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Catheter Cardiovasc Interv. 2019 Nov 1;94(5):669-676. doi: 10.1002/ccd.28159. Epub 2019 Mar 13.

Catheter-based retrograde coronary sinus infusion is a practical delivery technique for introducing biological molecules into the cardiac system.

Author information

1
Cook BioDevice, Cook Regentec LLC, Indianapolis, Indiana.
2
Human Therapeutics Division, Intrexon Corporation, Germantown, Maryland.
3
Non-Clinical Testing, Cook Research Incorporated, West Lafayette, Indiana.
4
Cell Manufacturing Solutions, Cook Regentec LLC, Indianapolis, Indiana.
5
Emerging Therapies, Precigen, Inc., Germantown, Maryland.
6
Division of Cardiothoracic Surgery, University of Miami, Miller School of Medicine, Miami, Florida.

Abstract

OBJECTIVES:

To demonstrate coronary sinus (CS) retrograde catheterization as a practicable technique for delivering biologics into the heart.

BACKGROUND:

There are many options to deliver biologics into the heart. However, there is no single optimal technique when considering safety, biologic retention, and reproducibility. Retrograde delivery has the potential to address many of these concerns. This study evaluated retrograde CS infusion of luciferase-expressing plasmid in a porcine model using the AdvanceĀ® CS Coronary Sinus Infusion Catheter and bioluminescence imaging to track the expression of the infused biological markers.

METHODS:

Plasmid was delivered retrograde into the CS in one of three infusion volumes. Twenty-four hours post-infusion, hearts were excised and underwent bioluminescence imaging to characterize the expression of the infusates. Heart and lung biopsies were also assessed for luciferase expression using RT-qPCR.

RESULTS:

Retrograde infusion was safe and successful in all nine test subjects. Luciferase detection was inconsistent in the low volume group. Bioluminescence was confined predominantly along the posterolateral left ventricle for medium volume infusions and was more broadly dispersed along the anterior side of the heart for high volume infusions. Tissue mRNA analysis corroborated the bioluminescence results, with the highest concentration of luciferase expression localized in the left ventricle.

CONCLUSIONS:

Retrograde CS infusion is a promising technique for delivering biological molecules to the heart. Specifically, this study demonstrated that the low pressure coronary venous system accommodates a wide range of infusion volumes and that biological infusates can be maintained in situ following the resumption of coronary venous flow.

KEYWORDS:

animal models; coronary blood flow/physiology/microvascular function; heart failure; imaging, angiographic/fluoroscopic; interventional devices/innovation; stem cell/regenerative therapy

PMID:
30866153
DOI:
10.1002/ccd.28159

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