Abstract
Objectives
To report outcomes in a pilot study of autologous mitochondrial transplantation (MT)
in pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation
(ECMO) for severe refractory cardiogenic shock after ischemia-reperfusion injury (IRI).
Methods
A single-center retrospective study of patients requiring ECMO for postcardiotomy
cardiogenic shock following IRI between May 2002 and December 2018 was performed.
Postcardiotomy IRI was defined as coronary artery compromise followed by successful
revascularization. Patients undergoing revascularization and subsequent MT were compared
with those undergoing revascularization alone (Control).
Results
Twenty-four patients were included (MT, n = 10; Control, n = 14). Markers of systemic
inflammatory response and organ function measured 1 day before and 7 days following
revascularization did not differ between groups. Successful separation from ECMO—defined
as freedom from ECMO reinstitution within 1 week after initial separation—was possible
for 8 patients in the MT group (80%) and 4 in the Control group (29%) (P = .02). Median circumferential strain immediately following IRI but before therapy
was not significantly different between groups. Immediately following separation from
ECMO, ventricular strain was significantly better in the MT group (−23.0%; range,
−20.0% to −28.8%) compared with the Control group (−16.8%; range, −13.0% to −18.4%)
(P = .03). Median time to functional recovery after revascularization was significantly
shorter in the MT group (2 days vs 9 days; P = .02). Cardiovascular events were lower in the MT group (20% vs 79%; P < .01). Cox regression analysis showed higher composite estimated risk of cardiovascular
events in the Control group (hazard ratio, 4.6; 95% confidence interval, 1.0 to 20.9;
P = .04)
Conclusions
In this pilot study, MT was associated with successful separation from ECMO and enhanced
ventricular strain in patients requiring postcardiotomy ECMO for severe refractory
cardiogenic shock after IRI.
Graphical abstract
Graphical Abstract
Key Words
Abbreviations and Acronyms:
BCH (Boston Children's Hospital), COI (conflicts of interest), ECMO (extracorporeal membrane oxygenation), IRB (institutional review board), IRI (ischemia-reperfusion injury), MT (mitochondrial transplantation), OHT (orthotopic heart transplant), VAD (ventricular assist device)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: November 30, 2020
Accepted:
October 27,
2020
Received in revised form:
October 9,
2020
Received:
April 15,
2020
Footnotes
Supported by the Richard A. and Susan F. Smith President's Innovation Award, The Sidman Family Foundation, The Michael B. Rukin Charitable Foundation, The Kenneth C. Griffin Charitable Research Fund, Bulens Family Fund, and The Boston Investment Conference.
Identification
Copyright
© 2020 by The American Association for Thoracic Surgery
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Access this article on ScienceDirectLinked Article
- Commentary: Mitochondrial transplantation for ischemia-reperfusion injury—a new revolution or tilting at windmills?The Journal of Thoracic and Cardiovascular SurgeryVol. 162Issue 3
- PreviewThe last 2 decades have been marked by explosive and exponential research activity aimed at regeneration and improvement of myocardial function in children. Stem cell therapies have been extensively trialed in the setting of ischemia-reperfusion injury, albeit without widespread clinical application.1 In a detailed study recently published in Nature, injection of alive or dead stem cells or a chemical inducer of innate immunity all resulted in activation of innate immunity and improvement in myocardial function.
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- PreviewIschemia–reperfusion injury (IRI) underlies the mechanism of myocardial dysfunction in various cardiac surgery settings. Altered mitochondrial architecture and function are hallmarks of IRI.1 Serving as the final arbiter of life and death, mitochondria are not only required to generate ATP but also can trigger apoptosis and necrosis.2
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- Commentary: Autologous mitochondrial transplantation: An exciting innovation that needs evidence of efficacyThe Journal of Thoracic and Cardiovascular SurgeryVol. 162Issue 3
- PreviewGuariento and colleagues1 describe a pilot clinical trial of a conceptually innovative form of regenerative therapy—autologous mitochondrial transplantation (MT)—in ischemia-reperfusion injury. This approach extends an earlier report from this group describing the first in-human use of autogenous MT in extracorporeal membrane oxygenation-dependent patients.2 The authors should be credited as the primary innovators of MT for cardiac regeneration and this study serves as the next step in the translation of this approach after extensive preclinical studies.
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