Keywords: Cell therapy, Stem cells, Myocardium, Angina

Transcoronary unselected and selected autologous bone marrow mononuclear cell (ABMMC) implants had shown their clinical and imaging benefit in patients with acute and chronic myocardial disease. Different procedures had been used to assure and improve cell homing and reach ischemic and hypokinetic ventricular areas. PRST was demonstrated to be useful in poorly perfused ventricular areas. Here, we show our outcomes using PRST in heavily treated chronic RA patients with ABMMC from May to October 2005: 10 consecutive patients, with a median age of 65 years (range, 41–81); male/female ratio, 9:1, with infarcted and ischemic myocardium, functional class (CCF) III–IV RA; 80% had Grade II–III congestive cardiac failure (NYHA), and two patients had Grade IV congestive cardiac failure. None of these patients were candidates for myocardial revascularization surgery or angioplasty. Basal ejection fraction was 40.5% (range, 30–69%). After signed informed consent, a median volume of 264 ml (range 210–350 ml) of bone marrow was obtained from iliac puncture under local anesthesia. Leuko-concentration was performed using HES 6% and refrigerated centrifugation under sterile conditions. Concentrated cells were implanted retrogradely by coronarography of the venous sinus, and in selected veins, there was previous occlusion of the balloon “overwire” for 8 to 10 min. Median number of mononuclear and CD34+ cells infused were 7.34×10⁸ and 1.97×10⁷, respectively, in a median volume of 40 ml (range, 40–50 ml). Cell infusion was performed under a pressure of 2–4 atm. During and after the procedures, no arrhythmia, no increase in enzymes, or no hemodynamic changes were observed. After a median time of 21 days, ABMMC led to a significant relief of angina symptoms and improvement in functional class. By Week +4, all patients improved their contractibility in previously hypokinetic sectors. By 90 to 150 days, gamma studies demonstrated a reduction in total perfusion defect size by more than 10%. Median EJ improved significantly after procedure to 49.5% (range, 34–69%, P=.001), and nitrate requirement was reduced at this point. Unselected ABMMC transplantation by PRST is feasible and safe, and it allows to infuse a large volume of cells in poorly irrigated coronary vessels. This study suggests the potential improvement of symptoms, functional capacity, myocardial perfusion, and contractility with retrograde approach of ABMMC transplantation in chronic coronary patients.

Fig. 1. Significant changes in the myocardial perfusion at four months.