[Therapeutic angiogenesis with the use of vascular endothelial growth factor 165 gene in the myocardium of miniature swine].

The purpose of the present study was to examine whether adenovirus-mediated vascular endothelial growth factor l65 (VEGFl65) can enhance collateral vessel formation of coronary artery and improve regional myocardial perfusion and function. Using a miniature swine model of chronic myocardial ischemia, the replication-deficient recombinant adenovirus vector containing complementary deoxyribonucleic acid (cDNA) for human VEGFl65 (Ad-VEGFl65) or for beta-galactosidase (Ad-Gal) was administered directly into the ischemic myocardium in the left circumflex (LCX) distribution. Myocardial perfusion and function were assessed by electrocardiogram-gated single photon emission computed tomography (SPECT) imaging and collateral vessel development of coronary artery was assessed by ex vivo coronary angiography (CAG). Four weeks after Ad-VEGF165 administration, SPECT imaging demonstrated a significant reduction in ischemic area (P<0.01) and ischemic severity (P<0.01), and a substantial improvement in left ventricular ejection fraction (P<0.01) and regional wall motion in the LCX distribution (P<0.05), as compared with that of control animals and that before administration of Ad-VEGFl65. Collateral vessel development with Rentrop Grading was also significantly greater in Ad-VEGF165 animals than in the Ad-Gal control animals (P<0.05). It's concluded that Ad-VEGFl65 can induce collateral vessel development in ischemic myocardium and result in significant improvement in myocardial perfusion and function.

[Inhibition of ERK1/2 activity and c-fos mRNA after coronary artery balloon injury by intracoronary radiation in swine].

The effect of intracoronary radiation on extracellular signal regulated kinase 1/2 (ERK1/2) activity and c-fos mRNA after coronary artery balloon injury was investigated in swine. Twenty three swines were randomly divided into a radiation group and a control group after coronary balloon over stretch. The dilated segments in the radiation group were exposed to a dose of 20 Gy by a catheter based radiation system. The animals were sacrificed at 3 (6 swines from each group) and 30 days (6 swines from radiation group and 5 from control group) after the operation. The injured segments were processed to examine c-fos gene expression by reverse transcription polymerase chain reaction (RT PCR) and to measure the activity of ERK1/2 biochemically. Intracoronary radiation decreased significantly the ERK1/2 activity and gene expression of c-fos in the radiation treated animals 3 days after coronary balloon injury (20.5%,P<0.01; 47.7%,P<0.05), but neither ERK1/2 activity nor c-fos gene expression was significantly affected by endovascular radiation in animals 30 days after balloon injury. Therefore, both ERK1/2 and c-fos may be involved in inhibiting restenosis.

Defibrase, a purified fibrinolytic protease from snake venom in acute myocardial infarction.

To investigate the thrombolytic effects of defibrase in AMI, 157 pts with AMI were studied. Of the 157 pts, 87 were assigned to defibrase thrombolysis and 70 to the conventional therapy plus heparin (control). Coronary arteriography was performed in 36 pts of the defibrase group and 26 of the control group. Pretreatment coronary arteriography was performed in 10 pts and total occlusion of infarct-related artery (IRA) was demonstrated in 7. Thirty to 45 min after either intracoronary or intravenous defibrase thrombolysis, recanalization occurred in 4 of the 7 pts. The perfusion and stenosis was improved in 2 of the 3 pts with patent IRA. Of the 10 pts who underwent emergency coronary arteriography after the onset of i.v. defibrase thrombolysis, 6 were shown to have patent IRAs. Of the 16 pts who underwent coronary arteriography two weeks after the i.v. defibrase thrombolysis, 13 were shown to have patent IRAs. In contrast, only 11 of the 26 pts in the control group had patent IRAs two weeks after admission to the hospital. Of the 36 angiographic cases of the defibrase group, 15 underwent follow-up coronary arteriography, only 1 pt showed reocclusion. In comparison to the control group, the pts in the defibrase group had earlier CPK peaking, higher percentage of pts with LVEF > 0.5, a lower mortality and complication rate. Major spontaneous bleeding complications were rarely seen with defibrase. The results indicate that defibrase is an effective thrombolytic agent with a reasonable recanalization rate, low reocclusion rate and a low rate of bleeding complications.

[Coronary thrombolysis with defibrase].

Clinical use of defibrase (DF), a fibrinolytic agent from venom of Agkistrodon acutus, was investigated in patients with acute myocardial infarction (AMI). Patients with AMI were randomized to tow groups, one receiving conventional therapy and DF, the other a control group having conventional treatment only. The patients in the DF group received intravenous DF 0.05 u or 0.075 u/kg over 1 hour immediately after the attack and 0.025 u/kg over 4 hours on the 5 th and 10 th day. The control patients received conventional therapy only. Of the patients randomized, 21 had coronary angiography and left ventriculography. Recanalization was seen in 10 of the 10 patients treated with DF, while only in 3 of the 11 patients in the control group. LVEF in the DF group was higher than that in the control group (61% vs 50%). However the difference was not significant. In the DF group, two patients developed petechia and blood oozing at the site of intravenous injection and one patient developed gum bleeding; all patients had transient thrombocytopnia, which returned to normal within 5 days. There was no intracranial hemorrhage, gross hematuria or hematemesis. In conclusion, DF possess thrombolytic as well as anticoagulant effects with minor bleeding complication. Early infusion of DF yields high patency rate and shows a trend toward preservation of LV function.