MYOCARDIAL-INFARCTION AND THE MYOCYTE IGF(1) AUTOCRINE SYSTEM

To determine the effects of acute myocardial infarction on the extent and distribution of mural stress on surviving myocardial tissue, coron ary artery occlusion was surgically produced in rats. Following haemod ynamic measurements in vivo, the characteristics of cardiac anatomy we re determined and found to consist of an increase in mid-chamber lumin al diameter and a decrease in wall thickness. The combination of these phenomena resulted in an eight-fold increase in diastolic wall stress on the remaining viable portion of the wall and severe impairment of left and right ventricular performance. Since insulin-like growth-fact or-1 (IGF(1)) and its receptor (IGF(IR)) are required for cell growth in vitro, the possibility was raised that an autocrine IGF(1)-IGF(IR) system may be present in vivo and may become activated in viable ventr icular myocytes shortly after infarction. Therefore, the unaffected my ocytes of the left ventricle were enzymatically dissociated and the ex pression of IGF(IR) and IGF(1) mRNAs were measured at 12 h and at 1, 2 -3, and 7 days after surgery. The level of IGF(IR) mRNA increased at 1 2 h and remained elevated at 1 and 2-3 days following coronary artery ligation. In addition, an increased level of IGF(IR) protein was found on these cells. This phenomenon was coupled with the enhanced express ion of IGF(1) mRNA in the muscle cells at all points. Thus, the marked elevation in ventricular loading after coronary occlusion may activat e the IGF(1)-IGF(IR) autocrine system of the unaffected cells, modulat ing the cellular growth processes implicated in short-term ventricular remodelling of the infarcted heart.