Mechanisms of Myocardial ischemia–reperfusion Injury and the Cytoprotective Role of Minocycline: Scope and Limitations

References

• Collard CD , GelmanS . Pathophysiology, clinical manifestations, and prevention of ischemia–reperfusion injury . Anesthesiology94 ( 6 ), 1133 – 1138 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Hausenloy DJ , YellonDM . Myocardial ischemia–reperfusion injury: a neglected therapeutic target . J. Clin. Invest.123 ( 1 ), 92 – 100 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Gallagher DJ , SettleKL . A new tetracycline minocycline compared with ampicillin in general practice . N. Z. Med. J.83 ( 558 ), 105 – 107 ( 1976 ).
   PubMed Web of Science ®Google Scholar
• Ulgen BO , FieldMG, QureshiWet al. The role of minocycline in ischemia–reperfusion injury: a comprehensive review of an old drug with new implications . Recent Pat. Cardiovasc. Drug Discov.6 ( 2 ), 123 – 132 ( 2011 ).
   PubMedGoogle Scholar
• Kumar V , AbbasAK, FaustoN, AsterJ . Robbins and Cotran Pathologic Basis of Disease.Elsevier India, India ( 2010 ).
   Google Scholar
• Pike MM , LuoCS, ClarkMDet al. NMR measurements of Na+ and cellular energy in ischemic rat heart: role of Na+–H+ exchange . Am. J. Physiol.265 ( 6 Pt 2 ), H2017 – H2026 ( 1993 ).
   PubMedGoogle Scholar
• Krause S , HessML . Characterization of cardiac sarcoplasmic reticulum dysfunction during short-term, normothermic, global ischemia . Circ. Res.55 ( 2 ), 176 – 184 ( 1984 ).
   PubMed Web of Science ®Google Scholar
• Schafer C , LadilovY, InserteJet al. Role of the reverse mode of the Na+/Ca2+ exchanger in reoxygenation-induced cardiomyocyte injury . Cardiovasc. Res.51 ( 2 ), 241 – 250 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Sanada S , KomuroI, KitakazeM . Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures . Am. J. Physiol. Heart Circ. Physiol.301 ( 5 ), H1723 – H1741 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Inserte J , BarbaI, Poncelas-NozalMet al. cGMP/PKG pathway mediates myocardial postconditioning protection in rat hearts by delaying normalization of intracellular acidosis during reperfusion . J. Mol. Cell. Cardiol.50 ( 5 ), 903 – 909 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Haworth RA , HunterDR . The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site . Arch. Biochem. Biophys.195 ( 2 ), 460 – 467 ( 1979 ).
   PubMed Web of Science ®Google Scholar
• Cohen MV , YangXM, DowneyJM . The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis . Circulation115 ( 14 ), 1895 – 1903 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Sun J , MurphyE . Protein S-nitrosylation and cardioprotection . Circ. Res.106 ( 2 ), 285 – 296 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Penna C , PerrelliMG, TullioFet al. Post-ischemic early acidosis in cardiac postconditioning modifies the activity of antioxidant enzymes, reduces nitration, and favors protein S-nitrosylation . Pflugers Arch.462 ( 2 ), 219 – 233 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Tsang A , HausenloyDJ, MocanuMM, YellonDM . Postconditioning: a form of ‘modified reperfusion’ protects the myocardium by activating the phosphatidylinositol 3-kinase–Akt pathway . Circ. Res.95 ( 3 ), 230 – 232 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Qiao X , XuJ, YangQJet al. Transient acidosis during early reperfusion attenuates myocardium ischemia reperfusion injury via PI3k–Akt–eNOS signaling pathway . Oxid. Med. Cell. Longev.2013, 126083 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Murphy E , SteenbergenC . Mechanisms underlying acute protection from cardiac ischemia–reperfusion injury . Physiol. Rev.88 ( 2 ), 581 – 609 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Braunersreuther V , JaquetV . Reactive oxygen species in myocardial reperfusion injury: from physiopathology to therapeutic approaches . Curr. Pharm. Biotechnol.13 ( 1 ), 97 – 114 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Webster KA . Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species . Future Cardiol.8 ( 6 ), 863 – 884 ( 2012 ).
