A study to determine if basic fibroblast growth factor (bFGF) reduces myocardial infarct size in acute coronary arterial occlusion.

We investigated the angiogenic and myocardial salvage effects of bFGF. Twelve beagles with ligated left anterior descending coronary arteries were divided into two groups: a FGF group administered bFGF intravenously, and a Control group, after CAG immediately post-ligation. One week post-ligation, CAG was repeated. The heart was sliced along the short axis. For each section, the fluorescein Na staining deficit area (DA) and ratio of DA to total area (DAR), TTC staining of the infarct area (IA) and ratio of IA to total area (IAR), and Masson trichrome staining of the fibrosed area (MA) and ratio of MA to total area (MAR), were calculated. The increase in the number of collateral vessels, seen on CAG from post-ligation to 1 week later, was significantly greater in the FGF group. No significant differences in IAR or MAR were seen between the groups. However, DAR and DA/IA were significantly less in the FGF group. In conclusion, bFGF had no effect on infarct size, but stimulated the growth of collateral vessels and improved coronary blood flow in IA.

Elevated circulating levels of basic fibroblast growth factor and vascular endothelial growth factor in patients with acute myocardial infarction.

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have both shown strong angiogenetic effects in ischemic animal models and it has been reported that these growth factors were increased after acute myocardial ischemia. However, there have been few reports on the serum levels of bFGF and VEGF after acute myocardial infarction (AMI), in particular there has not been a comparative study of bFGF and VEGF in human subjects. The time course of circulating levels of bFGF and VEGF was examined in 36 patients with AMI who were within 24h of the onset of the AMI. The serum bFGF and VEGF levels of 50 age- and sex-matched healthy volunteers served as the baseline value. All the patients had undergone coronary angiography on the day of admission (Day 0), but prior to that the serum bFGF and VEGF levels were examined by enzyme-linked immunoassay. The serum bFGF and VEGF levels were also evaluated on Days 7, 14 and 28. Creatine kinase, myosin light chain I and troponin-T were measured subsequently and radionuclide examinations were performed during the early phase of AMI to determine the infarct size. The serum bFGF levels were significantly increased at Day 0 and were maintained until Days 7 and 14. Although serum VEGF levels at Day 0 were similar to the baseline values, they showed a remarkable increase by Days 7 and 14. A high serum level of bFGF was detected in the acute phase of AMI, and a later increase in VEGF was determined in the sub-acute phase, which suggest that these 2 growth factors play an important role at different time points of the reconstructing process of infarcted myocardial tissue.

Low-dose basic fibroblast growth factor and vascular endothelial growth factor for angiogenesis in canine acute hindlimb insufficiency.

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have shown strong angiogenetic effects in ischemic animals; however, whether such a beneficial effect could be achieved using low doses remains to be determined. The effects of identical low-level doses of these substances on the creation of collateral circulation in canine acute hind limb insufficiency were evaluated. Anesthetized dogs that had undergone left femoral artery occlusion received 20 microg (2 microg/kg) intravenous boluses of either bFGF or VEGF 3 times at 2-day intervals for the first week only, animals on vehicle saline injection served as controls. All groups, control (n=8), bFGF-treated (n=8), and VEGF-treated (n=6) underwent angiography, blood flow measurement (in ml/min) on the day of ligation (day 0), and at 7, 14 and 28 days, then underwent ischemic limb muscle biopsy at 28 days. Angiogenic-treated groups showed remarkable enhanced collateral circulation at 7 days, which was maintained up to 28 days, and the main collateral source artery of the angiogenic-treated groups dilated by 14 days. Many neovascularized arterioles in specimens of the angiogenic groups were recognized without any tissue edema or necrosis. Even low doses of bFGF or VEGF were enough to augment collateral circulation with no side-effects, and short treatment after acute ischemia was effective. Low-dose bFGF or VEGF may be therapeutical effective options in patients with acute lower limb vascular disease.

Pentasomy X mosaic in two adult sisters with diabetes mellitus.

Pentasomy X mosaic in two adult sisters with non-insulin dependent diabetes mellitus is described. The younger sister had schizophrenia, and both were mentally retarded, but no apparent somatic abnormalities were found. Chromosome analyses revealed karyotype 45,X/46,XX/47,XXX/48,XXXX/49,XXXXX mosaic with a low frequency of aneuploidy on cultured peripheral lymphocytes and 46,XX on cultured skin fibroblasts in both sisters. The low frequency of X chromosome aberration may be responsible for the lack of somatic abnormalities and the long life in both sisters. The association of pentasomy X mosaicism and diabetes mellitus however appears to be coincidental.