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Hyperoxia-induced cardiotoxicity and ventricular remodeling in type-II diabetes mice

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Abstract

Hyperoxia, or supplemental oxygen, is regularly used in the clinical setting for critically ill patients in ICU. However, several recent studies have demonstrated the negative impact of this treatment in patients in critical care, including increased rates of lung and cardiac injury, as well as increased mortality. The purpose of this study was to determine the predisposition for arrhythmias and electrical remodeling in a type 2 diabetic mouse model (db/db), as a result of hyperoxia treatment. For this, db/db and their heterozygous controls were treated with hyperoxia (> 90% oxygen) or normoxia (normal air) for 72-h. Immediately following hyperoxia or normoxia treatments, mice underwent surface ECG. Excised left ventricles were used to assess ion channel expression, including for Kv1.4, Kv1.5, Kv4.2, and KChIP2. Serum cardiac markers were also measured, including cardiac troponin I and lactate dehydrogenase. Our results showed that db/db mice have increased sensitivity to arrhythmia. Normoxia-treated db/db mice displayed features of arrhythmia, including QTc and JT prolongation, as well as QRS prolongation. A significant increase in QRS prolongation was also observed in hyperoxia-treated db/db mice, when compared to hyperoxia-treated heterozygous control mice. Db/db mice were also shown to exhibit ion channel dysregulation, as demonstrated by down-regulation in Kv1.5, Kv4.2, and KChIP2 under hyperoxia conditions. From these results, we conclude that: (1) diabetic mice showed distinct pathophysiology, when compared to heterozygous controls, both in normoxia and hyperoxia conditions. (2) Diabetic mice were more susceptible to arrhythmia at normal air conditions; this effect was exacerbated at hyperoxia conditions. (3) Unlike in heterozygous controls, diabetic mice did not demonstrate cardiac hypertrophy as a result of hyperoxia. (4) Ion channel remodeling was also observed in db/db mice under hyperoxia condition similar to its heterozygous controls.

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References

  1. Panguluri SK, Tur J, Chapalamadugu KC, Katnik C, Cuevas J, Tipparaju SM (2013) MicroRNA-301a mediated regulation of Kv4.2 in diabetes: identification of key modulators. PLoS ONE 8:e60545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Khavandi K, Khavandi A, Asghar O, Greenstein A, Withers S, Heagerty AM, Malik RA (2009) Diabetic cardiomyopathy—a distinct disease? Best Pract Res Clin Endocrinol Metab 23:347–360

    Article  PubMed  Google Scholar 

  3. Barth AS, Tomaselli GF (2009) Cardiac metabolism and arrhythmias. Circ Arrhythm Electrophysiol 2:327–335

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ozturk N, Olgar Y, Ozdemir S (2013) Trace elements in diabetic cardiomyopathy: an electrophysiological overview. World J Diabetes 4:92–100

    Article  PubMed  PubMed Central  Google Scholar 

  5. Morita H, Watanabe A, Morimoto Y, Kawada S, Tachibana M, Nakagawa K, Nishii N, Ito H (2017) Distribution and prognostic significance of fragmented QRS in patients with Brugada syndrome. Circ Arrhythm Electrophysiol 10(3):e004765

    Article  PubMed  Google Scholar 

  6. Steger A, Sinnecker D, Berkefeld A, Muller A, Gebhardt J, Dommasch M, Huster KM, Barthel P, Schmidt G (2015) Fragmented QRS. Relevance in clinical practice. Herzschrittmacherther Elektrophysiol 26:235–241

    Article  PubMed  Google Scholar 

  7. Nishiyama A, Ishii DN, Backx PH, Pulford BE, Birks BR, Tamkun MM (2001) Altered K(+) channel gene expression in diabetic rat ventricle: isoform switching between Kv4.2 and Kv1.4. Am J Physiol Heart Circ Physiol 281:H1800–H1807