   PubMedGoogle Scholar
• Toyokuni S . Reactive oxygen species-induced molecular damage and its application in pathology . Pathol. Int.49 ( 2 ), 91 – 102 ( 1999 ).
   PubMed Web of Science ®Google Scholar
• Kim JS , JinY, LemastersJJ . Reactive oxygen species, but not Ca2+ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia–reperfusion . Am. J. Physiol. Heart Circ. Physiol.290 ( 5 ), H2024 – H2034 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Zorov DB , JuhaszovaM, SollottSJ . Mitochondrial ROS-induced ROS release: an update and review . Biochim. Biophys. Acta1757 ( 5–6 ), 509 – 517 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Krijnen PA , NijmeijerR, MeijerCJ, VisserCA, HackCE, NiessenHW . Apoptosis in myocardial ischaemia and infarction . J. Clin. Pathol.55 ( 11 ), 801 – 811 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Shingu M , NobunagaM . Chemotactic activity generated in human serum from the fifth component of complement by hydrogen peroxide . Am. J. Pathol.117 ( 2 ), 201 – 206 ( 1984 ).
   PubMed Web of Science ®Google Scholar
• Schreck R , RieberP, BaeuerlePA . Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1 . EMBO J.10 ( 8 ), 2247 – 2258 ( 1991 ).
   PubMed Web of Science ®Google Scholar
• Akgur FM , BrownMF, ZibariGBet al. Role of superoxide in hemorrhagic shock-induced P-selectin expression . Am. J. Physiol. Heart Circ. Physiol.279 ( 2 ), H791 – H797 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Sellak H , FranziniE, HakimJ, PasquierC . Reactive oxygen species rapidly increase endothelial ICAM-1 ability to bind neutrophils without detectable upregulation . Blood83 ( 9 ), 2669 – 2677 ( 1994 ).
   PubMed Web of Science ®Google Scholar
• Penna C , RastaldoR, MancardiDet al. Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K+ channel and protein kinase C activation . Basic Res. Cardiol.101 ( 2 ), 180 – 189 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Tsutsumi YM , YokoyamaT, HorikawaY, RothDM, PatelHH . Reactive oxygen species trigger ischemic and pharmacological postconditioning: in vivo and in vitro characterization . Life Sci.81 ( 15 ), 1223 – 1227 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Jeremias I , KupattC, Martin-VillalbaAet al. Involvement of CD95/Apo1/Fas in cell death after myocardial ischemia . Circulation102 ( 8 ), 915 – 920 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Krown KA , PageMT, NguyenCet al. Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death . J. Clin. Invest.98 ( 12 ), 2854 – 2865 ( 1996 ).
