(Circulation. 2000;102:III-326.)
© 2000 American Heart Association, Inc.
Myocardial Protection and Vascular Biology |
Anti-Stunning and Anti-Infarct Effects of Adenosine-Enhanced Ischemic Preconditioning
From the Division of Cardiothoracic Surgery and Biometrics Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.
Correspondence to Dr James D. McCully, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 77 Ave Louis Pasteur, Room 144, Boston, MA 02115.
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.
Methods and 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).
Key Words: adenosine • myocardial infarction • stunning, myocardial • ischemia • reperfusion
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