Adrenergic activation confers cardioprotection mediated by adenosine, but is not required for ischemic preconditioning.
BACKGROUND
The aim of this study was to determine whether (1) adrenergic activation is cardioprotective, (2) adrenergic cardioprotection occurs via adenosine receptor activation, and (3) ischemic preconditioning requires alpha-adrenergic activation.


METHODS
Anesthetised open chest rabbits underwent 30 min coronary occlusion and 3 h reperfusion. Ischemic preconditioning was elicited with 5 min coronary occlusion and 10 min reperfusion. Activation of adrenergic receptors with endogenous norepinephrine was achieved with tyramine (0.28 mg/kg/min intravenously for 5 min). Adenosine receptors were blocked with 8-p-sulfophenyl theophylline (10 mg/kg intravenously), alpha 1-adrenergic receptors were selectively blocked with prazosin (0.1 mg/kg intravenously), and alpha-adrenergic receptors were blocked with phentolamine (4 mg/kg intravenously).


RESULTS
Ischemic preconditioning reduced risk-adjusted infarct volume by 79% (P < 0.0005). This protection was attenuated by adenosine receptor blockade. Tyramine infusion resulted in a 1305% change from baseline plasma norepinephrine concentration (P < or = 0.01), and reduced infarct volume by 55% (P = 0.01). Adenosine receptor blockade abolished this protection. Blockade of alpha 1-adrenergic receptors with prazosin failed to abolish ischemic preconditioning (79 versus 89% reduction in infarct volume, without and with prazosin, respectively). Similarly, non-selective blockade of alpha-adrenergic receptors also failed to abolish ischemic preconditioning (79 versus 57% reduction without and with phentolamine, respectively).


CONCLUSIONS
We conclude that the cardioprotection of ischemic preconditioning and alpha-adrenergic activation both involve adenosine, but ischemic preconditioning does not require alpha-adrenergic activation.
Haessler
R
R
Department of Anesthesiology, Oregon Health Sciences University, Portland, USA.
Kuzume
K
K
Wolff
R A
RA
Kuzume
K
K
Chien
G L
GL
Davis
R F
RF
Van Winkle
D M
DM
D000241:Adenosine / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000503:physiopathology; D009638:Norepinephrine / Q000502:physiology; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013806:Theophylline / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D013806:Theophylline; D000241:Adenosine; D009638:Norepinephrine; D014439:Tyramine; D011224:Prazosin; D010646:Phentolamine