Zoledronate (Zol), one of the class of bisphophonate drugs, is commonly used to treat
postmenopausal osteoporosis. Treatment of liposomal
bisphosphonates has been shown to worsen
myocardial infarct repair in an experimental model. 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, a dose known to treat experimental
osteoporosis in rats, n = 15) was administered subcutaneously to female Sprague-Dawley rats 1 day before coronary artery
ligation. Rats receiving
phosphate-buffered saline (n = 12) were used as controls. Left ventricular function,
infarct size, and remodeling were studied at 4 weeks postinfarction. Zol pretreatment did not affect left ventricular ejection fraction in hearts with
myocardial infarction (49.5 ± 1.4% in Zol; 50.6 ± 2.1% in
phosphate-buffered saline).
Infarct size was similar in Zol versus untreated hearts (34.2% ± 2.9% in Zol; 33.4% ± 2.9% in
phosphate-buffered saline). Left ventricular cavity volume and circumference,
infarct thickness, and expansion index were comparable between the groups. To investigate a potential effect of Zol on tissue macrophage infiltration after
myocardial infarction, heart specimens were harvested 48 hours postinfarction and sections were immunostained with CD68 antibody, a macrophage-specific marker. Results of macrophage immunostaining revealed that the level of tissue macrophage infiltration was similar between groups. In conclusion, administration of Zol before
myocardial infarction had no adverse effects on cardiac contractile function,
infarct size, or remodeling. These results suggest that treatment of Zol given before the onset of
myocardial infarction does not cause worsening of
infarct repair.