Transcoronary stem cell delivery using physiological endothelium-targeting perfusion technique: the rationale and a pilot study involving a comparison with conventional over-the-wire balloon coronary occlusions in patients after recent myocardial infarction

Abstract

Introduction: Recent evidence shows poor efficacy of over-the-wire balloon catheter (OTW) coronary occlusive technique adopted widely for intracoronary bone marrow stem cell (BMSC) delivery. The waterfall effect of OTW-balloon inflation/deflation with reactive > or = 2-fold flow velocity increase might be partly responsible for poor BMSC retention.

Aim: To evaluate the safety, feasibility and tolerability of perfusion-infusion BMSC delivery with the facilitation of cell rolling in contact with the coronary endothelium (a pre-requisite for downstream transmigration).

Methods: We randomly assigned 11 patients (age 41-72 years) with first anterior myocardial infarction treated with PTCA+stent and LVEF < or =45% at 6-9 days to OTW in-stent occlusive (3 x 3 min.) BMSC delivery or cell infusion via a perfusion catheter with multiple side holes (SH-PC).

Results: OTW and SH-PC patients had a similar infarct size (mean peak CK 4361 vs 4717 U/L), LVEF (41.2% vs 40.3%), infused mononuclear cell number (2.99 x 108 range 0.61-7.48 x 108 vs 3.28 x 108 range 1.64-4.39 x 108), CD 34(+) number (1.79 x 106 vs 1.62 x 106), cell viability (91.5% vs 91.8%) and clonogenicity (CFU assay). None of the SH-PC, but 67% of OTW patients, had ST-segment elevation with chest pain (and nsVT in one) that limited OTW occlusion tolerance to 50-110 sec. At 6 months DLVEF in the OTW vs SH-PC patients was +4.2% (2-6) vs +8.8% (5-16) by MRI and +4.8 (2-7) vs +13.8% (2-24) by SPECT.

Conclusions: Our work indicates that the SH-PC technique can be used safely for intracoronary BMSC transplantation. Further research is needed to determine whether the putative advantages of physiological SH-PC delivery translate into enhanced BMSC homing.