Sl. Hale et Ra. Kloner, Effect of combined K-ATP channel activation and Na+/H+ exchange inhibitionon infarct size in rabbits, AM J P-HEAR, 279(6), 2000, pp. H2673-H2677
Citations number
26
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
We tested if combining treatment with cariporide, an Na+/H+ exchange inhibi
tor, and diazoxide, a mitochondrial ATP-sensitive K+ (K-ATP) channel opener
, would reduce myocardial infarct size (IS) to a greater extent than either
intervention alone. Four groups of rabbits were studied (n = 10 each): car
iporide (0.3 mg/kg), diazoxide (10 mg/kg), both drugs, and saline control,
given 15 min before a 30-min coronary artery occlusion and 3 h reperfusion.
IS in controls comprised 47 +/- 6% of the risk region. Cariporide reduced
IS by 55% compared with control (21 +/- 3%), but diazoxide did not signific
antly reduce IS compared with controls (37 +/- 6%). Combined treatment resu
lted in an IS of 18 +/- 5%. Also we determined that diazoxide did not poten
tiate a subthreshold dose of cariporide nor did a mitochondrial KATP channe
l blocker, 5-hydroxydecanoate (5-HD), prevent cariporide from reducing IS.
Thus cariporide reduced necrosis by 50% in this model, both in the presence
and absence of K-ATP channel blockade. There was no significant difference
in IS reduction between the group receiving cariporide alone and the group
receiving combined treatment. Because the effect of cariporide was not blo
cked by 5-HD, it is unlikely that K-ATP channels play a role as an end effe
ctor in cariporide's mechanism.