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Related Research Units

Cardiac Surgery Research

Research Overview

Dr. McCully’s research focuses on the mechanisms and subcellular localization of the biochemical and molecular events contributing to myocardial cell death. In particular, his lab has investigated the discriminant and/or coordinate mechanisms leading to ischemia/reperfusion injury in the neonate, child, mature and aged male and female with particular emphasis on the development of novel and specific cardioprotective protocols. 

Recently he has developed a novel approach to cardioprotection using autologous mitochondrial transplantation. His research has demonstrated that transplantation of autogeneic mitochondria into the ischemic zone of the myocardium during early reperfusion significantly enhances post-ischemic functional recovery. These studies have shown that the transplanted mitochondria act externally and then are internalized by myocardial cells to provide myocellular rescue and cardioprotection. The transplanted mitochondria upregulate cytokines associated with enhanced post-infarct cardiac function and improvement of cardiac remodeling and upregulate protein pathways associated with the generation of precursor metabolites for energy and cellular respiration with no immune or auto-immune response. The transplanted mitochondria are internalized through actin-dependent endocytosis and rescue cell function by increasing ATP content and oxygen consumption rate. Significantly, he has demonstrated that internalized mitochondria replace depleted or damaged mitochondrial (mt) DNA. 

Publications

  1. Recommendations for mitochondria transfer and transplantation nomenclature and characterization. Nat Metab. 2025 Jan; 7(1):53-67. View Abstract
  2. Mitochondrial transplantation normalizes transcriptomic and proteomic shift associated with ischemia reperfusion injury in neonatal hearts donated after circulatory death. Sci Rep. 2024 12 28; 14(1):31236. View Abstract
  3. Xenotransplantation of mitochondria: A novel strategy to alleviate ischemia-reperfusion injury during ex vivo lung perfusion. J Heart Lung Transplant. 2024 Nov 12. View Abstract
  4. Mitochondria Transplantation: Rescuing Innate Muscle Bioenergetic Impairment in a Model of Aging and Exercise Intolerance. J Strength Cond Res. 2024 Jul 01; 38(7):1189-1199. View Abstract
  5. Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states. Stem Cell Res Ther. 2024 May 31; 15(1):157. View Abstract
  6. Mitochondrial Transplantation's Role in Rodent Skeletal Muscle Bioenergetics: Recharging the Engine of Aging. Biomolecules. 2024 Apr 18; 14(4). View Abstract
  7. Mitochondrial transplantation: the advance to therapeutic application and molecular modulation. Front Cardiovasc Med. 2023; 10:1268814. View Abstract
  8. Model of Ischemia and Reperfusion Injury in Rabbits. J Vis Exp. 2023 Nov 03; (201). View Abstract
  9. Mitochondria Transplantation Mitigates Damage in an In Vitro Model of Renal Tubular Injury and in an Ex Vivo Model of DCD Renal Transplantation. Ann Surg. 2023 12 01; 278(6):e1313-e1326. View Abstract
  10. Mitochondrial transplantation preserves myocardial function and viability in pediatric and neonatal pig hearts donated after circulatory death. J Thorac Cardiovasc Surg. 2024 01; 167(1):e6-e21. View Abstract
  11. Mitochondrial transplantation: Effects on chemotherapy in prostate and ovarian cancer cells in vitro and in vivo. Biomed Pharmacother. 2023 May; 161:114524. View Abstract
  12. Transcriptomic and proteomic pathways of diabetic and non-diabetic mitochondrial transplantation. Sci Rep. 2022 12 21; 12(1):22101. View Abstract
  13. Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists. Science. 2022 08 05; 377(6606):621-629. View Abstract
