Combined Use Of Transmyocardial Stents With Gene Therapy In The Treatment Of Coronary Artery Disease

Objective:End-stage coronary artery disease with refractory angina represents a therapeutic challenge that is as yet unconquered by our modern day armamentarium. The objective of our research was to determine the efficacy of combined use of transmyocardial stent with gene therapy in a porcine model of acute myocardial infarction.Methods:43 Chinese mini swine have been divided into 4 groups randomly:group myocardial infarction(group MI,n₁=14),group transmyocardial stent(group ST,n₂=10),group vascular endothelial growth factor(group VEGF, n₃=10),group transmyocardial stent and VEGF(group ST+VEGF,n₄=9).In group MI, an acute myocardial infarction animal model was established by ligating the left descending coronary artery.In group ST,after the establishment of the model,3 transmyocardial stents were implanted.In group VEGF,an expression plasmid containing the gene-encoding VEGF₁₆₅(300μg)was administered directly into the myocardium at 6 sites.In group ST+VEGF,both transmyocardial stents and expression plasmid containing the gene-encoding VEGF₁₆₅were applied.4 weeks later,echocardiography,pathological analysis,RT-PCR and immunohistochemical examination have been done.Results:The density of blood vessel in group ST,VEGF and ST+VEGF was significantly higher than group MI(group ST:6.47±1.35,group VEGF:5.01±1.33,group ST+VEGF:9.47±1.52 vs group MI:3.44±0.85/HPF,P＜0.05). The capillary density and arteriole density in group ST+VEGF were the highest in these groups statistically(P＜0.05).Echocardiography showed that in group ST,left ventricular ejection fraction was 62.17±3.43%,FS was 33.00±2.45%and regional wall motion score index(WMSI)was 1.58±0.58.All these were ameliorated significantly compared with group MI(P＜0.05).In group VEGF and ST+VEGF, WMSI was 1.30±0.45 and 1.60±0.55 respectively.Both were ameliorated statistically. Expression of VEGF was detected in group ST,VEGF and ST+VEGF,but in group VEGF and ST+VEGF the level of expression was higher.Conclusion:It is feasible and safe to implant transmyocardial stents in acute myocardial infarction model. Although the channel cannot remain patent in long term,the prolonged stimulation can cause moderate-serious inflammation reaction and proficient angiogenesis. Combined use of transmyocardial stent with gene therapy has synthetic effect for the treatment of acute myocardial infarction in porcine model and can significantly increase the vascular density.