Abstract 4493: Intracoronary Administration with Short-Acting β-Blocker at the Time of Reperfusion Limits Infarct Size in Pig
Myocardial reperfusion (R) injury (I) is produced by physical stress on cardiomyocytes with fragile sarcolemmal membrane upon restoration of contractile activity. We hypothesized that intracoronary administration with short-acting β-blocker prevents RI by selectively inhibiting contraction in the area at risk of infarction with a minimal effect on global cardiac function. In the pigs without coronary occlusion, administration with short-acting β-blocker landiorol (60 μg for 1 min followed by 20 μg/min) into the proximal left anterior descending coronary artery (LAD) through a microcatheter depressed segmental wall thickening (SWT) by 25 % within 3 min in the anteroseptal wall (ASW) without an effect on SWT in the posterior wall (PW) associated with 8 % decrease of heart rate and 7 % decrease of cardiac output. The depression of regional contraction and global hemodynamic changes returned to the baseline within 5 min after discontinuation of landiorol. To examined the effect of landiorol on RI, the proximal LAD was occluded for 60 min using transluminal coronary angioplasty balloon (TCAB) and landiorol was administered into the LAD for 1 min (60 μg) before deflation of TCAB and for the first 10 min (20 μg/min) during R, which significantly inhibited the recovery of SWT in the ASW without a significant difference in SWT in the PW and global cardiac function compared to the control group given saline into the LAD. This transient inhibition of contraction in the area at risk of infarction was associated with significant inhibition of sub-sarcolemmal bleb formation in the infarction border 10 min after R as evaluated by electronmicroscopy, significant inhibition of creatine kinase-MB release during R, and reduction of infarct size/risk area (32±5% vs 48±4% in the control group, p<0.05) 3 hrs after R. The recovery of SWT in the ASW 3 hrs after R was significantly enhanced in the landiorol-treated heart. Continuous landiorol treatment for 3 hrs during R did not significantly reduce infarct size/risk area compared to the brief landiorol treatment. These results suggest that selective and brief intracoronary administration with landiorol at the time of R prevents RI with a trivial inhibitory effect on global cardiac function.