EFFECTS OF EPOXYEICOSATRIENOIC ACIDS ON ISOLATED HEARTS AND VENTRICULAR MYOCYTES

Effects of cytochrome P-450 metabolites of arachidonic acid, epoxyeico satrienoic acids (EETS; 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET), w ere examined in isolated guinea pig hearts and ventricular myocytes. A ddition of 1-16 ng/ml EETs to normal isolated hearts produced no effec ts on contractility or coronary pressure. In hearts subjected to 60 mi n of low-flow ischemia, impairment of contractility and declines in he art rate and coronary perfusion pressure were similar in the presence or absence of 1 ng/ml EETs. However, in the presence of either 5,6- or 11,12-EET, recovery was delayed for the first 10 min only. No signifi cant differences were found in any group regarding heart rate, coronar y perfusion pressure, or energy metabolite content after 30 min of rep erfusion. In myocytes, both 5,6- and 11,12-EET (100 pg/ml, 1.0 ng/ml, and 20 ng/ml) significantly increased cell shortening as well as intra cellular calcium concentrations, whereas 8,9- or 14,15-EET was without effect on these parameters. These results describe for the first time the direct effects of various EETs on cardiac cell function as well a s their ability to modulate some of the myocardial responses to postis chemic reperfusion. The results suggest a potential role for these sub stances in the response of the heart to pathological insult.