Disease relevance of Ischemic Preconditioning

• BACKGROUND: We have previously reported that ischemic preconditioning increases 5'-nucleotidase activity and adenosine release during ischemia and reperfusion [1].
• Dipyridamole potentiates the myocardial infarct size-limiting effect of ischemic preconditioning [2].
• Effect of ischemic preconditioning on interstitial purine metabolite and lactate accumulation during myocardial ischemia [3].
• Pretreatment with pertussis toxin (PTX), depletion of norepinephrine stores with reserpine, or blockade of alpha 1-adrenoceptors with prazosin prevented the effects of ischemic preconditioning [4].
• CONCLUSIONS: In humans, ischemic preconditioning during brief repeated coronary occlusions is completely abolished by pretreatment with glibenclamide, thus suggesting that it is mainly mediated by KATP channels [5].

High impact information on Ischemic Preconditioning

• In vivo studies showed that cardioprotection elicited either by cardiac-specific transgenic activation of PKCepsilon or by ischemic preconditioning enhances the formation of PKCepsilon-Lck modules [6].
• However, prazosin blunted the infarct size-limiting effect of ischemic preconditioning (infarct size: 42.8 +/- 3.7%) [7].
• Scavenging of reactive oxygen species reversed the effect of ischemic preconditioning, and H(2)O(2) preconditioning mimicked ischemic preconditioning [8].
• Ischemic preconditioning: from adenosine receptor to KATP channel [9].
• Protection of cardiac mitochondria by diazoxide and protein kinase C: implications for ischemic preconditioning [10].

Chemical compound and disease context of Ischemic Preconditioning

• OBJECTIVES: The goal of this study was to investigate the effect of three different doses of acetylsalicylic acid (aspirin) (ASA) on the late phase of ischemic preconditioning (PC) against myocardial stunning [11].
• Glucosylceramide synthase activity and ceramide levels are modulated during cerebral ischemia after ischemic preconditioning [12].
• CONCLUSIONS: This study strongly suggests that increased exogenous glucose utilization during low-flow ischemia mediates ischemic preconditioning without increasing total anaerobic glycolytic flux [13].
• OBJECTIVE: Acetylcholine (ACh) mimics ischemic preconditioning (PC) and therefore protects the heart against lethal ischemia [14].
• The results also suggest that ischemic preconditioning enhances bradykinin release in the myocardial interstitial fluid during subsequent ischemia, which is likely one of the mechanisms of cardioprotection of ischemic preconditioning [15].

Biological context of Ischemic Preconditioning

• PD 81,723, an allosteric enhancer of the A1 adenosine receptor, lowers the threshold for ischemic preconditioning in dogs [16].
• In conclusion, ischemic preconditioning confers dramatic protection against prolonged ischemia via inhibition of apoptosis through down-regulation of caspase 3 activity, independent of calpain-like activity or Bcl-2 expression [17].
• In conclusion, the hepatoprotective effects of ischemic preconditioning are associated with activation of NF-kappaB and SAPKs that are associated with entry of hepatocytes into the cell cycle, a critical biological effect that favors survival of the liver against ischemic and IR injury [18].
• Exact adjustment of the Embden-Meyerhof pathway (EMP) is an important issue in ischemic preconditioning (IP) because an attenuated ischemic lactate accumulation contributes to myocardial protection [19].
• Energy metabolism after ischemic preconditioning in streptozotocin-induced diabetic rat hearts [20].

Anatomical context of Ischemic Preconditioning

• Oral sulfonylurea hypoglycemic agents prevent ischemic preconditioning in human myocardium. Two paradoxes revisited [21].
• The adenosine A(2) receptor agonist, CGS-21680, and DB-cAMP decreased sinusoidal endothelial cell killing to the same extent as ischemic preconditioning, but the adenosine A(1) receptor agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA), had no effect [22].
• METHODS: Fifty patients undergoing angioplasty of a major epicardial coronary artery were randomly allocated to either ischemic preconditioning or intracoronary estrogen administration in the presence or absence of glibenclamide (glyburide) [23].
• In the pancreas, inhibition of ATP-sensitive potassium channels induces release of insulin; but in the heart, inhibition of these channels prevents ischemic preconditioning, an endogenous cardioprotective mechanism that protects the heart from lethal injury [24].
• Since the sympathetic nervous system enhances cardiac function and energy consumption, we investigated the relation between ischemic preconditioning and the turnover rate of noradrenaline (NA) in the rat heart [25].

Associations of Ischemic Preconditioning with chemical compounds

• Finally, mitochondrial adenosine 5'-triphosphate-sensitive K+ channels open, and the latter may be the final mediator of protection for ischemic preconditioning [9].
• Ischemic preconditioning in pigs: a graded phenomenon: its relation to adenosine and bradykinin [26].
• The goal of this study was to determine the role of the Janus tyrosine kinase (JAK)-signal transducers and activators of transcription (STAT) pathway in the late phase of ischemic preconditioning (PC) [27].
• The aim of this study was to establish whether glibenclamide, a selective KATP channel blocker, abolishes the ischemic preconditioning observed in humans during coronary angioplasty following repeated balloon inflations [5].
• Alpha-adrenoceptor stimulation with exogenous norepinephrine or release of endogenous catecholamines mimics ischemic preconditioning [28].

Gene context of Ischemic Preconditioning

• The goal of this study was to interrogate the role of inducible NO synthase (iNOS) in the late phase of ischemic preconditioning (PC) in vivo [29].
• We propose that transient increases in TNF-alpha levels may substitute for, as well as, mediate the hepatoprotective effects of ischemic preconditioning against hepatic IR injury [30].
• Ischemic preconditioning also activated p38 kinase and JNK-1, which are known to converge on cyclin D1 regulation [18].
• Caspase activity, measured by poly (adenosine diphosphate ribose) polymerase (PARP) proteolysis and a specific caspase-3 fluorometric assay, was inhibited by ischemic preconditioning [17].
• Here we examined whether ischemic preconditioning down-regulates activation of the mixed lineage kinase-JNK signaling pathway via NMDA receptor-mediated Akt1 activation [31].

Analytical, diagnostic and therapeutic context of Ischemic Preconditioning

• Exposures to adenosine during the ischemic preconditioning procedure and enhanced release of adenosine during reperfusion synergistically contribute to the infarct size-limiting effects [1].
• Protein kinase C (PKC) and the ATP-dependent K+ channel (KATP channel) have been implicated in the mechanism of ischemic preconditioning in animal models [32].
• The disulfide reducing agent dithiothreitol (1 mmol/L) removed the protection provided by ischemic preconditioning, if added to the perfusion buffer either before or after the preconditioning procedure [33].
• In multivariate analysis, body mass index of the donor, graft steatosis, and ischemic preconditioning were significantly predictive of the posttransplant peak of ASAT [34].
• These data not only demonstrate the utility of real-time polymerase chain reaction for sensitive and accurate measurement of mRNA expression in normal and injured tissues but also suggest a potential role of TNF-alpha in the phenomenon of ischemic preconditioning [35].

References