Methods: Wild-type and mutant C. elegans were exposed to isoflurane, halothane, or air under otherwise identical conditions. After varying recovery periods, the animals were challenged with hypoxic, azide, or hyperthermic incubations. After recovery from these incubations, mortality was scored.
Results: Isoflurane- and halothane-preconditioned animals had significantly reduced mortality to all three types of injuries compared with air controls. Concentrations as low as 1 vol% isoflurane (0.64 mm) and halothane (0.71 mm) induced significant protection. The onset and duration of protection after anesthetic were 6 and 9 h, respectively. A mutation that blocks inhibition of neurotransmitter release by isoflurane did not attenuate the preconditioning effect. A loss-of-function mutation of the Apaf-1 homolog CED-4 blocked the preconditioning effect of isoflurane, but mutation of the downstream caspase CED-3 did not. 相似文献
Methods: Guinea pig hearts (Langendorff preparation; n = 96) underwent pretreatment with sevoflurane (APC) or no treatment (control), before global ischemia and 120 min reperfusion. Ischemia durations were 20, 25, 30, 35, 40, and 45 min.
Results: At 120 min reperfusion, developed (systolic-diastolic) left ventricular pressure was increased by APC compared with control for ischemia durations of 25-40 min. Infarction was decreased by APC for ischemia durations of 25-40 min, but not 20 or 45 min. APC improved coronary flow and vasodilator responses for all ischemia durations longer than 25 min, and decreased ventricular fibrillation on reperfusion for ischemia durations longer than 30 min. 相似文献
Methods: PD98059, an inhibitor of extracellular signal-regulated protein kinase (MEK-ERK1/2), and SB203580, an inhibitor of p38 MAPK, were used to evaluate the role of MAPKs with respect to postischemic functional recovery in isolated perfused rat hearts subjected to ischemic preconditioning (IPC) and anesthetic preconditioning (APC). Western blot analyses were used to determine the degree of ERK1/2 and p38 MAPK activation after the application of the preconditioning stimulus and after ischemia-reperfusion. Immunohistochemical staining served to visualize subcellular localization of activated MAPKs.
Results: PD98059 and SB203580 abolished postischemic functional recovery in IPC but not in APC. IPC but not APC markedly activated ERK1/2 and p38 MAPK, which were abrogated by coadministration of the specific blockers. Conversely, IPC and APC enhanced ERK1/2 activity after ischemia-reperfusion as compared to nonpreconditioned hearts, and IPC in addition enhanced p38 MAPK activity. Coadministration of PD98059 and SB203580 during IPC but not during APC inhibited postischemically enhanced MAPK activities. Moreover, chelerythrine and 5-hydroxydecanoate, effective blockers of IPC and APC, annihilated IPC- and APC-induced enhanced postischemic responses of MAPKs. Finally, administration of PD98059 during ischemia-reperfusion diminished the protective effects of IPC and APC. Immunohistochemistry revealed increased ERK1/2 activity primarily in intercalated discs and nuclei and increased p38 MAPK activity in the sarcolemma and nuclei of IPC-treated hearts. 相似文献
Methods: Langendorff-prepared guinea pig hearts were exposed to 0.4 mm sevoflurane once for 15 min (H1-15; n = 8) or 0.4 mm (H2-5; n = 8) or 0.2 mm sevoflurane (L2-5; n = 8) twice for 5 min, with a 5-min washout period interspersed. Sevoflurane was then washed out for 20 min before 30 min of global no-flow ischemia and 120 min of reperfusion. Control hearts (n = 8) were not subjected to APC. Left ventricular pressure was measured isovolumetrically. Ventricular infarct size was determined by tetrazolium staining and cumulative planimetry. Values are expressed as mean +/- SD.
Results: The authors found a better functional return and a lesser percentage of infarction on reperfusion in H2-5 (28 +/- 9%) than in H1-15 (36 +/- 8%; P < 0.05), L2-5 (43 +/- 6%; P < 0.05), or control hearts (52 +/- 7%; P < 0.05). 相似文献
Methods: Hearts from male rats were isolated, Langendorff perfused, and randomly assigned to one of three groups: (1) the control group: hearts were continuously perfused for 130 min; (2) the IR group: 30 min of equilibration, 15 min of baseline, 25 min of ischemia, 60 min of reperfusion; and (3) the APC + IR group: 30 min of equilibration, 10 min of sevoflurane exposure and a 5-min washout, 25 min of global ischemia, 60 min of reperfusion. Tissue samples were acquired at the end of reperfusion. NF-[kappa]B activity was determined by electrophoretic mobility shift assay. The NF-[kappa]B inhibitor, I[kappa]B-[alpha], was determined by Western blot analysis. Myocardial inflammatory mediators, including tumor necrosis factor [alpha], interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase, were also assessed by Western blot analysis.
Results: Nuclear factor [kappa]B-DNA binding activity was significantly increased at the end of reperfusion in rat myocardium, and cytosolic I[kappa]B-[alpha] was decreased. Supershift assay revealed the involvement of NF-[kappa]B p65 and p50 subunits. APC with sevoflurane attenuated NF-[kappa]B activation and reduced the expression of tumor necrosis factor [alpha], interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase. APC also reduced infarct size and creatine kinase release and improved myocardial left ventricular developed pressure during IR. 相似文献
Methods: The PKC blockers chelerythrine and rottlerin and the adenosine triphosphate-dependent potassium (KATP) channel blockers HMR-1098 and 5-hydroxydecanoate were used to assess the role of PKC and KATP channels in isolated perfused rat hearts subjected to IPC or APC (1.5 minimum alveolar concentration isoflurane) followed by 40 min of ischemia and 30 min of reperfusion. Immunohistochemical techniques were used to visualize PKC translocation after preconditioning. In addition, the phosphorylation status of PKC isoforms was assessed.