    Article  CAS  PubMed  Google Scholar 

  8. Li X, Xu Z, Li S, Rozanski GJ (2005) Redox regulation of Ito remodeling in diabetic rat heart. Am J Physiol Heart Circ Physiol 288:H1417–H1424

    Article  CAS  PubMed  Google Scholar 

  9. Sato T, Kobayashi T, Kuno A, Miki T, Tanno M, Kouzu H, Itoh T, Ishikawa S, Kojima T, Miura T, Tohse N (2014) Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2. Am J Physiol Heart Circ Physiol 306:H1054–H1065

    Article  CAS  PubMed  Google Scholar 

  10. Panguluri SK, Tur J, Fukumoto J, Deng W, Sneed KB, Kolliputi N, Bennett ES, Tipparaju SM (2013) Hyperoxia-induced hypertrophy and ion channel remodeling in left ventricle. Am J Physiol Heart Circ Physiol 304:H1651–H1661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wunsch H, Linde-Zwirble WT, Angus DC, Hartman ME, Milbrandt EB, Kahn JM (2010) The epidemiology of mechanical ventilation use in the United States. Crit Care Med 38:1947–1953

    Article  PubMed  Google Scholar 

  12. Hovaguimian F, Lysakowski C, Elia N, Tramer M (2013) Effect of intraoperative high inspired oxygen fraction on surgical site infection, postoperative nausea and vomiting, and pulmonary function: systematic review and meta-analysis of randomized controlled trials. Anesthesiology 119:303–316

    Article  CAS  PubMed  Google Scholar 

  13. Iscoe S, Beasley R, Fisher JA (2011) Supplementary oxygen for nonhypoxemic patients: O2 much of a good thing? Crit Care 15:305

    Article  PubMed  PubMed Central  Google Scholar 

  14. Johnston AJ, Steiner LA, Gupta AK, Menon DK (2003) Cerebral oxygen vasoreactivity and cerebral tissue oxygen reactivity. Br J Anaesth 90:774–786

    Article  CAS  PubMed  Google Scholar 

  15. Floyd TF, Clark JM, Gelfand R, Detre JA, Ratcliffe S, Guvakov D, Lambertsen CJ, Eckenhoff RG (2003) Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA. J Appl Physiol 95:2453–2461

    Article  PubMed  Google Scholar 

  16. Farquhar H, Weatherall M, Wijesinghe M, Perrin K, Ranchord A, Simmonds M, Beasley R (2009) Systematic review of studies of the effect of hyperoxia on coronary blood flow. Am Heart J158:371–377

    Article  Google Scholar 

  17. Kutsogiannis DJ, Bagshaw SM, Laing B, Brindley PG (2011) Predictors of survival after cardiac or respiratory arrest in critical care units. CMAJ 183:1589–1595

    Article  PubMed  PubMed Central  Google Scholar 

  18. Damiani E, Adrario E, Girardis M, Romano R, Pelaia P, Singer M, Donati A (2014) Arterial hyperoxia and mortality in critically ill patients: a systematic review and meta-analysis. Crit Care 18:711

    Article  PubMed  PubMed Central  Google Scholar 

  19. Helmerhorst HJF, Schultz MJ, van der Voort PHJ, Bosman RJ, Juffermans NP, de Jonge E, van Westerloo DJ (2014) Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care 4:23

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kilgannon JH, Jones AE, Shapiro NI, Angelos MG, Milcarek B, Hunter K, Parrillo JE, Trzeciak S, Emergency Medicine Shock Research Network, I (2010) Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA 303:2165–2171

    Article  CAS  PubMed  Google Scholar 

  21. Rincon F, Kang J, Vibbert M, Urtecho J, Athar MK, Jallo J (2014) Significance of arterial hyperoxia and relationship with case fatality in traumatic brain injury: a multicentre cohort study. J Neurol Neurosurg Psychiatry 85:799–805

