Myocardial systolic function was assessed before a 20 min coronary artery occlusion and during the subsequent 3 weeks of reperfusion by echocardiography and tissue tracking imaging. Throughout reperfusion, rabbits received either IVA (10 mg/kg/day, n=9) or vehicle (Control, n=8) using implanted osmotic pumps. At 3 weeks reperfusion, LV remodeling was investigated by histology and expression of several proteins (SERCA2a, RyR2-P, phospholamban, FKBP12) involved in calcium handling.
After 3 weeks, IVA induced a significant decrease in heart rate by ?0 % as compared to Control (214¡À9 vs 266¡À14 bpm, respectively). In Control rabbits, ejection fraction and regional systolic displacement were significantly decreased as compared to baseline values (43¡À4 % vs 63¡À2 % and 1.4¡À0.2 vs 2.8¡À0.2 mm, respectively) and were associated with LV enlargement and interstitial fibrosis within the reperfused zone (risk zone: 30¡À2 % of LV and infarct size: 8 % of LV). Chronic administration of IVA prevented the reduction in ejection fraction (58¡À3 % vs 66¡À3 % in baseline) and the decrease in regional systolic displacement (1.9¡À0.3 vs 2.6¡À0.3 mm). This improvement was not related to a difference in infarct size and interstitial fibrosis. Interestingly, this was associated with a significant increase in FKBP12 expression in the reperfused area without any changes in SERCA2a, RyR2-P and phospholamban.
Heart rate reduction with IVA significantly improves systolic function after 3 weeks of reperfusion. This beneficial effect might result from an adaptation of calcium handling as suggested by the increase in FKBP12 expression.