   PubMed Web of Science ®Google Scholar
• Shoshan-Barmatz V , KeinanN, Abu-HamadS, TyomkinD, AramL . Apoptosis is regulated by the VDAC1 N-terminal region and by VDAC oligomerization: release of cytochrome C, AIF and Smac/Diablo . Biochim. Biophys. Acta1797 ( 6–7 ), 1281 – 1291 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Tsujimoto Y , ShimizuS . VDAC regulation by the Bcl-2 family of proteins . Cell Death Differ.7 ( 12 ), 1174 – 1181 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Smith MA , SchnellmannRG . Calpains, mitochondria, and apoptosis . Cardiovasc. Res.96 ( 1 ), 32 – 37 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Gao G , DouQP . N-terminal cleavage of bax by calpain generates a potent proapoptotic 18-kDa fragment that promotes bcl-2-independent cytochrome C release and apoptotic cell death . J. Cell. Biochem.80 ( 1 ), 53 – 72 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Lee WK , AbouhamedM, ThevenodF . Caspase-dependent and -independent pathways for cadmium-induced apoptosis in cultured kidney proximal tubule cells . Am. J. Physiol. Renal Physiol.291 ( 4 ), F823 – F832 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Vaisid T , BarnoyS, KosowerNS . Calpain activates caspase-8 in neuron-like differentiated PC12 cells via the amyloid-beta-peptide and CD95 pathways . Int. J. Biochem. Cell Biol.41 ( 12 ), 2450 – 2458 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Bajaj G , SharmaRK . TNF-alpha-mediated cardiomyocyte apoptosis involves caspase-12 and calpain . Biochem. Biophys. Res. Commun.345 ( 4 ), 1558 – 1564 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Chen Q , PaillardM, GomezLet al. Activation of mitochondrial mu-calpain increases AIF cleavage in cardiac mitochondria during ischemia–reperfusion . Biochem. Biophys. Res. Commun.415 ( 4 ), 533 – 538 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Ye H , CandeC, StephanouNCet al. DNA binding is required for the apoptogenic action of apoptosis inducing factor . Nat. Struct. Biol.9 ( 9 ), 680 – 684 ( 2002 ).
   PubMedGoogle Scholar
• Leung AW , HalestrapAP . Recent progress in elucidating the molecular mechanism of the mitochondrial permeability transition pore . Biochim. Biophys. Acta1777 ( 7–8 ), 946 – 952 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Hausenloy DJ , YellonDM . The mitochondrial permeability transition pore: its fundamental role in mediating cell death during ischaemia and reperfusion . J. Mol. Cell. Cardiol.35 ( 4 ), 339 – 341 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Heusch G , BoenglerK, SchulzR . Inhibition of mitochondrial permeability transition pore opening: the Holy Grail of cardioprotection . Basic Res. Cardiol.105 ( 2 ), 151 – 154 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Griffiths EJ , HalestrapAP . Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion . Biochem. J.307 ( Pt 1 ), 93 – 98 ( 1995 ).
   PubMedGoogle Scholar
• Nakagawa T , ShimizuS, WatanabeTet al. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death . Nature434 ( 7033 ), 652 – 658 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Brenner C , MoulinM . Physiological roles of the permeability transition pore . Circ. Res.111 ( 9 ), 1237 – 1247 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Garcia-Dorado D , Ruiz-MeanaM, InserteJ, Rodriguez-SinovasA, PiperHM . Calcium-mediated cell death during myocardial reperfusion . Cardiovasc. Res.94 ( 2 ), 168 – 180 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Miyazaki S , FujiwaraH, OnoderaTet al. Quantitative analysis of contraction band and coagulation necrosis after ischemia and reperfusion in the porcine heart . Circulation75 ( 5 ), 1074 – 1082 ( 1987 ).
   PubMed Web of Science ®Google Scholar
• Marchant DJ , BoydJH, LinDC, GranvilleDJ, GarmaroudiFS, McmanusBM . Inflammation in myocardial diseases . Circ. Res.110 ( 1 ), 126 – 144 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Eltzschig HK , EckleT . Ischemia and reperfusion – from mechanism to translation . Nat. Med.17 ( 11 ), 1391 – 1401 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Andrassy M , VolzHC, IgweJCet al. High-mobility group box-1 in ischemia–reperfusion injury of the heart . Circulation117 ( 25 ), 3216 – 3226 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Xu H , YaoY, SuZet al. Endogenous HMGB1 contributes to ischemia–reperfusion-induced myocardial apoptosis by potentiating the effect of TNF-α/JNK . Am. J. Physiol. Heart Circ. Physiol.300 ( 3 ), H913 – H921 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Kulik L , FlemingSD, MoratzCet al. Pathogenic natural antibodies recognizing annexin IV are required to develop intestinal ischemia–reperfusion injury . J. Immunol.182 ( 9 ), 5363 – 5373 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Yang Z , DayYJ, ToufektsianMCet al. Myocardial infarct-sparing effect of adenosine A2A receptor activation is due to its action on CD4+ T lymphocytes . Circulation114 ( 19 ), 2056 – 2064 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Schomig A , DartAM, DietzR, MayerE, KublerW . Release of endogenous catecholamines in the ischemic myocardium of the rat. Part A: locally mediated release . Circ. Res.55 ( 5 ), 689 – 701 ( 1984 ).