    Article  PubMed  Google Scholar 

  22. Rincon F, Kang J, Maltenfort M, Vibbert M, Urtecho J, Athar MK, Jallo J, Pineda CC, Tzeng D, McBride W, Bell R (2014) Association between hyperoxia and mortality after stroke: a multicenter cohort study. Crit Care Med 42:387–396

    Article  PubMed  Google Scholar 

  23. Nelskyla A, Parr MJ, Skrifvars MB (2013) Prevalence and factors correlating with hyperoxia exposure following cardiac arrest–an observational single centre study. Scand J Trauma Resusc Emerg Med 21:35

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kallet R, Matthay MA (2013) Hyperoxic acute lung injury. Respir Care 58:123–141

    Article  PubMed  PubMed Central  Google Scholar 

  25. Xu D, Guthrie JR, Mabry S, Sack TM, Truog WE (2006) Mitochondrial aldehyde dehydrogenase attenuates hyperoxia-induced cell death through activation of ERK/MAPK and PI3K-Akt pathways in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 291:L966–L975

    Article  PubMed  Google Scholar 

  26. Shosholcheva M, Jankulovski N, Kartalov A, Kuzmanovska B, Miladinova D (2017) Synergistic effect of hyperoxia and biotrauma on ventilator-induced lung injury. Pril (Makedon Akad Nauk Umet Odd Med Nauki) 38:91–96

    Google Scholar 

  27. Visser YP, Walther FJ, el Laghmani H, Laarse A, Wagenaar GT (2010) Apelin attenuates hyperoxic lung and heart injury in neonatal rats. Am J Respir Crit Care Med 182:1239–1250

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gole Y, Gargne O, Coulange M, Steinberg JG, Bouhaddi M, Jammes Y, Regnard J, Boussuges A (2011) Hyperoxia-induced alterations in cardiovascular function and autonomic control during return to normoxic breathing. Eur J Appl Physiol 111:937–946

    Article  PubMed  Google Scholar 

  29. Seals DR, Johnson DG, Fregosi RF (1991) Hyperoxia lowers sympathetic activity at rest but not during exercise in humans. Am J Physiol 260:R873–R878

    CAS  PubMed  Google Scholar 

  30. Waring WS, Thomson AJ, Adwani SH, Rosseel AJ, Potter JF, Webb DJ, Maxwell SR (2003) Cardiovascular effects of acute oxygen administration in healthy adults. J Cardiovasc Pharmacol 42:245–250

    Article  CAS  PubMed  Google Scholar 

  31. Chapalamadugu KC, Pangulur SK, Bennett ES, Kolliputi N, Tipparaju SM (2015) High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation. Toxicol Appl Pharmacol 282:100–107

    Article  CAS  PubMed  Google Scholar 

  32. Rezende PC, Rahmi RM, Uchida AH, da Costa LM, Scudeler TL, Garzillo CL, Lima EG, Segre CA, Girardi P, Takiuti M, Silva MF, Hueb W, Ramires JA, Kalil Filho R (2015) Type 2 diabetes mellitus and myocardial ischemic preconditioning in symptomatic coronary artery disease patients. Cardiovasc Diabetol 14:66

    Article  PubMed  PubMed Central  Google Scholar 

  33. Vinokur V, Berenshtein E, Bulvik B, Grinberg L, Eliashar R, Chevion M (2013) The bitter fate of the sweet heart: impairment of iron homeostasis in diabetic heart leads to failure in myocardial protection by preconditioning. PLoS ONE 8:e62948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Vogel WM, Apstein CS (1988) Effects of alloxan-induced diabetes on ischemia-reperfusion injury in rabbit hearts. Circ Res 62:975–982

    Article  CAS  PubMed  Google Scholar 

  35. Forrat R, Sebbag L, Wiernsperger N, Guidollet J, Renaud S, de Lorgeril M (1993) Acute myocardial infarction in dogs with experimental diabetes. Cardiovasc Res 27:1908–1912

