Role of adenosine in isoflurane-induced cardioprotection.
BACKGROUND
This investigation tested the hypothesis that adenosine (A1) receptor blockade modulates the cardioprotective effects of isoflurane.


METHODS
Hemodynamics and percentage segment shortening (%SS) in the left anterior descending coronary artery (LAD) perfusion territory were evaluated in barbiturate-anesthetized dogs (n = 31) at selected intervals after pretreatment with the selective A1 receptor antagonist (8-cyclopentyl-1,3,dipropyl-xanthine; DPCPX 0.8 mg/kg, intravenously) or drug vehicle in the presence or absence of 1 minimum alveolar concentration (MAC) isoflurane. Dogs were subjected to five 5-min occlusions and reperfusions of the LAD, followed by 180 min of final reperfusion. Isoflurane was administered for 30 min before and during LAD occlusions and reperfusions and was discontinued at the onset of final reperfusion. Two other groups of dogs (n = 17) were used to measure interstitial concentrations of purines in the LAD region using a microdialysis technique in the presence and absence of isoflurane.


RESULTS
Dogs receiving drug vehicle or DPCPX exhibited no recovery of %SS after 180 min of reperfusion (-5 +/- 7 and 5 +/- 11% of baseline, respectively, +/- SEM). In contrast, dogs receiving isoflurane alone demonstrated complete recovery of %SS at 60 min after reperfusion. DPCPX pretreatment partially attenuated isoflurane-induced enhancement of recovery of %SS (34 +/- 11% of baseline 180 min after reperfusion; P < 0.05). Interstitial purine concentrations were increased during multiple occlusions and reperfusions of the LAD in dogs not receiving isoflurane, but they were unchanged by coronary artery occlusion and reperfusion in dogs receiving isoflurane.


CONCLUSIONS
The results indicate that isoflurane-induced cardioprotection in stunned myocardium is partially mediated by adenosine type 1 receptor activation and is accompanied by decreases in endogenous adenosine release.
Kersten
J R
JR
Medical College of Wisconsin, Milwaukee 53226, USA.
Orth
K G
KG
Pagel
P S
PS
Mei
D A
DA
Gross
G J
GJ
Warltier
D C
DC
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D007530:Isoflurane