Efficacy of the non-adenosine analogue A1 adenosine receptor agonist (BR-4935) on cardiovascular function after cardiopulmonary bypass

Thorac Cardiovasc Surg. 2010 Mar;58(2):86-92. doi: 10.1055/s-0029-1186271. Epub 2010 Mar 23.


Background: We tested the hypothesis that pharmacological preconditioning with a newly developed, potent non-adenosine analogue A1AdoR agonist (BR-4935) improves biventricular cardiac and endothelial function after cardiopulmonary bypass.

Methods: Twelve anesthetized dogs underwent cardiopulmonary bypass. Dogs were divided into two groups: group 1 (n = 6) received saline vehicle, group 2 (n = 6) received BR-4935 before cardiopulmonary bypass. Biventricular hemodynamic variables were measured using a combined pressure-volume conductance catheter. Coronary blood flow, ATP content, malondialdehyde and myeloperoxidase levels and vasodilatative responses to acetylcholine and sodium nitroprusside were also determined.

Results: Administration of the A1AdoR agonist led to a significantly better recovery of left and right ventricular systolic function after 60 minutes of reperfusion. Although the vasodilatative response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly greater increase in coronary blood flow in the BR-4935 group. In addition, the ATP content was significantly higher in the same group. Furthermore, malondialdehyde and myeloperoxidase levels significantly decreased in the A1AdoR group.

Conclusion: Pharmacological preconditioning with a new, potent non-adenosine analogue A1AdoR agonist improves biventricular function recovery and endothelial function after hypothermic cardiac arrest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adenosine A1 Receptor Agonists*
  • Adenosine Triphosphate / metabolism
  • Aminopyrine / analogs & derivatives*
  • Aminopyrine / pharmacology
  • Animals
  • Cardiopulmonary Bypass / adverse effects*
  • Cardiotonic Agents / pharmacology*
  • Coronary Circulation / drug effects*
  • Coronary Vessels / drug effects*
  • Coronary Vessels / physiopathology
  • Disease Models, Animal
  • Dogs
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Malondialdehyde / metabolism
  • Myocardial Contraction / drug effects
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Nitroprusside / pharmacology
  • Peroxidase / metabolism
  • Recovery of Function
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology
  • Ventricular Function, Left / drug effects*
  • Ventricular Function, Right / drug effects*


  • Adenosine A1 Receptor Agonists
  • BR-4935
  • Cardiotonic Agents
  • Vasodilator Agents
  • Aminopyrine
  • Nitroprusside
  • Malondialdehyde
  • Adenosine Triphosphate
  • Peroxidase
  • Acetylcholine