    Article  CAS  PubMed  Google Scholar 

  36. Liu Y, Thornton JD, Cohen MV, Downey JM, Schaffer SW (1993) Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction. Circulation 88:1273–1278

    Article  CAS  PubMed  Google Scholar 

  37. Roglic G, Unwin N, Bennett PH, Mathers C, Tuomilehto J, Nag S, Connolly V, King H (2005) The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care 28:2130–2135

    Article  PubMed  Google Scholar 

  38. Stahn A, Pistrosch F, Ganz X, Teige M, Koehler C, Bornstein S, Hanefeld M (2014) Relationship between hypoglycemic episodes and ventricular arrhythmias in patients with type 2 diabetes and cardiovascular diseases: silent hypoglycemias and silent arrhythmias. Diabetes Care 37(2):516–520

    Article  CAS  PubMed  Google Scholar 

  39. Pistrosch F, Ganz X, Bornstein SR, Birkenfeld AL, Henkel E, Hanefeld M (2015) Risk of and risk factors for hypoglycemia and associated arrhythmias in patients with type 2 diabetes and cardiovascular disease: a cohort study under real-world conditions. Acta Diabetol 52(5):889–895

    Article  CAS  PubMed  Google Scholar 

  40. Kato T, Yamashita T, Sekiguchi A, Sagara K, Takamura M, Takata S, Kaneko S, Aizawa T, Fu LT (2006) What are arrhythmogenic substrates in diabetic rat atria? J Cardiovasc Electrophysiol 17(8):890–894

    Article  PubMed  Google Scholar 

  41. Kato T, Yamashita T, Sekiguchi A, Tsuneda T, Sagara K, Takamura M, Kaneko S, Aizawa T, Fu LT (2008) AGEs-RAGE system mediates atrial structural remodeling in the diabetic rat. J Cardiovasc Electrophysiol 19(4):415–420

    Article  PubMed  Google Scholar 

  42. Farag YM, Gaballa MR (2011) Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant 26:28–35

    Article  PubMed  Google Scholar 

  43. Huynh K, Bernardo BC, McMullen JR, Ritchie RH (2014) Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol Ther 142:375–415

    Article  CAS  PubMed  Google Scholar 

  44. Feng B, Chen S, Chiu J, George B, Chakrabarti S (2008) Regulation of cardiomyocyte hypertrophy in diabetes at the transcriptional level. Am J Physiol Endocrinol Metab 294:E1119–E1126

    Article  CAS  PubMed  Google Scholar 

  45. Soltysinska E, Speerschneider T, Winther SV, Thomsen MB (2014) Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice. Cardiovasc Diabetol 13:122

    Article  PubMed  PubMed Central  Google Scholar 

  46. Venardos K, De Jong KA, Elkamie M, Connor T, McGee SL (2015) The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice. PLoS ONE 10:e0120934

    Article  PubMed  PubMed Central  Google Scholar 

  47. Hall ME, Maready MW, Hall JE, Stec DE (2014) Rescue of cardiac leptin receptors in db/db mice prevents myocardial triglyceride accumulation. Am J Physiol Endocrinol Metab 307:E316–E325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Dalbøge LS, Almholt DLC, Neerup TSR, Vassiliadis E, Vrang N, Pedersen L, Fosgerau K, Jelsing J (2013) Characterisation of age-dependent beta cell dynamics in the male db/db mice. PLoS ONE 8:e82813

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kawasaki F, Matsuda M, Kanda Y, Inoue H, Kaku K (2005) Structural and functional analysis of pancreatic islets preserved by pioglitazone in db/db mice. Am J Physiol Endocrinol Metab 288:E510–E518

    Article  CAS  PubMed  Google Scholar 

  50. Hadour G, Ferrera R, Sebbag L, Forrat R, Delaye J, de Lorgeril M (1998) Improved myocardial tolerance to ischaemia in the diabetic rabbit. J Mol Cell Cardiol 30:1869–1875

