Lower retention after retrograde coronary venous infusion compared with intracoronary infusion of mesenchymal stromal cells in the infarcted porcine myocardium

Abstract

Background Commonly used strategies for cell delivery to the heart are intramyocardial injection and intracoronary (IC) infusion, both having their advantages and disadvantages. Therefore, alternative strategies, such as retrograde coronary venous infusion (RCVI), are explored. The aim of this confirmatory study was to compare cardiac cell retention between RCVI and IC infusion. As a secondary end point, the procedural safety of RCVI is assessed. Methods Four weeks after myocardial infarction, 12 pigs were randomised to receive mesenchymal stromal cells, labelled with Indium-111, via RCVI (n=6) or IC infusion (n=6). Four hours after cell administration, nuclear imaging was performed to determine the number of cells retained in the heart both in vivo and ex vivo. Procedure-related safety measures were reported. Results Cardiac cell retention is significantly lower after RCVI compared with IC infusion (in vivo: RCVI: median 2.89% vs IC: median 13.74%, p=0.002, ex vivo: RCVI: median 2.55% vs IC: median 39.40%, p=0.002). RCVI led to development of pericardial fluid and haematomas on the frontal wall of the heart in three cases. Coronary venous dissection after RCVI was seen in three pigs, of which one also developed pericardial fluid and a haematoma. IC infusion led to no flow in one pig. Conclusion RCVI is significantly less efficient in delivering cells to the heart compared with IC infusion. RCVI led to more procedure-related safety issues than IC infusion, with multiple cases of venous dissection and development of haematomas and pericardial fluid collections.