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Adenosine protects against attenuation of flow reserve and myocardial function after coronary occlusion and
W W Nichols1, F A Nicolini, B C Yang
1Department of Medicine, University of Florida College of Medicine, Gainesville 32610-0277.
Insights
Adenosine administration during reperfusion protects against coronary artery occlusion-induced injury. This treatment preserved coronary flow reserve and myocardial function, while reducing leukocyte infiltration in dogs.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Ischemia-Reperfusion Injury
Background:
- Coronary artery occlusion and reperfusion impair coronary blood flow reserve and myocardial function.
- These events also lead to increased myocardial leukocyte infiltration.
- Understanding protective strategies against such injury is crucial for cardiovascular health.
Purpose of the Study:
- To investigate the protective effects of intracoronary adenosine on occlusion and reperfusion-induced cardiac dysfunction.
- To assess adenosine's impact on coronary flow reserve, myocardial function, and leukocyte infiltration.
- To determine if adenosine can mitigate the negative consequences of ischemia-reperfusion in a canine model.
Main Methods:
- Fourteen dogs underwent 1-hour left anterior descending (LAD) coronary artery occlusion followed by 1-hour reperfusion.
- Seven dogs received intracoronary adenosine, while seven received a saline control, starting before reperfusion.
- Coronary flow reserve, myocardial shortening fraction, and myeloperoxidase activity were measured to assess outcomes.
Main Results:
- Saline-treated dogs exhibited significantly impaired coronary flow reserve and reduced myocardial shortening fraction post-reperfusion.
- Adenosine-treated dogs were fully protected against the loss of coronary flow reserve and maintained myocardial function.
- Myocardial myeloperoxidase activity, an indicator of leukocyte infiltration, was significantly lower in adenosine-treated dogs.
Conclusions:
- Intracoronary adenosine administration effectively protects against the detrimental effects of coronary artery occlusion and reperfusion.
- Adenosine preserves coronary flow reserve and regional myocardial function.
- Adenosine mitigates myocardial leukocyte infiltration during the reperfusion phase.
Abstract:
Total coronary artery occlusion and reperfusion result in attenuation of coronary blood flow reserve, regional myocardial dysfunction, and myocardial leukocyte infiltration. To examine the effects of intracoronary adenosine on these occlusion and reperfusion-induced perturbations, we subjected 14 dogs to total left anterior descending (LAD) coronary artery occlusion (1 hour) and reperfusion (1 hour). Seven dogs received adenosine (3.75 mg/min into the LAD distal to the occlusion) over a 1-hour period starting 5 minutes before reperfusion, and the remaining seven dogs received saline solution. One dog in each group died of ventricular fibrillation during coronary artery occlusion. Coronary flow reserve, measured as peak reactive hyperemia (10 and 20 seconds of total coronary artery occlusion) and peak coronary blood flow response to acetylcholine (0.01 to 1.0 micrograms) and nitroglycerin (5 to 25 micrograms), was impaired in the LAD region after LAD occlusion and reperfusion in the saline-treated dogs (all p < 0.01 vs before occlusion and reperfusion); LAD regional myocardial shortening fraction measured by ultrasonic crystals was also diminished after occlusion and reperfusion in saline-treated dogs (-5% +/- 1% vs 12% +/- 2%; p < 0.02). The adenosine-treated dogs showed total protection against loss of coronary flow reserve (peak reactive hyperemia and blood flow increase in response to acetylcholine and nitroglycerin; all p values not significant vs before LAD occlusion and reperfusion). LAD regional myocardial shortening fraction was also preserved in adenosine-treated dogs (9% +/- 2% vs 14% +/- 2%; p not significant). Myocardial myeloperoxidase activity, measured as an index of myocardial leukocyte infiltration, was greater (p < 0.02) in the LAD ischemic-reperfused regions than in nonischemic circumflex regions in the saline-treated dogs. A similar difference in myeloperoxidase activities in the reperfused and control regions was not observed in the adenosine-treated dogs. Thus adenosine protects against loss of coronary flow reserve and regional myocardial function in dogs subjected to coronary artery occlusion and reperfusion.