Cellular therapy reverses myocardial dysfunction.

OBJECTIVES: Cellular cardiomyoplasty refers to the implantation of autologous skeletal muscle cells into the myocardium to reinforce its structure and function. In this study a reproducible method for the creation of a myocardial lesion was developed. The functional benefit of cell implantation was evaluated by 2-dimensional echocardiography for global contraction and color kinesis echocardiography, which allows the precise assessment of the regional contraction. METHODS: A left ventricular intramyocardial injection with snake cardiotoxin was carried out on a sheep model to induce a well-delineated transmural lesion. Three weeks later, the lesion was assessed by echocardiography. Thereafter, autologous skeletal muscle cells or culture media (control) were injected into the lesion. Two months after cell implantation, the myocardial contraction was again evaluated by echocardiography and the implanted cells were analyzed by a fast myosin heavy chain antibody. RESULTS: 1. The snake cardiotoxin produced a well-delineated transmural lesion in all animals. 2. Echocardiographic studies showed a significant improvement in global and regional left ventricular function in cell-treated sheep. 3. Histologic analyses demonstrated satellite cell survival at the periphery of the lesions. CONCLUSION: Satellite cells implanted in a cardiotoxin-induced myocardial lesion survived for a 2-month period and were associated with a significant functional improvement of both local and global contraction.

The activity of c-myb antisense oligonucleotide to prevent intimal hyperplasia is nonspecific.

BACKGROUND: We sought to determine the efficacy and specificity of a new c-myb antisense by inhibiting neointimal hyperplasia in a rat abdominal aorta injury model. Using c-myb antisense oligonucleotides, inhibition of vascular smooth muscle cell proliferation has been reported. METHODS: Sixty-six male Wistar rats had a de-endothelialization of the abdominal aorta. Following a double blind randomization protocol, F127 pluronic gel containing one of the five oligonucleotides or plain gel was applied around the aorta: 1) 18-mer c-myb antisense (AS18) with four contiguous guanosines (G-quartet); 2) 15-mer c-myb antisense (AS15) without G-quartet; 3) 1-bp mismatch AS15 without G-quartet (MM1); 4) an oligonucleotide with G-quartet (4G), whereas the other bases were chosen at random; 5) 1-bp mismatch 4G without G-quartet (MM2). After 21 days all rats were sacrificed and aortas harvested for histomorphometric evaluation. Four rats were given fluorescent-labeled oligonucleotides to study in vivo localization after local advential delivery. RESULTS: Morphometric analysis showed significant suppression of neointimal hyperplasia in AS18 and 4G and MM2 groups compared with GEL, AS15 and MM1 groups (p<0.05). The oligonucleotide-labeled aortas showed penetration of the oligonucleotides into the media which increased with time. CONCLUSIONS: Our findings pointed to the potential non specificity of the c-myb antisense oligonucleotide in vivo. Such results will minimize the importance of antisense strategy as a potential therapeutic for preventing neointimal hyperplasia. The two oligonucleotides with a G-quartet inhibited neointimal hyperplasia in our model. Exploring a non-antisense mechanism, G-quartet oligonucleotides as potential drugs to reduce neointimal hyperplasia is attractive.

The Microspheres based Detoxification System (MDS). A new extracorporeal blood purification technology based on recirculated microspherical adsorbent particles.

Plasma sorption processes have so far been performed with filters and appropriate adsorption columns. In this paper, we introduce a newly developed plasma sorption system, which is based on the high adsorption capacity of microspheres in a recirculation system. The technology has been applied successfully in vitro to eliminate endotoxins, low density lipoproteins (LDL) and barbiturates from human plasma.