Background: Retrograde perfusion preserves ischemic myocardium when initiated shortly after coronary artery occlusion. However, benefits diminish as the delay increases. In this study, we used this technique to deliver agents known to reduce the injury associated with the reperfusion of ischemic myocardium. We proposed that the local delivery of lidocaine or L-arginine before reperfusion would reduce the damage caused during reperfusion, even after a delay between onset of ischemia and intervention designed to approximate clinical reality.
Methods: In a porcine model of myocardial ischemia, the left anterior descending coronary artery was snared immediately distal to its second diagonal branch. After 1 hour of occlusion, 34 animals were randomized into six groups: no intervention (control) (n = 6); administration of normal saline solution into the great cardiac vein (Retro-NS) (n = 6); administration of lidocaine either intravenously (i.v.-LID) (n = 6) or retrograde (Retro-LID) (n = 6); and administration of L-arginine either intravenously (i.v.-L-ARG) (n = 5) or retrograde (Retro-L-ARG) (n = 5). After 90 minutes of ischemia, the snare was released, and the myocardium was reperfused for 3 hours. Two-dimensional echocardiograms were made prior to occlusion and 60, 150, 210, and 270 minutes after occlusion. The infarct size and the area at risk were determined by lissamine green and triphenyltetrazolium chloride staining with computer planimetric quantification. Regional wall motion was assessed by a wall motion score: normal = 1; mild hypokinesia = 2.0; severe hypokinesia = 2.5; and akinesia = 3.
Results: The area of the left ventricle at risk for infarction was similar in all groups and represented 25.4% (5.2% [standard deviation]) of the left ventricular mass (p = 0.63). The percent area of infarction in the area at risk after 3 hours of reperfusion was 76.7% (7.1% for the control group, 73.9% (5.7%) for the Retro-NS group, 72.1% (8.7%) for the i.v.-LID group, 54.5% (10.2%) for the Retro-LID group, 58.8% (4.0%) for the i.v.-L-ARG group, and 54.3% (4.0%) for the Retro-L-ARG group p < 0.005, Retro-LID and Retro-L-ARG versus Control, Retro-NS, and i.v.-LID; p < 0.03, i.v.-L-ARG versus control and Retro-NS). No significant difference in wall motion scores between groups was detected by echocardiography (p = 0.578).
Conclusions: Retrograde delivery of lidocaine or L-arginine before reperfusion reduces infarct size without acutely affecting wall motion after 90 minutes of ischemia and 3 hours of reperfusion. Lidocaine must be present before reperfusion to have an effect, whereas L-arginine is beneficial if it is delivered at the time of reperfusion.