    Article  CAS  PubMed  Google Scholar 

  51. Crow RS, Hannan PJ, Folsom AR (2003) Prognostic significance of corrected QT and corrected JT interval for incident coronary heart disease in a general population sample stratified by presence or absence of wide QRS complex: the ARIC Study with 13 years of follow-up. Circulation 108:1985–1989

    Article  PubMed  Google Scholar 

  52. Yan GX, Antzelevitch C (1998) Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome. Circulation 98:1928–1936

    Article  CAS  PubMed  Google Scholar 

  53. Tse G, Lai ET, Tse V, Yeo JM (2016) Molecular and electrophysiological mechanisms underlying cardiac arrhythmogenesis in diabetes mellitus. J Diabetes Res 2016:2848759

    Article  PubMed  PubMed Central  Google Scholar 

  54. Hasslacher C, Wahl P (1977) Diabetes prevalence in patients with bradycardiac arrhythmias. Acta Diabetol Lat 14:229–234

    Article  CAS  PubMed  Google Scholar 

  55. Movahed MR, Hashemzadeh M, Jamal MM (2005) Diabetes mellitus is a strong, independent risk for atrial fibrillation and flutter in addition to other cardiovascular disease. Int J Cardiol 105:315–318

    Article  PubMed  Google Scholar 

  56. Meek S, Morris F (2002) ABC of clinical electrocardiography. Introduction. I—leads, rate, rhythm, and cardiac axis. BMJ 324(7334):415–418

    Article  PubMed  PubMed Central  Google Scholar 

  57. Goncalves AC, Tank J, Diedrich A, Hilzendeger A, Plehm R, Bader M, Luft FC, Jordan J, Gross V (2009) Diabetic hypertensive leptin receptor-deficient db/db mice develop cardioregulatory autonomic dysfunction. Hypertension 53:387–392

    Article  PubMed  Google Scholar 

  58. Senador D, Kanakamedala K, Irigoyen MC, Morris M, Elased KM (2009) Cardiovascular and autonomic phenotype of db/db diabetic mice. Exp Physiol 94:648–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Schaan BD, Dall’Ago P, Maeda CY, Ferlin E, Fernandes TG, Schmid H, Irigoyen MC (2004) Relationship between cardiovascular dysfunction and hyperglycemia in streptozotocin-induced diabetes in rats. Braz J Med Biol Res 37:1895–1902

    Article  CAS  PubMed  Google Scholar 

  60. De Angelis K, Schaan BD, Maeda CY, Dall’Ago P, Wichi RB, Irigoyen MC (2002) Cardiovascular control in experimental diabetes. Braz J Med Biol Res 35:1091–1100

    Article  PubMed  Google Scholar 

  61. Baslaib F, Alkaabi S, Yan AT, Yan RT, Dorian P, Nanthakumar K, Casanova A, Goodman SG, Canadian Acute Coronary Syndrome Registry I (2010) QRS prolongation in patients with acute coronary syndromes. Am Heart J 159:593–598

    Article  PubMed  Google Scholar 

  62. Kurl S, Makikallio TH, Rautaharju P, Kiviniemi V, Laukkanen JA (2012) Duration of QRS complex in resting electrocardiogram is a predictor of sudden cardiac death in men. Circulation 125:2588–2594

    Article  PubMed  Google Scholar 

  63. Deen JF, Rhoades DA, Noonan C, Best LG, Okin PM, Devereux RB, Umans JG (2017) Comparison of QRS duration and associated cardiovascular events in American Indian men versus women (The Strong Heart Study). Am J Cardiol 119:1757–1762

    Article  PubMed  Google Scholar 

  64. Zhou Y, Jelinek H, Hambly BD, McLachlan CS (2017) Electrocardiogram QRS duration and associations with telomere length: a cross-sectional analysis in Australian rural diabetic and non-diabetic population. J Electrocardiol 50:450–456