  14. Mitochondrial transplantation for organ rescue. Mitochondrion. 2022 05; 64:27-33. View Abstract
  15. A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion. J Vis Exp. 2021 02 02; (168). View Abstract
  16. Mitochondrial Transplantation for Ischemia Reperfusion Injury. Methods Mol Biol. 2021; 2277:15-37. View Abstract
  17. A Multi-Mode System for Myocardial Functional and Physiological Assessment during Ex Situ Heart Perfusion. J Extra Corpor Technol. 2020 Dec; 52(4):303-313. View Abstract
  18. Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury. J Thorac Cardiovasc Surg. 2021 Sep; 162(3):992-1001. View Abstract
  19. Commentary: Independent, additive or linked: A novel therapeutic option for the treatment of pulmonary hypertension may involve more than one mechanism. J Thorac Cardiovasc Surg. 2022 05; 163(5):e375-e376. View Abstract
  20. Autogenous mitochondria transplantation for treatment of right heart failure. J Thorac Cardiovasc Surg. 2021 07; 162(1):e111-e121. View Abstract
  21. Mitochondrial transplantation by intra-arterial injection for acute kidney injury. Am J Physiol Renal Physiol. 2020 09 01; 319(3):F403-F413. View Abstract
  22. Mitochondrial transplantation for myocardial protection in ex-situ?perfused hearts donated after circulatory death. J Heart Lung Transplant. 2020 11; 39(11):1279-1288. View Abstract
  23. Mitochondrial transplantation for myocardial protection in diabetic hearts. Eur J Cardiothorac Surg. 2020 05 01; 57(5):836-845. View Abstract
  24. Letter by McCully et al Regarding Article, "Mitochondria Do Not Survive Calcium Overload". Circ Res. 2020 04 10; 126(8):e56-e57. View Abstract
  25. Mitochondrial Transplantation for Myocardial Protection in Ex-Situ Perfused Hearts Donated after Cardio-Circulatory Death. J Heart Lung Transplant. 2020 Apr; 39(4S):S87. View Abstract
  26. Reply: Intracoronary Delivery of Mitochondria to Prevent Ischemia-Reperfusion Injury: Challenging Pathway From Bench to Bedside. JACC Basic Transl Sci. 2020 Feb; 5(2):209. View Abstract
  27. A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy. JACC Basic Transl Sci. 2019 Dec; 4(8):871-888. View Abstract
  28. Mitochondrial transplantation enhances murine lung viability and recovery after ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2020 01 01; 318(1):L78-L88. View Abstract
  29. Preischemic autologous mitochondrial transplantation by intracoronary injection for myocardial protection. J Thorac Cardiovasc Surg. 2020 Aug; 160(2):e15-e29. View Abstract
  30. Delayed Transplantation of Autologous Mitochondria for Cardioprotection in a Porcine Model. Ann Thorac Surg. 2020 03; 109(3):711-719. View Abstract
  31. Mitochondrial transplantation ameliorates acute limb ischemia. J Vasc Surg. 2020 03; 71(3):1014-1026. View Abstract
  32. Mitochondrial transplantation prolongs cold ischemia time in murine heart transplantation. J Heart Lung Transplant. 2019 01; 38(1):92-99. View Abstract
  33. Mitochondrial transplantation: applications for pediatric patients with congenital heart disease. Transl Pediatr. 2018 Apr; 7(2):169-175. View Abstract
  34. Alloreactivity and allorecognition of syngeneic and allogeneic mitochondria. Mitochondrion. 2019 05; 46:103-115. View Abstract
  35. Transit and integration of extracellular mitochondria in human heart cells. Sci Rep. 2017 12 12; 7(1):17450. View Abstract
  36. Invited Commentary. Ann Thorac Surg. 2017 10; 104(4):1304-1305. View Abstract
  37. Mitochondrial transplantation: From animal models to clinical use in humans. Mitochondrion. 2017 05; 34:127-134. View Abstract
  38. Autologous mitochondrial transplantation for dysfunction after ischemia-reperfusion injury. J Thorac Cardiovasc Surg. 2017 07; 154(1):286-289. View Abstract
