1005-82 Myocardial and Coronary Vascular Protection After Coronary Occlusion and Reperfusion by Selective Sinoatrial Node Inhibition

Improved regional myocardial function and abnormal flow reserve resulting from myocardial ischemic injury has been observed with β-blockade. To determine if heart rate reduction alone would offer similar protection, anesthetized dogs were subjected to left anterior descending (LAD) occlusion and given a selective SA node inhibitor (ZD7288 0.5mg/kg, n=5 or buffer, n=7). After 1 hour of occlusion they were reperfused. ZD7288 decreased heart rate by 28±2% (153 ± 14 to 120 ± 11 bpm, p < 0.05) at 1 hr after reperfusion. In buffer-treated dogs, peak reactive hyperemic (RH) response after 20 sec LAD occlusion, (index of coronary flow reserve), fell from 276 ± 22% to 135 ± 18% and LAD regional shortening fraction (SF, by ultrasonic crystals) decreased from 9.7 ± 1.5% to 0.6 ± 0.1% after reperfusion (both, p < 0.001). In ZD7288-treated dogs, peak RH and SF after reperfusion (227 ± 19% and 4.2 ± 0.8%, respectively) were preserved (p < 0.05) vs buffertreated dogs. Despite similar area of left ventricular (LV) at risk, infarct area (as % of LV). was also smaller in ZD7288-treated vs. buffer-treated dogs (14.0 ± 0.5 vs 23.0 ± 1.10%, P < 0.05). Heart rate was maintained constant with atrial pacing in five other ZD7288-treated dogs and neither peak RH or SF were preserved compared with buffer-treated dogs.Thus, selective SA node inhibition alone, induced after coronary occlusion, results in myocardial and coronary vascular protection after reperfusion. Selective SA node inhibition may have clinical utility in acute myocardial patients who are not candidates for beta blockers