Abstract 1082: Effects of Heat Shock Protein Induction on Atrial Fibrillation Caused by Acute Atrial Ischemia
Background: Heat shock proteins (HSPs) are known to have cytoprotective actions. Acute atrial ischemia (AI) promotes atrial fibrillation (AF), consistent with the known association between AF and coronary artery disease. Geranylgeranylacetone (GGA) is a well-tolerated orally active HSP inducer. This study assessed the effects of GGA on AF associated with AI.
Methods: Three groups of mongrel dogs were studied after median thoracotomy under morphine/chloralose:
a group subjected to AI without GGA (AI-CTL, n=8 dogs),
dogs that underwent AI after GGA pre-treatment (AI-GGA, n=7), and
dogs receiving GGA pretreatment without AI (n=5).
Isolated AI was produced by occluding a right atrial coronary artery branch. GGA (120 mg/kg/day) was started 1 day before the experiment. Conduction changes were assessed with 240-electrode mapping. Measurements were obtained at pre-ischemic baseline and then 0.5, 3 and 5 hrs after AI onset.
Results: AI significantly reduced conduction velocity (CV) in the ischemic region of AI-CTL dogs (Table⇓). Phase-delay analysis showed that AI increased maximum phase delays (P95) reflecting local conduction slowing and increased the conduction heterogeneity index (CHI=P95-P5/P50). GGA pretreatment attenuated AI-induced conduction slowing as reflected by CV, P95 and CHI (Table⇓) in AI-GGA dogs. AI greatly increased the mean duration of burst pacing induced AF (DAF) in AI-CTL, and GGA attenuated AI-induced AF promotion. GGA treatment alone, without AI, did not alter DAF or conduction indices over a 5-hour control experiment. AI slightly prolonged atrial ERP (eg, at 3-hr AI: from 95±6 to 118±10 ms, p<0.05), an effect also prevented by GGA. GGA therapy increased HSP protein expression on Western blot.
Conclusion: GGA suppresses ischemia-related AF by preventing AI-induced conduction abnormalities. These results suggest that HSP induction protects against ischemic AF and might be a useful new anti-AF intervention in coronary disease patients.