Myocardial dysfunction and coronary vasoconstriction induced by platelet-activating factor in the post-infarcted...

Myocardial injury was produced in separated groups of anesthetized rabbits by occlusion of the left circumflex coronary artery for 1 h followed by reperfusion for 2, 4, or 6 h after release of the occlusive ligature. The ischemically-injured and reperfused hearts subsequently were isolated and perfused using a modified Langendorff apparatus. Platelet-activating factor in the form of AGEPC (1-0-hexadecyl-2-acetyl-sn-glyceryl-phosphorylcholine), 40 nmol in 1 ml, was infused above the coronary ostia over 15 s. Thromboxane B2 (TxB2- and peptidoleukotrienes (LT) were measured in the lymphatic effluent from the heart. Noninfarcted hearts (isolated hearts and sham-operated animals) served as procedural controls and lyso-GEPC (1-0-hexa-decyl-2-0-lyso-sn-glyceryl-phosphorylcholine), 40 nmol in 1 ml, served as the agonist control. After the infusion of AGEPC in the infarcted hearts, coronary perfusion pressure and left ventricular end-diastolic pressure increased while left ventricular peak systolic pressure decreased. The observed changes coincided with TxB2 peak release at 1 min and LT peak release at 2 min. The longer post-ischemic reperfusion time was associated with increasingly greater changes in these parameters. In hearts isolated after 6 h of reperfusion, the functional changes and the appearance of TxB2 and LT in response to the administration of AGEPC reached a significant level (ANOVA) with respect to those base-line values and the values obtained with hearts from sham-operated animals. Minimal changes occurred in noninfarcted hearts or with the administration of the biologically inactive phospholipid, lyso-GEPC. Histologic evaluation of cardiac tissue showed a progressive time-dependent migratory increase of leukocytes from the intra- and perivascular areas toward the region of infarcted myocardium. Platelet aggregates were seen in the intravascular spaces. The data are consistent with the suggestion that the infiltrating leukocytes and platelets may serve as a source for the synthesis and release of TxB2 and LT in acutely infarcted hearts upon exposure to AGEPC. If it is possible for AGEPC to be synthesized and released from vascular endothelial or inflammatory cells leading to the formation of thromboxane A2 and LT from reperfused myocardium, then these substances may participate in increasing coronary artery resistance and in the development of myocardial dysfunction during the evolution of an acute myocardial infarction and especially during the phase of perfusion.