Adenosine-enhanced ischemic preconditioning modulates necrosis and apoptosis: effects of stunning and ischemia-reperfusion.
BACKGROUND
Adenosine-enhanced ischemic preconditioning extends the protection of ischemic preconditioning by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery.


METHODS
The effects of adenosine-enhanced ischemic preconditioning on necrosis and apoptosis were investigated in the sheep heart using models of stunning (15 minutes regional ischemia, 120 minutes reperfusion) and ischemia-reperfusion (30 and 60 minutes regional ischemia, 120 minutes reperfusion). Ischemic preconditioned hearts received 5 minutes regional ischemia, 5 minutes reperfusion before ischemia. Adenosine-enhanced ischemic preconditioned hearts received a 10 mmol/L adenosine bolus (10 mL) through the left atrium coincident with ischemic preconditioning. Adenosine hearts received a 10 mmol/L bolus (10 mL) of adenosine. Regional ischemic hearts received no pretreatment.


RESULTS
Minimal apoptosis (< 45 per 3,000 myocytes) was observed in the stunning models but was significantly increased with ischemia-reperfusion in regional ischemic hearts after 30 minutes (p < 0.05 versus ischemic preconditioning, adenosine, or adenosine-enhanced ischemic preconditioning) and in adenosine and ischemic preconditioned hearts after 60 minutes ischemia (p < 0.05 versus adenosine-enhanced ischemic preconditioning). DNA laddering was apparent after 60 minutes ischemia in regional ischemia, adenosine, and ischemic preconditioning but not in adenosine-enhanced ischemic preconditioned hearts.


CONCLUSIONS
Adenosine-enhanced ischemic preconditioning significantly ameliorates necrosis and apoptosis in the regional ischemic blood-perfused heart.
Stadler
B
B
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Phillips
J
J
Toyoda
Y
Y
Federman
M
M
Levitsky
S
S
McCully
J D
JD
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D020287:In Situ Nick-End Labeling; D019194:Ischemic Preconditioning; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D017682:Myocardial Stunning / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D012756:Sheep
D000241:Adenosine