The effect of adenosine A1 receptor antagonism on return of spontaneous circulation and short-term survival in prolonged ventricular fibrillation.
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.
Mader
Timothy J
TJ
Department of Emergency Medicine, Baystate Medical Center/Tufts University School of Medicine, Boston, Massachusetts, USA. timothy.mader@bhs.org
Menegazzi
James J
JJ
Rittenberger
Jon C
JC
Suffoletto
Brian S
BS
Callaway
Clifton W
CW
Salcido
David D
DD
Logue
Eric S
ES
Sherman
Lawrence D
LD
D000241:Adenosine / Q000378:metabolism; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D003326:Coronary Circulation / Q000187:drug effects*; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D008297:Male; D011897:Random Allocation; D016019:Survival Analysis; D013552:Swine; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology*
C097280:1,3-dipropyl-8-(2-(5,6-epoxy)norbornyl)xanthine; D058916:Adenosine A1 Receptor Antagonists; D014970:Xanthines; D000241:Adenosine