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

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 Advance® 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.

Therapeutic payload delivery to the myocardium: Evolving strategies and obstacles

“… 29 Retrograde delivery via coronary sinus infusion has also been explored, with preclinical studies showing potential for plasmid delivery and retention over a significant range of injectate volumes. 30 Moreover, coronary sinus infusion has been evaluated in clinical studies of autologous bone marrow delivery for patients with both ischemic and nonischemic heart failure (HF). 23 This small clinical trial (60 patients) concluded that coronary sinus infusion is a safe delivery technique and that bone marrow treatment improved LV ejection fraction in both patient populations.…”

Preconditioning with selective autoretroperfusion: In vivo and in silico evidence of washout hypothesis

“…Unlike the obstructed coronary arterial system, the coronary venous system remains healthy and unobstructed, and thus has enormous potential for therapy delivery (Katti and Patil, 2012;Rodenberg et al, 2019), including retrograde delivery of arterial blood (Kassab et al, 1985). Although envisioned a century ago (Pratt, 1898;Beck and Stanton, 1948), therapeutic retroperfusion (a type of coronary sinus intervention), has not been adopted clinically because complicated equipment has been required to regulate perfusion to prevent damage to the coronary venous system when exposed to arterial pressures.…”