ST-segment elevation and ventricular fibrillation without coronary spasm by intracoronary injection of acetylcholine and/or ergonovine maleate in patients with Brugada syndrome

J Am Coll Cardiol. 2002 Nov 20;40(10):1841-7. doi: 10.1016/s0735-1097(02)02494-4.


Objectives: The study examined whether patients with Brugada syndrome are sensitive to vagal stimulation or ischemia.

Background: Experimental studies have suggested that a prominent transient outward current (I(to))-mediated action potential notch and a subsequent loss of the action potential dome in the epicardium, but not in the endocardium, give rise to ST-segment elevation and subsequent ventricular fibrillation (VF).

Methods: We evaluated the frequency of coronary spasm, augmentation (> or =0.1 mV) of ST-segment elevation in leads V(1) to V(3), and induction of VF by intracoronary injection of acetylcholine (ACh) and/or ergonovine maleate (EM) in 27 symptomatic patients with Brugada syndrome and 30 control subjects.

Results: The coronary spasm was induced in 3 (11%) of the 27 patients with Brugada syndrome and in 13 (43%) of the 30 control subjects. ST-segment elevation was augmented by 11 (33%) of the 33 right coronary injections (ACh: 6/11 [55%]; EM: 5/22 [23%]), without coronary spasm, but not by any of the left coronary injections in patients with Brugada syndrome. Ventricular fibrillation was induced by 3 (9%) of the 33 right coronary injections (ACh: 2/11 [18%]; EM: 1/22 [5%]), but not by any of the left coronary injections. In contrast, neither ST-segment elevation nor VF was observed in any of the control subjects.

Conclusions: Our results support the hypothesis that mild ischemia and vagal influences act additively or synergistically with the substrate responsible for the Brugada syndrome to elevate the ST-segment and precipitate VF. These observations suggest that Brugada patients may be at a higher risk for ischemia-related sudden death.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage*
  • Adult
  • Aged
  • Bundle-Branch Block / complications*
  • Coronary Vasospasm / chemically induced*
  • Coronary Vessels
  • Death, Sudden, Cardiac / etiology*
  • Dose-Response Relationship, Drug
  • Electrocardiography*
  • Ergonovine / administration & dosage*
  • Female
  • Heart Conduction System / drug effects
  • Humans
  • Injections, Intravenous
  • Japan
  • Male
  • Middle Aged
  • Syndrome
  • Vasodilator Agents / administration & dosage*
  • Ventricular Fibrillation / chemically induced*


  • Vasodilator Agents
  • Acetylcholine
  • Ergonovine