DEMONSTRATION OF MYOCARDIAL REPERFUSION INJURY IN HUMANS - RESULTS OF A PILOT-STUDY UTILIZING ACUTE CORONARY ANGIOPLASTY WITH PERFLUOROCHEMICAL IN ANTERIOR MYOCARDIAL-INFARCTION

Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans. Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single-photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis. At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 +/- 3.1% vs. 8 +/- 2.3%, p < 0.02; and -1.6 +/- 0.4 vs. -2.9 +/- 0.2 SD/chord, p < 0.05). Tomographic infarct size expressed as a percent of the left ventricle was also reduced in Fluosol-treated patients (3.5 +/- 2.2% vs. 18.3 +/- 4.7%, p < 0.05). No significant differences in collateral blood flow, extent of coronary artery disease or residual stenosis after angioplasty were observed. This preliminary study suggests that myocardial reperfusion injury may be an important factor in limiting myocardial salvage in patients undergoing reperfusion. These findings have important clinical implications because adjunctive therapy may further amplify the beneficial effects of mechanical or pharmacologic reperfusion. Additional prospective randomized trials must be done to confirm and extend these preliminary results.