Objective: Myocardial gene and cellular therapies have revived the use of porcine ischemic heart models. Commonly applied ameroid-obstruction produces inconsistent coronary stenoses and myocardial lesions, whereas abrupt coronary occlusion causes arrhythmias and sudden death. To produce a constant myocardial lesion after adaptation to ischemia, we surgically modified the ameroid-model by ligation. As a pilot study for further cell therapy research, the spontaneous myocardial response is described.
Materials and methods: Simultaneously with ameroid application, a loose loop of nonabsorbable thread was placed around the left circumflex artery (LCx) on 11 domestic piglets. Three weeks later, the loop was tightened. Coronary arteriograms with Rentrop collateral grading from 0 to 3, and 99mTc-single photon emission computerized tomography studies were performed 1 to 5 wk after ligation. At autopsy, the hearts were analyzed macroscopically, histologically, and with von Willebrandt factor-staining.
Results: LCx-banding was well-tolerated in nine animals, of which angiographic occlusion was gained in eight. Postmortem analysis revealed a 5 to 10 cm(2) transmural or subendocardial lateral myocardial infarction in all except one heart. One week after occlusion, LCx showed well-developed collateral filling (Rentrop-grade 2.7 +/- 0.4), which remained unchanged at 5 wk. On single photon emission computerized tomography-scans, lateral wall perfusion increased spontaneously between 1 and 5 wk (P = 0.02), and von Willebrandt factor revealed clusters of neovascularization at the borders of infarct areas.
Conclusions: This new modification of ameroid model standardizes myocardial lesion, which might reduce animal number in preclinical studies, thus having ethical aspect. The remarked potential for spontaneous recovery in ischemic porcine myocardium should be considered in preclinical therapeutic studies.