Controlled coronary hydrodynamics at the time of reperfusion reduces postischemic injury

Background: In a canine preparation of 2 hours of coronary occlusion and 2 hours of reperfusion, we tested the hypothesis that controlled hydrodynamic conditions (coronary pressure and flow) of reperfusion would decrease infarct size and improve regional functional recovery. Methods: In 28 anesthetized, open-chest dogs, segmental contractile work and diastolic stiffness (sonomicrometry), and myocardial blood flow (15 μm microspheres) were measured in the segment per fused by the left anterior descending (LAD) and circumflex coronary arteries. After 2 hours of LAD occlusion, reperfusion was established using an extracorporeal perfusion circuit to control intracoronary pressure and blood flow. Twelve dogs did not complete the protocol or meet exclusion criteria. In eight dogs (abrupt group), blood flow was abruptly restored and continued for 2 hours of reperfusion. In eight dogs (ramp group), blood flow was adjusted so that LAD perfusion pressure was linearly incremented over the first 30 minutes of reflow, and equalized to mean arterial pressure thereafter. Results: Two hours of LAD occlusion reduced myocardial blood flow in the ischemic zone from 67.7 ± 11.7 to 11.7 ± 4.7 mL/min/100g (P< 0.05) in the abrupt group, and from 64.3±5.8 to 12.5 ± 3.2 in the ramp protocol (no significant group difference). After 2 hours of reperfusion, myocardial blood flow in the ischemic zone was 31% higher (117.4 ± 17.6 vs 81.4 ± 17.0mL/min/100g P = 0.02), whereas segment work recovered to a greater extent (50.3% ± 19.3% vs 1.4% ± 4.1% of baseline, P=0.03) in the ramp than the abrupt group. Segmental diastolic stiffness was increased by 421 % of baseline with abrupt reperfusion, but was significantly reduced (P< 0.01) in the ramp group. Area of necrosis (triphenyltetrazolium chloride stain), expressed as a percent of the area at risk, was reduced by 67% in the ramp group compared with the abrupt group (16.8% ±3.0% vs 50.1% ± 4.6%, P=0.0001). Conclusions: Slowly increasing coronary pressure and blood flow during the early phase of reperfusion 1) increases postischemic systolic and diastolic functional recovery, 2) improves postischemic blood flow, and 3) reduces infarct size by 67%. These data suggest that the mode of reperfusion may be a factor in determining myocardial injury after reversible occlusion.