Anesthetic-induced preconditioning - Previous administration of isoflurane decreases myocardial infarct size in rabbits
ABSTRACT Experimental evidence suggests that ATP-sensitive potassium channels are involved in myocardial ischemic preconditioning. Because some pharmacologic effects of isoflurane are mediated by K(ATP) channels, the authors tested the hypothesis: Isoflurane administration, before myocardial ischemia, can induce or mimic myocardial preconditioning.
Myocardial infarct size was measured in three groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed in their pretreatment: Group 1 (control, N = 13) no pretreatment, Group 2 (ischemic preconditioning, N = 8), 5 min of coronary occlusion and 15 min of reperfusion; Group 3 (isoflurane pretreatment; N = 15), 15 min of isoflurane (1.1% end-tidal) and 15 min of washout. Hemodynamics were monitored serially. Myocardial infarct size and the area at risk were defined using triphenyltetrazolium chloride staining and fluorescent microspheres, respectively, and both were measured using computerized planimetry.
Infarct size expressed as a percentage of area at risk was 23.4 +/- 8.5% (mean +/- SD) in the isoflurane group compared with 33.1 +/- 13.3% in controls, and 8.7 +/- 6.2% in the ischemia-preconditioned group. Analysis for coincidental regressions, followed by tests for equality of slope and elevation, showed that the linear relationship between infarct size and area at risk was significantly (P < 0.05) different in all three groups because of differences in line elevation. Minor differences in hemodynamic variables were found between groups, which were unlikely to account for the significant differences in infarct size.
Preadministration of isoflurane, before myocardial ischemia, reduces myocardial infarct size, and mimics myocardial preconditioning.
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ABSTRACT: The present review discusses intracellular signaling moieties specific to membrane lipid rafts (MLRs) and the scaffolding proteins caveolin and introduces current data promoting their potential role in the treatment of pathologies of the heart and brain. MLRs are discreet microdomains of the plasma membrane enriched in gylcosphingolipids and cholesterol that concentrate and localize signaling molecules. Caveolin proteins are necessary for the formation of MLRs, and are responsible for coordinating signaling events by scaffolding and enriching numerous signaling moieties in close proximity. Specifically in the heart and brain, caveolins are necessary for the cytoprotective phenomenon termed ischemic and anesthetic preconditioning. Targeted overexpression of caveolin in the heart and brain leads to induction of multiple pro-survival and pro-growth signaling pathways; thus, caveolins represent a potential novel therapeutic target for cardiac and neurological pathologies.Frontiers in Physiology 10/2012; 3:393. DOI:10.3389/fphys.2012.00393 · 3.50 Impact Factor
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ABSTRACT: We compare the cardioprotective effects of anesthetic preconditioning by propofol and/or isoflurane in rats with ischemia-reperfusion injury. Male adult Wistar rats were subjected to 60 min of anterior descending coronary artery occlusion followed by 120 min of reperfusion. Before the long ischemia, anesthetics were administered twice for 10 min followed by 5 min washout. Isoflurane was inhaled at 1 MAC (0.016) in I group, whereas propofol was inhaled intravenously at 37.5 mg/(kg(h) in P group. A combination of isoflurane and propofol was administered simultaneously in I+P group. In control (without anesthetic preconditioning, C group), remarkable myocardial infarction and apoptosis accompanied by an increased level of cardiac troponin T were noted 120 min after ischemia-reperfusion. As compared to those of control group, I and P groups had comparable cardioprotection. In addition, I+P group shares with I and P groups the comparable cardioprotective effects in terms of myocardial infarction and cardiac troponin T elevation. A combination of isoflurane and propofol produced no additional cardioprotection.Journal of Zhejiang University SCIENCE B 10/2009; 10(10):740-7. DOI:10.1631/jzus.B0920119 · 1.29 Impact Factor
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ABSTRACT: Cardioprotection against ischaemia by anaesthetic-induced preconditioning (APC) is well established. However, the mechanism underlying Ca(2+) overload attenuation by APC is unknown. The effects of APC by isoflurane on the cardiac L-type Ca channel were investigated. In a model of in vivo APC, Wistar rats were exposed to isoflurane (1.4%), delivered via a vaporizer in an enclosure, prior to thoracotomy. The Dahl S rats were similarly preconditioned to determine strain-dependent effects. Whole-cell patch clamp using cardiac ventricular myocytes was used to determine the L-type Ca(2+) current (I(Ca,L)) characteristics and calmodulin (CaM) levels were determined by Western blot analysis. Cytosolic Ca(2+) levels were monitored using fluo-4-AM. Action potential (AP) simulations examined the effects of APC. In Wistar rats, APC significantly accelerated I(Ca,L) inactivation kinetics. This was abolished when external Ca(2+) was replaced with Ba(2+), suggesting that Ca(2+)-dependent inactivation of I(Ca,L) was modulated by APC. Expression levels of CaM, a determinant of I(Ca,L) inactivation, were not affected. Attenuation of cytosolic Ca(2+) accumulation following oxidative stress was observed in the APC group. Simulations showed that the accelerated inactivation of I(Ca,L) resulted in a shortening of the AP duration. The Dahl S rat strain was resistant to APC and changes in I(Ca,L) inactivation were not observed in cardiomyocytes prepared from these rats. APC triggered persistent changes in the inactivation of cardiac L-type Ca channels. This can potentially lead to a reduction in Ca(2+) influx and attenuation of Ca(2+) overload during ischaemia/reperfusion.British Journal of Pharmacology 02/2009; 156(3):432-43. DOI:10.1111/j.1476-5381.2008.00026.x · 4.99 Impact Factor