Pig model of chronic myocardial ischemia and its investigation by ultrasonic integrated backscatter and Doppler tissue imaging

Objective: To construct an animal model of chronic ischemic myocardium, and evaluate it by ultrasonic integrated backscatter (IBS) and Doppler tissue imaging (DTI). Methods: An Ameroid constrictor was placed around the porcine left circumflex coronary artery (LCX). The calibrated average image intensity (%AII), cyclic variation of IBS (CVIB), transmural gradient index (TGI) of CVIB in lateral-posterior wall (LPW), and DTI spectrum of LPW in left ventricular papillary muscle level short axis view (LVPM-SAM) and apical four chamber view (AP-4CV) at normal state, 2, 4, 6 and 8 weeks postoperatively were measured. Results: Normal %AII, CVIB and TGI were 2.29±0.32, 9.69±2.22dB and 0.22±0.08, respectively. The %AII increased gradually postoperatively. The CVIB decreased also gradually, and the decrease was higher in subepicardium than in subendocardium. Most of TGI decrease occurred from 2 to 4 weeks postoperatively and became zero at 8 weeks (P<0.01); Normal V S (peak systolic velocity) of AP-4CV was higher than that of LVPM-SAM (P<0.01). V E (peak early diastolic velocity) of AP-4CV was lower than that of LVPM-SAM (P<0.05). V S and V E were all decreased after operation (P<0.01). The decrease of V S in AP-4CV was greater than that in LVPM-SAM. Conclusion: The pathological changes of the myocardium in human ischemic heart disease (IHD) are similar to that of Ameriod model. IBS and DTI can detect echo changes and ventricular wall motion in chronic ischemic myocardium, and provide more information for clinical investigation and treatment of IHD.

Treatment of chronical myocardial ischemia by adenovirus-mediated hepatocyte growth factor gene transfer in minipigs

Growth factor gene transfer-induced therapeutic angiogenesis has become a novel approach for the treatment of myocardial ischemia. In order to provide a basis for the clinical application of an adeno- virus with hepatocyte growth factor gene (Ad-HGF) in the treatment of myocardial ischemia, we estab- lished a minipig model of chronically ischemic myocardium in which an Ameroid constrictor was placed around the left circumflex branch of the coronary artery (LCX). A total of 18 minipigs were ran- domly divided into 3 groups: a surgery control group, a model group and an Ad-HGF treatment group implanted with Ameroid constrictor. Ad-HGF or the control agent was injected directly into the ischemic myocardium, and an improvement in heart function and blood supply were evaluated. The results showed that myocardial perfusion remarkably improved in the Ad-HGF group compared with that in both the control and model groups. Four weeks after the treatment, the density of newly formed blood vessels was higher and the number of collateral blood vessels was greater in the Ad-HGF group than in the model group. The area of myocardial ischemia reduced evidently and the left ventricular ejection fraction improved significantly in the Ad-HGF group. These results suggest that HGF gene therapy may become a novel approach in the treatment of chronically ischemic myocardium.