Abstract 3500: Delayed Recovery of Myocardial Blood Flow After Intracoronary Stem Cell Administration
Objectives. Intracoronary stem cell (SC) transfer in patients with acute myocardial infarction (AMI) may result in temporary no-flow or reduced flow of the infarct-related artery (IRA). The aim of the present study was to investigate the changes in absolute myocardial blood flow (AMF) after intracoronary (ic.) injections of mesenchymal SC (MSC) in open-chest reperfused AMI in pigs.
Methods. AMI was created by percutaneous balloon occlusion of the LAD in female domestic pigs. Male MSCs, cultured and transiently transfected with Luciferase (Luc-MSC) were delivered (9.6±1.1 ×106) ic. with stop-flow technique in the open IRA 20±3 days post-MI in female pigs. Before, immediately after and 3 and 24h post intracoronary Luc-MSC therapy, the AMF and fractional flow reserve (FFR) were measured by a sensor-tipped guidewire, positioned in the distal part of the IRA, using sidehole infusion catheter. After euthanasia, the heart was excised, and in vitro bioluminescense and quantitative real-time TaqMan PCR was performed to detect the sex-mismatch MSCs in the female hearts. Tissue luciferase activity was measured in the homogenized cardiac tissues of the distal LAD territory using dual-luciferase reporter assay.
Results. The AMF decreased significantly immediately after ic. MSC delivery (from 56.4±19.2 to 45.7±11.3 ml/min, p=0.039), and remained low at 3h (42.3±16.7 ml/min, p=0.033) with incomplete recovery at 24h (47.8±6.7 ml/min, p=0.117) as compared with baseline value. FFR decreased gradually form 0.96±0.1 to 0.91±0.21 immediately post MSC therapy (p=0.223), 0.90±0.17 at 3h (p=0.236) and 0.79±0.18 at 24h (p=0.021). In vitro bioluminescence displayed transfected Luc-MSCs along the proximal and mid part of the LAD, but not in the distal myocardium. Cardiac tissue samples of the infarcted area contained only very limited number of Y-chromosome-MSCs (max 346 sry copied/million cardiac cells at 24h), with retention of 1.8% at 3h and 1.4% at 24h of the originally injected cells determined by luciferase assay.
Conclusion. Ic. injection of SCs results in immediate decrease of AMF, with delayed and partial recovery 24h post-delivery. The migration of the SC through the endothelium into the infarcted area might be hindered by the altered coronary pressure conditions.