Effects of a heat shock protein inducer on the atrial fibrillation substrate caused by acute atrial ischaemia.

Abstract

AIMS:

Heat shock proteins (HSPs) are a set of endogenous cytoprotective factors activated by various pathological conditions. This study addressed the effects of geranylgeranylacetone (GGA), an orally active HSP inducer, on the atrial fibrillation (AF) substrate associated with acute atrial ischaemia (AI).

METHODS AND RESULTS:

Four groups of mongrel dogs were studied: (1) a group subjected to AI without GGA (AI-CTL, n = 13 dogs); (2) dogs that underwent AI after GGA pretreatment (120 mg/kg/day; AI-GGA, n = 12); (3) dogs receiving GGA pretreatment without AI (n = 5); (4) control dogs for tissue sampling (n = 5). Isolated right AI was produced by occluding a right atrial (RA) coronary-artery branch. AI reduced ischaemic-zone conduction velocity (CV, from 94 +/- 3 to 46 +/- 5 cm/s; P < 0.01) and increased maximum local phase delays (P95, from 1.6 +/- 0.1 to 4.6 +/- 0.6 ms/mm; P < 0.01), conduction heterogeneity index (CHI, from 0.7 +/- 0.1 to 2.9 +/- 0.5; P < 0.01), and the mean duration of burst pacing-induced AF (DAF, from 44 +/- 18 to 890 +/- 323 s; P < 0.01) in AI-CTL dogs. GGA pretreatment attenuated ischaemia-induced conduction abnormalities (CV, 77 +/- 8 cm/s; P95, 2.1 +/- 0.4 ms/mm; CHI, 1.1 +/- 0.2; all P < 0.01 vs. AI-CTL) and DAF (328 +/- 249 s; P < 0.01) in AI-GGA dogs. GGA treatment alone, without ischaemia, did not alter DAF or conduction indices. AI slightly prolonged atrial refractory period, an effect also prevented by GGA. GGA significantly increased HSP70 protein expression in RA tissues of ischaemic hearts.

CONCLUSIONS:

GGA prevents ischaemia-induced atrial conduction abnormalities and suppresses ischaemia-related AF. These results suggest that HSP induction might be a useful new anti-AF intervention for patients with coronary artery disease.

• Authors: Masao Sakabe, Akiko Shiroshita-Takeshita, Ange Maguy, Bianca J J M Brundel, Akira Fujiki, Hiroshi Inoue, Stanley Nattel
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 78 Issue 1 Pg. 63-70 (Apr 01 2008) ISSN: 0008-6363 [Print] England
• PMID: 18238941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Diterpenes
• HSP70 Heat-Shock Proteins
• Heat-Shock Proteins
• geranylgeranylacetone

Topics

• Action Potentials
• Administration, Oral
• Animals
• Anti-Arrhythmia Agents (administration & dosage, pharmacology)
• Atrial Fibrillation (etiology, metabolism, prevention & control)
• Disease Models, Animal
• Diterpenes (administration & dosage, pharmacology)
• Dogs
• HSP70 Heat-Shock Proteins (metabolism)
• Heart Atria (metabolism)
• Heat-Shock Proteins (metabolism)
• Myocardial Ischemia (complications, drug therapy, metabolism)
• Myocardium (metabolism)
• Time Factors
• Up-Regulation