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Mechanisms underlying Endothelin‐1 effects on ischemic ventricular tachycardia in canine myocardium
Author(s) -
Gopinathannair Rakesh,
Xing Dezhi,
Chaudhary Ashok,
Martins James B
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.971.14
Subject(s) - endocardium , cardiology , medicine , ventricular tachycardia , endothelin receptor , effective refractory period , fissipedia , tachycardia , anesthesia , endothelin 1 , carnivora , refractory period , receptor
Background: Endothelin‐1(ET‐1) induces ventricular tachycardia (VT), possibly by promoting triggered activity (TA). We studied ET‐1 and the ET‐A receptor blocker, BQ123, in a model of focal or reentrant VT, to test the hypothesis that focal VT and TA were selectively affected. Methods: Anesthetized dogs (n=38) with 1‐3 hours of coronary artery occlusion underwent 3‐D activation mapping to identify mechanisms of VT. If VT was not inducible, ET‐1 (0.15–0.45 mcg/kg IV) was infused. If VT was reproducibly induced at baseline, BQ123 (2.5 mcg/kg IV) was given. Effects on action potential (AP), delayed and early afterdepolarizations (DADs and EADs), and TA of ischemic endocardium were studied in vitro with microelectrodes. Results: Of 15 dogs without VT, ET‐1 promoted induction of VT of mixed reentrant and focal origin in 5 (p<0.05 (*) vs. saline alone). In 11 dogs, BQ123 prevented reentrant VT in 4 of 6* vs. 0/5 with focal VT. ET‐1 and BQ123 infusion did not change effective refractory period, pacing threshold, mean arterial pressure, or infarct size. In vitro, ET‐1 infusion did not induce and BQ123 did not prevent EADs, DADs, or TA but ET‐1 superfusion with rapid pacing produced AP alternans in 8 of 15 tissues. Conclusions: ET‐1 promotes focal and reentrant VT but ischemic sites in vitro did not show TA. BQ123 preferentially blocked reentrant VT. The effect of ET‐1 on ischemic reentrant VT may be mediated by triggering AP alternans.