Importance of endogenous adenosine during ischemia and reperfusion in neonatal porcine hearts.
BACKGROUND
Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective.


RESULTS
Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow) or 90 minutes of zero-flow ischemia, all with 60 minutes of reperfusion. Hearts were treated with either saline, the adenosine receptor blocker 8-sulfophenyltheophylline (8SPT, 300 micromol x L(-1)), or the nucleoside transport inhibitor draflazine (1 micromol x L(-1)). In separate groups, biopsies were obtained before and at the end of ischemia. Compared with saline, 8SPT did not significantly alter functional recovery in either protocol. Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P<.001 for both) and in the zero-flow protocol (76+/-3% versus 59+/-4% [saline] and 46+/-9% [8SPT], P<.05 for both). In the zero-flow protocol, draflazine also significantly reduced ischemic contracture and release of creatine kinase. Tissue adenosine at the end of ischemia was elevated by draflazine compared with saline-treated hearts: after low-flow ischemia to 0.10+/-0.05 versus 0.00+/-0.00 micromol x g(-1) dry wt (P<.05) and after zero-flow ischemia to 1.73+/-0.82 versus 0.15+/-0.03 micromol x g(-1) dry wt (P<.05).


CONCLUSIONS
In neonatal porcine hearts, endogenous adenosine produced during ischemia does not influence ischemic injury or functional recovery. Elevating endogenous adenosine by draflazine elicits cardioprotection in both low-flow and zero-flow conditions.
Sommerschild
H T
HT
University of Oslo, Institute for Experimental Medical Research, Norway. hilchen.sommerschild@ioks.uio.no
Grund
F
F
Offstad
J
J
Jynge
P
P
Ilebekk
A
A
Kirkebøen
K A
KA
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D003402:Creatine Kinase / Q000378:metabolism; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D010879:Piperazines / Q000494:pharmacology; D013552:Swine; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D010879:Piperazines; C072040:draflazine; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D003402:Creatine Kinase; D000241:Adenosine