Year: 2009
Type: other
Abstract: Reperfusion Ischemia Reperfusion IschemiaChapter 1 13 Anesthetic pre-and postconditioning and helium Anesthetics, especially volatile anesthetics 3 4 24 and the noble gas xenon [25][26][27][28] are known to mimic the strong cardioprotection exerted by ischemic preconditioning and to induce cardioprotection against reperfusion injury, a phenomenon that is known as anesthetic-induced preconditioning.As for early preconditioning, this holds also true for the late phase of preconditioning.[29][30][31] However, not all inhalational gases induce myocardial preconditioning: nitrous oxide is the only anesthetic gas that does not precondition rat hearts in vivo.32 There are other nonanesthetic gases which might well precondition the heart: the noble gas helium was able to precondition rabbit myocardium 33 , and this effect was mediated via modulation of mitochondrial permeability transition pore (mPTP) and via activation of phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (Erk1 or 2).33 These pathways have been shown to be also involved in xenoninduced preconditioning.25 28 Although xenon might be a suitable anesthetic especially for patients at high cardiac risk during the perioperative period (no hemodynamic side effects 34 , organprotective effects in the heart 22 26 , brain 35 , and endothelium 36 ), high costs and difficulties of its application yet prohibited its clinical use on a routine basis.Helium might be a perfect alternative as an organprotective gas: as a nonanesthetic gas it might be administered to patients who are subjected to organ ischemia (vascular surgery, organ transplantation, cardiac surgery) or who recently underwent regional ischemia (stroke, angina pectoris, myocardial infarction, organ transplantation) without the `side-effect` of being anesthetized.37 Like xenon, helium lacks hemodynamic side effects and improves hemodynamics in mechanically ventilated patients with chronic obstructive pulmonary disease.38 A recent review suggested a certain beneficial effect of heliox in patients with severe airway obstruction.39 40 Heliox is also used clinically in children with ventilation disorders.[41][42][43] Helium is not expensive and is easy to administer via a normal face mask.41 Signaling pathways of preconditioningThe signaling transduction pathways of preconditioning are characterized by the existence of triggers, initiating the signal transduction cascade after the stimulus Chapter 1 15 postconditioning protects the myocardium by activating the mitogen activated protein kinase 1/2-extracellular regulated kinase 1/2 (MEK1/2-Erk1/2) pathway at time of myocardial reperfusion.5 Zatta et al. 64 suggested the survival kinase PKC-ε as a potential mediator of postconditioning-induced protection in intact rat hearts. Common pathways in pre-and postconditioningPreconditioning and postconditioning may share some signaling pathways, the so called reperfusion injury salvage kinase (RISK) pathway (see Fig. 3).65 The enzymes belonging to this pathway are activated during reperfusion by a preconditioning and/or postconditioning stimulus.It has been shown that phosphorylation of PI3K/Akt as well as Erk1/2 during reperfusion protects the myocardium against reperfusion injury.Furthermore, inhibition of glycogen synthase kinase-3beta (GSK-3β) leads to inhibition of mPTP opening.66 The mPTP is a possible end-effector in the signalling cascade of cardioprotection against reperfusion injury.59 60 67 Interestingly, activation of mK Ca channels and simultaneous opening of the mPTP was shown to abolish the cardioprotection by mK Ca channel activation alone but vice versa blockade of mK Ca channels and simultaneous blockade of the mPTP was still protective.51 This further underlines that the mPTP might be an end-effector in the mechanism of cardioprotection.PC stimulus Akt MEK1/2 GSK3β PKC Erk1/2 PI3K Mitochondria (inhibit mPTP opening) mK Ca mK ATP PKA PostC stimulus Ischemia PC stimulus Akt MEK1/2 GSK3β PKC Erk1/2 PI3K Mitochondria (inhibit mPTP opening) mK Ca mK ATP PKA PostC stimulus Ischemia Chapter 1 17Hyperglycemia and diabetes mellitus Hyperglycemia is associated with increased mortality after acute myocardial infarction in diabetic patients as well as in patients without diabetes mellitus, 70 however, the reasons for this increased risk are poorly understood.One possible explanation for the poor prognosis of diabetic patients after cardiovascular events is the loss of endogenous protective mechanisms (e.g.ischemic preconditioning), either by the resulting hyperglycemia or by diabetes itself.The protective effects of both, ischemic and pharmacological preconditioning are diminished or abolished in animals with hyperglycemia or in diabetic subjects.71 72 These results are consistent with clinical findings that prodromal angina (as a clinical correlate of ischemic preconditioning) before myocardial infarction does not limit infarct size in diabetic patients.14 73 Mitochondrial dysfunction might be one reason for this failure to precondition diabetic myocardium.74 Preconditioning by volatile anesthetics was abolished by hyperglycemia.75 Furthermore, type 1 diabetes blocked the infarct size reducing effect of late preconditioning, and hyperglycemia blocked ischemic preconditioning independently of plasma insulin concentrations and plasma osmolality.72 76 Blood glucose reduction by shortterm insulin treatment was not able to restore the cardioprotection in the diabetic animals.76 In contrast, transient severe and moderate glucose deprivations preconditioned the isolated rat heart.77 Recently, it has been demonstrated that desflurane induced preconditioning is also blocked by hyperglycemia.78 These data show that hyperglycemia has detrimental effects on endogenous cardioprotective mechanisms. AgingThe aging of the population will result in an increase of the incidence and prevalence of chronic diseases such as cardiovascular diseases.The morbidity and mortality of myocardial infarction increases with age [79][80][81] ; possibly due to an aging related loss of potency of cardioprotective strategies, e.g.preconditioning.82 Sniecinski et al. demonstrated a reduced efficacy of sevoflurane preconditioning with advanced age in isolated rat myocardium.83 In a recent study it was shown that isoflurane-induced preconditioning and isoflurane-stimulated reactive oxygen species production are attenuated in the senescent myocardium.84 Mio et al. could show that in human atrial cardiomyocytes isoflurane preconditioning and mitochondrial function are affected with increasing age.85 A study by Lee et al. 78.Weber NC, Goletz C, Huhn R et al.Blockade of anaesthetic-induced preconditioning in the hyperglycaemic myocardium The regulation of different mitogen-activated protein kinases.
Author: Ragnar Huhn
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2169539639