  39. Mitochondrial Transplantation in Myocardial Ischemia and Reperfusion Injury. Adv Exp Med Biol. 2017; 982:595-619. View Abstract
  40. Myocardial rescue with autologous mitochondrial transplantation in a porcine model of ischemia/reperfusion. J Thorac Cardiovasc Surg. 2017 04; 153(4):934-943. View Abstract
  41. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection. PLoS One. 2016; 11(8):e0160889. View Abstract
  42. Mitochondrial transplantation for therapeutic use. Clin Transl Med. 2016 Mar; 5(1):16. View Abstract
  43. Cellular and Molecular Mechanisms of Low Cardiac Output Syndrome after Pediatric Cardiac Surgery. Curr Vasc Pharmacol. 2016; 14(1):5-13. View Abstract
  44. Actin-dependent mitochondrial internalization in cardiomyocytes: evidence for rescue of mitochondrial function. Biol Open. 2015 Apr 10; 4(5):622-6. View Abstract
  45. Superparamagnetic iron oxide nanoparticles function as a long-term, multi-modal imaging label for non-invasive tracking of implanted progenitor cells. PLoS One. 2014; 9(9):e108695. View Abstract
  46. Rapid isolation and purification of mitochondria for transplantation by tissue dissociation and differential filtration. J Vis Exp. 2014 Sep 06; (91):e51682. View Abstract
  47. Preliminary biomarkers for identification of human ascending thoracic aortic aneurysm. J Am Heart Assoc. 2013 Nov 14; 2(6):e000138. View Abstract
  48. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2013 Apr 01; 304(7):H966-82. View Abstract
  49. Pressure-overload hypertrophy of the developing heart reveals activation of divergent gene and protein pathways in the left and right ventricular myocardium. Am J Physiol Heart Circ Physiol. 2013 Mar 01; 304(5):H697-708. View Abstract
  50. Microarray and proteomic analysis of the cardioprotective effects of cold blood cardioplegia in the mature and aged male and female. Physiol Genomics. 2012 Nov 01; 44(21):1027-41. View Abstract
  51. Differential expression of collagen type V and XI alpha-1 in human ascending thoracic aortic aneurysms. Ann Thorac Surg. 2009 Aug; 88(2):506-13. View Abstract
  52. Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart. Physiol Genomics. 2009 Jul 09; 38(2):125-37. View Abstract
  53. Injection of isolated mitochondria during early reperfusion for cardioprotection. Am J Physiol Heart Circ Physiol. 2009 Jan; 296(1):H94-H105. View Abstract
  54. Cardioplegia and diazoxide modulate STAT3 activation and DNA binding. Ann Thorac Surg. 2007 Oct; 84(4):1272-8. View Abstract
  55. Age- and gender-related differences in mitochondrial oxygen consumption and calcium with cardioplegia and diazoxide. Ann Thorac Surg. 2007 Mar; 83(3):1102-9. View Abstract
  56. Reduction and redistribution of gap and adherens junction proteins after ischemia and reperfusion. Ann Thorac Surg. 2006 Oct; 82(4):1472-9. View Abstract
  57. Age- and gender-related differences in ischemia/reperfusion injury and cardioprotection: effects of diazoxide. Ann Thorac Surg. 2006 Jul; 82(1):117-23. View Abstract
  58. Opening of mitochondrial KATP channels enhances cardioprotection through the modulation of mitochondrial matrix volume, calcium accumulation, and respiration. Am J Physiol Heart Circ Physiol. 2004 Nov; 287(5):H1967-76. View Abstract
  59. Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2004 May; 286(5):H1923-35. View Abstract
  60. Mitochondrial ATP-sensitive potassium channels in surgical cardioprotection. Arch Biochem Biophys. 2003 Dec 15; 420(2):237-45. View Abstract
  61. Mitochondrial DNA deletions in coronary artery bypass grafting patients. Eur J Cardiothorac Surg. 2003 Nov; 24(5):777-84. View Abstract
  62. The mitochondrial K(ATP) channel and cardioprotection. Ann Thorac Surg. 2003 Feb; 75(2):S667-73. View Abstract