    Article  PubMed  Google Scholar 

  65. O’Brien PJ, Smith DE, Knechtel TJ, Marchak MA, Pruimboom-Brees I, Brees DJ, Spratt DP, Archer FJ, Butler P, Potter AN, Provost JP, Richard J, Snyder PA, Reagan WJ (2006) Cardiac troponin I is a sensitive, specific biomarker of cardiac injury in laboratory animals. Lab Anim 40:153–171

    Article  PubMed  Google Scholar 

  66. Bagi Z, Erdei N, Toth A, Li W, Hintze TH, Koller A, Kaley G (2005) Type 2 diabetic mice have increased arteriolar tone and blood pressure: enhanced release of COX-2-derived constrictor prostaglandins. Arterioscler Thromb Vasc Biol 25:1610–1616

    Article  CAS  PubMed  Google Scholar 

  67. Casis O, Gallego M, Iriarte M, Sanchez-Chapula JA (2000) Effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricle. Diabetologia 43:101–109

    Article  CAS  PubMed  Google Scholar 

  68. Nerbonne JM, Kass RS (2005) Molecular physiology of cardiac repolarization. Physiol Rev 85:1205–1253

    Article  CAS  PubMed  Google Scholar 

  69. Gidh-Jain M, Huang B, Jain P, El-Sherif N (1996) Differential expression of voltage-gated K+ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction. Circ Res 79:669–675

    Article  CAS  PubMed  Google Scholar 

  70. Kaprielian R, Wickenden AD, Kassiri Z, Parker TG, Liu PP, Backx PH (1999) Relationship between K+ channel down-regulation and [Ca2+]i in rat ventricular myocytes following myocardial infarction. J Physiol 517(Pt 1):229–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ (2000) Modulation of A-type potassium channels by a family of calcium sensors. Nature 403:553–556

    Article  CAS  PubMed  Google Scholar 

  72. Wang Y, Xu H, Kumar R, Tipparaju SM, Wagner MB, Joyner RW (2003) Differences in transient outward current properties between neonatal and adult human atrial myocytes. J Mol Cell Cardiol 35:1083–1092

    Article  CAS  PubMed  Google Scholar 

  73. Suzuki T, Shioya T, Murayama T, Sugihara M, Odagiri F, Nakazato Y, Nishizawa H, Chugun A, Sakurai T, Daida H, Morimoto S, Kurebayashi N (2012) Multistep ion channel remodeling and lethal arrhythmia precede heart failure in a mouse model of inherited dilated cardiomyopathy. PLoS ONE 7:e35353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Dartsch T, Fischer R, Gapelyuk A, Weiergraeber M, Ladage D, Schneider T, Schirdewan A, Reuter H, Mueller-Ehmsen J, Zobel C (2013) Aldosterone induces electrical remodeling independent of hypertension. Int J Cardiol 164:170–178

    Article  PubMed  Google Scholar 

  75. Kuo HC, Cheng CF, Clark RB, Lin JJ, Lin JL, Hoshijima M, Nguyen-Tran VT, Gu Y, Ikeda Y, Chu PH, Ross J, Giles WR, Chien KR (2001) A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia. Cell 107:801–813

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Dr. Kolliputi for giving us access to qRT-PCR instrument and hyperoxia chamber. We also thank Dr. Noujaim for his advice for this manuscript.

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., MDC-30, Tampa, FL, 33612, USA

    Jennifer Leigh Rodgers & Siva Kumar Panguluri

  2. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Eva Samal & Subhra Mohapatra

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Rodgers, J.L., Samal, E., Mohapatra, S. et al. Hyperoxia-induced cardiotoxicity and ventricular remodeling in type-II diabetes mice. Heart Vessels 33, 561–572 (2018). https://doi.org/10.1007/s00380-017-1100-6

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