Reduced infarct size in the rabbit heart in vivo by ethylisopropyl-amiloride. A role for Na+/H+ exchange.
Inhibition of Na+/H+ exchange with amiloride analogues has been shown to offer functional protection during ischemia and reperfusion and reduce infarct size in isolated rat hearts and intact pigs. The aim of the present study was to examine if pre- or postischemic treatment with ethylisopropylamiloride (EIPA), a selective Na+/H+ exchange inhibitor, could reduce infarct size in an in situ rabbit model of regional ischemia and reperfusion. Anesthetized, open-chest rabbits were subjected to 30 min of regional ischemia and 180 min of reperfusion. The risk zone was determined by fluorescent particles, and infarct size was determined by TTC staining. Preischemic treatment with EIPA (0.65 mg/kg) significantly reduced infarct size from 45.8 +/- 3.5% of the risk zone in the control group to 10.6 +/- 3.1% (p < 0.01). EIPA-treatment during the first part of the reperfusion period did not reduce infarct size compared to controls (41.9 +/- 3.5%). We conclude that EIPA, when administered prior to ischemia, reduces infarct size in the rabbit heart of in situ, a protection most likely due to inhibition of Na+/H+ exchange.
Bugge
E
E
Department of Medical Physiology, University of Tromso, Norway.
Munch-Ellingsen
J
J
Ytrehus
K
K
D000584:Amiloride / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D000889:Anti-Arrhythmia Agents; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; C039614:ethylisopropylamiloride