Effects of cellular cardiomyoplasty on ventricular remodeling assessed by Doppler echocardiography and topographic immunohistochemistry.
BACKGROUND
Myocardial infarction (MI) promotes deleterious remodeling of the myocardium, resulting in ventricular dilation and pump dysfunction. Supplementing infarcted myocardium with neonatal myocyte would attenuate deleterious remodeling and so the present study used Doppler echocardiography and histology to analyze the cardiac function and histological regeneration of the damaged myocardium after cellular cardiomyoplasty.


RESULTS
Experimental MI was induced by 24-h coronary ligation followed by reperfusion in adult male Lewis rats and neonatal myocytes were injected directly into the infarct and peri-infarct regions. Three groups of animals were studied at 4 weeks after cellular cardiomyoplasty: noninfarcted control (control), MI plus sham injection (MI), and MI plus cell injection (MI + cell). Ventricular remodeling and cardiac performance were assessed by Doppler echocardiography or contrast echocardiography. At 4 weeks after cellular cardiomyoplasty, MI + cell hearts exhibited attenuation of global ventricular dilation and cardiac function compared with MI hearts not receiving cellular cardiomyoplasty. Immunohistochemically, connexin-43-positive small cells were observed in the vicinity of the infarction in MI + cell heart. By electron microscopy, these cells contained myofilaments with Z-bands and poorly developed intercalated disks, suggesting neonatal myocardial cells. Furthermore, the myocardial cells were often making close contact with interstitial cells.


CONCLUSIONS
Implanted neonatal myocytes form viable grafts after MI, resulting in attenuated ventricular dilation and enhanced contractile function. Echocardiography, electron microscopy, and immunohistochemistry are useful methods for assessing the functional and histological regeneration of the damaged myocardium.
Yoshiyama
Minoru
M
Department of Internal Medicine and Cardiology, Graduate School of Medicine, Osaka City University, Japan.
Hayashi
Tetsuya
T
Nakamura
Yasuhiro
Y
Omura
Takashi
T
Izumi
Yasukatsu
Y
Matsumoto
Ryo
R
Takeuchi
Kazuhide
K
Kitaura
Yasushi
Y
Yoshikawa
Junichi
J
D008841:Actin Cytoskeleton; D000818:Animals; D018421:Cardiomyoplasty / Q000379:methods*; D017690:Cell Transplantation; D018031:Connexin 43 / Q000032:analysis; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D006334:Heart Function Tests; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D032342:Muscle Cells / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration; D020257:Ventricular Remodeling / Q000502:physiology*
D018031:Connexin 43