Transendocardial cell injection is not superior to intracoronary infusion in a porcine model of ischaemic cardiomyopathy: a study on delivery efficiency

Abstract

Stem cell therapy is a new strategy for chronic ischaemic heart disease in patients. However, no consensus exists on the most optimal delivery strategy. This randomized study was designed to assess cell delivery efficiency of three clinically relevant strategies: intracoronary (IC) and transendocardial (TE) using electromechanical mapping guidance (NOGA) compared to surgical delivery in a chronic pig model of ischaemic cardiomyopathy. Twenty-four animals underwent delivery of 107 autologous Indium-oxine-labelled bone marrow-derived mesenchymal stem cells (MSC) 4 weeks after infarction and were randomized to one of three groups (n = 8 each group): IC, TE or surgical delivery (reference group). Primary endpoint was defined as percentage (%) of injected dose per organ and assessed by in vivo gamma-emission counting. In addition, troponin and coronary flow were assessed before and after MSC injection. Blinded endpoint analysis showed no significant difference in efficiency after surgical (16 ± 4%), IC (11 ± 1%) and TE (11 ± 3%) (P = 0.52) injections. IC showed less variability in efficiency compared with TE and surgical injection. Overall, TE injection showed less distribution of MSC to visceral organs compared with other modalities. Troponin rise and IC flow did not differ between the percutaneous groups. This randomized study showed no significant difference in cell delivery efficiency to the myocardium in a clinically relevant ischaemic large animal model between IC and TE delivery. In addition, no differences in safety profile were observed. These results are important in view of the choice of percutaneous cell delivery modality in future clinical stem cell trials.

Assessment of coronary microvascular resistance in the chronic infarcted pig heart

“…The MI was induced as previously described [17]. Briefly, animals were sedated and general anesthesia was maintained by continuous infusion of midazolam (0.7 mg/kg/hr), sufentanil citrate (6 μg/kg/hr) and pancurorium bromide (0.1 mg/kg/hr) via the canulated ear vein.…”

Necrostatin‐1 alleviates reperfusion injury following acute myocardial infarction in pigs

“…Pressure-volume loops were measured using a 7-F conductance catheter, as previously described [20]. Briefly, LV pressure and volumes were measured and stored using a Leycom CFL-512 (CD Leycom, Zoetermeer, the Netherlands).…”

Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia

“…Percutaneous coronary cell delivery is less invasive and demonstrates the most frequent application route in the clinical setting. Until now, controversy existed about whether intramyocardial or intracoronary administration was superior [26–28]. Some studies have shown that systemic intravenous administration of cells could hardly home to the heart because of the pulmonary first‐pass effect.…”