Intravenous co-infusion of adenosine and norepinephrine preconditions the heart without adverse hemodynamic effects.
OBJECTIVE
A simple intervention is needed that could protect the heart against infarction during limited-access coronary artery bypass grafting. Adenosine and norepinephrine can precondition the heart with resulting protection, but adverse hemodynamic effects prevent clinical application. Because heart rate, blood pressure, and contractility effects of these two drugs are diametrically opposite, a mixture might be beneficial.


METHODS
A superficial branch of the left coronary artery of rabbits was surrounded with a suture. Infarction was produced in all hearts by a 30-minute coronary artery occlusion. Infarct size after reperfusion was measured and is presented as a percentage of the risk zone. The effect of 5-minute intravenous co-infusion of adenosine (20 mg/kg) and norepinephrine (0.1 mg/kg) 15 minutes before ischemia was examined. In addition, the protective effect of three sequential intravenous bolus injections of adenosine at either 0.2 or 0.4 mg/kg was evaluated.


RESULTS
Thirty minutes of regional ischemia caused infarction of 40% +/- 4% of the risk zone. The combination of adenosine and norepinephrine caused no change in blood pressure but rather protected the heart, with infarction of only 9% +/- 2% of the risk zone (p = 0.0001 vs control). Adenosine-norepinephrine co-infusion still protected the heart when the interval between infusion and ischemia was extended to 60 minutes, but it did not protect with a 120-minute interval. Intravenous bolus injections of adenosine resulted in cardiac slowing and marked hypotension. Boluses of 0.2 mg/kg resulted in a minimal, but significant, reduction in infarct size, whereas the higher dose provided no protection.


CONCLUSIONS
Adenosine-norepinephrine co-infusion provides a feasible and safe parenteral method for preconditioning the heart.
Cohen
M V
MV
Department of Medicine, University of South Alabama College of Medicine, Mobile 36688, USA.
Thornton
J D
JD
Thornton
C S
CS
Sato
H
H
Miki
T
T
Downey
J M
JM
D000241:Adenosine / Q000008:administration & dosage*; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D009638:Norepinephrine / Q000008:administration & dosage*; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D002317:Cardiovascular Agents; D000241:Adenosine; D009638:Norepinephrine