Anti-stunning and anti-infarct effects of adenosine-enhanced ischemic preconditioning.
BACKGROUND
Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing post-ischemic functional recovery. In this study, the anti-infarct effects and the anti-stunning effects of APC in contributing to enhanced post-ischemic functional recovery were determined and compared with IPC.


RESULTS
Sheep (n=96) were subjected to 15, 30, 45, or 60 minutes of regional ischemia and 120 minutes of reperfusion. IPC hearts received 5 minutes of regional ischemia and 5 minutes of reperfusion before ischemia/reperfusion. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine hearts (ADO) received a bolus injection of adenosine before ischemia/reperfusion. Regional ischemia (RI) hearts received no pretreatment. Infarct size/area at risk was determined by tetrazolium staining. Regional myocardial function was determined by sonomicrometry. Segment shortening after 15 minutes of ischemia in which no infarct was incurred was 32. 1+/-10.6% in RI, 70.6+/-8.5% in IPC, and 77.4+/-6.0% in APC hearts. Segment shortening after 30 minutes of ischemia was 60.7+/-6.3% in APC hearts (P:<0.05 versus RI, ADO, IPC) but was <37% in all other groups. Infarct size/area at risk after 30 and 60 minutes of ischemia was, respectively, 25.8+/-5.7% and 49.8+/-6.0% in RI, 12. 9+/-3.0% and 29.2+/-5.0% in ADO, 11.6+/-2.4% and 24.6+/-2.7% in IPC, and 5.1+/-1.6% and 12.4+/-2.0% in APC hearts (P:<0.05 versus RI, ADO, IPC).


CONCLUSIONS
APC and IPC exhibit anti-infarct and anti-stunning effects in the ovine heart, but these effects are rapidly diminished with IPC. APC significantly extends these effects, providing for significantly enhanced infarct size reduction and post-ischemic functional recovery (P:<0.05 versus IPC).
Toyoda
Y
Y
Division of Cardiothoracic Surgery and Biometrics Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Di Gregorio
V
V
Parker
R A
RA
Levitsky
S
S
McCully
J D
JD
D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006334:Heart Function Tests / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D016014:Linear Models; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000378:metabolism / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects; D012756:Sheep; D013997:Time Factors
D000241:Adenosine