PROTEIN-C ACTIVATION FOLLOWING CORONARY-ARTERY OCCLUSION IN THE INSITU PORCINE HEART

Background. Activated protein C, the body's natural anticoagulant, may play a role in protecting the heart during and following an occlusion of the left anterior descending coronary artery (LAD) in the porcine heart. Methods and Results. Infusion of 1 unit thrombin over 30 seconds into the LAD of juvenile pigs produced a prolongation of the Xa clotting time (153 +/- 14%) in blood drawn from the anterior interventricular vein (AIV). The action of the anticoagulant was blocked by a polyclonal immunoglobulin G antibody directed against porcine activated protein C. A brief (30 seconds) occlusion of the LAD induced a similar prolongation of the Xa clotting time (138 +/- 11%), which was also blocked by the polyclonal antibody. To determine whether activated protein C helps sustain the heart during and following a 2-minute occlusion, three groups of pigs were studied: 11 controls, six receiving activated porcine protein C, and nine receiving a monoclonal antibody (HPC4) that blocks protein C activation. Relative to the controls, HPC4-treated animals recovered function, as measured by the maximum time derivative of left ventricular pressure and segmental shortening, more slowly and were not able to sustain this recovery. Animals receiving activated protein C recovered more quickly and sustained this recovery. Conclusions. These data indicate that an ischemic insult induces rapid activation of protein C in the coronary microcirculation and that blocking this activation impairs recovery.