title: Effects of low flow and hypoxia on myocardial retention of technetium-99m BMS181321.
abstract: 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 microCi) 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.
authors.affiliation: William K. Warren Medical Research Institute of the University of Oklahoma Health Sciences Center, Tulsa, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Okada
authors.forename: K N
authors.initials: KN
authors.lastname: Nguyen
authors.forename: H W
authors.initials: HW
authors.lastname: Strauss
authors.forename: G
authors.initials: G
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009593:Nitroimidazoles / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D051381:Rats; D013667:Technetium; D013997:Time Factors
chemical_list: D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; C082027:BMS 181321; D013667:Technetium