Effects of low flow and hypoxia on myocardial retention of technetium-99m BMS181321

The purpose of the present study was to determine whether graded levels of low-flow ischemia would lead to graded differences in uptake and clearance of BMS181321. Using a perfused rat heart model, 7.4 MBq (200 μCi) of BMS181321 was infused over 20 min, followed by a 60-min clearance phase. Activity was monitored using an NaI detector. Four groups were studied using Krebs-Henseleit buffer perfusion using low flow or hypoxia: group 1 = 12 ml/min, group 2 = 3 ml/min, and group 3 = 1 ml/min during uptake and clearance phases, and group 4 = 12 ml/min with hypoxia during clearance. Control and low-flow groups were also perfused using red blood cells and albumin. There was a stepwise increase in peak myocardial uptake (% injected dose) as flow progressively decreased (group 1= 2.4% ± 0.2% SEM, group 2 = 13.1% ± 0.7%, group 3 = 28.6% ± 2.4%, P < 0.05). Group 3/group 1 mean peak activity ratio was 12:1. Mean 1-h fractional retention significantly increased in a stepwise manner as flow decreased (group 1 = 0.32 ± 0.02, group 2 = 0.43 ± 0.03, group 3 = 0.59 ± 0.05, P < 0.05). Group 3/group 1 mean 1-h clearance activity ratio was 30:1. Groups 5 and 6 perfused with red blood cells and albumin demonstrated similar increases in peak uptake and 1-h retention in the low-flow hearts. This study demonstrates a stepwise increase in uptake and a stepwise increase in retention rate of BMS181321 with progressive reduction in flow.