Intracoronary adenosine administered after reperfusion limits vascular injury after prolonged ischemia in the canine model

Abstract

Myocardial salvage after reperfusion may be limited by deleterious vascular changes in the previously ischemic microcirculatory bed. This could result in a progressive decrease in blood flow in the capillary bed to potentially viable myocytes (no-reflow phenomenon). The effect of intracoronary adenosine on these changes was assessed in 15 closed-chest dogs subjected to 2 hours of proximal left anterior descending artery (LAD) occlusion followed by 3 hours of reperfusion. Animals randomly received adenosine (n = 8) 3.75 mg/min into the proximal LAD or an equivalent volume of saline (control) (n = 7) for 1 hour after reperfusion. Endothelial-dependent and independent coronary vasodilator reserve was determined using a chronically implanted volume-flowmeter on the mild-LAD at baseline at 1 and 3 hours after reperfusion with acetylcholine and papaverine infusions, respectively, into the proximal vessel. Regional myocardial blood flow was measured serially with radioactive microspheres and regional contractile function with contrast ventriculography. Both agonists produced a significant increase in LAD flow before occlusion. Endothelial-dependent and independent vasodilatory reserve was significantly reduced (p < 0.05) at 1 and 3 hours after reperfusion in control animals compared with adenosine treatment. A progressive decrease in mild-LAD flow and increase in coronary vascular resistance after reperfusion was observed in control animals (p < 0.05). The treated group manifested improved regional myocardial blood flow in endocardial regions from the central (0.73 ± 0.15 versus 0.24 ± 0.11 ml/g/min; p < 0.02) and lateral ischemic zones (0.80 ± 0.15 versus 0.34 ± 0.12 mg/g/min; p < 0.05) 3 hours after reperfusion. A significant reduction (p < 0.05) in endocardial and midmyocardial flow compared with baseline was seen in control animals at 3 hours. Intravascular and interstitial neutrophil infiltration was reduced in adenosine animals and this was associated with relative ultrastructural preservation of endothelial cells. Regional ventricular function in the ischemic zone was improved in the adenosine group 3 hours after reperfusion (13.4 ± 3.9% versus -5.3 ± 1.6%; p < 0.001). This study demonstrates that selective administration of adenosine after reperfusion significantly attenuates functional and structural abnormalities in the microvasculature after prolonged (2 hours) regional ischemia in the canine model. Prevention of microvascular injury and the no-reflow phenomenon by adenosine may preserve reversibly injured myocytes following restoration of blood flow to previously ischemic myocardium.