Results: Chelerythrine, rottlerin, and 5-hydroxydecanoate blocked IPC and APC with respect to functional recovery, albeit IPC at higher concentrations. HMR-1098 did not affect IPC or APC. PKC[delta] and PKC[epsilon] translocated to nuclei in both IPC and APC, which was inhibited by chelerythrine and rottlerin. PKC[delta] translocated to mitochondria but not to the sarcolemma, and PKC[epsilon] translocated to the sarcolemma and intercalated disks but not to mitochondria. Interestingly, PKC[epsilon] was accumulated at the intercalated disks in control and preconditioned hearts. Phosphorylation of PKC[delta] on serine643 was increased in IPC and APC and blocked by chelerythrine and rottlerin, whereas phosphorylation of PKC[delta] on threonine505 was increased only in IPC and not blocked by chelerythrine or rottlerin. PKC[epsilon] on serine729 did not change its phosphorylation status. 相似文献
Methods: Male Fischer 344 rats of three age groups (2-4, 10-12, and 20-24 months) were used. Hearts were Langendorff perfused. Six hearts in each age group were pretreated with 10 min of sevoflurane and a 5-min washout before 25 min of ischemia and 60 min of reperfusion. Six control hearts in each age group received no treatment before ischemia. Nuclear magnetic resonance was used to measure intracellular Na, intracellular Ca, and intracellular pH, respectively. Left ventricular developed pressure, creatine kinase, and infarct size were measured.
Results: Ischemia decreases intracellular pH and increases intracellular Na and intracellular Ca in all age groups. APC blunts the pH decreases in young adult and middle-aged rats, but not in aged rats. APC decreased intracellular Na and intracellular Ca accumulation during ischemia in young adult and middle-aged hearts. APC improved adenosine triphosphate recovery in young rats but not in aged rats. Creatine kinase and infarct sizes were significantly reduced and left ventricular developed pressure was improved with APC in the young adult and middle-aged groups but not the aged group. 相似文献
Methods: Studies were conducted in buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as index of contractility. Neutrophils and platelet-activating factor were added to perfusate for 10 min followed by 30 min of recovery. The effect of selective pretreatment of the neutrophils and the hearts with 1.0 minimum alveolar concentration isoflurane or sevoflurane on the neutrophil-induced contractile dysfunction was assessed. Studies were performed in the absence and presence of the nonselective adenosine receptor antagonist 8-phenyltheophylline (10 [mu]m). Neutrophil retention was determined from difference between those administered and collected in coronary effluent and from myeloperoxidase concentration in myocardial samples. Superoxide production of neutrophils was measured by spectrophotometry.
Results: Under control conditions (no anesthetic pretreatment), activated neutrophils caused marked and persistent reductions in left ventricular developed pressure, associated with increases in neutrophil retention and myeloperoxidase activity. Pretreatment of the neutrophils or the heart with either isoflurane or sevoflurane abolished these effects. Pretreatment of the neutrophils also reduced the platelet-activating factor-induced increase in superoxide production by 29 and 33%, respectively. 8-Phenyltheophylline blunted the effects of anesthetic pretreatment of the neutrophils, whereas it did not alter the effects of anesthetic pretreatment of the heart. 相似文献
Methods: Barbiturate-anesthetized dogs (n = 91) were instrumented for measurement of hemodynamics and randomly assigned to receive IPC (four 5-min coronary occlusions interspersed with 5-min reperfusions), APC (1.0 minimum alveolar concentration of isoflurane for 30 min), or PPC (selective mitochondrial KATP channel opener diazoxide, 2.5 mg/kg intravenous) in the presence or absence of pretreatment with oral aspirin (650 mg), the selective COX-2 inhibitor celecoxib (200 mg), or acetaminophen (500 mg) administered 24, 12, and 2 h before experimentation in 12 separate experimental groups. All dogs were subjected to a 60-min coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size and coronary collateral blood flow were quantified with triphenyltetrazolium staining and radioactive microspheres, respectively. Myocardial 6-keto-prostaglandin F1[alpha], a stable metabolite of prostacyclin, was measured (enzyme immunoassay) in separate experiments (n = 8) before and after isoflurane administration, in the presence or absence of celecoxib.
Results: No significant differences in baseline hemodynamics or the left ventricular area at risk for infarction were observed between groups. IPC, isoflurane, and diazoxide all decreased myocardial infarct size (9 +/- 1, 12 +/- 2, and 11 +/- 1%, respectively) as compared with control (30 +/- 1%). Celecoxib alone had no effect on infarct size (26 +/- 3%) but abolished IPC (30 +/- 3%), APC (30 +/- 3%), and PPC (26 +/- 1%). Aspirin (24 +/- 3%) and acetaminophen alone (29 +/- 2%) did not alter infarct size or abolish APC-induced protection (18 +/- 1 and 19 +/- 1%, respectively). Isoflurane increased myocardial 6-keto-prostaglandin F1[alpha] to 463 +/- 267% of baseline in the absence but not in the presence (94 +/- 13%) of celecoxib. 相似文献