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: Preconditioning has been shown to reduce myocardial damage caused by ischaemia-reperfusion injury peri-operatively. Volatile anaesthetic agents have the potential to provide myocardial protection by anaesthetic preconditioning and, in addition, they also mediate renal and cerebral protection. A number of proof-of-concept trials have confirmed that the experimental evidence can be translated into clinical practice with regard to postoperative markers of myocardial injury; however, this effect has not been ubiquitous. The clinical trials published to date have also been too small to investigate clinical outcome and mortality. Data from recent meta-analyses in cardiac anaesthesia are also not conclusive regarding intra-operative volatile anaesthesia. These inconclusive clinical results have led to great variability currently in the type of anaesthetic agent used during cardiac surgery. This review summarises experimentally proposed mechanisms of anaesthetic preconditioning, and assesses randomised controlled clinical trials in cardiac anaesthesia that have been aimed at translating experimental results into the clinical setting. © 2015 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists of Great Britain and Ireland.Anaesthesia 04/2015; 70(4):467-482. DOI:10.1111/anae.12975 · 3.85 Impact Factor
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ABSTRACT: The pharmacological conditioning of the heart with anaesthetics such as volatile anaesthetics or opioids is a phenomenon whereby a transient exposure to an anaesthetic agent protects the heart from the harmful consequences of myocardial ischemia and reperfusion injury. The cellular and molecular mechanisms of anaesthetic conditioning appear largely to mimic those of ischemic pre- and postconditioning. Progress has been made on the understanding of the underlying mechanisms although the order of events and the specific targets of anaesthetics that trigger protection are not always clear. In the laboratory the protection afforded by certain anaesthetics against cardiac ischemia and reperfusion injury is powerful and reproducible but this has not necessarily translated into similarly robust clinical benefits. Indeed, clinical studies and meta-analyses delivered variable results when comparing in the laboratory setting protective and non-protective anaesthetics. Reasons for this include underlying conditions such as age, obesity and diabetes. Animal models for disease or aging, human cardiomyocytes derived from stem cells of patients and further clinical studies are employed to better understand the underlying causes that prevent a more robust protection in patients.British Journal of Pharmacology 10/2014; 172(8). DOI:10.1111/bph.12981 · 4.99 Impact Factor
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ABSTRACT: Utilisation of high-frequency drills is known to increase noise induced hearing loss due to increasing the damages of inner ear cells. This study aimed to investigate whether preconditioning by using dexmedetomidine (DEX) decreased the occurrence of ischemia in inner cells of the ear. We utilised a transgenic zebrafish line Brn3C, and the embryos were collected from breeding adult zebrafish. Five-day-old larvae were cultured at the density of 50 embryos, and the larvae were classified into 4 groups: control, cisplatin group, DEX group, and DEX+yohimbine; adrenoreceptor blocker group. The DEX group was categorised into 3 subgroups by dosage; 0.1, 1, and 10 µM. Preconditioning was performed for 150 minutes and then exposed to cisplatin for 6 hours. The experiment was performed in 7 replicates for each group and the number of hair cells in 3 parts of the neuromasts of each fish was determined. Hair cell apoptosis by cisplatin was attenuated more significantly in the DEX preconditioning group than in the control group. However, the preconditioning effects were not blocked by yohimbine. The results of this study suggest that hearing loss caused by vibration-induced noise could be reduced by using DEX and may occur through other mechanisms rather than adreno-receptors.Clinical and Experimental Otorhinolaryngology 12/2014; 7(4):275-280. DOI:10.3342/ceo.2014.7.4.275 · 0.84 Impact Factor