Cardioprotective effects of diltiazem reevaluated by a novel myocardial ischemic model in Chinese miniature swine

Aim： To develop a new model of myocardial ischemia in Chinese miniature swine and reevaluate the cardioprotective effects of diltiazem. Methods： Myocardial ischemia was induced by injecting self-embolus into the left anterior descending （LAD） coronary artery in qualified miniature swine. Diltiazem （5 mg·kg^-1·d^-1） was orally administered to the swine by mixing into normal pig diet from 1 to 6 d after self-embolus injection. The coronary angiography, 30 point body surface electrocardiogram （BS-ECG）, hemodynamics, biochemistry, quantitative histology and pathohistology were determined 6 d after self-embolus injection. Results： Embolization occurred in the LAD coronary artery of the Chinese miniature swine injected by self-embolus. There were significant myocardial ischemia and large cardiac muscle infarction in the Chinese miniature swine, which were accompanied with increased BS-ECG, decreased hemodynamic indexes of the cardiac output, cardiac index, left cardiac work and left cardiac work index, and increased systemic vascular resistance index. Pathohistological analysis revealed myocardial degen- eration, necrosis, fibrosis, inflammatory cell infiltration and granulation tissue hyperblastosis （n=6）. Diltiazem diminished the extent of the LAD embolism, ameliorated myocardial ischemia, improved the hemodynamic indexes, increased the plasma superoxide dismutase activity, decreased the plasma malondialdehyde content, narrowed the myocardial ischemic area and weakened the pathohistological damage in the cardiac muscle （n=6）. Conclusion： Myocardial ischemia induced by injecting self-embolus into the LAD coronary artery in Chinese miniature swine is quite close to clinical pathophysiological conditions. Diltiazem is effective to inhibit the myocardial ischemia and restore the heart function in this novel model.