Hypoxia-Inducible Factor 1-Alpha Release After Intracoronary Versus Intramyocardial Stem Cell Therapy in Myocardial Infarction

We have investigated the effect of stem cell delivery on the release of hypoxia-inducible factor 1 alpha (HIF-1 alpha) in peripheral circulation and myocardium in experimental myocardial ischemia. Closed-chest, reperfused myocardial infarction (MI) was created in domestic pigs. Porcine mesenchymal stem cells (MSCs) were cultured and delivered (9.8 +/- 1.2x10(6)) either percutaneously NOGA-guided transendocardially (Group IM) or intracoronary (Group IC) 22 +/- 4 days post-MI. Pigs without MSC delivery served as sham control (Group S). Plasma HIF-1 alpha was measured at baseline, immediately post-and at follow-up (FUP; 2 h or 24 h) post-MSC delivery by ELISA kit. Myocardial HIF-1 alpha expression of infarcted, normal myocardium, or border zone was determined by Western blot. Plasma level of HIF-1 alpha increased immediately post-MI (from 278 +/- 127 to 631 +/- 375 pg/ml, p<0.05). Cardiac delivery of MSCs elevated the plasma levels of HIF-1 alpha significantly (p<0.05) in groups IC and IM immediately post-MSC delivery, and returned to baseline level at FUP, without difference between the groups IC and IM. The myocardial tissue HIF-1 alpha expression in the infarcted area was higher in Group IM than in Group IC or S ( 1,963 +/- 586 vs. 1,307 +/- 392 vs. 271 +/- 110 activity per square millimeter, respectively, p<0.05), while the border zone contained similarly lower level of HIF-1 alpha, but still significantly higher as compared with Group S. Trend towards increase in myocardial expression of HIF-1 alpha was measured in Group IM at 24 h, in contrast to Group IC. In conclusion, both stem cell delivery modes increase the systemic and myocardial level of HIF-1 alpha. Intramyocardial delivery of MSC seems to trigger the release of angiogenic HIF-1 alpha more effectively than does intracoronary delivery.