Adenosine in myocardial protection given through three windows of opportunity. An experimental study with pigs.
OBJECTIVE
Adenosine (ADO) has been shown to have beneficial effects against tissue injury after myocardial ischemia. However, the timing and dose of ADO administration have not been defined. This study was designed to determine the cardioprotective effect of exogenous ADO in an experimental open heart surgery model in pigs.


METHODS
The animals were openly divided into two groups both undergoing 30 min of total cardiac arrest. In the control group animals received cold crystalloid cardioplegic solution. In the ADO group ADO was added to cardioplegic solution and in addition ADO was infused to the superior vena cava for 2 h starting 30 min before cardiac arrest. The pumping function of the heart was measured with echocardiography and myocardial blood flow was measured with microspheres and positron emission tomography (PET). Cardiomyocyte apoptosis was detected and tumor necrosis factor (TNF) levels were measured.


RESULTS
Better post-ischemic pumping function was found in the ADO group (relative decrease 43.7% vs 55.4%, p = 0.20 between the groups). The cardiac output decreased significantly from the baseline values (p < 0.05 in both groups). There was a temporary decrease in myocardial blood flow post-ischemically, followed by a compensatory increase during the later reperfusion period. The cardiomyocyte apoptosis was induced significantly in both groups.


CONCLUSIONS
In this experiment two important details were noticed. Firstly, cardiomyocyte apoptosis is involved in ischemia-reperfusion injury associated with open heart surgery. Secondly, PET is a comparable method with the microsphere technique when coronary flow is studied. No significant effects of ADO against ischemia-reperfusion injury could be shown. However, there were some signsof positive outcome, even though statistical significance could not be reached.
Vähäsilta
T
T
Department of Surgery, Turku University Hospital, Finland.
Virtanen
J
J
Saraste
A
A
Luotolahti
M
M
Pulkki
K
K
Valtonen
M
M
Voipio-Pulkki
L M
LM
Savunen
T
T
D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis; D002302:Cardiac Output; D002314:Cardioplegic Solutions; D002315:Cardiopulmonary Bypass; D005260:Female; D007036:Hypothermia, Induced; D020287:In Situ Nick-End Labeling; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008863:Microspheres; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014665:Vasodilator Agents / Q000008:administration & dosage*
D002314:Cardioplegic Solutions; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D000241:Adenosine