Objective To investigate the effect of gene transfection of FKBP12.6 on cardiac function and pathological changes of canine heart failure induced by rapid ventricular pacing.  Methods Three weeks after onset of rapid ventricular pacing (250 beats/min)

28 canines were divided into 4 groups. Either pcDNA3.1-FKBP12.6 plasmid encoding human FKBP12.6 gene(transfection groupⅠ

Ⅱ; observed at the 4th or 14th day respectively after trasnfection) or empty vector(controlⅠ

Ⅱ) was transferred into myocardium under ultrasonic microbubble destruction. After the transfection

maintenance pacing at a reduced rate(190 beats/min) was continued until end-point of experiment. Echocadiographic data were collected three times(before pacing

before transfection and endpoint). The pathological change of myocardium is assessed by HE staining and electron microscope. Semiquantative RT-PCR identified FKBP12.6 expression in myocardium.  Results Gene transfection of FKBP12.6 elevated expression of FKBP12.6 mRNA 3.4 folds at day 4，and 1.7 folds at day 14 respectively

compared with control group. The pathology indicated relative severe changes were observed in control groups and it further aggravated in group control Ⅱ. Cardiac function was significantly improved in transfection group Ⅰ and this effect was stable at least 2 weeks. Eject fraction (EF)

fractionar shorting (FS) are still lower than prepacing although they increase in transfection groups. Left ventricular enddiastolic diameter(LVEDD) and left ventricular enddiastolic volume(LVEDV) decreased at day 14 but LVEDD remained unchanged at day 4 compared with pre-transfection.  Conclusion Gene transfection of FKBP12.6 improves cardiac function in the failing heart

reverses myocyte remodeling and promotes recovery from pathological changes. Thereby it is a novel gene therapy for human heart failure.