The effects of drugs modulating K(+) transport on Rb(+) uptake and distribution in pig hearts following regional ischemia: (87)Rb MRI study.
The effects of drugs that can modulate passive permeability of K(+) into cardiomyocytes in normal and reperfusion-damaged cardiac muscle were assessed. Rubidium ion (Rb(+)) was used as a K(+) tracer and (87)Rb-MRI as a detection method. The left anterior descending artery (LAD) of isolated pig hearts perfused with Krebs-Henseleit buffer (KHB) was occluded for 2 h and subsequently reperfused for 2 h with KHB containing 4.7 mM RbCl instead of KCl. The buffer contained either a blocker of ATP-sensitive K(+) channels (K(ATP)), glibenclamide (Glib, 3 micro M), a K(ATP) opener, pinacidil (Pin, 10 micro M), a K(+)/Na(+)/2Cl(-) co-transporter inhibitor, bumetanide (Bum, 10 micro M) or no drug (control). Upon reperfusion three-dimensional (87)Rb MR images were acquired to obtain kinetics of Rb(+) uptake and its distribution. Areas at risk (AAR) and areas of necrosis were determined by Evans Blue and triphenyl tetrazolium chloride staining, respectively. Rb(+) uptake kinetics in the remote posterior (Pos) wall were similar in all groups. The kinetics remained monoexponential in the affected anterior (Ant) wall and the uptake rates were 32, 36, 37 and 21% of that in the Pos wall in the control, Glib, Pin and Bum groups, respectively. Infarct sizes determined histologically as a percentage of total ventricular (left + right) mass (14-22%) corresponded to sizes of areas with 20-40% of maximal Rb image intensity [I(Rb)(max), 15-22%], except for the Pin group (12.5 vs 21%). The sizes of areas with 20-50% of I(Rb)(max) (30-36%) closely correlated with those of AAR determined histologically (31-33%). Lactate dehydrogenase release did not differ in all groups. We conclude that: (1) reperfusion damage quickly inhibits Rb(+) uptake; (2) Rb(+) uptake in normal and reperfused tissue does not significantly depend on K(ATP) or the K(+)/Na(+)/2Cl(-) cotransporter; (3) areas with 20-40% of maximal image intensity correspond to infarct areas.
Institute for Biodiagnostics, National Research Council, Winnipeg, Canada. kupriyanov@ibd.nrc.ca
Valery V
VV
Kupriyanov
Bo
B
Xiang
Jiankang
J
Sun
Olga
O
Jilkina
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012016:Reference Values; D015424:Reperfusion / Q000009:adverse effects; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics*; D034421:Sus scrofa; D014018:Tissue Distribution
D015221:Potassium Channels; D019275:Radiopharmaceuticals; D012414:Rubidium Radioisotopes; D002034:Bumetanide; D020110:Pinacidil; D011188:Potassium; D005905:Glyburide