Effects of Zoledronate in the Repair of Chronically Infarcted Rat Myocardium

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 mu g/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 phosphatebuffered 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.