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Cardioprotective Effect of Adenosine Pretreatment in Global Myocardial Ischemia
Kyoko Komatsu, M.D.; Mieko Chinzei, M.D.; Masakazu Hayasida, M.D.; Atsuo Fukunaga, M.D.; Kazuo Hanaoka, M.D.
Department of Anesthesiology, The University of Tokyo Hospital, Tokyo, Japan
INTRODUCTION: Pretreatment with adenosine prior to regional myocardial ischemia exerts cardioprotective effects 1). It has not been known, however, whether pretreatment with adenosine prior to cardiac arrest, which causes global myocardial ischemia, exerts such cardioprotective effects. We investigated the effects of pretreatment with systemic adenosine on survival and hemodynamics following induced cardiac arrest and subsequent resuscitation.

METHODS: The study protocol was reviewed and approved by the Institution's Animal Research Committee. Twenty rabbits weighing approximately 3kg were anesthetized with intramuscular ketamine 35mg/kg and xylazine 5mg/kg. The ear vein was cannulated with 24-gauge plastic catheter for fluid and drug administration. The ear artery was cannulated with 22-gauge plastic catheter for blood pressure (ABP) monitoring and blood sampling. A 3.5mm pediatric tracheal tube was inserted via tracheotomy. Then animals were anesthetized with 1% isoflurane. Ventilation was controlled to maintain end-tidal CO2 tension between 30 and 40mmHg. Via sternotomy an electromagnetic flow probe was placed on the ascending aorta to monitor cardiac output (CO). Miller's catheter-tip transducer was inserted into the left ventricle to monitor intraventricular pressure (LVP). ABP, CO, LVP and LVdP/dt (rate of tension development) were continuously monitored throughout the study period. Animals were randomly divided into 2 groups; The adenosine group (n=10) and the control group (n=10) received I.V. infusions of adenosine in saline (50mg/kg over 30min) and saline alone, respectively. After the infusions, baseline hemodynamic variables were recorded. Then ventricular fibrillation (Vf) was induced using a fibrillator directly applied on the ventricular wall. The fibrillatior was removed after 2 minutes of Vf. If Vf continued, direct electrical defibrillation was attempted but only once. When CO remained higher than 50% of the baseline level 30 minutes after the defibrillation attempt, the animal was classified as successfully resuscitated. Statistical analyses were performed with 2-way ANOVA, Scheffe's test, unpaired t test and chi-square test.

RESULTS: There was no difference between groups in baseline hemodynamic variables. After induced Vf, seven animals in the adenosine group and only one in the control group were successfully resuscitated (p<0.01). CO and LVdP/dt remained significantly higher in the adenosine group than in the control group after resuscitation.

DISCUSSION: I.V. infusion of adenosine prior to induced cardiac arrest significantly increased probability of successful resuscitation and improved post-resuscitation hemodynamics. Pretreatment with systemic adenosine thus exerted significant cardioprotective effect also in global myocardial ischemia.

REFERENCE:1)Circulation 95(11):2500-2507;1997

Anesthesiology 2001; 95:A679
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