  63. Diazoxide amelioration of myocardial injury and mitochondrial damage during cardiac surgery. Ann Thorac Surg. 2002 Dec; 74(6):2138-45; discussion 2146. View Abstract
  64. A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs. Ann Thorac Surg. 2002 Oct; 74(4):1201-7. View Abstract
  65. Oxygenated multidose delivery of crystalloid esmolol cardioplegia as an alternative to high potassium cardioplegia. J Thorac Cardiovasc Surg. 2002 Aug; 124(2):219-20. View Abstract
  66. Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis. Eur J Cardiothorac Surg. 2002 Mar; 21(3):424-33. View Abstract
  67. Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor. Ann Thorac Surg. 2002 Feb; 73(2):575-81. View Abstract
  68. Effects of NHE-1 inhibition on cardioprotection and impact on protection by K/Mg cardioplegia. Ann Thorac Surg. 2001 Sep; 72(3):836-43; discussion 843-4. View Abstract
  69. Adenosine-enhanced ischemic preconditioning modulates necrosis and apoptosis: effects of stunning and ischemia-reperfusion. Ann Thorac Surg. 2001 Aug; 72(2):555-63; discussion 563-4. View Abstract
  70. Opening of mitochondrial ATP-sensitive potassium channels enhances cardioplegic protection. Ann Thorac Surg. 2001 Apr; 71(4):1281-8; discussion 1288-9. View Abstract
  71. Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion. Am J Physiol Heart Circ Physiol. 2001 Feb; 280(2):H591-602. View Abstract
  72. Perfusion with lipopolysaccharide negative blood eliminates lipopolysaccharide induced lung injury. ASAIO J. 2001 Jan-Feb; 47(1):45-9. View Abstract
  73. Differential role of sarcolemmal and mitochondrial K(ATP) channels in adenosine-enhanced ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2000 Dec; 279(6):H2694-703. View Abstract
  74. Inhibition of RNA transcription modulates magnesium-supplemented potassium cardioplegia protection. Ann Thorac Surg. 2000 Dec; 70(6):2107-12. View Abstract
  75. Anti-stunning and anti-infarct effects of adenosine-enhanced ischemic preconditioning. Circulation. 2000 Nov 07; 102(19 Suppl 3):III326-31. View Abstract
  76. Alternatives for myocardial protection: adenosine-enhanced ischemic preconditioning. Ann N Y Acad Sci. 1999 Jun 30; 874:295-305. View Abstract
  77. Adenosine-enhanced ischemic preconditioning provides myocardial protection equal to that of cold blood cardioplegia. Ann Thorac Surg. 1999 Mar; 67(3):699-704. View Abstract
  78. Calcium channel blocker enhances lung preservation. J Heart Lung Transplant. 1999 Feb; 18(2):127-32. View Abstract
  79. Does PGE1 attenuate potassium-induced vasoconstriction in initial pulmonary artery flush on lung preservation? J Heart Lung Transplant. 1999 Feb; 18(2):139-42. View Abstract
  80. Adenosine-enhanced ischemic preconditioning provides enhanced cardioprotection in the aged heart. Ann Thorac Surg. 1998 Dec; 66(6):2037-43. View Abstract
  81. Adenosine-enhanced ischemic preconditioning decreases infarct in the regional ischemic sheep heart. Ann Thorac Surg. 1998 Aug; 66(2):382-7. View Abstract
  82. Adenosine-enhanced ischemic preconditioning provides enhanced postischemic recovery and limitation of infarct size in the rabbit heart. J Thorac Cardiovasc Surg. 1998 Jul; 116(1):154-62. View Abstract
  83. Developmental differences in cytosolic calcium accumulation associated with global ischemia: evidence for differential intracellular calcium channel receptor activity. Circulation. 1997 Nov 04; 96(9 Suppl):II-233-8; discussion II-238-9. View Abstract
  84. Amelioration of ischemic calcium overload correlates with high-energy phosphates in senescent myocardium. Am J Physiol. 1997 Jul; 273(1 Pt 2):H418-25. View Abstract
  85. Mechanisms of in vitro cardioprotective action of magnesium on the aging myocardium. Magnes Res. 1997 Jun; 10(2):157-68. View Abstract
