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Effects of Zoledronate in the Repair of Chronically Infarcted Rat Myocardium

Zoledronate (Zol), a class of bisphophonate drugs, is commonly used to treat post‐menopausal osteoporosis. Treatment of liposomal bisphosphonates, a technique that is often used to deplete tissue macrophages, has experimentally shown to worsen myocardial infarct repair. The purpose of this study was to investigate the effect of Zol in the repair of chronically infarcted myocardium without liposomal encapsulation to mimic the clinical setting. Zol (20 μg/kg) was subcutaneously administered to rat 1 day prior to coronary ligation. Rats receiving phosphate‐buffered saline were utilized for experimental comparison (control). Left ventricular function and infarct size and remodeling were studied at 4 weeks post‐infarction. Zol pre‐treatment did not affect left ventricular ejection fraction in hearts with myocardial infarction (49.5 ± 1.4% in Zol; 50.6 ± 2.1% in control). Infarct size was similar in Zol‐treat versus control hearts (34.2 ± 2.9% in Zol; 33.4 ± 2.9% in control). Left ventricular cavity volume and circumference, infarct thickness, and expansion index were comparable between the groups. In conclusion, administration of Zol prior to myocardial infarction had no adverse effects on cardiac function, infarct size, and remodeling. These results suggest that treatment with Zol in patients with an increased risk of myocardial infarction is safe and does not cause worsening of infarct repair.