   PubMed Web of Science ®Google Scholar
• Briest W , ElsnerC, HemkerJ, Muller-StrahlG, ZimmerHG . Norepinephrine-induced expression of cytokines in isolated biventricular working rat hearts . Mol. Cell. Biochem.245 ( 1–2 ), 69 – 76 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Podgoreanu MV , WhiteWD, MorrisRWet al. Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery . Circulation114 ( Suppl. 1 ), I275 – 281 ( 2006 ).
   PubMedGoogle Scholar
• Holman BL , IdoineJ, FliegelCPet al. Detection and localization of experimental myocardial infarction with 99m Tc-tetracycline . J. Nucl. Med.14 ( 8 ), 595 – 599 ( 1973 ).
   PubMed Web of Science ®Google Scholar
• Brayton JJ , YangQ, NakkulaRJ, WaltersJD . An in vitro model of ciprofloxacin and minocycline transport by oral epithelial cells . J. Periodontol.73 ( 11 ), 1267 – 1272 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Romero-Perez D , FricovskyE, YamasakiKGet al. Cardiac uptake of minocycline and mechanisms for in vivo cardioprotection . J. Am. Coll. Cardiol.52 ( 13 ), 1086 – 1094 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Kraus RL , PasiecznyR, Lariosa-WillinghamK, TurnerMS, JiangA, TraugerJW . Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity . J. Neurochem.94 ( 3 ), 819 – 827 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Lee SM , YuneTY, KimSJet al. Minocycline inhibits apoptotic cell death via attenuation of TNF-alpha expression following iNOS/NO induction by lipopolysaccharide in neuron/glia co-cultures . J. Neurochem.91 ( 3 ), 568 – 578 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Pacher P , SzaboC . Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors . Cardiovasc. Drug Rev.25 ( 3 ), 235 – 260 ( 2007 ).
   PubMedGoogle Scholar
• Tao R , KimSH, HonboN, KarlinerJS, AlanoCC . Minocycline protects cardiac myocytes against simulated ischemia–reperfusion injury by inhibiting poly(ADP-ribose) polymerase-1 . J. Cardiovasc. Pharmacol.56 ( 6 ), 659 – 668 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Eefting F , RensingB, WigmanJet al. Role of apoptosis in reperfusion injury . Cardiovasc. Res.61 ( 3 ), 414 – 426 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Chen M , OnaVO, LiMet al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease . Nat. Med.6 ( 7 ), 797 – 801 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Scarabelli TM , StephanouA, PasiniEet al. Minocycline inhibits caspase activation and reactivation, increases the ratio of XIAP to smac/DIABLO, and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO . J. Am. Coll. Cardiol.43 ( 5 ), 865 – 874 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Pi R , LiW, LeeNTet al. Minocycline prevents glutamate-induced apoptosis of cerebellar granule neurons by differential regulation of p38 and Akt pathways . J. Neurochem.91 ( 5 ), 1219 – 1230 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Wang J , WeiQ, WangCY, HillWD, HessDC, DongZ . Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria . J. Biol. Chem.279 ( 19 ), 19948 – 19954 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Garcia-Martinez EM , Sanz-BlascoS, KarachitosAet al. Mitochondria and calcium flux as targets of neuroprotection caused by minocycline in cerebellar granule cells . Biochem. Pharmacol.79 ( 2 ), 239 – 250 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Corsaro A , ThellungS, ChiovittiKet al. Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline reverses the neurotoxic effects of the prion protein fragment 90-231 . Neurotox. Res.15 ( 2 ), 138 – 154 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Gieseler A , SchultzeAT, KupschKet al. Inhibitory modulation of the mitochondrial permeability transition by minocycline . Biochem. Pharmacol.77 ( 5 ), 888 – 896 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Theruvath TP , ZhongZ, PediaditakisPet al. Minocycline and N-methyl-4-isoleucine cyclosporin (NIM811) mitigate storage/reperfusion injury after rat liver transplantation through suppression of the mitochondrial permeability transition . Hepatology47 ( 1 ), 236 – 246 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Schwartz J , HolmuhamedovE, ZhangX, LovelaceGL, SmithCD, LemastersJJ . Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter . Toxicol. Appl. Pharmacol.273 ( 1 ), 172 – 179 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Nikodemova M , DuncanID, WattersJJ . Minocycline exerts inhibitory effects on multiple mitogen-activated protein kinases and IkappaBalpha degradation in a stimulus-specific manner in microglia . J. Neurochem.96 ( 2 ), 314 – 323 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Saklatvala J . The p38 MAP kinase pathway as a therapeutic target in inflammatory disease . Curr. Opin. Pharmacol.4 ( 4 ), 372 – 377 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Kelly KJ , SuttonTA, WeatheredNet al. Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury . Am. J. Physiol. Renal Physiol.287 ( 4 ), F760 – F766 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Pruzanski W , GreenwaldRA, StreetIP, LaliberteF, StefanskiE, VadasP . Inhibition of enzymatic activity of phospholipases A2 by minocycline and doxycycline . Biochem. Pharmacol.44 ( 6 ), 1165 – 1170 ( 1992 ).
   PubMed Web of Science ®Google Scholar
• Hu X , ZhouX, HeBet al. Minocycline protects against myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats . Eur. J. Pharmacol.638 ( 1–3 ), 84 – 89 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Lalu MM , PasiniE, SchulzeCJet al. Ischaemia–reperfusion injury activates matrix metalloproteinases in the human heart . Eur. Heart J.26 ( 1 ), 27 – 35 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Gonca E . The effects of zileuton and montelukast in reperfusion-induced arrhythmias in anesthetized rats . Curr. Ther. Res. Clin. Exp.75, 27 – 32 ( 2013 ).
   PubMedGoogle Scholar
• Hu X , WuB, WangXet al. Minocycline attenuates ischemia-induced ventricular arrhythmias in rats . Eur. J. Pharmacol.654 ( 3 ), 274 – 279 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Eberli FR . Stunned myocardium – an unfinished puzzle . Cardiovasc. Res.63 ( 2 ), 189 – 191 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Yemisci M , Gursoy-OzdemirY, VuralA, CanA, TopalkaraK, DalkaraT . Pericyte contraction induced by oxidative–nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery . Nat. Med.15 ( 9 ), 1031 – 1037 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Berg R , BuhariC . Treating and preventing no reflow in the cardiac catheterization laboratory . Curr. Cardiol. Rev.8 ( 3 ), 209 – 214 ( 2012 ).
   PubMedGoogle Scholar
• Pasceri V , PristipinoC, PellicciaFet al. Effects of the nitric oxide donor nitroprusside on no-reflow phenomenon during coronary interventions for acute myocardial infarction . Am. J. Cardiol.95 ( 11 ), 1358 – 1361 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Turer AT , HillJA . Pathogenesis of myocardial ischemia–reperfusion injury and rationale for therapy . Am. J. Cardiol.106 ( 3 ), 360 – 368 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Baystate Medical Center : Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation after Cardiac Surgery ( 2014 ). http://clinicaltrials.gov/show/NCT01422148
   Google Scholar
• Garrido-Mesa N , ZarzueloA, GalvezJ . Minocycline: far beyond an antibiotic . Br. J. Pharmacol.169 ( 2 ), 337 – 352 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Jennings RB , SommersHM, SmythGA, FlackHA, LinnH . Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog . Arch. Pathol.70, 68 – 78 ( 1960 ).
   PubMedGoogle Scholar