Intracoronary Delivery of Cardiac Stem Cells to the Right Ventricle: Preclinical Assessment in a Swine Model
Sunjay Kaushal, Brody Wehman, Osama Siddiqui, Godly Jack, Rachana Mishra, Tieluo Li, Mark Vesely. University of Maryland School of Medicine, Baltimore, MD USA.
Objective: Cell-based therapies are currently under investigation in patients with hypoplastic left heart syndrome. However, the optimal technique for cell delivery to the right ventricle has yet to be explored in a preclinical model.
Methods: Human c-kit+ cardiac stem cells (CSCs) were delivered to Yorkshire swine (n=12) via the proximal right coronary artery (RCA) over 4 three-minute inflation periods. To evaluate the effects of escalating cell dose on myocardial distribution, pigs were divided into three dosing groups (low: n=3; medium: n=3; high: n=3). In a fourth group (n=3), serial cardiac enzymes were measured at baseline, 6 and 24 hours post-infusion. Human CSCs were identified with immunohistochemistry.
Results: The majority of CSCs were identified in the lateral RV free wall in a dose-dependent manner (p for linear trend <0.01, Figure SA16-1), consistent with the anatomic course of the RCA. Few CSCs were identified in medial segments of the RV, RVOT and septum. Eight (75%) pigs experienced transient ST segment changes in the precordial leads during cell delivery, which resolved spontaneously. However, at 24 hours post-infusion, cardiac enzymes were markedly increased compared to baseline.
Conclusions: Intracoronary delivery results in a limited biodistribution of CSCs to the RV. Use of the stop-reflow technique in the proximal RCA may increase risk for ischemic injury. Alternative strategies, such as intramyocardial injection or cardiopulmonary bypass-assisted coronary infusion at the time of planned surgical intervention may provide a more homogenous distribution of cells and minimize risk of myocardial infarction in patients with non-ischemic etiologies of RV dysfunction.
Figure 1 – Biodistribution of Cardiac Stem Cells to the Right Ventricle FollowingIntracoronary Delivery to the Right Coronary Artery