  86. "Reperfusion Injury" and Myocardial Protection by Cardioplegia: An Opinion. J Thromb Thrombolysis. 1997 Jan; 4(1):131-132. View Abstract
  87. Myocardial protection in the elderly. Biology of the senescent heart. Ann N Y Acad Sci. 1996 Sep 30; 793:305-18. View Abstract
  88. Developmental differences in cytosolic calcium accumulation associated with surgically induced global ischemia: optimization of cardioplegic protection and mechanism of action. J Thorac Cardiovasc Surg. 1996 Jul; 112(1):175-84. View Abstract
  89. A brief period of retrograde hyperthermic perfusion enhances myocardial protection from global ischemia: association with accumulation of Hsp 70 mRNA and protein. J Mol Cell Cardiol. 1996 Feb; 28(2):231-41. View Abstract
  90. Improvement of pulmonary graft after storage for twenty-four hours by in vivo administration of lazaroid U74389G: functional and morphologic analysis. J Heart Lung Transplant. 1996 Jan; 15(1 Pt 1):35-42. View Abstract
  91. Magnesium cardioplegia enhances mRNA levels and the maximal velocity of cytochrome oxidase I in the senescent myocardium during global ischemia. Circulation. 1995 Nov 01; 92(9 Suppl):II405-12. View Abstract
  92. Lung preservation threshold in a compromised septic lung injury model. Ann Thorac Surg. 1995 Oct; 60(4):958-62; discussion 962-3. View Abstract
  93. Heat-shock gene expression in alcoholic liver disease in the rat is related to the severity of liver injury and lipid peroxidation. Proc Soc Exp Biol Med. 1995 Oct; 210(1):12-9. View Abstract
  94. Myocardial mitochondrial calcium accumulation modulates nuclear calcium accumulation and DNA fragmentation. Ann Thorac Surg. 1995 Aug; 60(2):338-44. View Abstract
  95. Impact of initial flush potassium concentration on the adequacy of lung preservation. J Thorac Cardiovasc Surg. 1995 Jun; 109(6):1090-5; discussion 1095-6. View Abstract
  96. Effect of type of dietary fat and ethanol on antioxidant enzyme mRNA induction in rat liver. J Lipid Res. 1995 Apr; 36(4):736-44. View Abstract
  97. The rapid expression of myocardial hsp 70 mRNA and the heat shock 70 kDa protein can be achieved after only a brief period of retrograde hyperthermic perfusion. J Mol Cell Cardiol. 1995 Mar; 27(3):873-82. View Abstract
  98. Heat-shock protein 70 mRNA is induced by anaerobic metabolism in rat hearts. Circulation. 1994 Nov; 90(5 Pt 2):II299-305. View Abstract
  99. Magnesium cardioplegia reduces cytosolic and nuclear calcium and DNA fragmentation in the senescent myocardium. Ann Thorac Surg. 1994 Oct; 58(4):1005-11. View Abstract
  100. Myocardial cytosolic calcium accumulation during ischemia/reperfusion: the effects of aging and cardioplegia. J Card Surg. 1994 May; 9(3 Suppl):449-52. View Abstract
  101. Magnesium cardioplegia prevents accumulation of cytosolic calcium in the ischemic myocardium. J Mol Cell Cardiol. 1993 Dec; 25(12):1387-90. View Abstract
  102. Isolation and characterization of a previously unrecognized myosin heavy chain gene present in the Syrian hamster. J Mol Biol. 1991 Apr 20; 218(4):657-65. View Abstract
  103. RNA transcription and translation in the hearts of normal and cardiomyopathic Syrian hamsters. Biochem Cell Biol. 1991 Jan; 69(1):88-92. View Abstract
  104. RNA transcription in myocardial-cell nuclei during postnatal development. A study establishing an assay system for transcription in vitro. Biochem J. 1988 Dec 01; 256(2):441-5. View Abstract
  105. Construction of cosmid genomic libraries for the normal and myopathic Syrian hamsters. Biochem Cell Biol. 1987 Nov; 65(11):997-1000. View Abstract
  106. Alterations in myocardial RNA synthesis and RNA polymerase activity during normal growth. Can J Physiol Pharmacol. 1983 Apr; 61(4):341-8. View Abstract

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