12-o-tetradeca-2-4-6-8-tetranoylphorbol-13-acetate and Coronary-Disease

The role of protein kinase C (C kinase) in the left ventricular relaxation impaired by global ischemia was investigated in anesthetised dogs. Left ventricular global ischemia model was made by coronary blood flow reduction and atrial pacing (100-180 beats/min). By this maneuver, the time constant T and left ventricular end-diastolic pressure (LVEDP) were increased in a pacing-rate dependent manner. Intracoronary infusion of H-7, an inhibitor of C kinase, suppressed the magnitudes of the increments of T and LVEDP, while intracoronary infusion of 12-O-tetradecanoyl-phorbol-13-acetate, an activator of C kinase, enhanced the increases of T and LVEDP caused by ischemia. In non-ischemic group, H-7 did not influenced T and LVEDP. The results indicate that C kinase is activated by myocardial ischemia and enhances impairment of left ventricular relaxation.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Calcium; Coronary Disease; Dogs; Isoquinolines; Myocardial Contraction; Piperazines; Protein Kinase C; Tetradecanoylphorbol Acetate