Cardioprotective effects of diltiazem reevaluated by a novel myocardial ischemic model in Chinese miniature swine
Abstract
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 degeneration,
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.
Keywords:
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 degeneration,
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.