The effect of adenosine A1 receptor antagonism on return of spontaneous circulation and short-term survival in prolonged ventricular fibrillation.

Abstract

BACKGROUND:

Endogenous adenosine (ADO) is cardioprotective during ischemia and its myocardial concentration increases during untreated ventricular fibrillation (VF). We have previously shown that ADO A1 receptor (ADOA1R) antagonism hastens the time-dependent decay in VF waveform morphology during the circulatory phase of cardiac arrest.

OBJECTIVE:

To determine the effect of ADOA1R antagonism on ROSC and short-term survival in prolonged VF.

METHODS:

Thirty-six swine were assigned by block randomization to one of three groups: a group that received only vehicle (CONTROL), an ADOA1R antagonist pretreatment group (PRE), and a group that was given ADOA1R antagonist during resuscitation (DURING). The animals were instrumented under anesthesia, and ADOA1R antagonist or vehicle, per group assignment, was infused 5 minutes prior to VF induction. At minute 8 of untreated VF, chest compression with ventilation was initiated and a standard drug cocktail, with ADOA1R antagonist or vehicle, was given. The first rescue shock (150 J biphasic) was delivered after 11 minutes of VF. Proportions with 95% confidence intervals (CIs) were calculated for the two outcome measures.

RESULTS:

The baseline characteristics and chemistry values for the three groups were mathematically the same. The DURING group had a greater proportion of female animals (seven of 12) in comparison with the CONTROL group (two of 12) (p=0.03). ADOA1R antagonism hastened the decay of VF as previously demonstrated, but the rate of ROSC was the same for all groups: CONTROL=seven of 12, PRE=six of 12, and DURING=seven of 12. There were also no differences in short-term survival: CONTROL=four of 12, PRE=five of 12, and DURING=seven of 12.

CONCLUSIONS:

In this study, ADOA1R antagonism had no effect on outcome whether given before induction of VF or upon resuscitation after 8 minutes of untreated VF. The role of endogenous ADO in prolonged VF remains unclear.

• Authors: Timothy J Mader, James J Menegazzi, Jon C Rittenberger, Brian S Suffoletto, Clifton W Callaway, David D Salcido, Eric S Logue, Lawrence D Sherman
• Journal: Prehospital emergency care (Prehosp Emerg Care) 2008 Jul-Sep Vol. 12 Issue 3 Pg. 352-8 ISSN: 1090-3127 [Print] England
• PMID: 18584504 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 1,3-dipropyl-8-(2-(5,6-epoxy)norbornyl)xanthine
• Adenosine A1 Receptor Antagonists
• Xanthines
• Adenosine

Topics

• Adenosine (metabolism)
• Adenosine A1 Receptor Antagonists
• Animals
• Cardiopulmonary Resuscitation (methods)
• Coronary Circulation (drug effects)
• Female
• Heart Conduction System (drug effects)
• Male
• Random Allocation
• Survival Analysis
• Swine
• Ventricular Fibrillation (drug therapy, metabolism)
• Xanthines (pharmacology)