Acute effects of direct cell implantation into the heart: a pressure-volume study to analyze cardiac function.
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).
Ishida
Michiko
M
Departments of Organ Transplantation, National Cardiovascular Center, Osaka, Japan.
Tomita
Shinji
S
Nakatani
Takeshi
T
Kagawa
Kiyokazu
K
Yamaguchi
Takeyoshi
T
Suga
Michiharu
M
Ohtsu
Yoshinori
Y
Yazawa
Hajime
H
Yagihara
Toshikatsu
T
Kitamura
Soichiro
S
D000818:Animals; D016026:Bone Marrow Transplantation; D002306:Cardiac Volume; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics; D007267:Injections; D023421:Models, Animal; D008955:Models, Cardiovascular; D013552:Swine; D013556:Swine, Miniature; D016277:Ventricular Function, Left; D017725:Ventricular Pressure