Acute effects of direct cell implantation into the heart: a pressure-volume study to analyze cardiac function.

ABSTRACT

BACKGROUND: To safely implant cells into the myocardium, we must establish a volume that prevents compromising cardiac performance. We studied pressure-volume (PV) to investigate the adverse effects of direct cell implantation in the acute phase. METHODS: We used 21 minipigs. In the normal heart model, we studied PV by measuring various parameters (including end-systolic pressure, end-systolic elastance, dp/dtmax, end-diastolic volume, and time constant of isovolumetric left ventricular pressure fall [Tau]). We injected solutions into the left ventricular free wall (15 cm(2)). Sampling points were at baseline and after injection of saline (Group I, n = 4) or of blood (Group II, n = 4) at volumes of 1 ml and 10 ml up to 30 minutes after injection. In Group II, we injected additional blood (10 ml) 4 times. In the ischemic heart model, 1 month after ligating the left anterior descending artery, we injected 1 ml saline (Group III, n = 4), bone marrow mononuclear cells (10(8) cells/1 ml; Group IV, n = 4), or bone marrow stromal cells (10(8) cells/1 ml; Group V, n = 3). We studied PV before and after injection. RESULTS: In Group I, we found no significant changes in parameters. In Group II, end-diastolic volume after 10-ml injection (24.4 +/- 3.6 ml) was smaller than end-diastolic volume at baseline (29.5 +/- 5.8 ml, p < 0.01). Tau after 10-ml injection (39.4 +/- 5.3 msec) was greater than at baseline (35.6 +/- 4.0 msec, p < 0.01). One pig died of ventricular fibrillation after a 20-ml injection of blood. We observed no detrimental effects in Groups III, IV, and V. CONCLUSIONS: More than 10 ml cell suspension compromised diastolic function. We safely performed direct injection of bone marrow cells (1 x 10(8)/1 ml).