (CD11b, CD42b) were measured by flow cytometry during reperfusion.

Results: Fifteen minutes of forearm ischemia followed by reperfusion diminished postocclusive endothelium-dependent hyperemic reaction at 15 and 30 min of reperfusion. Peri-ischemic inhalation of sevoflurane, targeted at 0.5-1 vol% end-tidal concentrations, markedly improved postocclusive hyperemic reaction. In addition, inhalation of sevoflurane attenuated activation of leukocytes, as measured by CD11b expression, after ischemia-reperfusion injury. No changes in CD42b expression were observed after ischemia-reperfusion of the forearm.