A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy

Borami Shin, MD; Mossab Y. Saeed, MD; Jesse J. Esch, MD; Alvise Guariento, MD; David Blitzer, MD; Kamila Moskowitzova, MD; Giovanna Ramirez-Barbieri, MD; Arzoo Orfany, MD; Jerusha K. Thedsanamoorthy, BA; Douglas B. Cowan, PhD; James A. Inkster, PhD; Erin R. Snay, BRS; Steven J. Staffa, MS; Alan B. Packard, PhD; David Zurakowski, PhD; Pedro J. del Nido, MD; James D. McCully, PhD

JACC: Basic to Translational Science (Dec 2019)

A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy

Borami Shin, MD,
Mossab Y. Saeed, MD,
Jesse J. Esch, MD,
Alvise Guariento, MD,
David Blitzer, MD,
Kamila Moskowitzova, MD,
Giovanna Ramirez-Barbieri, MD,
Arzoo Orfany, MD,
Jerusha K. Thedsanamoorthy, BA,
Douglas B. Cowan, PhD,
James A. Inkster, PhD,
Erin R. Snay, BRS,
Steven J. Staffa, MS,
Alan B. Packard, PhD,
David Zurakowski, PhD,
Pedro J. del Nido, MD,
James D. McCully, PhD

Affiliations

Borami Shin, MD: Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
Mossab Y. Saeed, MD: Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
Jesse J. Esch, MD: Harvard Medical School, Boston, Massachusetts; Department of Cardiology, Boston Children’s Hospital, Boston, Massachusetts
Alvise Guariento, MD: Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
David Blitzer, MD: Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
Kamila Moskowitzova, MD: Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
Giovanna Ramirez-Barbieri, MD: Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
Arzoo Orfany, MD: Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
Jerusha K. Thedsanamoorthy, BA: Harvard Medical School, Boston, Massachusetts; Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts
Douglas B. Cowan, PhD: Harvard Medical School, Boston, Massachusetts; Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts
James A. Inkster, PhD: Harvard Medical School, Boston, Massachusetts; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston Children’s Hospital, Boston, Massachusetts
Erin R. Snay, BRS: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston Children’s Hospital, Boston, Massachusetts
Steven J. Staffa, MS: Harvard Medical School, Boston, Massachusetts; Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts
Alan B. Packard, PhD: Harvard Medical School, Boston, Massachusetts; Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts
David Zurakowski, PhD: Harvard Medical School, Boston, Massachusetts; Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts
Pedro J. del Nido, MD: Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
James D. McCully, PhD: Department of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Address for correspondence: Dr. James D. McCully, Department of Cardiac Surgery, Boston Children’s Hospital, 300 Longwood Avenue, Enders-407, Boston, Massachusetts 02115.

Journal volume & issue: Vol. 4, no. 8
pp. 871 – 888

Abstract

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Summary: Mitochondrial dysfunction is the determinant insult of ischemia-reperfusion injury. Autologous mitochondrial transplantation involves supplying one’s healthy mitochondria to the ischemic region harboring damaged mitochondria. The authors used in vivo swine to show that mitochondrial transplantation in the heart by intracoronary delivery is safe, with specific distribution to the heart, and results in significant increase in coronary blood flow, which requires intact mitochondrial viability, adenosine triphosphate production, and, in part, the activation of vascular KIR channels. Intracoronary mitochondrial delivery after temporary regional ischemia significantly improved myocardial function, perfusion, and infarct size. The authors concluded that intracoronary delivery of mitochondria is safe and efficacious therapy for myocardial ischemia-reperfusion injury. Key Words: ischemia-reperfusion injury, mitochondria, mitochondrial transplantation, myocardial protection

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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